Q3 2022 Roivant Sciences Ltd Earnings Call

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Speaker 1: Today's conference is scheduled to begin shortly. Please continue to stand by and thank you for your patience.

[music].

Speaker 2: The End

Speaker 2: ["Pomp and Circumstance"]

Speaker 1: Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Roy Vant third quarter earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone. I would now like to hand the conference over to your speaker today, Paul Davis, head of communications. You may begin.

Good day, ladies and gentlemen, and thank you for standing by and welcome to the <unk> third quarter earnings call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question. During the session you will need to press star one on your telephone.

I would now like to turn the conference over to your Speaker today, Paul Davis head of Communications you may begin.

Speaker 3: Thank you and good morning. Thanks for joining today's call to discuss Roy Vant's third quarter results and business updates. I'm Paul Davis, the head of communications at Roy Vant. On the call today, we have Matt Klein, our chief executive officer, Richard Bullock, our chief financial officer, Frank Torti, our VAMP chair, Eric Banker, president and chief operating officer, and finally Mayuk Stokape, president and chief investment officer.

Thank you and good morning, Thanks for joining today's call to discuss <unk> third quarter results and business updates on Paul Davis head of communications and broadband on the call today, we have Matt Klein, our Chief Executive Officer, Richard Bullock, Our Chief Financial Officer, Frank <unk>, Our damn sure Eric banker, President and Chief operating Officer and finally.

President and Chief investment Officer.

Speaker 3: For those dialing in via phone, you can find the slides being presented today, as well as the press release announcing these updates on our IR website at www.investor.royvant.com. We'll also be providing the current slide numbers as we present to help you follow along.

For those dialing in by phone you can find the slides being presented today as well as the press release announcing these updates on our IR website at Www Dot Investor Dot one dot com will also be providing the current slide numbers as we presented to help you follow along.

I would like to remind you that we will be making certain forward looking statements. During today's presentation that reflect our current views and expectations, including those related to our financial performance and the potential attributes of our product candidates. We strongly encourage you to review the information that we have filed with the SEC, including the earnings release and Form 10-Q filed this morning for more information regarding these forward looking statements and related risks and.

Speaker 3: I would like to remind you that we will be making certain forward-looking statements during today's presentation that reflect our current views and expectations, including those related to our financial performance and the potential attributes of our product candidates. We strongly encourage you to review the information that we have filed with the SEC, including the earnings release and Form 10Q filed this morning for more information regarding these forward-looking statements and related risks.

<unk> will begin with Mac behind will review key business updates across broadband advance and provide a financial update we will end the call with a Q&A session without further Ado I'll turn it over to Matt.

Speaker 3: We'll begin with Matt Gline, who will review key business updates across Royvent and Advanced and provide a financial update. We will end the call with a Q&A session. Without further ado, I'll turn it over to Matt.

Speaker 3: Thank you, Paul. Good morning, everybody. And thank you for joining our third quarter earnings call. It's been an eventful quarter for us with that with a number of key updates, including immune events, putting the toclum ab back into the clinic and my senior Kravis, including favorable field sports decision on Genovans in December , including the introduction of a new program on at a new event at hemovans and myelovus plastic syndrome. So I'm excited to share those and other updates over the course of today's presentation.

Thank you Paul Good morning, everybody and thank you for joining our third quarter earnings call, it's been an eventful quarter for us.

With that.

A number of key updates including.

Putting the total NAV back into the clinic in myasthenia gravis, including favorable Appeals court decision on Gen event in December including the introduction of a new program.

At our new Vantiv Hemo, Vantiv Myelodysplastic syndrome, so I'm excited to share those and other updates over the course of today's presentation.

Speaker 3: I'll begin on slide four just by giving an overview of some of the key features of our business as well as some of the key updates, and then I'll go through a number of them in more detail.

I'll begin on slide four just by giving an overview of some of the key features of our business as well as some of the key updates and then I'll go through a number of them in more detail.

Speaker 3: So I want to start by saying that both the prior quarter and the coming year are incredibly exciting for Royvent as a company, with a number of important projects coming to fruition over the coming months and year. The first of those is our near-term commercial launch of topinor-off, a potential blockbuster in psoriasis, a topical treatment of psoriasis with an expected PDUFA date in the second quarter of 2022 and a launch thereafter. We'll talk more about that in the next couple of minutes.

So I want to start by saying the goal the prior quarter and the coming years are incredibly exciting for vitamins is a company with a number of important important projects coming to fruition over the over the coming months in here.

The first of those is our near term commercial launch of dependent off.

Potential blockbuster in psoriasis, a topical treatment for psoriasis with a with an expected <unk> date in the second quarter of 2022, and our launch thereafter, we'll talk more about that in a moment.

Speaker 3: That's backed by a number of updates in our broad clinical stage pipeline. We will have at least eight pivotal or proof of concept trials running by the end of this year. And that includes progress at our newest VAN, heme VANs with RBT2001 recently added to our pipeline of first in class or potential first in class oral SF3B1 modulator for transfusion dependent anemia and patients with low risk MDS.

It's backed by a number of updates on our broad clinical stage pipeline.

We will have at least eight pivotal or proof of concept trials running by the end of this year.

And that includes that includes progress at our newest Vamped heme event with RVP 2001 recently added to our pipeline of first in class or potential first in class B, one modulator for transfusion dependent anemia in patients with low risk Mds.

Speaker 3: low risk MDS. That includes updates at Immutavamp and Topolab, as I mentioned, and that includes other updates at a number of other programs, including our sickle cell disease program, as well as Nimlumab or anti-GFCS antibody with improved IMD and sarcoidosis.

Risk Mds that includes updates that immuno vantiv total app as I mentioned and that includes other updates at a number of other programs, including our sickle cell disease program as well as millimeter oriented GM CSF antibody with improved <unk> doses will.

Speaker 3: We'll be talking today a little bit more about strategy in our discovery platform, where we've made some significant progress in crystallizing our plans and adding capabilities that we think will give us differentiated strength at designing new small molecules, as well as a number of other areas of asymmetric potential upside, including Gen Event, with both our intellectual property and scientific capabilities delivering.

We will be talking today, a little bit more about strategy in our discovery platform, where we've made some significant progress and crystallizing our plans in and adding capabilities that we think will give us differentiated strength at designing small molecules as well as a number of other areas of eastern metric potential upside, including Jonathan with both their intellectual property and scientific capabilities.

Delivering.

Speaker 3: novel and important lipid nanoparticles for nucleic acid delivery, as well as continuing updates in our early-stage clinical pipeline. And all of that backed by a strong capital position with $2.2 billion in cash as of December 31st, plus a significant amount, about $870 million in public equity stakes and some private holdings including updated.

<unk>, an important lipid nanoparticles for nucleic acid delivery.

As well as continuing up based on our early stage clinical pipeline and all that backed by a strong capital position with $2 $2 billion in cash.

Remember 31, plus a significant amount.

$870 million of public equity Stakes in some private holdings, including update of that.

Speaker 3: So we'll start today's presentation by giving everyone an update on Tepenrof at Dermavant, which is a program that we're obviously very excited about starting on page six.

I will start today's presentation by.

Giving everyone an update on <unk>, which is which is a program that we're obviously very excited about starting on page six.

Speaker 3: So as a reminder, Tepidrof is a topical agent for the treatment of psoriasis. It's a therapeutic arrow hydrocarbon modulator. It's the only drug of that mechanism that works.

So as a reminder.

<unk> is a topical agents for the treatment of psoriasis, it's a therapeutic arrow hydrocarbon modulators the only such.

The only drug of that mechanism that we're aware of.

Speaker 3: And we are, we have our data on psoriasis and have an ongoing study in atopic dermatitis with data expected in the first half of 2023. I want to remind people as it comes to Tepenar off.

And that we are we have our data in psoriasis and have an ongoing study in atopic dermatitis with data expected in the first half of 2023 and I want to remind people as it comes to spin off some of the attributes that make us excited about the program, including a remarkable treatment effects.

Speaker 3: of some of the attributes that make us excited about the program, including a remarkable proven effect.

Speaker 3: with significant efficacy, efficacy that we think is as good or better than anything that has been observed in a topical before, with up to 40% of patients over the course of our clinical program completely clearing their psoriasis.

With that with significant efficacy efficacy that we think is.

As good or better than anything that is observed absorbed in a topical for.

With up to 40% of patients over the course of our clinical program completely clearing their psoriasis.

Speaker 3: with significant durability, so our drug continues to perform better in our long-term extension study, the longer that patients stay on it, including beyond 12 weeks.

With significant durability. So our book continues to perform better than our long term extension study the longer the patients stay on it including beyond 12 weeks.

Speaker 3: with what we believe to be a completely unique to topical's remit of benefit, where I mentioned 40% of the drugs, 40% of the patients who go on drug completely clear their psoriasis in our study. They stay clear of drug off therapy or mostly clear for about four months.

With what we believe to be a completely unique to topical related benefit where I mentioned, 40% of the drugs affordable none of the patients will go on drug completely clear their psoriasis in our study they stay clear of drug off therapy or mostly clear.

For about four months on median.

Speaker 3: which is something that's attractive to payers obviously, attractive to patients, attractive to physicians. And all that is coupled with a

Which is something thats attractive to payers, obviously attractive to patients and attractive to physicians and all that is coupled with.

Speaker 3: a very favorable safety and tolerability profile with no treatment related serious adverse events in any of our pivotal studies, the late stage studies.

A very favorable safety and Tolerability profile with no treatment related serious adverse events in any of our any of our pivotal studies late stage studies in that.

Speaker 3: with significant tolerability. So with no questions of tolerability for long duration therapy or duration across, or therapy across all different locations on the skin. So a profile that we think compares favorably certainly to the standard of care of topical corticosteroids without any of the, at least in our study, without any limitations on duration that you see with top corticosteroids, without any limitations on where you can use it on your body as observed with some of the potent topical corticosteroids.

With significant Tolerability, so with no no questions of Tolerability for long duration therapy.

Our duration of.

<unk> therapy across all different locations on the skin. So a profile that we think compares favorably certainly to the standard of care pump corticosteroids without any of the.

In our study without any limitations on duration that you see with the start of corticosteroids without any limitations on where you can get on your body as observed with some of the potent topical corticosteroids.

Speaker 3: On page seven, I want to remind people of one piece of relatively recently disclosed data that we think is exciting about the drug, which data we've shown previously, but to highlight the rapid onset of action is one of the things that we think will be important to this as we launch to Pinter off later this year. With our drug having achieved statistically significant improvement in PASI from baseline as early as we can, we're going to be able

On page seven I want to remind people.

One piece of relatively recently disclosed data that we think is exciting about the drug which data we've shown previously but the highlight the rapid onset of action is one of the things that we think will be important to this is we launched a interop later this year.

With our drug having achieved statistically significant improvement in <unk> from baseline as early as week two.

Speaker 3: in our study, and in fact a 20% reduction in disease activity in week two relative to vehicles. So we think there's a significant benefit here early on in treatment, and we think that will matter to patients.

Our study.

A 20% reduction in disease activity and we too.

Relative to vehicles. So we think there is a significant benefit here early on in treatment and we think that will matter to patients.

Speaker 3: In fact, on slate 8, and this is a new piece of information that we've put out this quarter relatively recently, Dermavant as part of our long-term extension study included patient satisfaction data. And you can see on this chart both on the left-hand side, patient satisfaction, these are the other topical treatments. And on the right-hand side, you can see patient satisfaction versus systemic drugs. And so one of the interesting is 80-plus percent of patients that are on PC they don't actually feel normal pain.ODUCT behavior can be usually very clinical, like emotion, man-to-man behavior, Rare Kawavia-Hiss, or cosmic Somalia, However, there are other treatments. And there still is a problem. In fact, on this chart,

In fact on slide eight and this is a new piece of information that we put out this quarter relatively recently.

Terminate as part of our long term extension study, including patient satisfaction data and you can see on this chart. Both on the left hand side patient satisfaction vis vis.

Other topical treatments and on the right hand side, you can see patient satisfaction.

Versus systemic drugs and so one.

One of the interesting is.

80 plus percent of patients.

Speaker 3: strongly agreed or agreed that Tepenorof was more effective than other topical drugs they'd used in the past and preferred Tepenorof to other topical drugs they've used in the past. And, you know, given the attributes that I described on the earlier slide here, both from a treatment effect perspective and a safety and tolerability perspective, we would have expected that. One of the things that's remarkable is over 2-thirds of patients, 67.8% of patients, also preferred Tepenorof to systemic drugs they'd used in the past.

Strongly agreed or agreed to Peter off was more effective than other topical drugs they'd used in the past and preferred dependent off other tropical drugs thats used in the past and so given the attributes as I described on the earlier slide here both from a.

A treatment effect perspective, and a safety and Tolerability perspective, we would have expected that one thing thats remarkable.

Over two thirds of patients 67, 8% of patients also preferred to pair off too systemic problems they've used in the past.

Speaker 3: which given the high level of efficacy associated with systemic therapy and the fact that often severe patients around systemic therapy, it was exciting to us to see just how many patients preferred to turn off to systemic drugs. So these are the kinds of data that matter to prescribers and the kind of data that matters to patients obviously. And we think the dermatologists are looking at this and are getting excited for our potential launch later this year.

Which given the high level of efficacy associated with systemic therapy, and the fact that often severe patients around systemic therapy. It.

It was exciting to us to see just how many patients preferred printer off just systemic drugs. So these are the kinds of data that matter to prescribers.

Does that matter to patients obviously, we think that dermatologists are looking at this and are getting excited for our potential launch later this year.

Speaker 3: On slide nine, a little bit about that launch.

On slide nine.

A little bit about that launch so.

Speaker 3: So we are fully preparing for a launch in the second quarter, including getting ready to deploy a specialty sales force capable of calling on dermatologists to write more than 80% of all commercial prescriptions in this rheisis market. To do that, we're going to hire 75 to 100 reps.

We are fully preparing for a launch in the second quarter.

Including.

We're getting ready to deploy a specialty sales force capable of calling on dermatologists write more than 80% of all commercial prescriptions in the psoriasis market to.

To do that we're going to hire 75 to 100 reps.

Speaker 3: which will allow us to reach the 6,000 highest value dermatology healthcare providers. And we think that will be supported by a key commercial leadership team, many of the members of which have already been hired. We're conducting a number more of those hires over the course of the coming quarter.

It will allow us to reach the 6000, the highest valued dermatology health care providers, and we think that will be supported by our key commercial leadership team. Many of many of the members of which have already been higher we're conducting a number more of those hires over the course of the coming quarter. So really excited about the execution of thermal demand from a very high quality team.

Speaker 3: So really excited about the execution of ThermoVac from a very high quality team that we're pleased to support.

We're pleased to support.

Speaker 3: On page 10, just a reminder of some of the recent progress at Dormavant, including that our NDA submission remains on track with no expectation of an advisory committee for PDUFA in the second quarter, including

On page 10, just a reminder of some of the recent progress at Durham event.

Including that R&D submission remains on track with no expectation of Advisory Committee for <unk> in the second quarter.

Including as.

Speaker 3: manufacturing commercial production readiness on track to ensure a high quality predictable supply of drug. And as I mentioned, the commercial organization is being built out as we speak. We did in this quarter have data from our SORING 1 and SORING 2 trials published in the New England Journal of Medicine, so that was an exciting sort of scientific closure to those trials. And then we continue to have strong enrollment in our ADORING 1 and ADORING 2 phase 3 trials evaluating T

Manufacturing commercial production readiness central on track to ensure a high quality and predictable supply and fraud.

Mentioned, the commercial organization is being built out as we speak we did in the quarter have a data from our sorting one and starting two trials published the New England Journal Medicine.

Unexciting sort of scientific closer to those trials and then we continue to have strong enrollment in our enduring wanted to during two phase III trials evaluating <unk> in atopic dermatitis.

Speaker 3: And we continue to expect top-line data from that program in the first half of 2023. So we're providing more updates on fenorrhophanate topic dermatitis over the course of this year. And we think that'll be an important part of the story for us as well.

We expect topline data from that program in the first half of 2023, so look forward to providing more updates on thinner off in atopic dermatitis over the course of this year.

And we think that'll be an important part of the story for us as well.

So with that I'm going to move on from Jupiter off to some other parts of our business.

Speaker 3: So with that, I'm going to move on from to pin it off to some other parts of our business.

Speaker 3: And on slide 12, just as a reminder, we have a broad clinical development stage pipeline. So this is our clinical and close to the clinic development stage pipeline with many programs. Pinarafka, we talked about, the Toklemab and the Munivam that we'll talk about a little bit later, and a number of other programs. Too many to talk about on a call like this one, but we look forward to sharing updates on many of these programs over the course of calls like this one in a conference presentation over the course of this year.

And on Slide 12, just as a reminder, we have a broad.

Clinical development stage pipeline. So this was our clinical and close to the clinic development stage pipeline with many programs spinoff that we talked about total amount, but I'm convinced that we'll talk about a little bit later.

And a number of other programs too many to talk about on a call like this one but we look forward to sharing updates on many of these programs over the course of calls like this one in a conference presentations over the course of this year.

And.

Speaker 3: You know, on page 13, just to highlight, 2022 is actually a really important year for us from a clinical development execution perspective. And even just among the things we've already talked about, three pivotal study initiations expected for Botoclamab and Immunivant this year. We remain on track to initiate a phase two trial of Namilumab for sarcoidosis. That's our anti-GMCSF antibody. And during this best quarter, the IND for that program in sarcoidosis has been approved.

On page 13, just to highlight 2022 was actually a really important year for us from a clinical development execution perspective.

And even just among the things we've already talked about three pivotal study initiation is expected for the total NAV, but immuno Vance this year.

We remain on track to initiate a phase II trial with Nomad sarcoidosis, Thats, our anti GM CSF antibody and during this past quarter. The IMD for that program in sarcoidosis has been approved.

Speaker 3: We remain on track to initiate a multiple-setting dose trial for our program at LYSE event with the IMD accepted in January of 2022. And we'll talk a little bit more about this program on this call. We're looking forward to conducting a robust open-label expansion of the ongoing Phase 1, 2 trial in ARVID-T 2001 at our newly formed heme event in lower-risk MDS. So many important clinical programs ongoing this year with an expectation of near-term data supporting what we think is going to be a unique and interesting Phase 1.

We remain on track to initiate a multiple ascending dose trial for for our program at <unk> with the <unk>.

<unk> accepted in January of 2022.

And we'll talk a little bit more about this program on this call.

Looking forward to conducting a robust open label extension of the ongoing phase one two trial in <unk> 2001 that our newly formed Hema Vance.

In low risk Mds so.

Many important clinical programs ongoing this year with an expectation of near term data supporting what we think is going to be a unique and interesting pipeline.

I'm going to start first on the development side by talking about <unk>, which is the newest vantiv family. It was just.

Speaker 3: I'm going to start first on the development side by talking about Hemovant, which is the newest vant in the vant family. It was just built around a program that we licensed just late last year. And so I'll start on page 15.

Built around the program that we in licensed just late last year and so I'll start on page 15.

Speaker 3: So the program here is called RVT-2001. It is a potential first-in-class small molecule SF3B1 modulator for the treatment of transfusion-dependent anemia in patients with lower risk MDS. So SF3B1, if you're not familiar with, is a target.

The program here is called <unk>, one is a potential first in class small molecule <unk> modulator for the treatment of transfusion dependent anemia in patients with lower risk Mds. So as a free if you wanted if youre not familiar with as a target.

Speaker 3: in the spliceosome and the program came from AZAI.

And this places on this program came from Adi.

Speaker 3: where AISI had been focused on developing it for higher risk progressive MDS patients as well as patients with AML and CMML, and it wasn't totally clear from their data whether it was exactly an appropriate therapy for that population, but as we looked at the data, and we're going to share some of it on today's call, we got excited about RBT2001 for a different patient population, namely the population of transfusion-dependent anemia.

I had been focused on developing it for higher risk progressive Mds patients as well as patients with AML and CML.

And it wasn't totally clear from their data or whether it was exactly an appropriate therapy for that population, but as we looked at the data and we're going to share some of it on today's call. We got excited about RV teachers 001 for a different patient population, namely the population of transfusion dependent anemia.

Speaker 3: or the treatment of transfusion-dependent media in lower risk myeloid plastic syndrome. And this is a market, as you may know, that has been recently validated by Luz Patricep, a BMS drug that launched...

<unk> differentiate independent media in lower risk Myelodysplastic syndrome, and this is a market as you may know that has been recently validated by.

Patterson proposal.

Our BMS drug.

<unk> launched.

Last year and is now annualizing at over $500 million of your platforms into launching bms's forecasting that to be in over $4 billion peak sales much of which coming from this lower risk Mds population.

Speaker 3: last year and is now annualizing at over $500 million a year five quarters into launch. And BMS is forecasting that to be an over $4 billion peak sales drug, much of which coming from this lower risk MDS population. And our interest in that population is driven, as I said, by some encouraging group of concept data in the 80-plus patient phase one, two study that's been conducted in our drug. And we'll talk some more about that data. And we have a multi-pronged development strategy to optimize the drug's impact on that patient population, which we'll get into.

Our interest in that population is driven as I said by some encouraging proof of concept data in the 80 plus patient phase one two study that's been conducted in our drug and we'll talk some more about that data and we have a multi plant multi pronged development strategy to optimize the drugs impact in that patient population, but we will get into.

So on page 16.

Speaker 4: So on page 16, A is a little bit of a reminder of what this patient population looks like, and B is a little bit of a discussion about how we expect our drug to play. So we're focused here, as I said, on the group of lower risk MDS patients. So there are about 17,000 new MDS cases each year, and about 115,000 MDS patients total. And low-risk patients are both a significant fraction, about two-thirds of new patients, as well as an even higher fraction of the prevalent population.

A little bit of a reminder of what this patient population looks like it can be as a little bit of a discussion about how we expect are going to place. So we're focused here as I said on the on the group of lower risk Mds patients. So there are about 17000, new Mds cases, each year and about 115000, Mds patients total and low risk patients are both significant fraction about two thirds of new pay.

<unk> as well as an even higher fraction of the prevalent population.

Speaker 3: So, and these are quite sick patients. Loric MDS is a chronic condition with therapy focused on management of symptoms. And first line therapy is mostly erythropoiesis stimulating agents, ESAs, but they're not very effective. And so there are a number of drugs approved for later line therapy, just a couple, with Patricept and Lenalidomide, each approved for subsets of patients.

So.

And these are these are quite sick patients, but risk Mds is a chronic condition with therapy focus on management of symptoms.

And first line therapies, mostly original cohesive stimulating agents Esa.

But they are not very effective.

So there.

There are a number of drugs approved for later line therapy, just a couple with Patterson and Lenalidomide.

Each approved for subsets of patients.

Speaker 3: Luspatricept is approved currently in second line therapy, although BMS has said they're continuing to develop it in earlier line therapy. Lenalidomide, which has significant toxicities, is really only approved for a mutant subset, the 5q-subset of MDS patients. And both of those drugs also be room for improvement. Luspatricept is effective in less than 50% of patients.

<unk> currently in second line therapy, although BMS has said, they're continuing to develop it in earlier line therapy, Lenalidomide, which has significant toxicity is really only approved for a mutant subset. The fact, you minus subset.

Mds patients in both of those drugs also.

Room for improvement with fatter surplus effective in la.

Less than 50% of patients.

Speaker 3: And so, you know, RVT 2001 is a potential oral therapy, first of all, which is different from lispatricept. In a genetically validated target that's mutated in up to 80% of certain subsets of the MDS patient population, which is thought to be an important target in driving MDS mutations in S03.1 are thought to be important.

So <unk> 2001, as a potential oral therapy first of all which is different from <unk>.

In a genetically validated target, that's mutated and up to 80% of certain subsets of the Mds patient population.

Which is thought to be an important.

An important target.

Driving Mds mutations inertia and that's just through the water, but could be important.

Speaker 3: Our initial plan is to target second line, principally in SF3V1 mutated patients, with the potential to expand across other spliceosome mutations, as well as to expand to patient populations who are refractory to the spatter staff, where as I said, there's still a significant potential lead and to go earlier in therapy.

Our initial plan is to target second line principally.

Principally in <unk> mutated patients with the potential to expand across other spliceosome mutations as well as to expand into patient populations, who are refractory to the spatter shaft, where as I said, there is still significant and to lead and to go earlier in therapy over time.

Speaker 3: So I want to talk on page 17 a little bit about our early clinical data and why we're excited about the program, and I'll highlight, this is a relatively high-risk program, in part because a lot of this data comes from relatively smaller ends and from cross-trial comparisons, but we think it paints an interesting picture.

I want to ask on page 17, a little bit about our early clinical data on why we're excited about the program.

Ill highlight because this is a relatively high risk program in part because a lot of this data comes from relatively smaller ends and from cross trial comparisons, but we think it paints an interesting picture.

Speaker 3: So in the existing phase one, two study that I referred to, with 84 patients for SMDS, AML and CMML.

Hi, Ely existing phase one two study that I referred to with 84 patient Trust Mds AML and CML.

Speaker 3: Only a relatively small subset of those patients, because it wasn't AZI's main treatment interest, were in our patient population of interest. Only 19 of the patients had lower risk transfusion-dependent MDS. And in that patient population, we saw a red blood cell transfusion independence rate of a little over 30%. Now, that in and of itself is not...

Only a relatively small subset of those patients because it wasn't as high as main treatment interest. We're in our patient population of interest only 19 of the patients had lower risk transfusion dependent Mds and in that patient population, we saw a red blood cell transfusion independence rate of little over 30% so that in and of itself is not necessarily.

<unk>.

Speaker 3: a particularly compelling result only in the sense that the spatter zap for example has responder rates in the 40s, but what was interesting upon further investigation is the subset of patients that we were focused on.

A particularly compelling results only in the sense of the scatter set for example, as responder rates in the <unk>, but what was interesting. Upon further investigation is the subset of patients that we were focused on.

Is that.

Speaker 3: It turned out to have been a highly sort of pre-treated patient population with 15 of the 19 patients having been pre-treated either with lenalidomide or with prior HMA therapy.

It turned out to have been a highly pretreated patient population with 15 of the 19 patients haven't been free treated either with lenalidomide or with prior HMA therapy, and what's interesting about that is both leach patter staffed and might a little mind in prior trials have struggled significantly in those pre treated patient populations so with Patterson.

Speaker 3: And what's interesting about that is both luspatercept and lenalidomide in prior trials have struggled significantly in those pretreated patient populations. So luspatercept, for example, had only achieved a 13% red blood cell transfusion independence rate among lenalidomide pretreated patients and luspatercepts phase two trial. And in fact, that result was so challenging that luspatercepts phase three study actually excluded lenalidomide for treated patients.

For example had only achieved a 13% red blood cell transfusion independence rate among lenalidomide pre treated patients that was better steps phase II trial and in fact that result was so challenging but we find ourselves phase III study actually excluded lenalidomide pretreated patients and Lenalidomide and investigator sponsored trials. So at 12% what's called an HIV that's a different end.

Speaker 3: And lenalidomide in an investigator-sponsored trial, so like 12% was called an HIE. That's a different endpoint. So sort of a transfusion reduction endpoint in HMA pretreated patients.

So we feel about transfusion reduction endpoint.

HMA pretreated patients.

Speaker 3: So that alone, first of all, is interesting. We saw a significantly higher response rate. In fact, over double the response rate of transfusion independence relative to the spatter of dulendalitamide in a similarly pretreated population.

So that alone and first of all it's interesting we saw a significantly higher response rate in fact over double the response rate of transfusion independence relative to spatter separate lenalidomide.

Any similarly pretreated population.

Speaker 3: Now further and on top of that, one of the things that's been interesting to us as we've studied the field is that both loose patterset and linoleidomide saw significant improvements as they moved to earlier line and less protruded patients. So loose patterset, for example, in that same study where they had only a 13% transfusion independence rate, saw 44% red blood cell transfusion independence for patients without linoleidomide protrusion. And as I mentioned, that led them to actually exclude linoleidomide protruded patients.

Further and on top of that one of the things that's been interesting to us as we've studied the field is that both was Patterson and Lenalidomide saw significant improvements as they move to earlier line and less pretreated patients. So with patterns that for example in that same study where they had had only a 13% transfusion independence rate saw 44% red blood cell transfusion dependence.

For patients without Lenalidomide for treatment and as I mentioned that let them to actually exclude lenalidomide pretreated patients from the phase II and in that same study that I mentioned for Lenalidomide on HMA pretreated patients.

Speaker 3: from their phase two. And in that same study that I mentioned for lenalidomide on HMAs for treated patients, you know, 38% response rate or 38% on this HIE for patients who have not been HMA for treated versus 12% post-HMAs. So...

38% response rate are 38% on this HIV.

Patients, who have not been HMA pretreated versus 12% post HMA. So again significant improvement as those products move earlier line settings, and so not only does our does our data suggests that we may have a significantly different factors significantly greater effect in heavily pretreated patients, but theres a chance if we see a similar improvement as well.

Speaker 3: Again, significant improvement as those drugs move earlier in the line of attack.

Speaker 3: And so not only does our data suggest that we may have a significantly different effect or significantly greater effect in heavily protruded patients, but there's a chance if we see a similar improvement as we move to earlier line patients, that we could have an overall best in category therapy.

Move to earlier line patients that we could have an overall best in category therapy for.

Speaker 3: for these transfusion-dependent MDS patients. So.

For these.

For these transfusion dependent Mds patients.

That data that is excited obviously this is a relatively recent program for the reasons I mentioned, but if we're successful we think we've got a couple of different paths.

Speaker 3: That data got us excited. Obviously, this is a relatively risky program for the reasons I mentioned. But if we're successful, we think we've got a couple of different paths to.

So an important program so.

Speaker 4: to an important program. So on page 18, in terms of what we're doing from here, so we're taking the existing ongoing phase one to trial and we're expanding it by 50 to 60 patients.

On page 18 in terms of what we're doing from here. So we're taking the existing ongoing phase one two trial and we're expanding it by 50 to 60 patients at.

Speaker 3: We expect to be able to do that over the course of the next year with data coming in 2020.

We expect to be able to do that over the course of the next year with data coming in 2023.

Speaker 3: We are going to focus on lower risk MDS patients with SF3B1 mutations. That's about 30% of MDS patients overall and a significantly higher portion of MDS patients in some of the more important subsets for this purpose.

We're going to focus on lower risk Mds patients with <unk> mutations, that's about 30% of Mds patients overall and a significantly higher portion.

Mds patients and some of the some of the more important subsets for this purpose.

Speaker 3: And we're going to specifically look for certain biomarkers, including a biomarker called aberrant TM14C transcripts.

And we're going through specifically look for certain biomarkers, including bought Merkle abrotine unfortunate to see transcripts, where in a small subset of our patients five out of seven responded so a very high response rate and those aberrant team member can see transcripts are associated with certain S&P one mutations in a way that gives us some some biological understanding of why that might be so we see.

Speaker 3: where in a small subset of our patients, five out of seven responded. So a very high response rate. And those aberrant Tm-14C transcripts are associated with certain SF-31 mutations.

Speaker 3: in a way that gives us some biological understanding of why that might be. So we see a couple of different paths to patient impact here.

A couple of different paths to patient impact here. Obviously, there is the possibility for a biomarker driven sort of very specific precision approach to treating certain patients. There is the possibility for therapy that can deliver for pretreated patients greater efficacy than the other existing therapies on the market and there is a possibility if we see it.

Speaker 3: Obviously, there's the possibility for a biomarker-driven sort of very specific precision approach to treating certain

Speaker 3: There's the possibility for therapy that can deliver for pretreated patients greater efficacy than the other existing therapies on the market. And there's a possibility if we see a continued improvement as we move to earlier line patients that we could have an overall best in category treatment effect, you know, in a market that's important and in a patient population that continues to have significant unmet need. And that couples with certain other attributes, including a relatively benign tolerability profile, as well as oral dosing, which is something that the other therapies don't currently have. So it's frustrating that as we move Shel fights over more peaks and that is the peak age that we're seeing so far. So what I'm going to say is as long as I'm going to mention this last few Laboratory NA Archie's everyone here is aware Download fan in the chat for778 331

Continued improvement as we move to earlier line patients, but we could have an overall best in category treatment effect.

In a market thats important and in the patient population is significant but that continues to have significant unmet.

That coupled with certain other attributes including.

A relatively benign tolerability profile as well as oral dosing, which is something that you don't currently have.

Got it.

One other note, which is the discharge because Asia I was testing it for higher risk Mds patients was dosed in a more acute setting.

Speaker 3: One other note, which is this drug, because AIGI was testing it for higher risk MDS patients.

Speaker 3: was dosed in a more acute setting. And we've improved our dosing to a more for chronic dosing paradigm, which we also think will help us deliver an appropriate amount of blood to these patients.

<unk>, our dosing to a more for chronic dosing paradigm, which we also think will help us deliver an appropriate amount of drug to these patients and the last thing I'll say on this as.

Speaker 4: The last thing I'll say on this is, although this is a relatively higher risk study, relatively minimal data decay has been observed in past MDS trials from phase two to phase three.

Although this is a relatively higher risk study.

Relatively minimal data Dk has been observed in the <unk>.

Past Mds trials for phase II phase III.

Speaker 3: And so our hope is that after we get data next year, we can be reasonably confident if that data are compelling, that we have a therapy that's going to be available.

So our hope is that after we get data next year, we can be reasonably confident that data are compelling that we have a therapy that matters and so so that's a little bit about our program in Mds. The last thing I'll say about this because I think it's a pretty good example of how we think about dealmaking and programs at Raymond James.

Speaker 3: And so that's a little bit about our program at MBS. The last thing I'll say about this is I think it's a pretty good example of how we think about deal making and programs at Royvent. So this was about an $8 million upfront cash and $7 million upfront equity payment for this therapy.

This was a bit.

About $8 million upfront cash and $7 million upfront equity payment for this therapy.

Speaker 3: which is, you know, we think attractive commercial terms, and overall, for around $50 million, we will get the answer to the question in this phase one, two study, which should set us up for interesting therapies, which is that the data are compelling, otherwise it will have been a relatively modest investment relative to where our overall portfolio is.

Which is we think attractive commercial terms and overall for around $50 million you will get the answer to the question of this phase one two study, which should set us up for interesting therapy data were compelling and otherwise it would've been a relatively modest investment relative to where our overall portfolio is so.

Speaker 3: an exciting program, something we're glad to have added to the pipeline, and something we're excited to share more about through this year and especially next year as we get data in 2023.

Siting programs something we're glad it add glad to have added to the pipeline and something we're excited to share more about through this year and especially next year as we get data in 2023.

Speaker 3: Next up, I'll just briefly review progress at Immutavamp. So Immutavamp has shared all of this at the end of last year or the beginning of this year. And so I won't go into great detail here, but we are very excited for the fact that the Tochil Map now has a clear path back into the clinic in nice and you grab us another indications. So I just wanted to remind people a little bit about that situation starting on page 20.

Next I'll just briefly review progress at immuno them. So immunomedics shared all of this at the end of last year at the beginning of this year and so on.

Won't go into great detail here, but we are very excited for the fact that <unk> now has a clear path back into the clinic in myasthenia gravis and other indications and so I just wanted to remind people are a little bit about that situation starting on page 20.

Speaker 3: which page 20 really is just a reminder that anti-SCR and antibodies have potential in a very large population of patients.

They just want it really is just a reminder, that <unk> antibodies have potential in a.

Very large population of patients there are.

Speaker 3: There are over a million U.S. patients and over a million European patients, over a million and a half European patients.

Over 1 million U S patients and over 1 million European patients over a million and half European patients.

Speaker 4: with autoantibody mediated autoimmune disease just in.

Auto antibody mediated.

Autoimmune disease just in.

Speaker 3: in this list of indications alone, and there are others. We've announced three indications, Mycenia, Gravis, Weihai, and TED at a new event. And we said we expect to announce two more through the middle of this year. So we'll talk a little bit more about that later. But a patient population we're excited about. And we think the FCRN class is going to matter a lot with the potential for double-digit billion dollars in overall market tax.

In this list of indications alone and there are others.

We've announced three indications myasthenia gravis way heightened and at a new event and we said we expect to announce two more through the middle of this year. So we'll talk a little bit more about that later, but the patient population. We're excited about and we think the <unk> class is going to matter a lot.

With the potential for sort of double digit billion overall market size.

So.

Speaker 3: So on slide 21, as a reminder, we announced at the beginning of this year.

On Slide 21, as a reminder, we announced at the beginning of this year a little bit more information about our plan for the phase III trial design in myasthenia gravis I don't want to highlight and this is a little bit of a schematic on this slide but just the way the autoimmune diseases are treated generally.

Speaker 3: a little bit more information about our plan for the phase three trial design in Myasthenia gravis.

Speaker 3: And I want to highlight, and this is a little bit of a schematic on this slide, but just the way that autoimmune diseases are treated generally.

Speaker 3: is often through a combination of induction and therapy with a possibility for rest.

As often through a combination of induction and maintenance therapy with a possibility of a rescue immunologists are used to treating diseases flexibly, they're used to using higher doses of therapy to get patients controlled they're used to being able to maintain patients chronically on drug and it used to be able to up used to being able to up titrate or down titrate, depending on severity of symptoms and re flare and took them out but.

And it's really the only anti <unk> antibody that is really being tested in that kind of treatment paradigm that matches the way myasthenia gravis patients experienced their disease and the way that immunologists reduced to treating so our trial has an induction phase where we test higher doses, including a 680 milligram dose for 12 weeks.

Speaker 3: the anti-FCR and antibody that is really being tested in that kind of treatment paradigm that matches the way myasthenia gravis patients experience their disease and the way that immunologists are used to treating them. So our trial has an induction phase where we test higher doses, including a 680 milligram dose for 12 weeks, a maintenance phase where we test lower doses going down to including a 340 milligram every other week dose. And then a long-term extension where we're able to optimize control of the patients, including both up and down titration as needed for each individual patient. And we think this will allow us to achieve a few things.

Speaker 3: a maintenance phase where we test lower doses going down to including a 340 milligram every other week dose. And then a long-term extension where we're able to optimize control of the patients including both up and down titration as needed for each individual patient. And we think this will allow us to achieve a few things. It will allow us to achieve fast treatment of disease symptoms. It will allow us to maintain on an individualized basis that treatment including managing.

Maintenance phase, where we have lower doses going down to rebuilding a 340 milligram every other week dose.

On a long term extension, where we're able to optimize control the patients, including both up and down titration as needed for each individual patient.

We think this will allow us to achieve a few things that will allow us to achieve.

Fast treatment of disease symptoms it will allow us to maintain on an individualized basis that treatment, including managing side.

Speaker 3: side effects such as cholesterol in a comfortable way for patients while their disease is controlled. And we think it will allow patients to titrate as they have disease flare-ups in order to manage their experience of symptoms.

Side effects such as cholesterol.

From a wafer patients while their disease is controlled and we think it will allow patients to titrate as they have disease flare ups in order to manage their experience of symptoms.

Speaker 4: You know, on slide 22, we show a little bit about how that stacks up versus some of our competitors, if Cartigiamod and Nipicalumab. And in short, we believe we are the only program that is designed to match.

On slide 22.

We saw a little bit about how that stacks up versus some of our competitors in particular amount in <unk> and in short. We believe we are the only program that is designed to match.

Speaker 4: the design sort of maxed out treatment paradigm in the sort of optimal way. And so F-cartigiamon, for example, was approved in more of a cyclical paradigm with...

At the design sort of Max factor and paradigm in their sort of optimal way and so.

T J Max for example was approved in more of a cyclical paradigm with four weeks of treatment on and then additional cycled. After after pause based on loss of response and remember the approved procedure amount as an IV administered therapy. Although there's also a bridge to a hit was on formulation nipper calendar <unk> has a loading dose so a little bit of induction therapy, but only one single loading dose.

Speaker 4: four weeks of treatment on and then additional cycles after pause based on loss of response. And remember, the approved F-crotigimod is an IV-administered therapy, although there's also a bridge to a haloson formulation. Nipocalumab has a loading dose, so a little bit of induction therapy, but only one single loading dose before going to a lower dose treatment paradigm. So not necessarily designed to maximize early treatment effect.

Before going to a lower dose treatment paradigm, so not necessarily designed to maximize early treatment effect.

Yes.

Speaker 4: And nipicalumab in the long-term extension study only allows for downtitration while we allow for both downtitration and rescue therapy. And nipicalumab again today is an IV therapy, although they've discussed a bridge for subcutaneous. And as a reminder, botoclamab addresses all three of these things. We have continuous dosing with induction and maintenance. We have downtitration and rescue therapy allowed. And as you may know, nipicalumab rather was developed from the beginning as a routine simple subcutaneous administer of injection, which we think will make this easiest for patients and physicians.

And <unk>. They are in the long term extension study only allows for downturn duration, while we allow for bolt down titration and rescue therapy and <unk> again today as an IV therapy, although they've discussed a virtuous up cutaneous and as a reminder, we are talking about addressing all three of these things we have continuous dosing with induction and maintenance, we are down titration and rescue therapy allowed.

As you May know we're.

We're talking about rather was developed from the beginning as a routine simple subcutaneous administered injection, which we think will make this easier for patients and physicians to match.

Speaker 4: On page 23, just as a reminder, the market for the toclamab is certainly not limited to myasthenia gravis, and we're excited to initiate pivotal trials in three indications total, including myasthenia gravis. And we're going to announce those two additional indications before August of this year. And so we're excited to share those indications as well as additional plans for those trials and move them back in touch to do so in the near future.

No.

On page 23, just as a reminder, the market for the total of that but certainly not limited device to the Rambus and we're excited to initiate pivotal trials in three indications total, including myasthenia gravis, and we're going to announce those two additional indications.

Before August of this year and so we're excited to share those indications as well as additional plans for those trials and move them back in touch to do so in the near future.

Speaker 4: So those are some updates on our development stage pipeline. There's obviously a number of other programs that we haven't had time to talk about today and we will in the future. But I want to move now to our discovery organization where we've been doing a fair amount of work over the past months to really crystallize our strategy and to focus on what we think are unique and differentiating capabilities. So I'm not going to talk much about specific programs or targets today, but I want to give you a sense for how we're thinking about the composition of this program in general.

So.

Those are some updates on our development stage pipeline. There's obviously a number of other programs that we haven't had time to talk about today and we will in the future, but I want to move now to our discovery organization, where we've been doing a fair amount of work over the past months to really crystallize our strategy and to focus on.

On what we think are unique and differentiating capabilities. So I'm not going to talk much about the specific programs or targets today, but don't want to give you a sense for how we're thinking about the composition of this program in general.

Speaker 4: And really, what I'll say is we've built ReuvenT Discovery with the idea that through our computational platform, we can target the 80% of targets that have been very difficult to drug historically using a variety of different techniques that are all.

Really what I'll say is we've built relevant discovery with the idea that through our computational platform. We can target the 80% of targets that have been very difficult to drug historically using a variety of different techniques that are all bolstered by our competition capability.

Speaker 4: bolstered by our computational capability. And the areas on which we're focused, the first of which we've talked about a bit, is hetero-bifunctionals, mostly targeted protein degraders, which is an area that we think our computational platform and wet lab capabilities really set us apart from the field.

He is on which we're focused first of all which we've talked about a bit is harrow by functional.

Mostly targeted protein degraders, which an area that we think our computational platform and <unk> capabilities really set us apart from the field.

Speaker 3: We're focused on covalency, which is an important emerging area, obviously a focus for a number of biotech companies, where we think a combination of proteomics.

We're focused on co balancing which is an important emerging area. Obviously, a focus for a number of biotech companies, where we think a combination of proteomics and competition tools will give us a unique ability to identify opportunities to drive historically difficult to drug proteins.

Speaker 3: and computational tools will give us a unique ability to identify opportunities to drug historically difficult to drug proteins.

Speaker 3: And then finally, we have an area that we call deficiency to best in class, which is, you know, we think the atom by atom understanding that we have of different proteins really gives us the ability to look at existing small molecules, whether they're development candidates or even in some cases approved therapies that have established potential either biologically or commercially, but have well understood limitations like an affinity or binding limitation or an off-target tox effect, and to be able to understand the geometries of those proteins and those affinity relationships and to optimize to resolve some of those deficiencies.

And finally, we have an area that we call it deficiency to best in class, which is we think the atom by atom understanding that we have of different proteins really gives us the ability to look at existing small molecules, whether their development candidates or even in some cases approved therapies that have established potential biologically or commercially but have well understood limitations like an affinity or binding.

Indication or off target tox effect and to be able to understand the geometries of those proteins are those affinity relationships and to optimize to resolve some of those efficiencies.

Speaker 3: So I'm going to talk about each of these briefly in turn, starting on page 26 with hetero-bifunctionals. So we've talked about this a little bit before, and this is an area that we're excited to be participating in the area, especially of targeted protein degradation. And in short, we think this is going to be a sort of cure app.

To talk about each of these briefly in turn.

Starting on page 26 in federal by functional so.

We've talked about this a little bit before.

This is an area that we're excited to be participating area, especially targeted protein degradation.

We think this is going to be a sort of the killer app.

Speaker 3: for computational tools in drug discovery. We've combined a really best in class wet lab chemistry team that has deep experience in discovery of new degraders.

For computational tools in.

<unk> in drug discovery, and we've combined are really best in class wet lab chemistry team that has deep experience in discovery of new graders.

Speaker 3: with a computational platform that gives us, we believe, the most accurate prediction of ternary complex formation, the most accurate prediction of ubiquitination.

Computational platform that gives us we believe the most accurate prediction of Treasury complex formation. The most accurate prediction of ubiquity nation of any that were aware of and in a way that lets us really get to the heart of the day greater discovery problem to understand how both the affinity of our small molecule by hand.

Speaker 4: of any that we're aware of and in a way that lets us really get to the heart of the degrader discovery problem to understand how both the affinity of a small molecule ligand at the warhead as well as the linker geometry and the E3 ligase ligand can come together to achieve an optimal ternary complex and to achieve ubiquitination at the highest possible rate. We think this will let us design degraders against targets that other people have struggled with where we can really optimize for ternary complex formation.

The warhead as well as the linker geometry, and the eastern leg. Its ligand can come together to achieve an optimal territory complex to achieve ubiquity nation at the highest possible rate. We think this will let us design integrators against targets that other people have struggled where we can really optimize current complex formation.

Speaker 4: You know, we feel like we're at a relatively unique corner of the greater space in the sense that we have

We feel like we're at a relatively unique corner of the greater space in the sense that we have.

Speaker 3: wet lab chemistry expertise and tools specific to hetero bifunctional, specific to degraders, that goes beyond what we believe is any of the other computational companies.

<unk> chemistry expertise and tools.

Specific to head or by functional specific to the graders that goes beyond what we believe is any of the other computational companies and on.

Speaker 3: And on the other side, we have expertise in modeling the graders and computational tools.

The other side, we have expertise in modeling the graders and computational tools.

Speaker 3: for modeling ternary complexes that we think go beyond the computational tools by a significant margin of any of our peers on the degrader side. And so we feel like we are at a unique corner having both the best computational capabilities of any degrader company and the best chemistry degrader capabilities of any computational company. And we feel like that sets us up for a differentiated environment.

For modeling turn very complex, but we think go beyond the computational tools by a significant margin of any of our peers on the greater side and so we feel like we are at a unique corner, having both the best computational capabilities of any of the greater company.

And the best wet lab chemistry, greater capabilities of any computational company and we feel like that sets us up for a differentiated opportunity. The first of the greater programs will enter the clinic. We believe this year and Theres a number of others behind it and we're excited to share it with some debate over the course of the year on a number of programs as we move forward.

Speaker 3: The first of Royman's DeGrader programs will enter the clinic, we believe, this year. And there's a number of others behind it. And we're excited to share pre-clinical data over the course of the year on a number of programs as we move forward.

So I think 27 I'll move to the next pillar here, which is on covalent <unk>. So again. This is an area that's got an increasing interest.

Speaker 3: So on page 27, I'll move to the next pillar here, which is on covalency. So again, this is an area that's got increasing...

Speaker 4: in biotech lately and we've built a team here of QA Proteomics experts as well as computational experts.

In biotech lately and we built the team here.

<unk> proteomics experts as well as computational experts that we think are going to set us aside here as well so what we've begun by doing here and this is a combination of chemo proteomics and computational tools is by mapping what we call the react on.

Speaker 4: computational tools is by mapping what we call the reactome, which is to understand the residues on the surface of a protein and how they map to different, how different amino acids map to that residue so that we can start to understand using a combination of chemoproteomic approaches and a deep computational understanding for the area around various covalent binding opportunities whether it is possible to drug some otherwise difficult to find drugs. So we use sort of chemoproteomics-based hit finding to screen proteins in their biological state and to find opportunities for binding. And then because our computational tools give us a very accurate understanding of protein to avoid…

Which is to understand the residue is on the surface of a protein and how they match different how different amino acids map to that residue. So that we can start to understand and kind of a combination of human chorionic approaches.

Deep computational understanding for the area around various covalent.

Finding opportunities whether it is possible to drug some otherwise difficult to find drugs. So we use sort of chemo proteomics space to get funding to screen protein in their biological state.

Speaker 4: and to find opportunities for binding. And then because our computational tools give us a very accurate understanding of protein geometry, including around the...

And to find opportunities for binding and then because of our computational tools give us a very accurate understanding of protein geometry, including around the <unk>.

Speaker 4: the Covalent binding sites, we can figure out how to design selective drugs against those chemo proteomics based hits.

The covalent binding sites, we can figure out how to design selective drugs.

Against those chemo proteomics based hits.

Speaker 4: So we think this is going to matter for a variety of protein categories that have been difficult to drug including things like transcription factors. And again we're excited to share some more information about programs coming out of this capability in the near future.

So we think this is going to matter for a variety of protein categories that have been difficult to drug including things like transcription factors.

And again, we're excited to share some more information about our program is coming out of this capability in the near future.

Speaker 4: And then finally, on slide 28, I talked a little bit about this in the intro here, but the other sort of pillar we've added here, something we're excited about in part because I think it's going to give us the ability to move very quickly, is to work on programs where there is starting chemical matter, where there's an understanding of affinity, an understanding of a relationship between a small molecule and a protein, but where there's some well-understood deficiency there, where there's an off-target tax effect that is understood and so we know...

And then finally.

On slide 28, I talked a little bit about some neutral here, but.

The other sort of pillar, we've added here, but something we're excited about in public spending is going to give us the ability to move very quickly.

Is to work on programs, where there is starting chemical matter, where there is an understanding of affinity.

And understanding of a relationship between small molecule protein, but where there is some well understood deficiency, there where theres an off target tax effect that is understood and so we know.

We are the off target Tox finding is taking place or was this a cell activity issue and maybe there is multiple isoforms of targeted it's really important to hit certain isoforms, but others were certainly mutant variants, but not others and what we feel like our computational tools are allowing us to do is to start from that starting chemical matter to really understand the limitations of that.

Speaker 3: where the off-target tox finding is taking place, or when there's a cell activity issue, maybe there's multiple isoforms at a target, and it's really important to hit certain isoforms but not others, or certain mutant variants but not others. And what we feel like our computational tools are allowing us to do.

Speaker 4: start from that starting chemical matter to really understand the limitations of that affinity or property relationship to the protein and to be able to work backwards and redesign or re-engineer those small molecules.

Affinity or property relationship to the protein and to be able to work backwards and redesign of reengineer those small molecules do to improve that efficiency and ultimately result in a best in class therapeutic and among the things. We're excited about this addition to being able to deliver meaningful patient impact is being able to do it fast to be able to go from start to a drug into the clinic quickly.

Speaker 3: to improve that deficiency and ultimately result in a best in class therapeutic. And among the things that are exciting about this, in addition to being able to deliver meaningful patient impact, is being able to do it fast. To be able to go from start to a drug in the clinic quickly.

Speaker 4: because we're starting from a well-understood problem and iterating rapidly from a computational perspective in a way that we think is going to happen.

Because we're starting from a well understood problem and Iterating rapidly from a competition perspective in a way that we think is going to is going to matter.

Speaker 4: So on slide 29, to wrap up the discussion on the discovery side.

So on slide 29, just to wrap up the discussion on the discovery side.

Speaker 4: You know, really we feel like our discovery strengths lie at the intersection between the computational platform that we spent a fair amount of time talking about, our molecular dynamics toolkit, our machine learning capabilities, our large GPU based supercomputer with force field engine that allows us to simulate all kinds of things including complex structures with a high level of precision. There are relatively few other companies in the world that can do that kind of thing. With unique experimental wet lab capabilities that have been hand chosen to pair with our computational tools, so chemo, proteomics and biophysics.

Really we feel like our discovery strength lie at the intersection between the computational platform that we spent a fair amount of time talking about our molecular dynamics toolkit. Our machine learning capabilities are large GPU based supercomputer forcefield engine that allows us to simulate all kinds of things to encourage complex structures at a high level of precision there are relatively few other companies in the world.

Can do that kind of thing with unique extremity <unk> capabilities that have been having chosen to pair with our computational tools. So chemo proteomics in biophysics.

Speaker 3: and went lab chemistry with greater expertise with specific tools and capabilities designed to pair with the modeling that we're doing. And then all of that fits together.

And wet lab chemistry with greater expertise was specific specific.

Specific tools and capabilities designed to pair with the modeling that we're doing and then all of that fits together with Ravens clinical expertise with our history of clinical development and we haven't talked about today, but remember that the that model has resulted in a positive phase III trials of <unk> that we've run without four FDA approved medicines currently at <unk> partner.

Speaker 3: with Reuven's clinical expertise and with our history of clinical development.

Speaker 3: And we haven't talked about it today, but remember that the VANT model has resulted in eight positive phase three trials of nine that we've run. With now four FDA approved medicines currently at CIMITAV-ANT and a partner. And so a long history of clinical development, including creative clinical development, and all of the programs coming out of our discovery engine across the pillars I just described, get the benefit of moving through that ecosystem. And we believe that will allow us to rapidly and successfully develop exciting drug candidates coming out of work.

Until a long history of clinical development, including creative clinical development and all of the programs coming out of our discovery engine across the door as I. Just described get the benefit of moving through that will have an ecosystem and we believe that will allow us to rapidly and successfully develop.

Exciting book units coming out of women discovery, So I wanted to share that update it's a little bit more precision than we've given in the past on what our discovery organization looks like and how we've divided it up from a capabilities and tools perspective.

Speaker 3: So I wanted to share that update. It's a little bit more precision than we've given in the past on what our discovery organization looks like and how we've divided it up from the capabilities and tools.

Speaker 3: And so I'm going to move on from here talk about a couple of other couple of other items including one source of summation metric potential I upside the people paying attention to. So, on slide 31 just as a reminder I'm going to talk a little bit about 10 advanced so.

So I'll move on from you were talking about.

A couple of other couple of other items, including one source of summation metro potential upside that people paying attention to so on slide 31, just as a reminder, I'm going to talk a little bit about churn event. So <unk> is a leading company in the field of nucleic acid delivery focused in particular not exclusively but largely on the design of novel lipid nanoparticle.

Speaker 3: Genovac is a leading company in the field of nucleic acid delivery.

Speaker 4: focused in particular, not exclusively, but largely on the design of novel lipid nanoparticles. There's deep history at Genovans in the area of lipid nanoparticles, dating back really to almost the very beginning of LMPs, certainly in their use in biotech.

The deep history of Gentiva, Anthony area of lipid nanoparticles hitting back really to almost the very beginning of LNP use.

Certainly in their use in biotech.

Speaker 3: And as you may know, what's exciting about LMPs is

As you May know whats exciting about <unk> is they are a tool for getting <unk>.

Speaker 3: They are a tool for getting fragile nucleic acids into the body and into target cells. Otherwise, nucleic acids degrade quickly and don't get to the sort of...

Fragile nucleic acids into the body and into target cells, otherwise I guess, it's a great quickly and don't get to sort of.

Speaker 4: part of the cell where it's needed in order for them to have the therapeutic effect. And LMPs allow nucleic acids like RNAi, like mRNA, to get into...

Part of the cell, where it's needed in order for them to have the therapeutic effects in lmb's allow nucleic acids like RNA I like mrna to get into.

Speaker 4: into cells so they can deliver a therapeutic benefit. LMPs have emerged as the primary means for delivering mRNA therapy. So…

And just to add into cells that they can deliver a therapeutic benefit.

<unk> have emerged as the primary use for delivering mrna therapy. So.

Speaker 4: almost all of the mRNA therapies in development are delivered via LMPs. And it's worth noting that LMPs are also occasionally used in delivery of RNAi, for example, based therapy. And in fact, Genovans LMP therapy is used in the delivery of the islands on Patro under LMP license from Arbutus.

Almost all of the mrna therapies in development are delivered.

<unk> and its worth noting the Lp's we're also.

Occasionally use the delivery of RNA eye for example, based therapy and in fact Gen events.

<unk> therapy is used in the delivering on items on Petro underwhelmed with the license from our view this.

So on slide 32, just to quickly note. We've had continued progress at <unk> this quarter.

Speaker 4: So on slide 32, just to quickly note, we've had continued progress at Genovant this quarter, including a recently announced collaboration with 270 Bio, providing access to our LMP technology to develop gene editing therapies for hemophilia A. So gene editing is another area where LMP has been highly relevant and we're excited to use our technology and collaboration to make some progress.

Including our recently announced collaboration with 270 bio.

Accessorial and technology develop gene editing therapies for hemophilia, a so gene editing is another area, where <unk> has been highly relevant and we're excited to use our technology and collaboration to make some progress.

Speaker 3: in that important field. And then on the intellectual property side, as many of you may know, in December the Federal Circuit Court of Appeals rejected Moderna's appeal.

In that important field and then on the intellectual property side as you May know in December the Federal Circuit Court of Appeals projected Madonna's appeal.

Speaker 4: of a PTAB decision. So Moderna had attempted to invalidate a number of our important LMP patents dating back to 2018. And in early December , the federal appeals court affirmed the validity of our patents in a way that was important to us and obviously something that you will listen to.

Pete had decisions. So Madonna had attempted to invalidate a number of our important that won't be patents dating back 2018 and in early December .

A federal Appeals court affirmed the validity of our patents in a way that that that was important to us and obviously something we were pleased to see.

Speaker 4: So we expect to provide further updates on Genovant in the near future and look forward to doing so.

We expect to provide further updates on churn event in the near future.

And look forward to doing so.

So I don't know.

Speaker 3: So I'm going to wrap up today's presentation portion today on slide 34 just by highlighting some of our key financial items from the quarter.

Wrap up today's presentation portion of today.

On slide 34, just by highlighting some of our key financial items from the quarter.

Speaker 3: So for the three months ended December 31st, 2021, we had R&D expense of 153 million with adjusted R&D expense of 119 million. We have G&A expense of 116 million with adjusted non-GAAP G&A expense of 61 million. For a total net loss of 306 million or an adjusted non-GAAP net loss of 157 million for the quarter.

So.

For the three months ended December 31, 2021, R&D expenses of 153 million with adjusted R&D expense of $119 million.

G&A expense of $116 million of adjusted non-GAAP G&A expense of $61 million for a total net loss of $306 million or an adjusted non-GAAP net loss of $157 million for the quarter.

Speaker 3: We ended the quarter with cash and cash equivalents of approximately $2.2 billion and limited debt. Our balance sheet gets about $204 million with a principal credit facility making up $32 million of that. And the remainder being the fair value of milestone payments related to the pin are off. That's about 690 million common shares issued in outstanding as of February .

We ended the quarter with cash and cash equivalents of approximately $2 2 billion and limited debt our balance sheet, that's about $204 million with the principal credit facility, making up $32 million of that and the remainder being the fair value of milestone payments related to dependent off.

About 690 million common shares issued and outstanding as of February nine.

Speaker 4: So, on slide 35, as I wrap up my presentation, thank you again for listening, just want to highlight that 2022 was an incredibly exciting year for us again. With the FDA approval decision for topinter off expected in the second quarter, with top-line data coming in the first half of next year, we're toclinab getting into multiple new programs in the clinic. With data expected, and what we'll share is we have it on additional patients in our tickle cell gene therapy at our event, we didn't spend any time today talking about it, but we continue to enroll patients.

So on slide 35, as I wrap up my presentation. Thank you again for listening just want to highlight the 2022 is an incredibly exciting year for us again with the FDA approval decision for <unk> expected in the second quarter with top line data coming in the first half of next year.

Total amount of getting into multiple new programs in the clinic with data expected.

And we will share it as we have it on additional patients in our sickle cell gene therapy or event, we didn't spend any time today talking about it but we continue to enroll patients in our phase one two trial in sickle cell disease and look forward to sharing more updates on that program over the course of this year also look forward to discussing the initiation of our phase II trial in sarcoidosis kind of and we're.

Speaker 3: in our phase 1, 2 trial on sickle cell disease, and we look forward to sharing more updates on that program over the course of this year. Also look forward to discussing the initiation of our phase 2 trial on sarcoidosis kind of event.

Speaker 4: We're going to continue to expand and enroll patients into our phase one, two trial in lower-stand BS that we talked about earlier and a number of other updates coming from around the pipeline, including

We're going to continue to expand.

And enrolled patients into our phase one two trial and lowest MBS that we talked about earlier, a number of other updates coming through around the pipeline, including.

Speaker 4: multiple programs generating data in our preclinical discovery pipeline that we look forward to driving further. So, I want to thank you again for listening. I obviously covered a fair amount of ground and looking forward to continuing to provide these updates. And at this point, I'll wrap up and go back to the operator for Q&A.

Multiple.

People programs generating data in our preclinical discovery pipeline that we look forward to driving further so I want to thank you again for listening obviously covered a fair amount of ground and looking forward to continuing to provide these updates at this point I'll wrap up and go back to the operator for Q&A.

Speaker 1: Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. Our first question comes from Robin Karnakis with CHWIS Securities. Your line is open.

Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound key our first question comes from Robyn.

<unk> with <unk> Securities. Your line is open.

Hi, Thanks for taking my question. So I actually had a question on RV team 2001, you penalize haven't done correct today, which is very helpful.

Speaker 5: I think you're taking the question. So I actually had a question on RBT 2001. You spent a lot of time going through it today, which is very helpful.

So just a little confused on when we'll get the next.

Speaker 5: So just a little confused on when we'll get the next updated data set. So you said you plan to amend the ongoing phase 1-2. Can you go into a little bit more granularity on, like, when you talk to the FDA, what your options are? It sounded like if you look at biomarkers, is there a quick pass to market? I think you said 2023 we might get phase 3 data. Just can you go into a little bit more detail because I think it's important to figure out, like, what the timelines are for readouts.

Updated data set.

CW plant and then ongoing phase one two.

Can you go into a little.

A bit more granularity on like when you talk to the FDA. What your options are it sounded like if you look at Biomarkers is there a quick path to market I think you said 2000.

'twenty three we might get.

Three data just can you go into a little bit more detail because I think it's important to figure out like what the timelines are for Readouts.

Yeah. So thanks, Robyn I appreciate the question and thanks, Thanks very much for listening in.

Speaker 3: Yeah, thanks Robin. I appreciate the question and thanks very much for listening. Sorry if I cause confusion, so I'll try and clear that up.

Sorry, if I caused confusion, so I'll try and cleared that up so well.

Speaker 3: So, you know, we are, the phase one, two study is ongoing. And so the fastest path for us to continue to enroll the patients we're focused on was to expand that phase one, two study.

We are at the phase one two study is ongoing and so the fastest path for us to continue to enroll the patients were focused on was to expand that phase one two study.

Speaker 3: We will provide an update on the enrollment in that study, on the trial expansion in the middle of this year. We expect to have data from that 50 to 60 patient cohort.

We'll provide an update on the enrollment in that study on the trial expansion in the middle of this year and we expect to have data from that 50 to 60 patient cohort in 2023, so that will be data from the phase one two trial, giving us responder rate information for a larger subset of assets <unk> one mutated.

Speaker 4: in 2023. So that'll be data from the phase one two trial giving us responder rate information for a larger subset of SF3V1 mutated low risk MDS patients.

Low risk Mds patients that data will be in 2023 of that data are positive. If it shows a compelling that's in that patient population. We will then initiate a pivotal program. So there will be a pivotal study before the drug is approvable in the indication.

Speaker 3: That data will be in 2023. If that data are positive, if it shows a compelling effect in that patient population, we will then initiate a pivotal program. So there will be a pivotal study before the drug is approvable in the indication.

<unk>.

Speaker 3: But we'll have the data next year. And the thing that I said when I was talking about the program is one of the things we like about MDS is the phase three trials tend to be pretty good at replicating the results of phase two studies. So we're hoping that once we have data next year, if it's compelling, we have a relatively straightforward lower risk path at that point to a therapeutic. But we're still going to have to go through a pivotal trial. The other thing I'd remind you about the phase one, too, is it's an open label study. And so there's a possibility that we at least will have some additional information over the course of the trial. But I would guide you to a 2023 for when I would expect to really know the end.

But we'll have the data next year and the thing that I said when I was talking about the program is one of things we like about Mds is the phase III trial tends to be pretty good at replicating the results of phase II studies. So we're hoping that once we have data next year. If it's compelling we have a relatively straightforward lower risk path at that point to a therapeutic but we're still gonna have to go through a pivotal trial. The only thing I would remind you about.

The phase one two is an open label study and so there is a possibility that we at least will have some additional information over the course of the trial, but I would guide towards 2023 for when I would expect to really know the answer there.

Got it and one other follow up on to tear off the Amgen guide guided double digit growth there.

Speaker 5: Got it. And one other follow-up. I'm just going to pin her off. The engine guide guided double-digit growth. They're obviously in different indications. But an impressive, you know, sort of analysis that patients like topical, you're topical over their systemic. Can you give a color on like what systemic they were on and what type of patients that you were looking at in that analysis?

They're obviously in different indications.

Impressive.

Sort of analysis that patients like topical your topical over their stomach can you give more color on like what systemic they were on and what type of patients.

We're looking at in that analysis.

Speaker 4: So this was all of the patients in our phase three study went through the survey.

So this was all of the patients in our phase III trial, and our phase III <unk> study went through the survey.

Speaker 4: There was no limitation on which prior therapies patients in the federal health program could be on.

No limitation on which prior therapies patients in the spinoff program could beyond so we don't necessarily know specifically they were just general psoriasis patient populations and so you assume that you had been on the kinds of things that psoriasis patients or on whether it's oral.

Speaker 3: So we don't necessarily know specifically. They were just general psoriasis patient populations. And so you assume they have been on the kinds of things that psoriasis patients are on, whether it's oils or injectable systemics.

Or injectable systemix.

Speaker 4: And so it really is a mixture. And the other thing I'll remind you is the patient population in our program overall was 10% mild, 80% moderate, 10% severe psoriasis patients. So you would expect a sort of grab bag of patients who have been on a variety of different systemic therapies. The only requirement was the patients be willing to wash out of whatever therapy they were on. So none of these patients were on systemic therapy at the time of the interop trial. Got it. Okay. Thank you very much.

And so it really is.

Sure.

The thing I'll remind you was the patient population our program overall was 10% mild 80% moderate at 10% severe psoriasis patients. So you would expect to sort of a grab bag of patients who had been on a variety of different systemic therapy. The only requirement was the patients be willing to wash out of whatever therapy. They were on so none of these patients were on systemic therapy at the time of Interop trials.

Got it okay. Thank you very much.

Thank you Robin and thanks again for the questions and thanks for that.

Thank you. Our next question comes from Ron <unk> with Cowen Your line is open.

Speaker 1: Thank you. Our next question comes from Yaron Ruber with Cowen. Your line is open.

Speaker 6: Great. Good morning. Thanks for taking my question. So, Matt, I got a couple. The first one is on 2001. When we look at the earlier phase one, they essentially did two different doses. You sort of alluded to it. They did a five-day on, nine-day off, and then they did sort of a 21-day on, seven days off.

Good morning, Thanks for taking my question.

So Matt I got a couple the first one is on the 2001.

When we look at the earlier phase one is essentially two different doses you sort of alluded to it at a five day on 90 day off in them.

Sort of a 21 day on seven days off.

When you're thinking about your dose to really get to the right therapeutic window. What are you thinking for the next 50 to 60 patients and then secondly can you comment was during a requested an unbundled.

Speaker 6: When you're thinking about your dose to really get to the right therapeutic window, what are you thinking for the next 50 to 60 patients?

Speaker 6: And then secondly, can you comment whether Moderna requested an en banc meeting from as a next step? I think they were supposed to do that within a month or so of the FC appeal. Thank you.

Meeting from is the next step I think they were supposed to do that within a month or so of the of the FC appeal. Thank you.

So I'll start with the 2001 question and I'll give a brief answer and then just in case, maybe much to anything I'll hand, it over to him.

Speaker 3: So I'll start with the 2001 question, and I'll give a brief answer, and then just in case maybe you've watched anything, I'll hand it over to him. In short, I don't think we've given the exact specifics in our intended dose, but we're moving away from that sort of episodic dosing to chronic administration of therapy at a lower daily dose, but where we think the pharmacokinetic effect will result in a potentially higher dose delivered over time. I don't know if you got anything you'd add to that.

In short I don't think we've given the exact specifics in our intended dose, but we're moving too we're moving away from that sort of episodic dosing.

Chronic administration of therapy at a lower daily dose, but where we think the pharmacokinetic effect was ultimate potentially higher dose delivered over time.

But anything you'd add to that yeah, I think hey, you're on different view one of the things that I think we have learned is that so far is that you can actually track.

Speaker 7: Yeah, I think what I hear on a nice year from you, one of the things that I think we have learned from the data sets so far is you can actually track.

Sort of a perturbation in transcription over time on that and I think what we find is that actually if you discontinue dose you're actually.

Speaker 7: of perturbation in transcription over time on dose. And I think what we find is that actually if you discontinue dose you actually lose the pharmacodynamic effect pretty quickly. And so as Matt said, I think we're looking to really kind of mimic the dosing that really, you know, plays with the drug's strength and will have an effect on why these inhibitions sort of continue.

Lose the Pharmacodynamic effect pretty quickly and so as Matt said I think we're looking at really kind of mimics the dosing that really.

Doug strength and will have an effect on <unk> inhibition sort of continuous.

Great. Thanks, Mike.

Speaker 4: Great, thanks Mayuk. And then on your other question.

And then on there.

Your other question.

Speaker 3: So on Genovans, and thanks for the question. I guess the short answer is Moderna has not requested an unbound curing in that process.

So and thanks for the question.

I guess the short answer is we don't know has not requested an unbundled hearing.

In that process.

So.

Go ahead Ron.

Speaker 6: Yeah, maybe as a quick follow up, and I know you can't say a lot, so maybe just share what you can. What do you see as the various scenarios of what might happen next? From your vantage point, especially as these drugs are moving away from EUA to getting official approvals.

Maybe as a quick follow up and I know you can't say a lot. So maybe just share what you can.

What do you see as the various scenarios of what what might happen next.

From your vantage point, especially as these drugs are moving away from EUA to getting efficient approvals I'm.

I'm talking about the corporate items.

Speaker 3: Yeah, thanks, Jeroen. And again, appreciate the question. We saw the Moderna approval earlier this quarter, obviously, an important step for their programs. So, you know, it's hard to comment on anything specific in terms of what next steps look like. But I'd say nothing has changed from any of the prior discussions we've had on this in terms of how we're thinking about it. And what I will say is, again, we're looking forward to providing more updates on Genovans in the near future.

Yes, Thanks, and again I appreciate the question, but we saw the limit on our approval.

Earlier this quarter obviously.

An important step for their programs. So it's hard to comment on anything specific.

In terms of what next steps look like.

I would say nothing has changed from any of the prior discussions we've had on this in terms of.

We're thinking about it and what I will say is again, we're looking forward to providing more updates on churn event in the near future.

Okay. Thank you.

Thanks, Ron.

Thanks for listening.

Speaker 1: Thank you. Our next question comes from Dennis Ding with Jefferies. Your line is open.

Thank you. Our next question comes from Dennis Yang with Jefferies. Your line is open.

Hi, good morning, Thanks for taking the question.

Speaker 8: Hi, good morning. Thanks for taking the question. Two questions for me. Number one is on Pinerov. Can you please do this?

Two questions for me one is on <unk>.

Give us a sense of your confidence level launching <unk> shrunk during COVID-19 .

Speaker 8: sense of your confidence level launching a psoriasis drug during COVID and perhaps internally what may constitute a good launch and perhaps while you're at it, comment on what consensus numbers are for calendar year 2022.

Perhaps internally what may constitute a good launch and perhaps why you are at it comment on what consensus numbers are for calendar year 2022, and then my second question is for learning.

Speaker 8: And then my second question is regarding the Moderna litigation.

The.

Litigation, So the press release and in your presentation, it's a nice comment on the strength.

Speaker 8: To press release and your presentation, some nice comments on the strength of Genovans and my people didn't really get next steps. Interestingly, the 10Q mentioned specifically...

And might be but I didn't really get next steps.

Interestingly, the 10-Q mentioned specifically.

Speaker 8: You know, Jenavant may commence litigation at any time.

Mike.

Commence litigation anytime to enforce a patent rights against infringement and I believe that it's a new disclosure that wasn't in prior 10 Qs. So so can you just please make some comments as to what youre, perhaps waiting for or if I can.

Speaker 8: to enforce the patent rights against infringers. And I believe that is a new disclosure that was in prior 10Qs. So can you just please make some comments as to what you're perhaps waiting for or if I can.

Speaker 8: to reframe the question, what are some gaining factors preventing Genovans from moving forward with medication?

Reframe. The question what are some gating factors, preventing 10 event from moving forward with litigation. Thank you very much.

Thanks, Dennis Thanks for thanks for listening and thank you very much for the questions. Both good questions. So I'll start to underpin it off.

Speaker 3: Thanks Dennis, thanks for listening and thank you very much for the questions, they're both good questions. So I'll start on to pin it off.

Speaker 3: So in terms of our level of confidence about the launch, during the last few weeks or so since the end of this pandemic.

So in terms of our level of confidence about the launch our level of confidence about the launch.

During.

Speaker 3: during the pandemic. So first of all, I think you heard of the patient satisfaction data. I think you heard it.

During during the pandemic. So first of all I think you heard at the patient satisfaction data I think you've heard it.

You've heard it from Todd on the sort of last quarter of this call and in other circumstances.

Speaker 3: You've heard it from Todd on the last quarter of this call and other circumstances.

Speaker 4: We are very confident about this drug. The treatment effect is significant. The durability and remittive benefit is significant. So we see a ton of opportunity. You know, I think as I've said before, the drug is both sort of optically and cross-drug comparisons more effective than, and we think more tolerable than the current sort of first-line topical standards of care, especially both photosteroids. So we see just a big opportunity for patients. And so it's hard not to feel confident.

We are very confident about this drug in.

The treatment effect is significant.

The durability and remit of benefit is significant.

So we see.

See a ton of opportunity.

I think as I've said before the drug is both.

Optically and restaurant comparisons more effective than and we think more tolerable than the current sort of first line topical standards of care, especially both clinical steroids. So we see.

Big opportunity for patients and so it's hard not to feel confident about the launch obviously theres a lot that goes into a launch of a product like this including getting pricing and access right getting out to the docs.

Speaker 3: Obviously, there's a lot that goes into a launch of a product like this, including...

Speaker 3: getting pricing access right, getting out to the docs. You know, these docs have been writing court of standard predictions for a very long time. And so making sure that doctors understand what Finneroff can do, understand how to use it with their patients. I think those things will take time. That education is important.

<unk> been writing corticosteroid predictions for prescriptions for a very long time, and so making sure that doctors understand what spinoff can do understand how to use it with their patients I think those things will take time that education is important.

Speaker 3: that to work with that physician community is important. I'm highly confident.

That worked with that physician communities important I'm highly confident.

Speaker 3: that we will be able to do all of that. And obviously, at medical conferences and similar, we've already been able to talk.

We will be able to do all of that and obviously at medical conferences and similar we've already been able to talk about the data that we've generated and we're looking forward to continuing to engage with the dermatology community. So I think we feel we feel good about the launch and we feel good about the timing of the launch I think it's an important year in psoriasis generally obviously, we're not the only product launching there's another topical launched.

Speaker 3: about the data that we've generated and we're looking forward to continuing to engage with the technology community. So I think we feel good about.

Speaker 3: launch and we feel good about the timing of the launch. I think it's an important year in psoriasis generally obviously we're not the only

Speaker 3: product launching, there's another topical launching, there's a new systemic therapy launching so there's a number of other programs and there's going to be a lot of focus and interest in interacting with water.

There is no.

Systemic therapy launching so theres a number of other programs, there's going to be a lot of focus and interest.

Speaker 4: in psoriasis and we feel good about getting out in the second quarter of this year and we feel good about what we think we're going to be able to deliver. We haven't given specific revenue guidance and I'm not going to do that right now, but looking forward to showing you what the drug can do over the course of this year and next.

In psoriasis and we feel good about we feel good about getting out in second quarter of this year and we feel good about what we think we're going to be able to deliver we have.

Haven't given specific revenue guidance, so I'm not going to do that right now.

But looking forward to showing you what the drug can do over the course of this year and next.

Speaker 3: That's what I'll say on Topenow. Rhonda, on...

That's what I'll say entrepreneur off.

Speaker 3: On your genuine question, and I apologize, I can't comment too much on the specifics here. You know, our 10Q disclosures, and you highlighted one of them, are accurate, and we don't have a ton to add in terms of beyond what it says in the...

On your question and I apologize I can't comment too much on the specifics here.

Our 10-Q disclosures you highlighted one of them are accurate and we attempt to add in terms of.

Beyond what it says in those disclosures.

But.

Speaker 3: But it's obviously something we're paying a lot of attention to and looking forward to sharing more as soon as we can.

It's obviously something we're paying a lot of attention to.

And looking forward to sharing more as soon as we can.

Thank you.

Thank you.

Our next question comes from Corinne Jenkins with Goldman Sachs. Your line is open.

Speaker 9: Hi, good morning. So maybe as we think about the Tippenroff launch, can you just help us understand kind of market access and the strategy there? What percentage of target lives should we expect to see and how can you get, like how quickly should we expect to see that market access?

Hi, and good morning.

As we think about the tender off launch can you just help us understand kind of the market access and the strategy there.

We have target lives, we expect to see and how can you get how quickly should we expect to see that market access.

Good luck.

Speaker 3: Yes, so thanks, Tran. That's a great question, and again, I appreciate your asking it. In any, obviously, in any therapeutic area, honestly, it's not just dermatology, but I'll say especially in dermatology, market access is an incredibly important dimension. The patient experience at the pharmacy is an incredibly important dimension. Making sure that patients and providers and pharmacies all know how to get patients on drugs is important. There's a lot out there for us to learn in the market around what this looks like.

Yes. So thanks, Thanks, Ron that's a great question and again I appreciate I appreciate you asking it.

Yes.

Obviously in any therapeutic area honestly, it's not just a mortality, but I'll say, especially in dermatology market access and incredibly important dimension.

Patient experience at the pharmacy is an incredibly important dimension, making sure that patients and providers and pharmacies all know how to get get patients on drug is important.

Theres a lot out there for us to loans.

In the market around what this looks like.

Speaker 4: including from the ongoing launch of Apsaora at InSight, where they've obviously been...

Including <unk>.

From the ongoing launch of <unk>.

At insight, where they've obviously been trimmed paving the way in terms of.

Speaker 3: sort of paving the way in terms of a novel topical on the market. In general, we're focused on a pretty balanced market access approach.

Of our novel topical in the markets in general will focus on a pretty balanced market access approach.

Speaker 4: We'll have an industry leading, we'll have a copay program, we'll contract with national and regional health plans, we'll contract with third party payers. We're hoping for unrestricted formulary reimbursement.

Have a industry leading.

Co pay program.

Attractive national and regional Health plans will contract with third party payers, we're hoping for unrestricted formulary reimbursement.

Speaker 3: And we just think with the efficacy and the durability of the drug, as well, frankly, as with the overall current treatment landscape, and with the fact that for the first time novel topicals are really offering an opportunity to keep patients on topical therapy and off systemic therapy in a durable and lasting way, we think we should be able to have an attractive profile for payers.

And we just think with the efficacy and the durability of the drug.

As well frankly as with the overall current treatment landscape and with the fact that for the first time novel Topicals are really offering an opportunity to keep patients.

On topical therapy and off systemic therapy, and a durable lasting way.

We should be able to have an attractive profile for payers.

Speaker 3: And so we expect to be able to deliver good coverage to the patient population. In terms of how quickly we're going to get exactly that coverage or what we're ramping up towards, I think we're looking for broad coverage. But it's important in launches like this in our view to be relatively patient and focused around it. So we'll provide some more information for exact expectations.

And so we expect to be able to deliver good coverage to the patient population in terms of how quickly we're going to sort of get exactly that coverage of what we are ramping up towards that I think we're looking for broad coverage, but its important launches like this in our view to be relatively patient focused around it. So we'll provide some more information about our exact expectations as the launch gets closer but that.

Speaker 3: as the launch gets closer. But suffice to say, we're focused on making the right decisions for patients and the product on pricing and on access.

Stay with focus on making the right decisions for for patients on the product on pricing and on access in that.

I think we're gonna be able to achieve a good mix.

Thank you and then maybe separately I just think they're going after more of that genetically identified strategy in Mds, but I'm curious how frequently these patients are getting.

Speaker 9: And then maybe separately, obviously you're going after more of a genetically identified strategy in MDS, but I'm curious how frequently these patients are getting the...

IDEXX screening.

Speaker 9: how that could factor into both the clinical and commercial strategy you have here for RBP.

That can factor into clinical and commercial strategy.

<unk> 2001.

Speaker 3: Yes, so as recently as a few years ago, not that many people were checking for S31 mutations, but it's actually become one of the main diagnostic criteria for RS-positive and RS-negative patients with lower risk MDS.

Yes, so as recently as a few years ago not that many people were checking pressure through Q1 mutations, but it's actually become one of the main diagnostic criteria for Rs positive and Rs negative patients with lower risk Mds. So it's actually it's a very common we screened for mutation at this point.

Speaker 3: So it's actually a very commonly screened for mutation at this point. And so we should be able to see it in most, we should be able to see the status of an SF31 mutation in most MDS patients. So it should be a good test. And then the other biomarker, the Averin T-M14C transcripts is a little bit of a newer and less common biomarker, but it's still checked relatively often. And so we should be able to screen for it and selectively enroll for it in a useful way.

So we should be able to see it in most would you be able to see the status of and Thats. It for me one mutation.

Most mds patients so.

It would be a good a good test and then the other Biomarkers you Havent chemo for TC transcripts is a little bit of a newer and less common biomarker, but still relatively often and so we should be able to screen for and selectively roll forward in a useful way.

Great. Thank you.

Thank you. Our next question comes from Nida material Garg with Citi. Your line is open.

Speaker 1: Thank you. Our next question comes from Nita Vitrito Garg with Citi. Your line is open.

Hey, guys. Thanks for taking my question just following up on some of the questions on <unk> I was just wondering if you could give us a little bit of a sense of how we should expect kind of the general pace of launch two to kind of proceed through the year.

Speaker 10: Hi guys, thanks for taking the question. Just following up on some of the questions on the PNRF, I was just wondering if you could give us a little bit of a sense of how we should expect kind of the general pace of the launch to kind of proceed through the year. You know, if you can kind of talk a little bit about also what metrics you expect to provide on earnings calls in the future once the drug is launched.

If you can kind of talk a little bit about.

Also what metrics.

To provide an earnings call or in the future.

So that would be great. Thanks.

Yes, thanks very much. Thanks. Thanks for the question I appreciate the focus here entrepreneur office obviously.

Speaker 3: Yeah, thanks very much. Thanks for the question and I appreciate the focus here on the webinar. It's obviously exciting for us so we're looking forward to it.

It's really exciting for us so we're looking forward to it.

Speaker 3: So in terms of the sort of shape or pace of the launch, I guess to go back to what I said a couple of comments ago, which is, you know, we are looking for a meaningful change in prescriber behavior here. So I think you got to start with that. These docs are very used to writing topical therapy, so that's good, but they're very used to writing corticosteroids, and that's going to require some reeducation. And so, you know, I think this is going to be a build. I think it's going to take

So in terms of the sort of shape or pace of the launch.

Just to go back to what I said, a couple of comments ago, which is we are looking for a meaningful change in prescriber behavior. Here. So I think you got to start with that these facts are very used to writing topical therapy. So that's good but they are very used to writing corticosteroids and thats going to require some reeducation.

And so I think this is going to be a build I think it's going to take some time and energy to do sort of a change of behavior and I think the exciting thing is we are building to a really interesting level, because we get to look out and change the paradigm, which is not something you get to do very often so.

Speaker 3: some time and energy to really sort of change behavior. And I think the exciting thing is we're building to a really interesting level because we get to look out and it changed the paradigm, which is not something you get to do very often. So I think it'll take a little bit of time to build that market. And I think we're sort of committed to doing that in the right way and starting from the bottoms up and educating the physicians and working on the access piece that we talked about before so that we reach the maximum number of patients with the product over time. We get sort of the right kind of sustained use of the product.

It will it will take a little bit of time to build that market.

And I think we're sort of committed to doing that in the right way and starting from the bottoms up and educating the physicians and working on the access piece that we talked about before so that we reach the maximum number of patients with the product over time get sort of the right kind of sustained use of the product.

Speaker 3: In terms of metrics, I would expect we're going to share the kinds of things that people share with similar launches, so we'll talk about our engagement, we'll talk about obviously script rates, although we won't need us for that, and we'll be keeping an eye on payer coverage on gross net things of that sort as the product gets launched. But you know, in general, we're really looking forward to just getting out there and getting out to patients.

In terms of metrics I would expect we're going to share the kinds of things that people share with similar launches. So we'll talk about our engagement will talk about.

Obviously script rates over us for that.

And we'll be keeping an eye on payer coverage on a gross net things of that sort.

As the product gets launched but.

In general we are moving forward to just getting out there and getting out to patients.

Got it thanks.

Our next question comes from Doug Tsao with H C. Wainwright Your line is open.

Speaker 1: Our next question comes from Doug Sal with HC Wainwright. Your line is open.

Hi, good morning, Thanks for taking the questions.

Speaker 3: Matt, maybe stepping back, as you referenced at the beginning of the call, you have $2 billion in cash. Obviously, the equity markets have been fairly challenged for healthcare for the last several months. I'm just curious, has that affected how you're thinking about business development and potentially your use of capital or capital allocation strategy?

Maybe stepping back as you referenced at the beginning of the call you have $2 billion in cash.

The equity.

<unk> had been kind of a challenge for health care for.

Several months I'm, just curious does that decade, how youre thinking about business development and potentially youre sort of use of capital in our capital allocation strategy.

Yes.

Speaker 3: Yes, so thanks for the question Doug, I really appreciate it.

Yes. So thanks for the question, Doug I really appreciate it.

Front and center on my mind.

Speaker 3: I think it's got for any biotech company right now, it's got to be front and center on your mind to make sure that you're

The answer I think its got for for any biotech company right now it's got to be front and center on your mind to make sure that you are.

Speaker 3: doing the maximum amount possible with the resources that you've got. We are extremely privileged in our capital position and we know that.

Doing the maximum maximum amount possible with the resources that you have got and we are extremely privileged in our capital position and we know that.

Speaker 3: And that privilege is particularly acute in markets like this one. So we're doing everything that you would expect in terms of making sure that we're allocating our capital extremely carefully and focusing on the areas where we have maximum possible impact for patients. And frankly, we're also doing everything we expect in terms of looking out across the marketplace for opportunities to take advantage of our relative capital strength. Obviously, it's not a position that everybody is fortunate enough to be in. And that creates opportunity for us. I think you see it.

And that privilege is particularly acute in markets like this one so.

We're doing everything that you would expect in terms of making sure that we're allocating our capital extremely carefully and focusing on the areas, where we have maximum possible impact for patients and frankly, we're also doing everything you'd expect in terms of looking out across the marketplace for opportunities to take advantage of our relative capital strength, obviously, it's not a position that everybody is fortunate enough to be in and that creates.

For Us I think you see it.

Speaker 3: in our past in licensing activity, you'll see it in our future in licensing activity. I think we're really focused on value. The MBS program obviously came from a guy who...

And our patent licensing activity, you'll see it in our future in licensing activity I think we're really focused on value.

The Mds program, obviously Kimberly.

Plenty of capital and stuff. So it wasn't exactly the same situation with a program, where we were able to acquire it very efficiently.

Speaker 3: plenty of capital and so it wasn't exactly the same situation. But a program where we were able to acquire it very efficiently because we saw a different possible application for it. I think you'll see things like that. You know, we have another new event that we've mentioned by name that haven't described in detail, prior event, which has another new program that again was a modest up front payment relative to the size and opportunity of that program. So I think you will continue to see us be opportunistic. I think you'll continue to see us deploy capital in focused, targeted ways where we think we can...

Because we saw a different possible application forward I think youll see things like that we have another new ramps that we've mentioned by name, but Havent described in detail prior events, which is another new program, but again it was a modest upfront payment relative to the size of the opportunity of that program. So, but I think you will continue to see us be opportunistic I think you'll continue to see us deploy capital in focused targeted ways, where we think we can.

Differentially bring something in.

Speaker 3: differentially bring something in efficiently. And in the meantime, I think you'll see us be very disciplined in how we use our cash so that we can maximize the application of our resources to its opportunities as a matter.

Sufficiently and in the meantime, I think youll see us be.

Very disciplined in how we use our cash so that we can maximize the application of our resources to opportunities that matter.

I guess as a follow up.

Speaker 11: I guess as a follow up, I mean, ask the different web, Matt, you know, historically becoming very active from business development standpoint, from a licensing standpoint and partnerships. Just curious, do you think, you know, just sort of going back to my comment about sort of the broader market, does that change your thinking and perhaps just outright M&A become more attractive just given, you know, current market valuations and opportunity dislocation in the marketplace?

Asked a different word Matt you know historically the company has been very active from a business development standpoint from an in licensing standpoint and partnerships.

Just curious do you think just sort of going back to my comment about sort of the broader.

Broader market does that change your thinking and perhaps just outright M&A become more attractive to skip.

Current market valuations and opportunity dislocation in the marketplace.

Yes, so first of all we haven't necessarily shied away from M&A, even in the past. So are the greater platform was required as an opioid with Greg Silicon Therapeutics last year, or so where we see good value we've always been happy to do that.

Speaker 3: Yes, so first of all, we haven't necessarily shied away from MMA even in the past. So, you know, our degrader platform was acquired as on copia. We've got to look into therapeutics last year. So where we see good value.

Speaker 3: We've always been happy to do that. And I guess.

And I guess Seth.

Speaker 3: Same with everybody else. I think it's been harder for us to find good value on the M&A side in the last couple of years because of the way the market has evolved. I think that's changed significantly. And so I think there's absolutely.

Same as everybody else I think it's been harder for us to find good value on the M&A side in the last couple of years because the way. The market has evolved I think that has changed significantly and so I think theres absolutely.

Speaker 3: an opportunity for us to take advantage of that. You know, being a public company obviously helps.

An opportunity for us to take advantage of that being a public company obviously helps.

Speaker 3: although those are all relative value considerations and we look at our own evaluation as well. But absolutely yes, we see opportunities for M&A.

Although those.

Those are all relative value considerations, and we look at our own valuation as well, but that but absolutely, yes, we see opportunities for M&A.

Speaker 3: and increasingly attractive opportunities for M&A after the macro change evaluation that we've seen over the past couple of months.

And increasingly attractive opportunities for M&A after the sort of macro change in valuations that we've seen over the past couple of months.

Okay, great. Thank you so much.

Thank you Doug.

Speaker 1: Thank you and I'm showing no further questions at this time. I'd like to turn it back to Matt for closing remarks.

Thank you and I'm showing no further questions at this time I would like to turn it back to Matt for closing remarks.

Speaker 3: Great. Well, thank you again, everybody, for listening. Thank you for all of your questions. It was great to hear everybody's focus. And obviously, we also are incredibly focused on Dopinaroff and incredibly focused on that launch coming up in the second quarter. So looking forward to getting back on the phone in the near future to talk more about that, talk more about updates elsewhere across the business. And in the meantime, thank you everybody for listening and excited to share this our second quarterly earnings update as a public company. So everyone, I hope you had a good weekend and have a great day.

Great well. Thank you again, everybody for listening. Thank you for all of your questions. It was that it was great to hear everybody everybody's focus and obviously, we also are incredibly focused on defender often incredibly focused on that launch coming up in the second quarter. So looking forward to getting back on the phone in the near future to talk more about that and talk more about upticks elsewhere across the business.

In the meantime, thank you everybody for listening in that central shared this our second quarterly earnings update as a public company.

I hope that it can we kind of have a great day.

This concludes today's conference call. Thank you for participating you may now disconnect everyone have a great day.

Speaker 1: This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone have a great day.

Goodbye.

Speaker 2: ["FirstTHblocks Audible

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Speaker 1: Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Roy Vant third quarter earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone. I would now like to hand the conference over to your speaker today, Paul Davis, head of communications. You may begin.

Good day, ladies and gentlemen, and thank you for standing by and welcome to the Ravenna third quarter earnings call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question. During the session you will need to press star one on your telephone.

I'd now like to turn the conference over to your Speaker today, Paul Davis head of Communications you may begin.

Thank you and good morning, Thanks for joining today's call to discuss <unk> third quarter results and business updates and Paul Davis added communications that write them on the call today, we have Matt Klein, our Chief Executive Officer, Richard Allen, Our Chief Financial Officer, Frank <unk>, Our advanced sure Eric banker, President and Chief operating Officer, and finally my youth.

Speaker 7: Thank you and good morning. Thanks for joining today's call to discuss Roy Vant's third quarter results and business updates. I'm Paul Davis, the head of communications at Roy Vant. On the call today, we have Matt Klein, our chief executive officer, Richard Bullock, our chief financial officer, Frank Torti, our VAMP chair, Eric Banker, president and chief operating officer, and finally Mayuk Sakape, president and chief investment officer.

President and Chief investment Officer.

Speaker 7: For those dialing in via phone, you can find the slides being presented today, as well as the press release announcing these updates on our IR website at www.investor.royvant.com. We'll also be providing the current slide numbers as we present to help you follow along.

For those dialing in by phone you can find the slides being presented today as well as the press release announcing these updates on our IR website at Www Dot investor not worried that dot com will also be providing the current slide numbers as we presented to help you follow along.

I would like to remind you that we will be making certain forward looking statements. During today's presentation that reflect our current views and expectations, including those related to our financial performance and the potential attributes of our product candidates. We strongly encourage you to review the information that we have filed with the SEC, including the earnings release and Form 10-Q filed this morning for more information regarding these forward looking statements and related risks and.

Speaker 7: I would like to remind you that we will be making certain forward-looking statements during today's presentation that reflect our current views and expectations, including those related to our financial performance and the potential attributes of our product candidates. We strongly encourage you to review the information that we have filed with the SEC, including the earnings release and Form 10Q filed this morning for more information regarding these forward-looking statements and related risks and uncertainties.

<unk> will begin with Mac buying will review key business updates across broken out in advance and provide a financial update we will end the call with a Q&A session without further Ado I'll turn it over to Matt.

Speaker 7: We'll begin with Matt Gline who will review key business updates across Royvent and Advance and provide a financial update. We will end the call with a Q&A session. Without further ado, I'll turn it over to Matt.

Speaker 3: Thank you, Paul. Good morning, everybody. And thank you for joining our third quarter earnings call. It's been an eventful quarter for us with that with a number of key updates, including immune events, putting the token ab back into the clinic and nicely gravis, including favorable fuel support decision on Genovans in December , including the introduction of a new program on at a new event at heme event and malatas plastic syndrome. So I'm excited to share those and other updates over the course of today's presentation.

Thank you Paul Good morning, everybody and thank you for joining our third quarter earnings call, it's been an eventful quarter for us.

With that.

With a number of key updates, including immuno Vance, putting the total NAV back into the clinic, a nice thing to grant us.

Including a favorable appeals court decision on jet event in December , including the introduction of a new program.

At our new vantage team of antigen Myelodysplastic syndrome, so im excited to share those and other updates over the course of today's presentation.

Speaker 3: I'll begin on slide four just by giving an overview of some of the key features of our business as well as some of the key updates, and then I'll go through a number of them in more detail.

I'll begin on slide four just by giving an overview of some of the key features of our business as well as some of the key updates and then I'll go through a number of them in more detail.

Speaker 3: So I want to start by saying that both the prior quarter and the coming year are incredibly exciting for Royvent as a company, with a number of important projects coming to fruition over the coming months and year. The first of those is our near-term commercial launch of to pin it off. A potential blockbuster in psoriasis, a topical treatment of psoriasis with an expected PDUFA date in the second quarter of 2022, and a launch thereafter. We'll talk more about that in a moment.

So I want to start by saying that both the prior quarter and the coming years are incredibly exciting for vitamins is a company with a number of important important projects coming to fruition over that over the coming months in here.

The first of those is our near term commercial launch of <unk> and Ralph.

Cancel blockbuster in psoriasis, a topical psoriasis with a with an expected <unk> date in the second quarter of 2022, and our launch thereafter, we'll talk more about that in a moment.

Speaker 3: That's backed by a number of updates in our broad clinical stage pipeline. We will have at least eight pivotal or proof of concept trials running by the end of this year. And that includes progress at our newest VAN, TEMA VAN with RBT2001 recently added to our pipeline of first in class or potential first in class oral SF3B1 modulator for transfusion dependent anemia and patients with low risk MDS.

Backed by a number of updates in our broad clinical stage pipeline.

We will have at least eight pivotal or proof of concept trials running by the end of this year.

And that includes that includes progress at our newest vantage advanced with RBC 2001 recently added to our pipeline of first in class potential first in class oral I sat through the one modulator for transfusion dependent anemia.

With low risk Mds.

Speaker 3: low risk MDS. That includes updates at Immutavamp and the ToccoLab, as I mentioned, and that includes other updates at a number of other programs, including our sickle cell disease program, as well as NOMAP, or anti-GFCS antibody with improved IMD and sarcoidosis.

Risk Mds that includes updates that immuno vantiv total app as I mentioned and that includes other updates at a number of other programs, including our sickle cell disease program as well as no map oriented GM CSF antibody with improved IMD and sarcoidosis will.

Speaker 3: We'll be talking today a little bit more about strategy in our discovery platform, where we've made some significant progress in crystallizing our plans and adding capabilities that we think will give us differentiated strength at designing new small molecules, as well as a number of other areas of asymmetric potential upside, including at Gen Event with both our intellectual property and scientific capabilities delivering a bronze- brigadier workshop, which will take goal-z gravs

We'll be talking today, a little bit more about strategy in our discovery platform, where we've made some significant progress and crystallizing our plans in and adding capabilities that we think will give us differentiated strength and designing small molecules as well as a number of other areas of asymmetric potential upside, including Jonathan with both our intellectual property and scientific capabilities.

Delivering novel and important lipid nanoparticles for nucleic acid delivery.

Speaker 3: novel and important lipid nanoparticles for nucleic acid delivery, as well as continuing updates in our early-stage clinical pipeline. And all that backed by a strong capital position with $2.2 billion in cash as of December 31st, plus a significant amount, but $870 million in public equity stakes and some private holdings including updated.

As well as continuing up based on our early stage clinical pipeline and all that backed by a strong capital position with $2 $2 billion in cash as of December 31, plus a significant amount, but $870 million of public equity Stakes in some private holdings you can update on that.

I will start todays presentation. Thank you.

Speaker 3: So I'm going to start today's presentation by giving everyone an update on Topenrov at Dermavant, which is a program that we're obviously very excited about starting on page six.

Giving everyone an update on <unk>, which is which is a program that we're obviously very excited about starting on page six so as a reminder.

Speaker 3: So as a reminder, Tepidrof is a topical agent for the treatment of psoriasis. It's a therapeutic arrow hydrocarbon modulator. It's the only drug of that mechanism that works.

<unk> is a topical agent for the treatment of psoriasis, it's a therapeutic arrow hydrocarbon modulators the only such.

It's the only drug of that mechanism that we're aware of.

Speaker 3: And we are, we have our data in psoriasis and have an ongoing study in atopic dermatitis with data expected in the first half of 2023. I want to remind people as it comes to interop.

And.

We are we have our data in psoriasis and have an ongoing study in atopic dermatitis with data expected in the first half of 2023 and I want to remind people as it comes to spinoff.

Speaker 3: of some of the attributes that make us excited about the program, including a remarkable treatment effect.

The attributes that make us excited about the program, including a remarkable treatment effects.

Speaker 3: with significant efficacy, efficacy that we think is as good or better than anything that has been observed in a topical before with up to 40% of patients over the course of our clinical program completely clearing of their psoriasis.

With that.

Significant efficacy efficacy that we think is.

As good or better than anything that is observed it observed in a topical for.

With up to 40% of patients over the course of our clinical program completely clearing their psoriasis with.

Speaker 3: with significant durability, so our drug continues to perform better in our long-term extension study, the longer the patients stay on it, including beyond 12 weeks.

With significant durability, you saw our growth continued to perform better than our long term extension study the longer the patients stay on including beyond 12 weeks.

Speaker 3: with what we believe to be a completely unique to topical's remit of benefit, where I mentioned 40% of the drugs, 40% of the patients who go on drug completely clear their psoriasis in our study. They stay clear of drug off therapy or mostly clear for about four months.

We believe to be a completely unique to topical related benefit where I mentioned, 40% of the drugs, but 40% of the patients who go on drug it's completely clear their psoriasis in our study they stay clear of drug off therapy or mostly clear.

For about four months on median.

Speaker 3: which is something that's attractive to payers obviously, attractive to patients, attractive to physicians. And all that is coupled with a...

Which is something that's attractive to payers, obviously attractive to patients and attractive to physicians and all of that is coupled with.

Speaker 7: a very favorable safety and tolerability profile with no treatment related serious adverse events in any of our pivotal studies, the late stage studies.

A very favorable safety and Tolerability profile with no treatment related serious adverse events in any of our any of our pivotal studies late stage studies in.

Yeah.

Speaker 3: with significant tolerability. So with no questions of tolerability for long duration therapy or duration across, or therapy across all different locations on the skin. So a profile that we think compares favorably certainly to the standard of care of topical corticosteroids without any of the, at least in our study, without any limitations on duration that you see with top corticosteroids, without any limitations on where you can use it on your body as observed with some of the top of the corticosteroids.

With significant tolerability, so with no with no questions of Tolerability for long duration therapy or duration of therapy.

Therapy across all different locations on the skin. So a profile that we think compares favorably certainly to the standard of care corticosteroids without any of that.

In our study without any limitations on duration that you see the top started corticosteroids without any.

Limitations on where you can use it on your body as observed with some of the book topical corticosteroids.

On page seven I want to remind people.

Speaker 7: On page seven, I want to remind people of one piece of relatively recently disclosed data that we think is exciting about the drug, which is data we've shown previously, but to highlight the rapid onset of action is one of the things that we think will be important to this as we launch to finish off later this year. With our drug having achieved statistically significant improvement in PASI from baseline as early as we can, we're going to be able

One piece of relatively recently disclosed data that we think is exciting about the drug which data we've shown previously but the highlight the rapid onset of action is one of the things that we think will be important to this is we launched a interop later this year.

With our drug having achieved statistically significant improvement in passing from baseline as early as week two.

Speaker 7: in our studies, and in fact a 20% reduction in disease activity in week two relative to vehicles. So we think there's a significant benefit here early on in treatment, and we think that will matter to patients.

In our study.

And in fact, a 20% reduction in disease activity and we too.

Relative to vehicles. So we think there is a significant benefit here early on in treatment and we think that will matter to patients in.

Speaker 3: In fact, on slate 8, and this is a new piece of information that we've put out this quarter relatively recently, Dermavant as part of our long-term extension study included patient satisfaction data. And you can see on this chart both on the left-hand side, patient satisfaction, these are the other topical treatments. And on the right-hand side, you can see patient satisfaction versus systemic drugs. And so one of the interesting is 80-plus percent of patients under Informatica received at an un encouraged care center with appointments Dingell Lutheran Hospital for Disease Control and Prevention. So remember to get there.INGELL abiding sam forreber visual

In fact on slide eight and this is a new piece of information that we've put out this quarter relatively recently.

As part of our long term extension study included patient satisfaction data and you can see on this chart. Both on the left hand side patient satisfaction vis vis.

Other topical treatments and on the right hand side, you can see patient satisfaction.

Versus systemic drugs and so one.

One of the interesting is the.

80, plus percent of patients strongly agreed or agreed to Peter off was more effective than other topical drugs they'd used in the past and preferred to get it off the other tropical drugs they've used in the past given the attributes as I described on the earlier slide here both from a.

Speaker 3: strongly agreed or agreed that Tepenorof was more effective than other topical drugs they'd used in the past and preferred Tepenorof to other topical drugs they've used in the past. And given the attributes that I described on the earlier slide here, both from a treatment effect perspective and a safety and tolerability perspective, we would have expected that. One of the things that's remarkable is over two thirds of patients, 67.8% of patients also preferred Tepenorof to systemic drugs they'd used in the past.

A.

The treatment effect perspective, and a safety and Tolerability perspective, we would have expected that one thing thats remarkable is over two thirds of patients 67, 8% of patients also preferred to pair off too systemic problems they've used in the past, which given the high level of efficacy associated with systemic therapy, and the fact that often severe patients around systemic therapy.

Speaker 3: Which given the high level of efficacy associated with systemic therapy and the fact that often severe patients are on systemic therapy, it was exciting to us to see just how many patients preferred to turn off to systemic drugs. So these are the kinds of data that matter to prescribers and the kind of data that matters to patients obviously. We think the dermatologists are looking at this and are getting excited for our potential launch later.

It was exciting to us to see just how many patients prefer to printer off just systemic drugs. So these are the kinds of data that matter to prescribers.

And the kind of things that matter to patients. Obviously, we think that dermatologists are looking at this and are getting excited for our potential launch later this year.

Speaker 7: On slide nine, a little bit about that launch.

On slide nine.

A little bit about that launch so we are fully preparing for a launch in the second quarter.

Speaker 7: So we are fully preparing for a launch in the second quarter, including getting ready to deploy a specialty sales force capable of calling on dermatologists to write more than 80% of all commercial prescriptions in this rheosis market. To do that, we're going to hire 75 to 100 reps.

Including.

Getting ready to deploy a specialty sales force capable of calling on dermatologists write more than 80% of all commercial prescriptions in the psoriasis market.

To do that we're going to hire 75% to 100 reps, which will allow us to reach the 6000, the highest value dermatology health care providers, and we think that.

Speaker 3: which will allow us to reach the 6,000 highest value dermatology healthcare providers. And we think that'll be supported by a key commercial leadership team, many of the members of which have already been hired. And we're conducting a number more of those hires over the course of the coming quarter.

That will be supported by our key commercial leadership team. Many of many of the members of which have already been hired and we're conducting a number more of those hires over the course of the coming quarters.

Speaker 3: So really excited about the execution of Thermapath from a very high quality team that we're pleased to support.

We're really excited about the execution of it there with that from a very high quality team that work.

We're pleased to support.

Speaker 3: On page 10, just a reminder of some of the recent progress at Dromavant, including that our NDA submission remains on track with no expectation of an advisory committee for PDUFA in the second quarter, including

On page 10, just a reminder of some of the recent progress at Durham event.

Including that R&D submission remains on track with no expectation of Advisory Convention Committee for <unk> in the second quarter.

Including.

Speaker 3: manufacturing commercial production readiness on track to ensure a high quality and predictable supply of drug. As I mentioned, the commercial organization is being built out as we speak. We did in the quarter have data from our Soaring 1 and Soaring 2 trials published in the New England Journal of Medicine, so that was an exciting sort of scientific closure to those trials. And then we continue to have strong enrollment in our Adoring 1 and Adoring 2 Phase 3 trials evaluating Angelina Holiday from breast cancer research.

Manufacturing commercial production readiness and on track to ensure a high quality predictable supplier as I.

And the commercial organization is being built out as we speak we did in the quarter have a data from our sorting one and starting two trials published New England Journal Medicine.

An exciting sort of scientific closer to those trials and then we continue to have strong enrollment in our adoring wanted to during two phase III trials evaluating <unk> in atopic dermatitis, and we continue to expect top line data from that program in the first half of 2023, So report providing more updates on <unk> in atopic dermatitis over the course of this year.

Speaker 3: And we continue to expect top-line data from that program in the first half of 2023. So we're looking forward to providing more updates on fenorophanate-optic dermatitis over the course of this year. And we think that'll be an important part of the story for us as well.

And we think that'll be an important part of the story for us as well.

So with that I'm going to move on from Jupiter off to some other parts of our business.

Speaker 3: So with that, I'm going to move on from, to pin it off to some other parts of our business.

Speaker 3: And on slide 12, just as a reminder, we have a broad clinical development stage pipeline. So this is our clinical and close to the clinic development stage pipeline with many programs. To turn it off, we talked about the Toklemab and the MoonVamp that we'll talk about a little bit later, and a number of other programs. Too many to talk about on a call like this one, but we look forward to sharing updates on many of these programs over the course of calls like this one and conference presentations over the course of this year.

And on Slide 12, just as a reminder, we haven't.

Rod do clinical development stage pipeline. So this is our clinical and close to the clinic development stage pipeline with many programs spinoff that we talked about the tokamak would've been event that we'll talk about a little bit later.

A number of other programs too many to talk about on a call like this one but we look forward to sharing updates on many of these programs over the course of calls like this one in a conference presentations over the course of this year.

And on page 13, just to highlight 2022 was actually a really important year for us from a clinical development execution perspective.

Speaker 3: You know, on page 13, just to highlight, 2022 is actually a really important year for us from a clinical development execution perspective. And even just among the things we've already talked about, three pivotal study initiations expected for Botoclamab and Immunivant this year. We remain on track to initiate a phase two trial with Manilamab for sarcoidosis, that's our anti-GMCSF antibody. And during this past quarter, the IMD for that program in sarcoidosis has been approved.

And even just among the things we've already talked about three pivotal study initiation is expected for the total nap and immune event this year.

We remain on track to initiate a phase II trial with Nomad sarcoidosis, Thats, our anti GM CSF antibody and during this past quarter. The IND for that program in sarcoidosis has been approved.

Speaker 7: We remain on track to initiate a multiple sending dose trial for our program at LYSE event with the IMD accepted in January of 2022. And we'll talk a little bit more about this program on this call. We're looking forward to conducting a robust, open label expansion of the ongoing phase one, two trial in ARVID-T 2001 at our newly formed Hemovant in lower risk MDS. So many important clinical programs ongoing this year with an expectation of near-term data supporting what we think is going to be a unique and interesting pipeline.

We remain on track to initiate a multiple ascending dose trial for for our program at <unk> with the <unk>.

<unk> accepted in January of 2022.

And we'll talk a little bit more about this program on this call.

Looking forward to conducting a robust open label extension of the ongoing phase one two trial in <unk> 2001 that our newly formed Hema Vance in lower risk Mds.

Many important clinical programs ongoing this year with an expectation of near term data supporting what we think is going to be a unique and interesting Taiwan.

I'm going to start first on the development side by talking about <unk>, which is the newest vantiv family. It was just.

Speaker 7: I'm going to start first on the development side by talking about Hemovant, which is the newest vant in the vant family. It was just built around a program that we licensed just late last year, and so I'll start on page 15.

Built around the program that we in licensed just late last year and so I'll start on page 15.

Speaker 3: So the program here is called RVT-2001. It is a potential first-in-class small molecule SF3B1 modulator for the treatment of transfusion-dependent anemia in patients with lower risk NDS. So SF3B1, if you're not familiar with, is a target.

So the program here is called <unk>.

It is a potential first in class small molecule <unk> modulator for the treatment of transfusion dependent anemia in patients with lower risk Mds. After if you want if you're not familiar with it as a target.

Speaker 3: in the spliceosome and the program came from AZAI.

Spliceosome and this program came from ACI.

Speaker 7: where ASI had been focused on developing it for higher risk progressive MDS patients as well as patients with AML and CMML, and it wasn't totally clear from their data whether it was exactly an appropriate therapy for that population, but as we looked at the data, and we're going to share some of it on today's call, we got excited about RVT2001 for a different patient population, namely the population of transfusion dependent anemia.

We're ACI had been focused on developing it for higher risk progressive Mds patients as well as patients with AML and CML.

It wasn't totally clear from their data or whether it was exactly an appropriate therapy for that population, but as we looked at the data and we're going to share some of it on today's call. We got excited about RPT choose <unk> for a different patient population, namely the population of transfusion dependent anemia or the triple.

Speaker 7: or the treatment of transfusion-dependent media in lower risk myelodysplastic syndrome. And this is a market, as you may know, that has been recently validated by Luz Patricep, with Lozol, a BMS drug that launched...

A transfusion dependent.

In lower risk Myelodysplastic syndrome, and this is a market as you may know that has been recently validated by Patterson.

Patterson Losel.

Our BMS drug.

That launched.

Speaker 7: last year and is now annualizing at over $500 million a year five quarters into launch. And BMS is forecasting that to be an over $4 billion peak sales drug, much of which coming from this lower risk MDS population. And our interest in that population is driven, as I said, by some encouraging proof of concept data in the 80-plus patient phase one, two study that's been conducted in our drug. And we'll talk some more about that data. And we have a multi-pronged development strategy to optimize the drug's impact on that patient population before getting into.

Last year and is now annualizing at over $500 million in year five quarters into launch and BMS is forecasting that to be in over $4 billion peak sales much of which coming from this lower risk Mds population.

Interest in that population is driven as I said by some encouraging proof of concept data in the 80 plus patient phase one two study that's been conducted in our drug and we'll talk some more about that data and we have a multi branded multi pronged development strategy to optimize the drugs impact in that patient population, which we'll get into.

Speaker 4: So on page 16, A is a little bit of a reminder of what this patient population looks like, and B is a little bit of a discussion about how we expect our drug to play. So we're focused here, as I said, on the group of lower risk MDS patients. So there are about 17,000 new MDS cases each year and about 115,000 MDS patients total. And low risk patients are both a significant fraction, about two thirds of new patients, as well as an even higher fraction of the prevalent population.

So on page 16.

A little bit of a reminder of what this patient population looks like and be as a little bit of a discussion about how we expect our drug to place. So we're focused here as I said on the on the group of lower risk Mds patients. So they're about 17000, new Mds cases, each year and about 115000, Mds patients total and low risk patients are both significant fraction about two thirds of new pay.

<unk> as well as an even higher fraction of the prevalent population.

Speaker 3: So, and these are quite sick patients. Low-risk MDS is a chronic condition with therapy focused on management of symptoms. And first-line therapy is mostly erythropoiesis-stimulating agents, ESAs, but they're not very effective. And so there are a number of drugs approved for later-line therapy, just a couple, with Patricept and Lenalidomide, each approved for subsets of patients.

So.

And these are these are quite sick patients low risk Mds is a chronic condition with therapy focus on management of symptoms.

And first line therapies, mostly original polices stimulating agents Esa.

But theyre not very effective.

So there.

There are a number of drugs approved for later line therapy, just a couple with Patterson and Lenalidomide.

Each approved for subsets of patients.

Speaker 3: Luspatricept is approved currently in second line therapy, although BMS has said they're continuing to develop it in earlier line therapy. Lenalidomide, which has significant toxicities, is really only approved for a mutant subset, the 5q-subset of MDS patients. And both of those drugs also be room for improvement. Luspatricept is effective in less than 50% of patients.

With <unk> currently in second line therapy, Although BMS has said, they're continuing to develop it in earlier line therapy, Lenalidomide, which has significant toxicities, there's really only approved for us a mutant subset. The fact, you minus subset.

Mds patients in both of those drugs also.

Room for improvement with Patterson is effective in.

Less than 50% of patients.

Speaker 4: And so, you know, RVT 2001 is a potential oral therapy, first of all, which is different from lispatricept. In a genetically validated target that's mutated in up to 80% of certain subsets of the MDS patient population, which is thought to be an important target in driving MDS mutations in S03D1 are thought to be important.

So <unk> 2001, as a potential oral therapy first of all what's different from <unk>.

Genetically validated target, that's mutated and up to 80% of certain subsets of the Mds patient population.

Which is thought to be an important.

An important target.

Driving Mds mutations in <unk> three.

Water, but could be important.

Speaker 3: Our initial plan is to target second line, principally in SF3V1 mutated patients, with a potential to expand across other spliceosome mutations, as well as to expand to patient populations who are refractory to the spatter staff, where as I said, there's still a significant lead end to go earlier in therapy.

Our initial plan is to target second line principally.

Principally in <unk> mutated patients with the potential to expand across other spliceosome mutations as well as to expand into patient populations, who are refractory to the spatter shaft, where as I said, there is still significant and to lead undergo earlier therapy over time.

Speaker 7: So I want to talk on page 17 a little bit about our early clinical data and why we're excited about the program, and I'll highlight, this is a relatively high-risk program, in part because a lot of this data comes from relatively smaller ends and from cross-trial comparisons, but we think it paints an interesting picture.

I want to ask on page 17, a little bit about our early clinical data on why we're excited about the program.

I'll highlight that this is a relatively high risk program in part because a lot of this data comes from relatively smaller ends and from cross trial comparisons, but we think it paints an interesting picture.

Speaker 7: So in the existing phase one, two study that I referred to, 84 patients for SMDS, AML and CMML.

Hi, Ely existing phase one two study that I referred to an 84 patient Trust Mds AML and CML.

Speaker 7: Only a relatively small subset of those patients, because it wasn't AZI's main treatment interest, were in our patient population of interest. Only 19 of the patients had lower risk transfusion-dependent MDS. And in that patient population, we saw a red blood cell transfusion independence rate of a little over 30%. Now, that in and of itself is not...

Only a relatively small subset of those patients because it wasn't as high as maybe treatment interest. We're in our patient population of interest only 19 of the patients had lower risk transfusion dependent Mds and in that patient population, we saw a red blood cell transfusion independence rate of a little over 30%.

That in and of itself is not necessarily.

Speaker 3: a particularly compelling result only in the sense that the spatter cell, for example, has responder rates in the 40s. But what was interesting upon further investigation is the subset of patients that we were focused on...

A particularly compelling results only in the sense of the status of that for example, as responder rates in the <unk>, but what was interesting. Upon further investigation is the subset of patients that we were focused on.

Is that.

Speaker 3: It turned out to have been a highly sort of pre-treated patient population with 15 of the 19 patients having been pre-treated either with lenalidomide or with prior HMA therapy.

It turned out to have been a highly pretreated patient population with 15 of the 19 patients haven't been free treated either with lenalidomide or with prior HMA therapy, and what's interesting about that is both loose powder staffed and lenalidomide in prior trials have struggled significantly in those patient populations. So who's Patterson.

Speaker 3: And what's interesting about that is both loose patterscept and lenalidomide in prior trials have struggled significantly in those pretreated patient populations. So loose patterscept, for example, had only achieved a 13% red blood cell transgendered independence rate among lenalidomide pretreated patients and loose patterscepts phase two trial. And in fact, that result was so challenging that loose patterscepts phase three study actually excluded lenalidomide pretreated patients.

For example, it only achieved a 13% red blood cell transfusion independence rate among lenalidomide pretreated patients that was better steps phase II trial and in fact that result was so challenging <unk> phase III study actually excluded lenalidomide pretreated patients and Lenalidomide and investigator sponsored trials. So at 12% withheld in HIV, that's a different end.

Speaker 3: And lenalidomide in an investigator-sponsored trial, so like 12% was called an HIE, that's a different endpoint, so sort of a transfusion reduction endpoint in HNA-pre-treated patients.

So Trevor transfusion reduction endpoint.

In HMA pretreated patients.

Speaker 3: So that alone, first of all, is interesting. We saw a significantly higher response rate. In fact, over double the response rate for infusion independence relative to lispatoseptor lenalidomide in a similarly pretreated population.

So that alone and first of all is interesting we saw a significantly higher response rate in fact over double the response rate of transfusion independence relative to spatter Scepter Lenalidomide.

In a similarly pretreated population.

Speaker 3: Now further and on top of that, one of the things that's been interesting to us as we've studied the field is that both loose patterset and linoleumide saw significant improvements as they moved to earlier line and less protruded patients. So loose patterset, for example, in that same study where they had only a 13% transfusion independence rate, saw 44% red blood cell transfusion independence for patients without linoleumide protrusion. And as I mentioned, that led them to actually exclude linoleumide protruded patients.

No further and on top of that one of the things that's been interesting to us as we've studied the field is that both with <unk> and Lenalidomide saw significant improvements as they moved earlier line in less pretreated patients. So with patterns that for example in that same study, where they had only a 13% transfusion independence rate saw 44% red blood cell transfusion dependence.

For patients without Lenalidomide for treatment and as I mentioned that let them to actually exclude lenalidomide pretreated patients from their phase III and in that same study that I mentioned for Lenalidomide on HMA pretreated patients.

Speaker 3: from their phase two. And in that same study that I mentioned for lenalidomide on HMAs for treated patients, you know, 38% response rate or 38% on this HIE for patients who have not been HMA for treated versus 12% post-HMAs. So,

38% response rate are 38% on this HIV.

For patients who have not been HMA pretreated versus 12% post HMA. So again significant improvement as those drugs move earlier line settings, and so not only does our does our data suggests that we may have a significantly different factors typically greater effect in heavily pretreated patients, but theres a chance if we see a similar improvement as well.

Speaker 3: significant improvement as those drugs move through earlier lines.

Speaker 3: And so not only does our data suggest that we may have a significantly different effect or significantly greater effect in heavily protruded patients, but there's a chance if we see a similar improvement as we move to earlier line patients, that we could have an overall best in category therapy.

Move to earlier line patients that we could have an overall best in category therapy.

Speaker 3: for these transfusion-dependent MDS patients. So.

For these.

For these transfusion dependent Mds patients.

That data got US excited obviously this is a relatively risky program for the reasons I mentioned.

Speaker 3: That data got us excited. Obviously, this is a relatively risky program for the reasons I mentioned. But if we're successful, we think we've got a couple of different paths to.

But if we're successful we think we've got a couple of different paths.

So an important program so.

Speaker 4: to an important program. So on page 18, in terms of what we're doing from here, so we're taking the existing ongoing phase 1 to trial and we're expanding it by 50 to 60 patients. We expect to be able to do that over the course of next year with data coming in 2020.

On page 18 in terms of what we're doing from here so.

We're taking the existing ongoing phase one two trial and we're expanding it by 50 to 60 patients at.

We expect to be able to do that over the course of the next year with data coming in 2023.

Speaker 3: We are going to focus on lower risk MDS patients with SF3-B1 mutations. That's about 30% of MDS patients overall and a significantly higher portion of MDS patients in some of the more important subsets for this purpose.

We're going to focus on lower risk Mds patients with <unk> mutations, that's about 30% of Mds patients overall and a significantly higher portion.

Of Mds patients and some of the some of the more important subsets for this purpose.

Speaker 3: And we're going to specifically look for certain biomarkers, including a biomarker called aberrant TM-14c transcripts.

And we're going to specifically look for certain biomarkers, including <unk> 14 to see transcripts, where in a small subset of our patients five out of seven responded so very high response rate and those aberrant heme up where can see transcripts are associated with certain S&P. One mutations in a way that gives us some biological understanding of why that might be so we see.

Speaker 3: We are in a small subset of our patients, five out of seven respondents, so a very high response rate. And those aberrant Tm-14C transcripts are associated with certain SF-31 mutations.

Speaker 3: in a way that gives us some biological understanding of why that might be. So we see a couple of different paths to patient impact here.

A couple of different paths to patient impact here. Obviously, there is the possibility for a biomarker driven sort of very specific precision approach to treating certain patients. There is the possibility for a therapy that can deliver for pretreated patients.

Speaker 3: Obviously, there's the possibility for a biomarker driven sort of very specific precision approach to treating certain

Speaker 3: There's the possibility for a therapy that can deliver for pretreated patients greater efficacy than the other existing therapies on the market. And there's a possibility if we see continued improvement as we move to earlier line patients that we could have an overall best in category treatment effect, you know, in a market that's important and in a patient population that continues to have significant unmet need. And that couples with certain other attributes, including a relatively benign tolerability profile, as well as oral dosing, which is something that the other therapies don't currently have. Thank you.

Greater efficacy than the other existing therapies on the market and there is a possibility if we see a continued improvement as we move to earlier line patients, but we could have an overall best in category treatment effect.

In a market thats important in a patient population significant but that continues to have significant unmet needs and that coupled with certain other attributes including.

A relatively benign tolerability profile as well as oral dosing, which is something that we don't currently have.

Got it.

One other note, which is the first drug because Asia I was testing it for higher risk Mds patients was dosed in a more acute setting.

Speaker 3: One other note, which is this drug, because AIGI was testing it for higher risk MDS patients.

Speaker 3: was dosed in a more acute setting. We've improved our dosing to a more chronic dosing paradigm, which we also think will help us deliver an appropriate amount of blood to these patients.

<unk>, our dosing to a more for chronic dosing paradigm, which we also think will help us deliver an appropriate amount of drug to these patients and the last thing I'll say on this is although this is a relatively higher risk study.

Speaker 3: The last thing I'll say on this is, although this is a relatively higher risk study, relatively minimal data decay has been observed in past MDS trials from phase two to phase three.

Relatively minimal data Dk has been observed in the past Mds trials for phase II phase III <unk> III.

Speaker 3: And so our hope is that after we get data next year, we can be reasonably confident if that data are compelling, that we have a therapy that.

So our hope is that after we get data next year, we can be reasonably confident that data are compelling that we have a therapy that matters and so so that's a little bit about our program in Mds. The last thing I'll say about this is I think it's a pretty good example of how we think about deal, making and programs at Raymond James.

Speaker 3: And so that's a little bit about our program at MDS. The last thing I'll say about this is I think it's a pretty good example of how we think about deal making and programs at Royvent. So this was about an $8 million upfront cash and $7 million upfront equity payment for this therapy.

This was about an $8 million upfront cash and $7 million upfront equity payment for this therapy.

Speaker 3: which is, you know, we think attractive commercial terms. And overall, for around $50 million, we will get the answer to the question in this phase one, two study, which should set us up for interesting therapies if the data are compelling. And otherwise, it will have been a relatively modest investment relative to where our overall portfolio is.

We think attractive commercial terms and overall for around $50 million you will get the answer to the question of this phase one two study, which should set us up for interesting therapy data are compelling and otherwise it would have been a relatively modest investment relative to where our overall portfolio is so.

Speaker 3: An exciting program, something we're glad to have added to the pipeline, and something we're excited to share more about through this year and especially next year as we get data in 2023.

An exciting program something we're glad it add glad to have added to the pipeline and something we're excited to share more about through this year and especially next year as we get data in 2023.

Speaker 3: Next up, I'll just briefly review progress at Immutavamp. So Immutavamp has shared all of this at the end of last year or the beginning of this year. And so I won't go into great detail here, but we are very excited for the fact that the POCA map now has a clear path back into the clinic in my opinion, perhaps in other indications. So I just wanted to remind people a little bit about that situation, starting on page 20.

Next I'll just briefly review progress at immuno them. So.

<unk> has shared all of this at the end of last year and the beginning of this year. So I won't go into great detail here, but we are very excited for the fact that <unk> now has a clear path back into the clinic.

Grants and other indications and so I just wanted to remind people are a little bit about that situation starting on page 20.

Speaker 3: which page 20 really is just a reminder that anti-SCR and antibodies have potential in a very large population of patients.

They just want it really is just a reminder, that <unk> antibodies have potential in a very large population of patients.

Speaker 3: There are over a million U.S. patients and over a million European patients, over a million and a half European patients.

There are over 1 million U S patients and over 1 million European patients over a million and a half European patients.

Speaker 3: with autoantibody mediated autoimmune disease just in.

With auto antibody mediated.

Autoimmune disease just in.

In this list of indications alone and there are others.

Speaker 3: in this list of indications alone, and there are others. We've announced three indications, my thing in Gravis, Weihai, and Ted at a move event. And we said we expect to announce two more through the middle of this year. So we'll talk a little bit more about that later. But a patient population we're excited about. And we think the FCRN class is going to matter a lot with a potential for double digit billion dollars in the world market.

We've announced three indications myasthenia gravis way heightened and at a new event and we said we expect to announce two more through the middle of this year. So we'll talk a little bit more about that later, but the patient population. We're excited about and we think the <unk> class is going to matter a lot.

With the potential for double digit billion overall market size.

So on.

Speaker 4: So on slide 21, as a reminder, we announced at the beginning of this year.

On Slide 21, as a reminder, we announced at the beginning of this year a little bit more information about our plan for the phase III trial design in myasthenia gravis I don't want to highlight and this is a little bit of a schematic on this slide but just the way the autoimmune diseases are treated generally.

Speaker 3: a little bit more information about our plan for the phase three trial design in Myasthenia gravis.

Speaker 4: And I want to highlight, and this is a little bit of a schematic on this slide, but just the way that autoimmune diseases are treated generally.

Speaker 4: is often through a combination of induction and maintenance therapy with the possibility for less.

As often through a combination of induction and maintenance therapy with a possibility to rescue immunologists are used to treating diseases flexibly. They are used to using higher doses of therapy to get patients controlled they're used to being able to maintain patients chronically on broadly just filled up used to being able to up titrate or down titrate, depending on severity of symptoms and re flare and.

Speaker 3: depending on severity of symptoms and reflare. And Botoclamab, the Immutomat is really the only anti-FCR and antibody that is really being tested in that kind of treatment paradigm that matches the way myasthenia and Gravis patients experience their disease and the way that immunologists are used to treating them. So our trial has an induction phase where we test higher doses, including a 680 milligram dose for 12 weeks. A maintenance phase where we test lower doses going down to including a 340 milligram every other week dose. And then a long-term extension where we're able to optimize control of the patients including both up and down.

Talking about but I'm going to answer is really the only anti <unk> antibody that is really being tested in that kind of treatment paradigm that matches the way myasthenia gravis patients experienced their disease and the way that immunologists reduced to treating so our trial has an induction phase where we test higher doses, including a 680 milligram dose for 12 weeks.

Speaker 4: a maintenance phase where we test lower doses going down to including a 340 milligram every other week dose. And then a long-term extension where we're able to optimize control of the patients including both up and down titration as needed for each individual patient. And we think this will allow us to achieve a few things. It will allow us to achieve fast treatment of disease symptoms. It will allow us to maintain on an individualized basis that treatment including managing.

Maintenance phase, where we test lower doses going down to rebuilding a 340 milligram every other week dose.

The long term extension, where we're able to optimize control the patients, including both up and down titration as needed for each individual patient.

We think this will allow us to achieve a few things that will allow us to achieve.

Fast treatment of disease symptoms it will allow us to maintain on an individualized basis that treatment, including managing side effects such as cholesterol in a comfortable way for patients. While they are diseases control and we think it will allow patients to titrate, how do they have disease flare ups in order to manage their experience of symptoms.

Speaker 4: side effects such as cholesterol in a comfortable way for patients while their disease is controlled. And we think it will allow patients to titrate as they have disease flare-ups in order to manage their experience of symptoms.

Speaker 7: You know, on slide 22, we show a little bit about how that stacks up versus some of our competitors, if for Kidramod and Nipicalumab. In short, we believe we are the only program that is designed to match

On slide 22, we show a <unk>.

Little bit about how that stacks up versus some of our competitors in particular amount into the calendar <unk>.

In short we believe we are the only program that is designed to match.

At this.

Speaker 7: uh the design sort of maxed out treatment paradigm in the sort of optimal way and so you know f-cartigiamon for example was approved in more of a cyclical paradigm with

And sort of Max that treatment paradigm and those are the optimal way in so <unk>. For example was approved in more of a cyclical paradigm with four weeks of treatment on and then additional cycled. After after a pause based on loss of response and remember the approved effort huge amount as an IV administered therapy. Although there is also a bridge to a he was on formulation.

Speaker 3: four weeks of treatment on and then additional cycles after pause based on loss of response. And remember, the approved F-Grotigimod is an IV administered therapy, although there's also a bridge to a haloson formulation. Nipocalumab has a loading dose, so a little bit of induction therapy, but only one single loading dose before going to a lower dose treatment paradigm. So not necessarily designed to maximize early treatment effect.

<unk> has a loading dose so a little bit of induction therapy, but only one single loading dose before going to a lower dose treatment paradigm, so not necessarily designed to maximize early treatment effect.

Speaker 3: And nipicalumab in the long-term extension study only allows for downtitration while we allow for both downtitration and rescue therapy. And nipicalumab again today is an IV therapy, although they've discussed a bridge for subcutaneous. And as a reminder, betoclimab addresses all three of these things. We have continuous dosing with induction and maintenance. We have downtitration and rescue therapy allowed. And as you may know, nipicalumab rather was developed from the beginning as a routine simple subcutaneous administer of injection, which we think will make this easiest for patients and physicians.

And <unk> in the long term extension study only allows for down titration, while we allow for bolt down titration and rescue therapy and <unk> again today as an IV therapy, although they've discussed a bridge for subcutaneous and as a reminder, we're talking about addressing all three of these things we have continuous dosing with induction and maintenance, we are down titration and rescue therapy allowed.

And as you may know.

Talking about rather was developed from the beginning as a routine simple subcutaneous administered injection, which we think will make this easier for patients and physicians to match.

Speaker 3: On page 23, just as a reminder, the market for the toclamab is certainly not limited to myasthenia gravis, and we're excited to initiate pivotal trials in three indications total, including myasthenia gravis. And we're going to announce those two additional indications before August of this year, until we're excited to share those indications, as well as additional plans for those trials and move them back in touch to do so in the near future.

On page 23, just as a reminder, the markets with a total that is certainly not limited device to the Rambus and we're excited to initiate pivotal trials in three indications total including myasthenia gravis.

We're going to announce those two additional indications before August of this year and so we're excited to share those indications as well as additional plans for those trials and many of them back and test to do so.

The near future.

So those are some updates on our development stage pipeline. There's obviously a number of other programs that we haven't had time to talk about today and we will in the future, but I want to move now to our discovery organization, where we've been doing a fair amount of work over the past months to really crystallize our strategy and to focus on.

Speaker 3: So those are some updates on our development stage pipeline. There's obviously a number of other programs that we haven't had time to talk about today and we will in the future. But I want to move now to our discovery organization where we've been doing a fair amount of work over the past months to really crystallize our strategy and to focus on what we think are unique and differentiating capabilities. So I'm not going to talk much about specific programs or targets today, but I want to give you a sense for how we're thinking about the composition of this program in general.

On what we think are unique and differentiating capabilities. So I'm not going to talk much about specific programs or targets today, but don't want to give you a sense for how we're thinking about the composition of this program in general and really what I'll say is we've built relevant discovery with the idea that through our computational platform. We can target the 80% of targets that have been very difficult to draw.

Speaker 3: And really, what I'll say is we've built Reuven Discovery with the idea that through our computational platform, we can target the 80% of targets that have been very difficult to drug historically, using a variety of different techniques that are all...

<unk> historically using a variety of different techniques that are all bolstered by our competition capability areas.

Speaker 7: bolstered by our computational capability. And the areas on which we're focused, the first of which we've talked about a bit is hetero-bifunctionals, mostly targeted protein degraders, which is an area that we think our computational platform and wetland capabilities really set us apart from the field.

Areas on which were focused first of which we've talked about a bit as harold by function holes.

Mostly targeted protein integrators, which an area that we think our computational platform and wet lab capabilities really set us apart from the field.

Speaker 3: We're focused on covalency, which is an important emerging area, obviously a focus for a number of biotech companies where we think a combination of proteomics.

We're focused on <unk>, which is an important emerging area, obviously, a focus for a number of biotech companies, where we think a combination of.

<unk> and computational tools.

Speaker 3: and computational tools will give us a unique ability to identify opportunities to drug historically difficult to drug proteins.

It will give us a unique ability to identify opportunities to drive historically difficult to drug proteins.

Speaker 4: And then finally, we have an area that we call deficiency to best in class, which is, you know, we think the atom by atom understanding that we have of different proteins really gives us the ability to look at existing small molecules, whether they're development candidates or even in some cases approved therapy, that have established potential either biologically or commercially, but have well understood limitations like an affinity or binding limitation or an off-target tox effect, and to be able to understand the geometries of those proteins and those affinity relationships and to optimize to resolve some of those deficiencies.

And then finally, we have an area that we call it deficiency to best in class, which is we think the atom by atom understanding that we have different proteins really gives us the ability to look at existing small molecules, whether their development candidates or even in some cases approved therapies that have established potential either biologically or commercially but have well understood limitations like an affinity or buy.

<unk> limitation on off target tox effect and to be able to understand the geometries of those proteins and those affinity relationships and to optimize to resolve some of those efficiencies.

Speaker 3: So I'm going to talk about each of these briefly in turn, starting on page 26, in petrobifunctionals. So we've talked about this a little bit before, and this is an area that we're excited to be participating, the area especially of targeted protein degradation. And in short, we think this is going to be a sort of killer app.

So I'm going to talk about each of these briefly in turn.

Starting on page 26 in federal by functional so.

We've talked about this a little bit before.

And this is an area that we're excited to be participate any area, especially targeted protein degradation.

In short we think this is going to be a sort of the killer app.

Speaker 4: for computational tools in drug discovery. We've combined a really best in class wet lab chemistry team that has deep experience in discovery of new degraders.

For computational tools.

In that drug discovery, we've combined are really best in class wet lab chemistry team that has deep experience in discovery and integrators with a comprehensive platform that gives us we believe the most accurate prediction of territory complex formation, the most accurate prediction.

Speaker 3: with a computational platform that gives us, we believe, the most accurate prediction of ternary complex formation, the most accurate prediction of ubiquitination.

Ubiquitin nation of any that were aware of and in a way that lets us really get to the heart of the do greater discovery problem to understand how both the affinity of our small molecule by end of the warhead as well as the linker geometry, and the eastern leg. Its ligand can come together to achieve an optimal territory complex and to achieve ubiquity nation of the high.

Speaker 7: of any that we're aware of and in a way that lets us really get to the heart of the degrader discovery problem to understand how both the affinity of a small molecule ligand at the warhead as well as the linker geometry and the E3 ligase ligand can come together to achieve an optimal ternary complex and to achieve ubiquitination at the highest possible rate. We think this will let us design degraders against targets that other people have struggled with where we can really optimize for complex formation.

It's possible right. We think this will let us designed integrators against targets that other people have struggled where we can really optimize the current complex formation.

Speaker 3: You know, we feel like we're at a relatively unique corner of the greater space in the sense that we have

We feel like we're at a relatively unique corner of into greater space in the sense that we have wet lab chemistry expertise and tools.

Speaker 4: wet lab chemistry expertise and tools specific to hetero bifunctional, specific to degraders, that goes beyond what we believe is any of the other computational companies.

Specific to head or by functional specific to integrators that goes beyond what we believe is any of the other computational companies and on.

Speaker 3: And on the other side, we have expertise in modeling to graders and computational tools.

The other side, we have expertise in modeling the graders and computational tools.

Speaker 3: for modeling ternary complexes that we can go beyond the computational tools by a significant margin of any of our peers on the degrader side. And so we feel like we are at a unique corner having both the best computational capabilities of any degrader company and the best chemistry degrader capabilities of any computational company. And we feel like that sets us up for a differentiated Sustainable Germansh During this period of time we enjoy

For modeling ternary complex is but we think though beyond the computational tools by a significant margin of any of our peers on the greater side and so we feel like we are at a unique corner, having both the best computational capabilities of any greater company.

And the best wet lab chemistry, greater capabilities of any computational company and we feel like that sets us up for a differentiated opportunity.

Speaker 4: The first of Royman's DeGrader programs will enter the clinic, we believe, this year, and there's a number of others behind it, and we're excited to share pre-clinical data with the course of the year on a number of programs as we move forward.

First of all even greater programs will enter the clinic, we believe this year and Theres a number of others behind it and we're excited to share it with some debate over the course of the year on a number of programs as we move forward.

So I think 27 I'll move to the next pillar here, which is on <unk>. So again. This is an area that's got an increasing interest.

Speaker 3: So on page 27, I'll move to the next pillar here, which is on covalency. So again, this is an area that's got increasing.

Speaker 3: in biotech lately and we've built a team here of QA Proteomics experts as well as computational experts.

In biotech lately and we've built a team here.

Q, what proteomics experts as well as computational experts that we think are going to set us aside here as well so what we've begun by doing here and this is a combination of chemo proteomics and computational tools is by mapping what we call the react on which is to understand the residue is on the surface of a protein and how they map to different how different amino acids map to that residue. So that we can start to understand.

Speaker 4: tools is by mapping what we call the reactome, which is to understand the residues on the surface of a protein and how they map to different, how different amino acids map to that residue so that we can start to understand using a combination of chemoproteomic approaches and a deep computational understanding for the area around various covalent finding opportunities, whether it is possible to drug some otherwise difficult to find drugs. So we use sort of chemoproteomics-based hit finding to screen proteins in their biological state and to find opportunities for binding. And then because our computational tools give us a very accurate understanding of protein geology.

Using a.

A combination of human chorionic approaches.

In a deep computational understanding for the area around various covalent.

But we are finding opportunities whether it is possible to drug some otherwise difficult to find drugs. So we use sort of chemo proteomics space to get funding to screen protein in their biological state and to find opportunities for binding and then because of our computational tools give us a very accurate understanding of protein geometry, including around the the.

Speaker 4: and to find opportunities for binding. And then because our computational tools give us a very accurate understanding of protein geometry, including around the...

Speaker 4: with covalent binding sites, we can figure out how to design selective drugs against those chemo proteomics based hits.

The covalent binding sites, we can figure out how to design selective drugs.

Against those steaming proteomics based yes.

Speaker 4: So we think this is going to matter for a variety of protein categories that have been difficult to drug, including things like transcription factors. And again, we're excited to share some more information about programs coming out of this capability in the near future.

We think this is going to matter for a variety of protein categories that have been difficult to drug including things like transcription factors.

And again, we're excited to share some more information about our programs coming out of this capability in the near future.

Speaker 3: And then finally, on slide 28, I talked a little bit about this in the intro here, but the other sort of pillar we've added here with something we're excited about in part because I think it's going to give us the ability to move very quickly, is to work on programs where there is starting chemical matter, where there's an understanding of affinity, and understanding of a relationship between a small molecule and protein, but where there's some well understood deficiency there where there's an off target tax effect that is understood and so we know

And then finally on slide 28, I talked a little bit about some neutral here, but.

The other sort of pillar, we've added here, but something we're excited about and harvesting is going to give us the ability to move very quickly.

As to work on programs, where there is starting chemical matter, where there is an understanding of affinity.

And understanding of the relationship between small molecule protein, but where there is some well understood deficiency. There. When there is an off target tox that is understood and so we know.

Speaker 7: where the off-target tox finding is taking place, or when there's a cell activity issue, maybe there's multiple isoforms of target, and it's really important to hit certain isoforms but not others, or certain mutant variants but not others.

We are the off target Tox, finding is taking place or when there is a cell activity issue, maybe theres multiple isoforms of target, that's really important to hit certain isoforms, but others, where certain areas, but not others and what we feel like our competition tool, allowing us to do is to start from that starting chemical matter to really understand the limitations of that.

Speaker 7: And what we feel like our computational tools are allowing us to do.

Speaker 3: start from that starting chemical matter to really understand the limitations of that affinity or property relationship to the protein and to be able to work backwards and redesign or re-engineer those small molecules.

Affinity or property relationship to the protein and to be able to work backwards and redesign of reengineer those small molecules do to improve that efficiency and ultimately result in a best in class therapeutic and among the things. We're excited about this industry being able to deliver meaningful patient impact is being able to do it fast to be able to go from start to a drug into the clinic quickly.

Speaker 4: to improve that deficiency and ultimately result in a best in class therapeutic. And among the things that are exciting about this, in addition to being able to deliver meaningful patient impact, is being able to do it fast. To be able to go from start to a drug in the clinic quickly.

Speaker 3: because we're starting from a well-understood problem and iterating rapidly from a computational perspective in a way that we think is going to happen.

We are starting from a well understood problem and Iterating rapidly from a competition perspective in a way that we think is going to is going to matter.

Speaker 3: So on slide 29, just to wrap up the discussion on the discovery side.

So on slide 29, just to wrap up the discussion on the discovery side.

Speaker 7: know, really we feel like our discovery strengths lie at the intersection between the computational platform that we spent a fair amount of time talking about, our molecular dynamics toolkit, our machine learning capabilities, our large GPU-based supercomputer with force field engine that allows us to simulate all kinds of things including complex structures with a high level of precision. There are relatively few other companies in the world that can do that kind of thing with unique experimental light-love capabilities that have been hand chosen to pair with our computational tools, so chemoproteomics and biophysics.

Really we feel like our discovery strengths lie at the intersection between the computational platform that we spent a fair amount of time talking about our molecular dynamics toolkit, our machine learning capabilities.

Our large GPU based supercomputer forcefield engine that allows us to simulate all kinds of things to encourage complex structures at a high level of precision there are relatively few other companies in the world that can do that kind of thing with unique extremity weightless capabilities that have been hand chosen to pair with our computational tools, so chemo proteomics in biophysics.

And wet lab chemistry with greater expertise with specific.

Speaker 3: and went lab chemistry with greater expertise with specific tools and capabilities designed to pair with the modeling that we're doing. And then all of that sits together.

With specific tools capabilities designed to pair with the modeling that we're doing and then all of that fits together with Ravens clinical expertise and with our history of clinical development and we haven't talked about today, but remember that the that model has resulted in a positive phase III trials of <unk> nine that we've run.

Speaker 3: with Raven's clinical expertise and with our history of clinical development.

Speaker 7: And we haven't talked about it today, but remember that the VANT model has resulted in eight positive phase three trials of nine that we've run with now four FDA approved medicines currently at CIMITAV-VANT and a partner. And so a long history of clinical development, including creative clinical development, and all of the programs coming out of our discovery engine across the pillars I just described, get the benefit of moving through that ecosystem and we believe that will allow us to rapidly and successfully develop exciting drug candidates coming out of VANT.

Without four FDA approved medicines currently execute event than a partner.

A long history of clinical development, including creative clinical development and all of the programs coming out of our discovery engine across the pillars. I just described get the benefit of moving through that will have an ecosystem and we believe that will allow us to rapidly and successfully develop exciting drug candidates coming out of Britain discovery. So I wanted to share that updated its a little bit more precision than we have.

Speaker 3: So I wanted to share that update. It's a little bit more precision than we've given in the past on what our discovery organization looks like and how we've divided it up from the capabilities and tools.

Given in the past on what our discovery organization looks like and how we divided it up from a capabilities and tools perspective.

Speaker 4: So I'm going to move on from here and talk about a couple of other items, including one source of summation metric potential upside that people have been paying attention to. So, on slide 31, just as a reminder, I'm going to talk a little bit about Chenivan.

So I'll move on from you were talking about a.

A couple of other couple of other items, including one source of summation metric potential upside that people paying attention to so on slide 31, just as a reminder, I'm going to talk a little bit about churn events. So <unk> is a leading company in the field as nucleic acid delivery focused in particular not exclusively but largely on the design of novel lipid nanoparticle.

Speaker 3: Genovant is a leading company in the field of nucleic acid delivery, focused in particular, not exclusively, but largely on the design of novel lipid nanoparticles. There's deep history of Genovant in the area of lipid nanoparticles, dating back really to almost the very beginning of LMPs, certainly in their use in biotech.

There's deep history of Gentiva Ankeny area of lipid nanoparticles dating back really to almost the very beginning of LNP use.

Certainly in their use in biotech.

Speaker 3: And as you may know, what's exciting about LMPs is...

And as you May know whats exciting about <unk> is they are a tool for getting <unk>.

Speaker 3: They are a tool for getting fragile nucleic acids into the body and into target cells. Otherwise, nucleic acids degrade quickly and don't get to the sort of...

Fragile nucleic acids into the body and into target cells, otherwise I guess, it's a great quickly and don't get to sort of.

Speaker 7: part of the cell where it's needed in order for them to have the therapeutic effect. And LMPs allow nucleic acids like RNAi, like mRNA, to get into...

Part of the cell, where it's needed in order for them to have the therapeutic effect and lmb's allow nucleic acids like RNA I like mrna to get into.

Speaker 7: into cells so they can deliver a therapeutic benefit. LMPs have emerged as the primary means for delivering mRNA therapy.

And just to enter cells. So they can deliver a therapeutic benefit.

<unk> have emerged as the primary use for delivering mrna therapy. So.

Almost all of the mrna therapies in development are delivered.

Speaker 7: almost all of the mRNA therapies in development are delivered via LMPs. And it's worth noting that LMPs are also occasionally used in delivery of RNAi, for example, based therapy. And in fact, Genovans LMP therapy is used in the delivery of the islands on Patro under LMP license from Arbutus.

Lnp's and it's worth noting the Lps were also.

Occasionally using delivery of RNA eye for example, based therapy and in fact churn events.

<unk> therapy is used in the delivering on items on Petro under LNP license from our view this.

So on slide 32, just to quickly we've had continued progress at <unk> this quarter.

Speaker 4: So on slide 32, just to quickly note, we've had continued progress at Genovant this quarter, including a recently announced collaboration with 270 Bio, providing access to our LMP technology, develop gene editing therapies for hemophilia A. So gene editing is another area where LMP has been highly relevant and we're excited to use our technology and collaboration to make some progress.

Including our recently announced collaboration with 270 bio providing answers around the technology develop gene editing therapies for hemophilia, a so gene editing is another area, where <unk> has been highly relevant and we're excited to use our technology and collaboration to make some progress.

Speaker 3: in that important field. And then on the intellectual property side, as many of you may know, in December , the Federal Circuit Court of Appeals rejected Moderna's appeal.

In that important field and then on the intellectual property side as you May know in December the Federal Circuit Court of Appeals rejected Mcdonald's appeal.

Speaker 4: of a PTAB decision. So Moderna had attempted to invalidate a number of our important LMP patents dating back to 2018. And in early December , the federal appeals court affirmed the validity of our patents in a way that was important to us and obviously something that was very significant for consumers, mems of IVs, IVs that we were supposed torecord this point.

A PDF decisions. So Madonna had attempted to validate a number of our important that won't be patents dating back 2018 and in early December .

A federal Appeals court affirmed the validity of our patents.

With that it was important to us and obviously something we were pleased to see so we expect to provide.

Speaker 4: So we expect to provide further updates on Genovant in the near future and look forward to doing so.

Further updates on churn event in the near future.

And look forward to doing so.

So.

Speaker 3: So I'm going to wrap up today's presentation portion today on slide 34 just by highlighting some of our key financial items from the quarter.

Wrap up today's presentation portion of today.

On slide 34, just by highlighting some of our key financial items from the quarter.

So for.

Speaker 7: So for the three months ended December 31st, 2021, we had R&D expense of 153 million with adjusted R&D expense of 119 million. We had G&A expense of 116 million with adjusted non-GAAP G&A expense of 61 million for a total net loss of 306 million or an adjusted non-GAAP net loss of 157 million for the quarter.

For the three months ended December 31, 2021, we had R&D expenses of 153 million with adjusted R&D expense of $119 million, we had G&A expense of $116 million of adjusted non-GAAP G&A expense of $61 million for a total net loss of $306 million or an adjusted non-GAAP net loss of $157 million for the quarter.

Speaker 4: We ended the quarter with cash and cash equivalents of approximately $2.2 billion and limited debt. Our balance sheet gets about $204 million with a principal credit facility making up $32 million of that and the remainder being the fair value of milestone payments related to the pin are off. I'm with about 690 million common shares issued and outstanding as of February .

We ended the quarter with cash and cash equivalents of approximately $2 2 billion and limited debt our balance sheet, that's about $204 million with the principal credit facility, making up $32 million of that and the remainder being the fair value of milestone payments related to dependent off.

We have about 690 million common shares issued and outstanding as of February nine.

Speaker 7: So, on slide 35, as I wrap up my presentation, thank you again for listening, just want to highlight that 2022 was an incredibly exciting year for us again. With the FDA approval decision for topinter off expected in the second quarter, with top one data coming in the first half of next year, with the toclinab getting into multiple new programs in the clinic, with data expected and what we'll share is we have it on additional patients in our tickle cell gene therapy at our event. We didn't spend any time today talking about it, but we continue to enroll patients and the C

So on slide 35, as I wrap up my presentation. Thank you again for listening just want to highlight the 2022 is an incredibly exciting year for us again with the FDA approval decision for <unk> expected in the second quarter with top line data coming in the first half of next year.

Total now of getting into multiple new programs in the clinic with data expected.

And we will share it as we have it on additional patients in our sickle cell gene therapy or event, we didn't spend any time today talking about it but we continue to enroll patients in our phase one two trial in sickle cell disease and look forward to sharing more updates on that program over the course of this year also look forward to discussing the initiation of our phase II trial in sarcoidosis or kind of and.

Speaker 4: in our phase one, two trial on sickle cell disease and look forward to sharing more updates on that program over the course of this year. Also look forward to discussing the initiation of our phase two trial on sarcoidosis at kind of end.

Speaker 4: We're going to continue to expand and enroll patients into our phase one, two trial in lower-stand BS that we talked about earlier and a number of other updates coming from around the pipeline, including...

We're going to continue to expand.

And enrolled patients into our phase one two trial in low risk Mds that we talked about earlier and number of other updates coming through around the pipeline, including.

Speaker 4: multiple programs generating data in our preclinical discovery pipeline that we look forward to driving further. So, I want to thank you again for listening. I obviously covered a fair amount of ground and looking forward to continuing to provide these updates. And at this point, I'll wrap up and go back to the operator for Q&A.

Multiple multiple programs generating data in our preclinical discovery pipeline that we look forward to driving further so thank you again for listening I, obviously covered a fair amount of ground and looking forward to continuing to provide these updates and at this point I'll wrap up and go back to the operator for Q&A.

Speaker 1: Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. Our first question comes from Robin Karnakis with Truist Securities. Your line is open.

Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw your question press. The pound key our first question comes from Robyn <unk> with <unk> Securities. Your line is open.

Hi, Thanks for taking my question. So I actually had a question on RV Tier 2001, you spent a lot of time going through today, which is very helpful.

Speaker 5: Hi, thanks for taking the question. So I actually had a question on RVT 2001. You spent a lot of time going through it today, which is very helpful.

Speaker 5: So, just a little confused on when we'll get the next updated data set. So, you said you plan to amend the ongoing Phase 1-2. Can you go into a little bit more granularity on, like, when you talk to the FDA, what your options are? It sounded like, if you look at biomarkers, is there a quick path to market? I think you said 2023 we might get Phase 3 data. Just can you go into a little bit more detail, because I think it's important to figure out, like, what the timelines are for readouts.

Just a little confused on when we'll get the next.

Updated data set.

Have you plant and then ongoing phase one two.

Can you go into a little bit more granularity on like when you talk to the FDA of what your options are it sounded like if you look at Biomarkers is there a quick path to market I think you said 2000 and.

'twenty three we might get.

<unk> III data just can you go into a little bit more detail because I think it's important to figure out like what the timelines are for Readouts.

Yeah. Thanks, Robin I appreciate the question and thanks, Thanks, very much for listening and sorry, if I caused confusion, so I'll try and cleared that up so well.

Speaker 4: Thanks, Robin. I appreciate the question. Thanks very much for listening. Sorry if I cause confusion, so I'll try and clear that up.

Speaker 7: So, you know, we are, the phase one, two study is ongoing. And so the fastest path for us to continue to enroll the patients we're focused on was to expand that phase one, two study.

We are at the phase one two study is ongoing and so the fastest path for us to continue to enroll the patients were focused on was to expand that phase one two study.

Speaker 3: We will provide an update on the enrollment in that study, on the trial expansion in the middle of this year. We expect to have data from that 50 to 60 patient cohort.

We will provide an update on the enrollment in that study on the trial expansion in the middle of this year and we expect to have data from that 50 to 60 patient cohort in 2023, so that will be data from the phase one two trial, giving us responder rate information for a larger subset of assets through Q1.

Speaker 4: in 2023. So that'll be data from the phase one two trial giving us responder rate information for a larger subset of SF3V1 mutated lower risk MDS patients.

David.

Low risk Mds patients that data will be in 2023 of that data are positive if it shows a compelling fashion that patient population. We will then initiate a pivotal program. So there will be a pivotal study before the drug is approvable in the indication.

Speaker 7: That data will be in 2023. If that data are positive, if it shows a compelling effect in that patient population, we will then initiate a pivotal program. So there will be a pivotal study before the drug is approvable in the indication.

Speaker 4: But we'll have the data next year. And the thing that I said when I was talking about the program is one of the things we like about MDS is the phase three trials tend to be pretty good at replicating the results of phase two studies. So we're hoping that once we have data next year, if it's compelling, we have a relatively straightforward, lower risk path at that point to a therapeutic. But we're still going to have to go through a pivotal trial. The other thing I'd remind you about the phase one, too, is it's an open label study. And so there's a possibility that we at least will have some additional information over the course of the trial. But I would guide toward 2023 for when I would expect to really know the answer.

But but we'll have the data next year and the thing that I said when I was talking about the program is one of things we like about Mds is the phase III trial tends to be pretty good at replicating the results of phase II studies. So we're hoping that once we have data next year. If it's compelling we have a relatively straightforward lower risk path at that point to a therapeutic but we're still gonna have to go through a pivotal trial, the only thing I would remind.

You about the phase one two is an open label study and so there is a possibility that we at least will have some additional information over the course of the trial, but I would guide towards 2023 for what I would expect to really know the answer there.

Got it and then one other follow up on the tenor of the Amgen guide guided double digit growth there.

Speaker 5: Got it. And one other follow-up. I'm just going to pin her off. The engine guide guided double-digit growth. They're obviously in different indications. But an impressive, you know, sort of analysis that patients like topical, you're topical over their systemic. Can you give a color on like what systemic they were on and what type of patients that you were looking at in that analysis?

They're obviously in different indications.

And impressive.

Sort of analysis that patients like topical your topical over their stomach can you give more color on like what systemic they were on and what type of patients.

We're looking at in that analysis.

Speaker 3: So this was all of the patients in our phase three study went through the survey. There was no limitation on which prior therapies patients in the Tepeneroth program could be on. So we don't necessarily know specifically. They were just general psoriasis patient populations, and so you assume they have been on the kinds of things that psoriasis patients are on, whether it's orals or injectable systemics.

So this was all of the patients in our phase III trial, and our phase III <unk> study went through the survey there was no limitation on which prior therapies patients in the spinoff program could beyond so we don't necessarily know specifically they were just general psoriasis patient populations and so you assume that.

<unk> been on the kinds of things that psoriasis patients or on whether it's oral or injectable systemix.

Speaker 3: And so it really is a mixture. And the other thing I'll remind you is the patient population in our program overall was 10% mild, 80% moderate, 10% severe psoriasis patients. So you would expect a sort of grab bag of patients who have been on a variety of different systemic therapy. The only requirement was the patients be willing to wash out of whatever therapy they were on. So none of these patients were on systemic therapy at the time of the Tepenaroff trial. Got it. Okay. Thank you very much.

And so it really is a.

Mixture.

The thing I'll remind you was the patient population our program overall was 10% mild 80% moderate 10% severe psoriasis patients. So you would expect to sort of a grab bag of patients who had been on a variety of different systemic therapy. The only requirement was the patients be willing to wash out of whatever therapy. They were on so none of these patients were on systemic therapy at the time of Interop trials.

Got it okay. Thank you very much.

Thank you Robin and thanks again for the questions. Thanks for listening.

Thank you. Our next question comes from Ron <unk> with Cowen Your line is open.

Speaker 1: Thank you. Our next question comes from Yaron Ruber with Cowen. Your line is open.

Speaker 6: Great. Good morning. Thanks for taking my question. So, Matt, I got a couple. The first one is on 2001. When we look at the earlier phase one, they essentially did two different doses. You sort of alluded to it. They did a five-day on, nine-day off, and then they did sort of a 21-day on, seven days off.Of course we don't really know where each other at least unfortunately we don't know

Good morning, Thanks for taking my question.

So Matt I got a couple the first one is on the 2001.

When we look at the earlier phase one is essentially two different doses you sort of alluded to it at a five day on 90 day off and then there's sort of a 21 day on seven days off.

When you're thinking about your dose to really get to the right therapeutic window. What are you thinking for the next 50 to 60 patients and then secondly can you comment wasn't maduro requested and unbundle.

Speaker 6: When you're thinking about your dose to really get to the right therapeutic window, what are you thinking for the next 50 to 60 patients?

Speaker 6: And then secondly, can you comment whether Moderna requested an en banc meeting from as a next step? I think they were supposed to do that within a month or so of the FC appeal. Thank you.

Meeting from is the next step I think there were supposed to do that within a month or so of the of the FCA deal. Thank you.

So I'll start with the 2001 question and I'll give a brief answer and then just in case, maybe much to anything I'll hand, it over to him.

Speaker 3: So I'll start with the 2001 question, and I'll give a brief answer, and then just in case maybe you've watched anything, I'll hand it over to him. In short, I don't think we've given the exact specifics in our intended dose, but we're moving away from that sort of episodic dosing to chronic administration of therapy at a lower daily dose, but where we think the pharmacokinetic effect will result in a potentially higher dose delivered over time. I don't know if you'd add anything to that.

In short I don't think we've given the exact specifics in our intended dose, but we're moving too we're moving away from that sort of episodic dosing.

Chronic administration of therapy at a lower daily dose, but where we think the pharmacokinetic effect was ultimate potentially higher dose delivered over time.

But anything you'd add to that yeah, I think hey, your on net debt from you what are the things that I think we have learned so far is that you can actually track.

Speaker 6: Yeah, I think what, hey, you're on a nice here from you. One of the things that I think we have learned from the data sets so far is you can actually track

Speaker 6: sort of perturbation in transcription over time on dose. And I think what we find is that actually if you discontinue dose you actually lose the pharmacodynamic effect pretty quickly. And so as Matt said, I think we're looking to really kind of mimic the dosing that really, you know, places the drug's strength and will have an effect on spicy zone inhibition sort of continue.

Sort of a perturbation in transcription over time on that and I think what we find is that actually if you discontinue dose you're actually.

You lose the Pharmacodynamic effect pretty quickly and so as Matt said I think we're looking at really kind of mimics the dosing that really.

With our strength and we will have an effect on <unk>.

Inhibition sort of continuous.

Great. Thanks, Mike and then.

Speaker 3: Great, thanks Mayuk. And then on your other question.

On your other question.

So and thanks for the question.

Speaker 3: So on Genovans, and thanks for the question. I guess the short answer is Moderna has not requested an unbound curing in that process.

I guess the short answer is we don't know has not requested non bunkering.

In that process.

And so.

Ron.

Speaker 12: Yeah, maybe as a quick follow-up, and I know you can't say a lot, so maybe just share what you can. What do you see as the various scenarios of what might happen next, from your vantage point, especially as these drugs are moving away from EUA to getting official approvals?

Yes, maybe as a quick follow up on I know you can't say a lot. So maybe just share what you can.

What do you see as the various.

Scenarios of what what might happen next.

From your vantage point, especially as these drugs are moving away from EUA to getting official approvals.

I'm talking about the Covid obviously.

Speaker 3: Yeah, thanks, your own and again appreciate the question. We saw the Moderna approval earlier this quarter. Obviously an important step for their programs. So it's hard to comment on anything specific.

Yes, Thanks, Ron and again appreciate the question we saw the limiter on our approval.

Earlier this quarter obviously.

Important step for their programs. So it's hard to comment on anything specific.

Speaker 3: in terms of what next steps look like. But I'd say nothing has changed from any of the prior discussions we've had on this in terms of how we're thinking about it. And what I will say is, again, we're looking forward to providing more updates on Genovans in the near future.

In terms of what next steps look like.

I would say nothing has changed from any of the prior discussions we've had on this in terms of.

We're thinking about it and what I will say is again, we're looking forward to providing more updates on gen event in the near future.

Okay.

Okay. Thank you.

Thanks, Ron.

Thanks for listening.

Speaker 1: Thank you. Our next question comes from Dennis Ding with Jefferies. Your line is open.

Thank you. Our next question comes from Dennis Yang with Jefferies. Your line is open.

Hi, good morning, Thanks for taking the question.

Speaker 8: Hi, good morning. Thanks for taking the question. Two questions for me. Number one is on Pinerov. Can you please give us...

Two questions for me one.

One is on <unk> can you please give us.

Speaker 8: sense of your confidence level launching a psoriasis drug during COVID and perhaps internally what may constitute a good launch and perhaps while you're at it, comment on what consensus numbers are for calendar year 2022.

Sense of your confidence level launching <unk> shrunk during COVID-19 .

Internally what may constitute a good launch and perhaps why you are at it comment on what consensus numbers are for calendar year 2022, and then my second question is regarding the.

Speaker 8: And then my second question is regarding the Moderna litigation.

The.

Litigation, So the press release and in your presentation. Some nice comments on the strength.

Speaker 8: The press release and your presentation had some nice comments on the strength of Genovans PEN-IP, but they didn't really get next steps. And interestingly, the PEN-Q mentioned specifically.

And might be but I didn't really get next steps and interestingly.

10-Q mentioned, specifically Ken event.

Speaker 8: you know, Jen and Van may commence litigation at any time.

Commence litigation anytime to enforce our patent rights against infringement and I believe that it's a new disclosure that wasn't in prior 10 Qs. So so can you just please make some comments as to what youre, perhaps waiting for or if I can.

Speaker 8: to enforce the patent rights against infringers. And I believe that is a new disclosure that was in prior 10Qs. So can you just please make some comments as to what you're perhaps waiting for or if I can.

Speaker 8: to reframe the question, what are some gaining factors preventing Genovans from moving forward with litigation?

Reframe. The question what are some gating factors preventing churn event from moving forward with litigation. Thank you very much.

Thanks, Dennis Thanks for thanks for listening and thank you very much for the questions. The bulk to both of your questions. So I'll start to underpin it off so in terms of our level of confidence about the launch our level of confidence about the launch.

Speaker 3: Thanks, Dennis. Thanks for listening and thank you very much for the questions. They're both good questions. So I'll start on to Pinner off.

Speaker 7: So in terms of our level of confidence about the launch, during this summer, I had encouraged theoso Dr.

During.

Speaker 4: during the pandemic. So, first of all, I think you heard of the patient satisfaction data. I think you heard it.

During during the pandemic. So first of all I think you heard at the patient satisfaction data I think you've heard it.

Speaker 7: You've heard it from Todd on the last quarter of this call and other circumstances.

You've heard it from Todd on the sort of last quarter of this call and in other circumstances.

Speaker 4: We are very confident about this drug. The treatment effect is significant. The durability and remittive benefit is significant. So we see a ton of opportunity. You know, I think as I've said before, the drug is both sort of optically and cross-trial comparisons more effective than and we think more tolerable than the current sort of first-line topical standards of care, especially both protocosteroids. So we see just a big opportunity for patients. And so it's hard not to feel confident.

We are very confident about this drug in.

The treatment effect is significant.

The durability and limited benefit is significant.

So we see.

We see a ton of opportunity.

I think as I've said before the drug is both.

Optically and crosstalk comparisons more effective than and we think more tolerable than the current sort of first line topical standards of care, especially both clinical steroids. So we see a big opportunity for patients.

So it's hard not to feel confident about the launch obviously theres a lot that goes into a launch of a product like this including.

Speaker 7: Obviously, there's a lot that goes into a launch of a product like this, including getting pricing access right, getting out to the docs. You know, these docs have been writing corticosteroid prediction prescriptions for a very long time. And so making sure the doctors understand what Spinerov can do, understand how to use it with their patients. I think those things will take time. That education is important.

You can access right getting out to the docs docs have been writing corticosteroid predictions for prescriptions for a very long time, and so making sure that doctors understand what <unk> can do understand how to use it with their patients I think those things will take time that education is important.

Speaker 3: that to work with that physician community is important. I'm highly confident that we will be able to do all of that. And obviously, at medical conferences and similar, we've already been able to talk about the data that we've generated, and we're looking forward to continuing to engage with the dermatology community. So I think we feel good about the launch, and we feel good about the timing of the launch. I think it's an important year in psoriasis. Generally, obviously, we're not the only.

That worked with that physician communities important I'm highly confident that we will be able to do all of that and obviously at medical conferences and similar we've already been able to talk about the data that we've generated and we're looking forward to continuing to engage with the dermatology community.

I think we feel we feel good about the launch and we feel good about the timing of the launch I think it's an important year in psoriasis generally obviously, we're not the only product launching there's another topical launching theirs.

Speaker 7: product launching, there's another topical launching, there's a new systemic therapy launching. So there's a number of other programs and there's going to be a lot of focus and interest.

Systemic therapy, launching so theres, a number of other programs and theres going to be a lot of focus and interest.

Speaker 3: in psoriasis and we feel good about getting out in the second quarter of this year and we feel good about what we think we're going to be able to deliver. We haven't given specific revenue guidance and I'm not going to do that right now, but looking forward to showing you what the drug can do over the course of this year and next. That's what I'll say on Topenoroff.

In psoriasis and we feel good about we feel good about getting out in the second quarter of this year and we feel good about what we think we're going to be able to deliver we haven't given specific revenue guidance. So I'm not going to do that right now.

But looking forward to showing you what the drug can do over the course of this year and next.

That's what I'll say entrepreneur off.

On.

Speaker 3: On your genuine question, and I apologize, I can't comment too much on the specifics here. You know, our 10Q disclosures, and you highlighted one of them, are accurate, and we don't have a ton to add in terms of beyond what it says in those.

On your dividend question and I apologize I can't comment too much on the specifics here.

Our 10-Q disclosures you highlighted one of them are accurate and we're going to attempt to add in terms of.

Beyond what it says.

Those disclosures.

Speaker 4: But it's obviously something we're paying a lot of attention to and looking forward to sharing more as soon as we can.

But.

It's obviously something we're paying a lot of attention to.

And looking forward to sharing more as soon as we can.

Thank you.

Thank you.

Our next question comes from Corinne Jenkins with Goldman Sachs. Your line is open.

Speaker 1: Our next question comes from Corinne Jenkins with Goldman Sachs. Your line is open.

Speaker 9: Hi, good morning. So maybe as we think about the Tippenroff launch, can you just help us understand kind of market access and the strategy there? What percentage of target lives should we expect to see and how can you get, like how quickly should we expect to see that market access?

Hi, and good morning.

As you think about the tender off launch can you just help us understand kind of the market access and the strategy there.

Can you just kind of get lives should we expect to see and how can you get how quickly should we expect to see that market access kind of based on that profile.

Speaker 3: Yes, so thanks, Tran. That's a great question. And again, I appreciate your asking it. In any, obviously, in any therapeutic area, honestly, it's not just dermatology, but I'll say especially in dermatology, market access is an incredibly important dimension. The patient experience at the pharmacy is an incredibly important dimension. Making sure that patients and providers and pharmacies all know how to get patients on drugs is important. There's a lot out there for us to learn in the market around what this looks like.

Yes. So thanks, Thanks, Ron that's a great question and again I appreciate I appreciate your asking it.

Yes.

Obviously in any therapeutic area honestly, it's not just a mortality, but I'll say, especially in dermatology market access and incredibly important dimensions.

Patient experience at the pharmacy is an incredibly important dimension, making sure that patients and providers and pharmacies all know how to get get patients on drug is important.

Theres a lot out there for us to learn.

In the market around what this looks like.

Speaker 4: including from the ongoing launch of Alzohora at InSight, where they've obviously been

Including <unk>.

From the ongoing launch of <unk>.

At insight, where they've obviously been trimmed paving the way in terms of our novel topical in the markets in general will focus on a pretty balanced market access approach will.

Speaker 7: sort of paving the way in terms of a novel topical on the market. In general, we're focused on a pretty balanced market access approach.

Speaker 7: We'll have an industry leading, we'll have a copay program, we'll contract with national and regional health plans, we'll contract with third party payers. We're hoping for unrestricted formula reimbursement.

Have a industry, leading will have a co pay program well contracted national health plans will contract with third party payers, we are hoping for unrestricted formulary reimbursements.

Speaker 3: And we just think with the efficacy and the durability of the drug, as well, frankly, as with the overall current treatment landscape and with the fact that for the first time novel topicals are really offering an opportunity to keep patients on topical therapy and off systemic therapy in a durable and lasting way, we think we should be able to have an attractive profile for payers.

And we just think with the efficacy and the durability of the drug.

As well frankly as with the overall current treatment landscape and with the fact that for the first time novel topical or really offering an opportunity to keep patients on topical therapy and off systemic therapy in a durable and lasting way.

We think we should be able to have an attractive profile for payers.

Speaker 3: And so we expect to be able to deliver good coverage to the patient population. In terms of how quickly we're gonna sort of get exactly that coverage or what we're ramping up towards, I think we're looking for broad coverage, but it's important in launches like this in order to be relatively patient and focused around it. So we'll provide some more information about our exact expectations.

So we expect to be able to deliver good coverage to the patient population in terms of how quickly we're going to sort of get exactly that coverage or what we're ramping up towards I think we're looking for broad coverage, but it's.

Important launches like this in our view to be relatively patient focused around it. So we'll provide some more information about our exact expectations as the launch gets closer but that but suffice to say, we're focused on making the right decisions for for patients on the product on pricing and on access.

Speaker 3: as the launch gets closer. But suffice to say, we're focused on making the right decisions for patients and the product on pricing and on access.

I think we're gonna be able to achieve a good mix.

Thank you and then maybe separately I just think they're going after more of that genetically identified strategy in Mds, but I'm curious how frequently these patients are getting the genetic screening.

Speaker 9: And then maybe separately, obviously you're going after more of a genetically identified strategy in MDS, but I'm curious how frequently these patients are getting the...

Speaker 9: how that could factor into both the clinical and commercial strategy you have here for RBP.

Contactor and clinical and commercial strategy.

<unk> 2001.

Speaker 3: Yes, so as recently as a few years ago, not that many people were checking for S of the main diagnostic criteria for RS-positive and RS-negative patients with lower risk MDS.

Yes, so as recently as a few years ago not that we're checking for Asia, one mutations, but it's actually become one of the main diagnostic criteria for Rs positive and Rs negative patients with lower risk Mds. So it's actually it's a very common we screened for mutation at this point.

Speaker 3: So it's actually a very commonly screened for mutation at this point. And so we should be able to see it in most, we should be able to see the status of an SN31 mutation in most MDS patients. So it should be a good test. And then the other biomarker, the Averin T-MIL-14C transcripts is a little bit of a newer and less common biomarker, but it's still checked relatively often. And so we should be able to screen for it and selectively enroll for it in a useful way.

So we should be able to see it in most would you be able to see the status of and Thats. It for me one mutation in most Mds patients. So it should be a good a good test and then the other biomarkers you Havent chemo for TC transcripts is a little bit of a.

A newer and less common biomarker, but still relatively often and so we should be able to screen for it and selectively and gulfport in a useful way.

Great. Thank you.

Thank you. Our next question comes from Nida <unk> Garg with Citi. Your line is open.

Speaker 1: Thank you. Our next question comes from Nita Vitrito Garg with Citi. Your line is open.

Hey, guys. Thanks for taking my question just following up on some of the questions on <unk> I was just wondering if you could give us a little bit of a sense of how we should expect kind of the general pace of the launch to to kind of proceed through the year.

Speaker 10: Hey guys, thanks for taking the question. Just following up on some of the questions to pin her off, I was just wondering if you could give us a little bit of a sense of how we should expect kind of the general pace of the launch to kind of proceed through the year. You know, if you can kind of talk a little bit about also what metrics you expect to provide on earnings calls in the future once the drug is launched.

If you can kind of talk a little bit about.

Also what metrics do you expect to provide an.

<unk> earnings calls in the future once its launched that'd be great. Thanks.

Yeah. Thanks very much. Thanks. Thanks for the question I appreciate the focus here entrepreneur office obviously.

Speaker 3: Yeah, thanks very much. Thanks for the question and I appreciate the focus here on the question. I'm looking forward to it.

Obviously exciting for us so we're looking forward to it.

Speaker 3: So in terms of the sort of shape or pace of the launch, I guess to go back to what I said a couple of comments ago, which is, you know, we are looking for a meaningful change in prescriber behavior here. So I think you got to start with that. These docs are very used to writing topical therapy, so that's good, but they're very used to writing corticosteroids, and that's going to require some reeducation. And so, you know, I think this is going to be a bill. I think it's going to take

So in terms of the sort of shape or pace of the launch.

Just to go back to what I said, a couple of comments ago, which is we are looking for a meaningful change prescriber behavior. Here. So I think you got to start with that the facts are very used to writing topical therapy. So that's good but they are very used to writing corticosteroids and that's going to require some reeducation.

And so I think this is going to be a bill I think it's going to take some time and energy to really sort of changed behavior and I think the exciting thing is we are building to a really interesting level, because we get to look out and yes. It <unk> change the paradigm, which is not something you get to do very often so I think it will it'll take a little bit of time to build that market.

Speaker 3: some time and energy to really sort of change behavior. And I think the exciting thing is we're building to a really interesting level because we get to look out and it changed the paradigm, which is not something you get to do very often. So I think it'll take a little bit of time to build that market. And I think we're sort of committed to doing that in the right way and starting from the bottoms up and educating the physicians and working on the access piece that we talked about before so that we reach the maximum number of patients with the product over time. We get sort of the right kind of sustained use of the product.

And I think we're sort of committed to doing that in the right way and starting from the bottoms up and educating the physicians and working on the access piece that we talked about before so that we reach the maximum number of patients with the product over time get sort of the right kind of sustained use of the product.

Speaker 4: In terms of metrics, I would expect we're going to share the kinds of things that people share with similar launches, so we'll talk about our engagement, we'll talk about obviously script rates, although we won't need us for that. And we'll be keeping an eye on payer coverage on gross net, things of that sort, as the product gets launched, but, you know, in general, we're really looking forward to just getting out there and getting out to patients.

In terms of metrics I would expect we're going to share the kinds of things that people share with similar launches so to talk about our engagement will talk about.

Obviously script rates, although you won't need us for that.

And we'll be keeping an eye on payer coverage on a gross net things of that sort.

As the product gets launched.

In general were looking forward to just getting out there and getting out to patients.

Got it thanks.

Our next question comes from Doug Tsao with H C. Wainwright Your line is open.

Speaker 1: Our next question comes from Doug Sow with HC Wainwright. Your line is open.

Hi, good morning, Thanks for taking the questions.

Matt maybe stepping back as you referenced at the beginning of the call you have $2 billion in cash obviously.

Speaker 11: Matt, maybe stepping back, as you referenced at the beginning of the call, you have $2 billion in cash. Obviously, the equity markets have been fairly challenged for healthcare for the last several months. I'm just curious, has that affected how you're thinking about business development and potentially your use of capital or capital allocation strategy?

The equity markets have been fairly challenged for health care for.

Several months I'm, just curious does that decade, how youre thinking in that business development and potentially your sort of use of capital in our capital allocation strategy.

Yes.

Speaker 3: Yes, so thanks for the question Doug, I really appreciate it.

Yes. So thanks for the question, Doug I really appreciate it.

Front and center on my mind.

Speaker 3: I think it's got for any biotech company right now, it's got to be front and center on your mind to make sure that you're.

The answer I think its got for for any biotech company right now it's got to be front and center in your mind to make sure that youre.

Speaker 3: doing the maximum amount possible with the resources that you've got. We are extremely privileged in our capital position and we know that.

Doing the maximum maximum amount possible with the resources that you have got and we are extremely privileged in our capital position and we know that.

Speaker 3: And that privilege is particularly acute in markets like this one. So we're doing everything that you would expect in terms of making sure that we're allocating our capital extremely carefully and focusing on the areas where we have maximum possible impact for patients. And frankly, we're also doing everything you expect in terms of looking out across the marketplace for opportunities to take advantage of our relative capital strength. Obviously, it's not a position that everybody is fortunate enough to be in. And that creates opportunity for us. I think you see it.

And that privilege is particularly acute in markets like this one so.

We're doing everything that you would expect in terms of making sure that we're allocating our capital extremely carefully and focusing on the areas, where we have maximum possible impact for patients and frankly, we're also doing everything you'd expect in terms of looking out across the marketplace for opportunities to take advantage of our relative capital strength, obviously, it's not a position that everybody is fortunate enough to be in and that creates.

For Us I think you see it.

Yes.

Speaker 3: in our past in licensing activity, you'll see it in our future in licensing activity. I think we're really focused on value. The MDS program obviously came to an end with...

In our past licensing activity, you'll see it in our future in licensing activity I think we're really focused on value.

The Mds program, obviously Kimberly.

Plenty of capital and such so it wasn't exactly the same situation, where the program, where we were able to acquire it very efficiently.

Speaker 3: plenty of capital and so it wasn't exactly the same situation. But a program where we were able to acquire it very efficiently because we saw a different possible application for it. I think you'll see things like that. You know, we have another new event that we've mentioned by name that haven't described in detail, PRI event, which has another new program that again was a modest up front payment relative to the size and opportunity of that program. So I think you will continue to see us be opportunistic. I think you'll continue to see us deploy capital in focused, targeted ways where we think we can.

Because we saw a different possible application forward I think youll see things like that we have another new ramps that we've mentioned by name, but Havent described in detail prior to Ams, which is another new program, but again it was a modest upfront payment relative to the size of the opportunity of that program. So, but I think you will continue to see us be opportunistic I think you'll continue to see us deploy capital in focused targeted ways, where we think we can.

Speaker 3: differentially bring something in sufficiently. And in the meantime, I think you'll see us be very disciplined in how we use our cash so that we can maximize the application of our resources to adopt to use a matter.

Differentially bring something in.

Sufficiently in the meantime, I think youll see us be.

Very disciplined in how we use our cash so that we can maximize the application of our resources to opportunities that matter.

I guess as a follow up.

Speaker 11: I guess as a follow up, I mean, ask the different web, Matt, you know, historically become very active from business development standpoint, from a licensing standpoint and partnerships. Just curious, do you think, you know, just sort of going back to my comment about sort of the broader market, does that change your thinking and perhaps just outright M&A become more attractive just given, you know, current market valuations and opportunity dislocation in the marketplace?

Asked a different way Matt historically, the company has been very active from a business development standpoint from an in licensing standpoint and partnerships.

Just curious do you think just sort of going back to my comment about sort of the broader market does that change your thinking and perhaps just outright M&A become more attractive to skip.

Current market valuations and opportunities dislocation in the marketplace.

Yes, so first of all we haven't necessarily shied away from M&A, even in the past so are the greater platform was required as an opioid.

Speaker 7: Yes, so first of all, we haven't necessarily shied away from MMA even in the past. So, you know, our degrader platform was acquired as on copia. We correct looking therapeutics last year. So where we see good value.

Greg Silicon Therapeutics last year, or so where we see good value we've.

Speaker 4: We've always been happy to do that. And I guess.

Always been happy to do that.

And I guess.

Speaker 4: same as everybody else. I think it's been harder for us to find good value on the M&A side in the last couple of years because the way the market has evolved, I think that's changed significantly and so I think there's absolutely...

Same as everybody else I think it's been harder for us to find good value on the M&A side in the last couple of years because the way the market has evolved I think thats changed significantly and so I think there's absolutely.

Speaker 4: an opportunity for us to take advantage of that. You know, being a public company obviously helps.

An opportunity for us to take advantage of that being a public company obviously helps.

Speaker 3: although those are all relative value considerations and we look at our own valuation as well. But absolutely, yes, we see opportunities for M&A.

Although.

Those are all relative value considerations, and we look at our own valuation as well.

But absolutely, yes, we see opportunities for M&A.

Speaker 3: and increasingly attractive opportunities for M&A after the macro change in valuation that we've seen over the past couple of months.

And increasingly attractive opportunities for M&A after the sort of macro change in valuations that we've seen over the past couple of months.

Okay, great. Thank you so much.

Thank you Doug.

Speaker 1: Thank you, and I'm showing no further questions at this time. I'd like to turn it back to Matt for closing remarks.

Thank you and I'm showing no further questions at this time I would like to turn it back to Matt for closing remarks.

Speaker 4: Great. Well, thank you again, everybody, for listening. Thank you for all of your questions. It was great to hear everybody's focus. And obviously, we also are incredibly focused on Dopinaroff and incredibly focused on that launch coming up in the second quarter. So we're looking forward to getting back on the phone in the near future to talk more about that, to talk more about updates elsewhere across the business. And in the meantime, thank you, everybody, for listening. And excited to have shared this hour's second quarterly earnings update as a public company. So everyone, I hope you had a good weekend and have a great day.

Great well. Thank you again everybody for listening. Thank you for all of your questions. It was it was great to hear everybody everybody's focus and obviously, we also are incredibly focused entrepreneur often incredibly focused on that launch coming up in the second quarter. So looking forward to getting back on the phone in the near future to talk more about that and talk more about upticks elsewhere across the business.

In the meantime, thank you everybody for listening and excited to have shared this our second quarterly earnings update as a public company. So.

We would hope that it can we kind of have a great day.

Speaker 1: This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone have a great day.

This concludes today's conference call. Thank you for participating you may now disconnect everyone have a great day.

Goodbye.