Q1 2022 Selecta Biosciences Inc Earnings Call
Certainly, we recently announced that the clinical hold on <unk>, our wholly owned gene therapy candidate for medic Malonic Academia MMA was lifted on March nine and we successfully completed an underwritten offering in April which raised approximately $38 7 million in cross proceeds.
With our more focused wholly owned portfolio and financial runway into mid 2024, we believe select is well positioned to execute on our clinical stage assets in biologics and gene therapies advance our proprietary ITG, partly absorbed into the clinic complete our Iga protein.
As can be candidate selection for our program and accelerate the development of <unk>.
The next generation and as specific precision immune tolerance platform.
We're incredibly excited to advance our <unk> platform and bring hope to the over 24 million Americans suffering from autoimmune diseases daily.
Our sharper strategic approach has allowed us to support and accelerate the development of our wholly owned pipeline with a focus on apologetic therapies for autoimmune diseases, and so put in biologics as well as provide transformative solutions for our gene therapy partners to unlock the true potential of.
<unk> associated virus or AAV gene therapies.
I would now like to walk you through key updates and recent strategic partnerships pertaining to the three pillars of our pipeline.
The current standard of care for autoimmune diseases utilizes immunosuppressive drugs, which are associated with side effects that often these patients vulnerable to serious infections and malignancies or treatments that provide only symptomatic relief.
Our approach is to re imagine the treatment paradigm for autoimmune disease by using our precision immune tolerance platform to restore natural immune system balance by inducing an expanding Amazon specific regulatory T cells, thus avoiding the need for systemic immune suppression for chronic symptom masking.
<unk>.
Recent preclinical data generated by our scientific team showed synergistic activity. When <unk> was combined with engineered IL two molecules that are selective for T. Rex.
This combination, which we call intra al chose a substantial increase in antigen specific T. Rex when co administered with a target antigen well beyond what we see with intra alone in which we already have observed clinically meaningful benefits.
We tested intra L for the ability to induce durable immune tolerance to co administered AAV gene therapy vector in mice.
We observed complete inhibition of anti <unk> antibody formation after multiple doses of gene therapy through 117 days.
Most excitingly. This effect was observed it will be considered separate theyre pretty doses per into alone. These results suggest that this combination of a <unk> selective IL two with <unk> has the potential to increase the potency durability and efficacy of the Amazon specific immune tolerance that <unk>.
And lists.
Current programs of engineered T. Rex selective IL two molecules focused on a generalized expansion of total existing T Rex, but not T. Regs specific for the <unk> responsible for the pathogenesis of autoimmune diseases. Thus, we believe <unk> has the potential to be a truly differentiated.
At first in class and specific immunotherapy for autoimmune disease that restores immune system balance in vivo.
We believe that our ability to induce and specific T. Rex enviable is potentially the most elegant solution to the intractable problem of restoring balance to the immune system.
Further we believe <unk> represents a transformative evolution of our precision immune tolerance platform with implications across all three pillars of our pipeline pipeline in particular, the potential to create breakthrough therapies for the treatment of autoimmune disease.
A key priority for <unk> in 2022 will be to accelerate the development of our proprietary engineered IL two molecule.
We have partnered with Cyrus biotechnology, a world leading protein engineering company spun out of David Pecos Lab at the University of Washington to speed. The development of next generation highly differentiated IL two new team to combine with <unk>.
We believe our intra platform is ideally suited to address primary biliary cholangitis or PBC, a T cell liver disease, driven by a well defined antigens.
In PBC.
June system mistakenly attacks tissue and deliver and damages the small buybacks treatments to help slow the progression and prevent complications PVC are available. However, these medications ultimately failed to control PBC and patients often require a liver transplant.
As shown in animal models of liver injury and inflammation the ability of <unk> to target the liver coupled with the expansion of Amazon Pacific T. Rex when equipment is so with IL. Two suggests that <unk> may be beneficial in the treatment of patients with PBC.
We are continuing our IND, enabling studies for this program.
In parallel we are evaluating additional targets and indications that would be well suited for our first in class antigen specific immunotherapy and will update the market as we add indications to our pipeline in autoimmune disease.
Moving on to our work in gene therapy, we believe select with the combination of <unk> and our proprietary IGT Protium <unk> has the potential to solve some of the most difficult challenges facing the AAV gene therapy field.
Patients, who have preexisting antibodies against the caps due to prior natural exposure to the AAV virus are often eligible for treatment. Additionally, the anti cancer immune response prevents the ability to re administer AAV vectors as a result gene therapies are considered onetime only treatment.
<unk>.
Currently 30% to 70% of the patient population put gene therapy trials are in eligible for inclusion due to preexisting neutralizing anti AAV antibodies, which are result of national inspections.
As many patients in need are unable to access potentially life altering therapies for which there may be few or no treatment alternatives.
IGT proteases have shown promise as a pre treatment to translate clear preexisting neutralizing antibodies and create a window during which AAV gene therapies could be administered.
Ever IGT put his argue right from bacteria and are themselves highly immunogenic. Additionally, some ITG proteases are derived from a common human pathogens and consequently, the vast majority of individuals have preexisting antibodies against these proteases.
<unk>, our proprietary ITG Proteus candidate that is designed to specifically cleef human ISG is derived from non human pathogen and we've observed low cross sell activity to preexisting anti ITG Proteus antibodies, we believe that the combination of <unk> with them tour Couldnt April .
Dosing of this enzyme therapy.
It is combination of zircon inventory has the potential to simultaneously address two of the biggest issues currently limiting AAV gene therapy.
<unk> to bring the power of gene therapies to those patients who would be otherwise in eligible for treatment due to preexisting antibodies and <unk> to mitigate the novel immune responses to AAV gene therapy and enable re dosing.
We believe that the combination of <unk> and <unk> has the potential to provide safer and more effective gene therapies to more patients and truly unlock the potential of the gene therapy modality by transforming a treatment into durable long term cure.
Preclinical studies suggest multiple potential benefits of <unk> in AAV gene therapy, including increased transient expression and the first dose mitigation of hepatic inflation.
Inflammation more durable transgene expression and inhibition of capsid specific b and T cell responses.
We are proud to have multiple presentations, both independently and in partnership with <unk> at the upcoming annual meeting of the American Society of gene and cell therapy or <unk>. This month.
Our presentations will highlight the ability of <unk> and into <unk> to mitigate anti AAV antibodies and enable repeat vector dosing.
In a single dose clinical study in healthy human volunteers conducted in partnership with <unk>, we observed the ability of <unk> to mitigate the formation of anti AAV neutralizing antibodies out to 30 days and our preclinical data in mice and nonhuman primates suggests that control of antibodies can be maintained with <unk>.
Two additional doses of <unk>.
Another major challenge for the gene therapy field relates to the serious toxicities associated with vector doses of 114 vg per cakes or higher.
And this problem will likely require a multi pronged approach, including engineering more efficient cabinets the.
The ability to re dose AAV vectors could provide a complementary strategy by enabling the administration administration of multiple lower doses of capsid.
We'd like to see the dosing paradigm for AAV gene therapy change from one and done to low and slow.
But giving multiple lower doses of gene therapy, we could potentially titrated up to the tenants are pretty level, while avoiding the unfortunate adverse events that have been seen at high doses of gene therapies initial studies in mice suggest that <unk> has the potential to mitigate anti AAV antibodies.
Responses at high vector doses up to five <unk> Vg per case.
We're also excited about our collaborations ginkgo bio works to design novel, AAV capsid with a goal of improving transduction efficiency liver <unk> any immunogenicity profile.
<unk> will design and engineered the capsid and selected will conduct all non clinical and clinical studies thereafter.
This partnership Leverages skincare cell engineering, and high throughput screening capabilities and select us in tour precision immune tolerance platform to advance gene therapy delivery.
By combining <unk> with more efficient cabinets, we could potentially reduce the dose of gene therapy and needed to see therapeutic benefit and further mitigate the risk of serious adverse events associated with high vector doses.
Moving on to our wholly owned gene therapy asset <unk>.
302.
On March nine the FDA cleared the IND application for our phase <unk> clinical trial of <unk> to a combination of <unk> with MMA 101 being developed for the treatment of MMA, a rare metabolic disease in which the body cannot breakdown certain proteins and fats.
The trial is expected to initiate in the second half of 2022 and will evaluate the safety and efficacy of <unk>, two and communication of neutralizing antibodies against the MMA 101 AAV capsid.
Hopeful that the phase one trial of <unk>, two will build on the growing body of evidence supporting the potential multi faceted benefits of <unk> for enhancing the efficacy and safety of AAV gene therapies, and the learnings from our MG Aviate Captain study in healthy volunteers.
We believe development of a wholly owned asset and MMA will provide an important regulatory and clinical blueprint for our leading gene therapy partners, including Takeda.
<unk> and ASP items.
We are seeing excellent progress across our gene therapy platform and we look forward to continuing to progress in tour in our wholly owned gene therapy programs to maximize the full potential of our platform. We plan to actively pursue business development and out licensing opportunities for both <unk> and <unk> for gene therapy applications.
Lastly, I want to provide an update on our biologics pipeline, which houses our most mature program.
<unk> has served as an important clinical validation for our precision immune tolerance platform with over 450 patients dosed to date.
Many biologics can be highly immunogenic, resulting in sub optimal responses due to the development of antidrug antibodies after multiple treatments.
Patients develop an immune response may be forced to discontinue treatment or experienced adverse reactions.
We believe that the use of <unk> as an adjunct to biologics offers a promising approach to minimize the health care and economic burden of antidrug antibodies.
<unk> is comprised of <unk> co administered with a proprietary your case to get the case for the treatment of chronic refractory gout and what's license to Swedish orphan <unk> or <unk> in 2020.
As a reminder, our phase III <unk> clinical program kicked off in the third quarter of 2020 and consist of two double blind placebo controlled trials of <unk> in.
In both trials <unk> will be evaluated at two doses of <unk>, one mixed cookie and one five mixed boutique and one dose of the Gatwick case.
Two mixed perfect.
The original enrollment target for both study was studies was 105 subjects.
On December one 2021, we closed enrollment in the 112 subjects for resolve one which is being conducted in the United States.
<unk> two enrollment is continuing a pace and is being conducted in four countries across eastern Europe , and the United States.
We have proactively undertaken steps to prioritize the safety of our patients and investigators as well as mitigate any potential disruptions due to the evolving geopolitical situation in Ukraine and Russia.
Firstly, we have temporarily suspended screening and randomization for new patients in both Russia, and Ukraine and have reserved existing clinical trial supplies in these countries for those already enrolled in the study.
Secondly to mitigate the risk of any delays, we proactively added 11 additional sites in the United States to offset the potential loss of subjects in Ukraine, and Russia and speed enrollment in dissolved two.
We now have 55 active sites and are on track to complete the study in Q4 2022.
Finally in agreement with our partner <unk>.
We have increased enrollment and resolved two to approximately 140 subjects in an effort to replace subjects enrolled in Russia, and Ukraine, who may be lost to operational issues. We anticipate that these mitigation efforts will see us complete both yourself studies in Q4 2022 with joined topline.
Data available in Q1 2023.
We continue to work closely with our partner <unk> or clinical trial providers and regulatory authorities to ensure the successful completion of the resolve program.
With extensive clinical data and <unk> currently in phase III, we believe our biologics pipeline is mechanistically de risked and select is well positioned to leverage these learnings into our second biologic indication in Iga nephropathy, a kidney disease that occurs when immune complexes of an antibody.
Called Uniqlo during a one or Iga one accumulate in the kidneys current treatments fail to address Iga proteins deposits. The underlying pathophysiology of the disease. We believe our novel approach, which combines <unk> with and <unk> has the potential to remove injurious.
From the kidneys improve markers of renal dysfunction and have a transformative impact on patients' lives.
We're currently working with IGN Biosciences on a first generation <unk> derived from the muscle is influenza bacteria. Additionally in October 2021, we entered the collaboration with Ginkgo bio works to generate a second generation <unk> designed to have lower midstream entity and when combined with <unk>.
<unk> have a potentially transformative they're pretty profile.
We plan to finalize clinical candidate selection by the end of the year.
We're extremely excited about the advancements across all three pillars of our pipeline and the value driving milestones ahead with that I will turn the call over to Kevin to run through our financial results for the first quarter ended March 31 2022, Kevin.
Thank you Carsten during the first quarter, we proactively took several steps to further bolster our balance sheet.
We prioritized our wholly owned portfolio to conserve resources.
We restructured our loan agreement to the FERC principal payments for an additional 12 months at.
Most notably on April six.
We priced an underwritten equity offering.
Approximately $38 7 million before fees and expenses.
As a result of these initiatives, we announced approximately $154 million in cash.
Cash equivalents.
Investments.
Restricted cash on hand as of April 11, 2022.
We believe our current liquidity will be sufficient to meet our operating requirements into mid 2024.
I would like to enter into the second quarter of 2022 with a strengthened cash balance that we believe will allow us to execute on our priorities despite geopolitical uncertainty Mac.
Macroeconomic volatility and biotechnology specific headwinds.
We have multiple clinical readouts and filings anticipated with our cash runway.
And we will continue to be careful stewards of stockholders' capital.
And execute our strategic plans expeditiously.
Reviewing our financial results in the quarter ended March 31 2022.
Net cash used in operating activities was $11 9 million for the first quarter of 2022 as compared to $12 1 million the same period in 2021.
Collaboration and license revenue recognized was $34 million for the first quarter of 2022.
As compared to $11 1 million for the same period in 2021.
Revenue was primarily driven by the shipment of clinical supply and the reimbursable costs incurred for the phase III <unk> clinical program.
Under the license agreement with Adobe.
Yeah.
Research and development expenses were $17 7 million for the first quarter of 2022.
As compared to $13 million for the same period in 2021.
The increase in cost was primarily the result of expenses incurred for the preclinical programs.
<unk> contract license and milestone payments.
General and administrative expenses were $5 5 million for the first quarter of 2022 as compared to $5 2 million for the same period in 2021.
The increase in cost was primarily the result of an increase in stock compensation expense.
For the first quarter of 2020 to collect reported net income of $28 8 million or basic net income per share of <unk> 23.
Compared to a net loss of $24 6 million or <unk> 22 per share for the same period in 2021.
I will now turn it back to Carsten for closing remarks.
Carsten.
Yeah.
Thank you Kevin in.
In summary, we're pleased with our progress in Q1 2022.
With the financial runway into mid 2024, we believe select acquisitions to reach potential transformation of inflection points across all three pillars offer pipeline.
Most notably we are excited by our plans to enter the clinic with <unk> 302.
Complete the resolve program with our partner <unk> advanced IND, enabling studies across our wholly owned pipeline support our numerous collaboration partners and rapidly progress our next generation positioning immune tolerance technology <unk> into the clinic.
We believe <unk> could represent a generational leap forward for the <unk> platform.
The strong synergistic effects, we have seen in our preclinical work support our belief that <unk> has the potential.
To unlock first in class antigen specific immunotherapies for autoimmune disease, as well as improve the efficacy and safety profile of therapies in biologics and gene therapy.
We will continue to deliver when our unrelenting commitment to solving the hardest challenges in autoimmune disease and help patients overcome autoimmunity and immunogenicity through our evolving in tour precision tolerance platform.
Before we conclude today's call I would also like to thank the entire selected team our investors and the many people who have been supportive along the way, including our patients and their families with that we're happy to take questions.
We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone.
If you are using a speakerphone please pick up your handset before pressing the keys.
If at any time. Your question has been addressed and you would like to withdraw. Your question. Please press Star then two at this time, we will pause momentarily to assemble our roster.
Our first question will come from John Newman with Canaccord. Please go ahead.
Hi, gentlemen, good morning, and thanks for taking my question.
I had a question about the work Youre doing with IL two.
Really interesting here.
I'm wondering is you've got a proprietary IL two program running here with Cyrus I'm wondering when you when you take inventory into the clinic in combination with IL. Two do you think you'll be taking in into the clinic with your proprietary IL two or might you investigate inventory.
Sure on its own first with unavailable.
Formulation. Thanks.
Hey, John it's a good good question.
So as you as you rightly said, we are working with Cyrus to develop a proprietary IL two routine and <unk>.
Planned to take it into the clinic with that IL two.
Having said that I mean, there are.
Other IL two's in clinical development.
And there's always the chance to look at those as well but for.
For now the plan is to take the combination.
With the IL two from Cyrus into the clinic first.
We believe that the data we have at least demonstrated so far combining <unk> with IL two in the mouse studies, where we see really a profound increase both an induction and expansion of T. Rex will be really meaningful in autoimmune disease.
The other piece, which we're excited about is that this not only limits us to autoimmune disease, but we're also really encouraged by the data we have seen in gene therapy, where the combination actually was dose sparing which is very encouraging.
See you potential application, combining with biologics as well.
Okay, Great and then just had one.
One additional question if I may.
<unk> also got some interesting work going on with your ICT protease and I know that.
This is a bit early but just curious as to how you might like to study that in the clinic. Once you get there just wondering if you'd look at antibodies against gene therapy vectors or if there are some other things that you'd like to evaluate that you think would be more meaningful.
Yeah, that's a great question.
Alright.
Peter M answer this but just to kind of frame it up for everyone. So our proprietary ICT protease is from a non human pathogens. So that we haven't seen any cross reactivity human Sera, which.
Which we believe is a major advantage and there are multiple applications, but the one we're most excited about is as a treatment for patients that had a prior AEP infection are not eligible for for gene therapy.
Peter maybe you can elaborate while we haven't really guided the detail, but how we might look at this from a proof of concept.
Thank you Kirsten Hi, John .
The ability to test the ITG protease.
Healthy volunteers, we think is a.
Real advantage because there is a renewed sense of.
AAV antibodies.
The population.
So we think that.
We would start.
A healthy volunteer study.
To look at the.
Asia move AAV antibodies.
In the population.
Good.
The potential for looking at multiple different gene therapies.
We have with pretreatment with <unk>.
So so.
So we think to be neutral clinical development is relatively straightforward in that way.
But of course, then we are looking for either with our proprietary <unk> program or OTC D potentially.
We're looking for or or other programs.
Looking for those programs, where we could then Tuesday clinically with a specific gene therapy.
First.
Relatively straightforward approach is to look at.
Oh bodies.
Okay.
Okay, great. Thank you.
Our next question will come from Rick Miller with Cantor Fitzgerald. Please go ahead.
Yeah.
Hi, Good morning. This is actually Christian sorry about that wanted to ask just based on the abstracts that were published for the Ash TCT Conference earlier this week and I know the presentations are very near term here, but could you talk about from a high level.
Questions are you looking to really answer with some of the studies that you haven't reported on yet and it looks like you had some promising effects on inhibiting a V or age 32, ITG antibodies versus methotrexate and you're looking at different capsid and routes of administration. So essentially how might some of these studies.
On presenting on help shape future directions of <unk> for gene therapy, either by you or a partner.
Yeah, Hey, Chris that's a great great question and actually I'll.
Let the man, who actually conducted the studies speak to it since we have <unk> on the call a K.
Hi, Kristen Yeah, Yeah, we have a lot of a really interesting presentation that S. J T. Both our own and also one we are.
Presenting with our partner asked trial.
So the study you referred to with the AAV RH $32 33 captured.
With what's actually being presented by.
Our colleague that a smile and thats it.
It's a very interesting study because.
Although in humans.
It's often seeing that you'll get this.
Increase in capsid specific CDA T cells.
That hasn't been so much noted in animal models.
But with the exception of this one captured.
Which has been previously.
By the Wilson group to induce capsid specific CDA.
So in this study.
The asphalt group used <unk> and also comparative to a multi dose regimen of methotrexate.
And.
The results are really pretty impressive that entered inhibited.
<unk> specific CDA T cells as well as anti AAV antibodies as expected.
Whereas methotrexate.
<unk> really had pretty marginal effects.
Other abstracts that were presenting relate to kind of.
Getting to being able to re dose AAV sorry, as you know we had the.
Humans are.
Healthy volunteer study that we also did with house file.
And.
And we have previously reported on that.
Finding rad.
We could inhibit <unk>.
<unk> antibodies out through 30 days with inventory and with a single dose of <unk> in healthy volunteers in our preclinical studies in both mice and nonhuman primates indicated that by giving additional monthly doses of <unk> tour, we can sustain that inhibition.
In addition.
Yeah.
Carcinoid I was alluding to earlier.
I think one of the big.
Aspirations that we have and I think really the whole field is.
Mitigation of these high dose factor toxicities and of course, one aspect is to engineer.
More efficient capsid transgene cassettes.
And certainly we're working with our partner ginkgo on better capsid.
Also feel like by changing the paradigm from dosing one and done.
To being able to do multiple doses are slow and low.
Would be a significant benefit so instead of giving one large factor dose if we could get multiple smaller doses. So we present two different posters one come combining <unk>.
With IL two some.
Tori al and the second combining <unk> with an anti bass Adrian.
We show that we can inhibit antibody formation to capsid doses as high as five times 10 to the 13th Pte procured and to our knowledge no. One no one has been able to mitigate antibody formation at such high vector doses.
Okay. Thank you for that looking forward to the presentation in a couple of weeks here and then just on <unk> I know you're doing a lot of work here on your extremely excited about the potential but could you maybe share for some of the work you're doing to at least narrow down some of the potential indications you might look.
To start with here, thanks, again for taking the questions.
Yes, that's a great question. So we actually have started.
With an area, we know really well wishes in gene therapy, and that's what cases referenced we're extremely excited results we see there.
We have guided to PBC as our lead indication.
We are working through.
A process right now to identify additional indications that are there.
Our T. Reg <unk> mediated were looking at this both from a scientific perspective, you know where do you have a high chance of techniques success looking at available data I mean, there was some data available already from phase one and some phase II.
From other companies that pursue IL two is an autoimmune disease that definitely helps to guide as well.
And we'll likely guide to another indication this year or a range of indications that we might potentially pursue so it's really a combination of whats what's a good proof of concept, where there's clear biomarkers, we think there's a high chance of techniques success.
<unk> with with commercial potential of course as well.
So I think thats kind of where we are right now we are conducting additional studies right now in animal models in autoimmune disease, which are always a bit lengthier and you can expect for us to to share some of those data as they come in.
Our next question will come from <unk> Shah with BTG. Please go ahead.
Hi, Thanks, very much for taking the question. So it's a false question about import I L. It's very interesting.
Data and just showed there seems to be a big difference between the combination in <unk> alone and also you said you are going to explore potential using gene therapy as well not just the autoimmune disease, but I guess you are now going to use <unk>.
<unk> L. In the plan MMA study and others.
Good point and in which way do you think you will be introducing in tour IL into gene therapy programs and is that going to be more likely your own gene therapy program or more for potential partnership discussions.
Yes, that's a great that's a great question.
So.
As you know <unk> alone in juices and specific.
T Rex.
Worse, IL two's alone only expand preexisting T Rex and really the combination you get the best of both worlds you get an induction and expansion of anesthetic T Rex, which really is differentiated.
We see the really the main application in autoimmune disease, where really want to tip the balance between T effector cells and T Rex and that's where we're really excited about.
But youre right. We were also seeing this being used in gene therapy.
But we will not at least initially include this in MMA.
In the MMA program, we were testing in tour based on the you know pretty compelling data we've generated in the empty capsid study.
I mean, there's always a chance to Amanda amended IND.
And add into our L down the line, but at least for now we're really focused on.
Getting the study started in the second half of this year.
But but it's definitely something that we continue to explore further to really fine tune the treatment paradigm in gene therapy.
Then a quick follow up if I may So you mentioned the next next generation Io to in the press release and was that next generation or able to comment what exactly are you trying to achieve or what.
What kind of improvement as compared to the current version.
Yeah, So we haven't exactly guidance.
Two our approach, but I think we've been pretty clear, we're working with a leading protein engineering companies Cyrus.
There come out of David Baker Slap in Seattle.
And obviously, we're trying to optimize.
The T Rex specific component.
And not have any effects on T effector cells.
There are multiple approaches if you look at the Io Io to field from fusion proteins Mew teams theres various approach, but we havent guided that the approach that we're taking for this program.
Okay, great. Thank you very much.
Our next question will come from Rajiv Prasad with William Blair. Please go ahead.
Thanks for taking the question.
I'm just curious to know kind of in your conversations with Kols in the gene therapy side.
With our S E T coming up what the.
The duration of effect you're kind of.
Is is for for gene therapy.
And kind of use it into or in the clinical setting. Thank you.
Yeah, that's that's a great question.
And obviously if you.
If you look at the data we have generated so far is that in the in the human proof of concept study with a single dose of <unk>, we're able to control NEP titers at day 30.
We know from the animal studies that <unk> extends the half life of AAV capsid.
So we see a rebound off the titers hour today 90, which as expected we have seen this in non human primates, but we've also shown that.
Once you control titles at day 30 to give two additional doses actually you are able to control the tightest long term and we.
We also believe that you know after day 90, there theres no more caps it around so no more antigen. So so our hypothesis and speaking with.
With Kols, but also the FDA, we believe that three monthly doses actually is.
<unk> is a reasonable path to go and that's how.
We approach it in our MMA program, where we plan to gear three monthly doses of <unk>.
Great.
Can you give us some color or context on the.
PBC model pre clinically and how well that mimics the music immune features of the disease and when we can expect data. Thank you.
What's the PBC.
Yes.
Yeah, Okay, Yeah, let's say, let's speak about the model.
Okay, you're on mute.
Sorry about that.
Yes, there's actually a couple of.
Interesting models for PVC in that these are genetic models of the disease are.
It is.
Spontaneous so you don't have to induce disease and these these animals. So.
So we think it's a more accurate reflection of natural disease and.
And certainly there are pretty well established in this field.
Our next question will come from Mr. <unk> with Mizuho. Please go ahead.
Hi, guys. Thanks for taking my questions.
I guess my first question is on.
<unk> just wondering if you need to consult with the FDA to increase the number of patients and if thats. The case, whether you have done so.
And I guess my second question is sort of jumping ahead, a little bit.
Regarding the gene therapy phase one MMA study just wondering about how you will disclose the data.
You do it either by patients by cohort.
Or wait until the study complete.
Thanks.
Thanks for your questions I'll give the first question to Peter.
Around how we handle the increase of number of patients.
Yes, Hi could you please repeat.
Your question.
Sure just wanted to know whether you need to consult with the FDA to increase the number of patients in the.
Phase III study.
If you have whether you have done so and if I may can I also add.
The topline data is now pushed out to first quarter of 2023 and I'm just wondering.
If that's functioning M. A result of the additional patients and additional clinical cytogenetic something else as well. Thanks.
Yeah sure Yeah, we did consult with the FDA.
Uh huh.
On the changes that we made to the protocol.
As well as we will handle the data from <unk>.
Russia and Ukraine.
We'll be continuing discussion with the FDA.
But the increase.
240 subjects.
He is underway.
The.
The issue of the.
The recruiting in Q1 of both Trump.
He is related to the increase in the number of subjects.
With cryo.
And as we reported will complete the trial this year meeting last patient last visit will.
It will be completed this year.
Because it'll be at the end of the year it'll take.
A couple of months too.
Lock the data.
Okay.
Thanks Peter.
Your second question is around MMA.
We will like the.
Port patient by patient.
As as we get results.
We get the first results basically 90 days after we dosed the first patient.
So we will likely reported.
Patient by patient basis asset beta comes.
Okay. Thank you.
Again, if you have a question. Please press Star then one our next question will come from Bill on Apache happen with H C. Wainwright. Please go ahead.
Hi can you hear me okay.
Yes. Thank you.
Alright, great. So couple of questions from our side.
Firstly with respect to MMA phase one trial.
Do you plan to include patients with isolated MMA only are those with MMA, plus a higher sustained level and what would be a rationale for that.
I'll give this question to Peter.
Okay.
Yes, all the subjects in the trial will have.
Newt.
No.
Okay great.
Clinically severe disease.
Okay.
Okay.
So secondly, with respect to our dissolved data released so your previous guidance for the top line was fourth quarter 2022 and.
For today's release, it's actually pushed over first quarter 2023. So just curious is there any advantage of combining the data from both the trial and then really thing it and one first quarter 2023 versus.
I really think there is only one data in fourth quarter of 2020. So given that this is all one enrollment was completed last year.
Yeah. It's a good question I mean, as we have decided.
So first of all the good news is that we have clarity now on the timing so and we've decided to increase the patient numbers to up to 140 in dissolved too.
Both studies will readout in by the end of this year in Q4 than we've decided to do a joint release, because they're so close together. It is cleaner to report both pivotal studies at the same time.
Okay.
Obviously inter Isle is pretty interesting I think <unk> been hearing theres a lot today just curious.
Can you comment on what kind of safety and Tolerability characteristics, you're looking for before initiation of your phase one.
Yes.
Yes, I think obviously we have.
Pretty good understanding of the safety and Tolerability of <unk> I mentioned that in the.
The main call of over 450 patients dose.
We will obviously do Tox studies with Piper IL, two but we see some indications from the phase one phase two studies other IL two molecules.
Which looked pretty promising as well.
Yeah.
Okay. That's it from me thanks for taking my questions.
Our next question will come from Chang Lu with need Ham. Please go ahead.
Hey, this is a channel for Gil Thank you for taking our questions.
Our first question is.
Is there any near term update or potential milestone from select us partners.
Yeah. Good question, we get a lot we do have multiple partnerships.
It's always difficult to guide, but obviously.
We have publicly disclosed that we are eligible to receive.
Milestones are.
Up to 80 million around clinical and regulatory milestones from our partner <unk>.
We haven't disclosed the exact timing, but obviously, it's an important milestones.
Coming up.
We also.
Have guided that <unk>.
Their option period.
Basically expires in June of this year.
And there's basically three scenarios one is they opt in we are a fully negotiated commercial term sheet.
The second is the.
<unk> is continuing to work, but there's also an option for them to extend the option period versus a pre negotiated payment.
And there's potential other milestones and it's very difficult to guide.
As they come in.
But I think what's important to note as well is that our cash guidance into mid 'twenty. Four doesn't include any of the milestone payments from any of the partnerships.
Thank you.
So our second question is.
So considering the high the higher activity of inventory.
So is there any logic to more of moving forward with an tour in earlier programs such as autoimmune.
Auto immune diseases like PBC.
Sure.
Uh huh.
That property.
Yes, that's exactly a great question and I think what's important is that we've seen very good clinical activity within tour alone.
I think that's very important.
But we're clearly, especially in auto immune disease are especially excited about about into our al in the context, where you have two in autoimmune diseases restore balance between T effector T. Rick.
And we believe that into our al.
<unk> is ideally suited to that but we stay.
Focus on the programs, we use into or alone.
S L 212 and MMA.
But for for autoimmune disease, specifically PVC.
We will likely take into our into the clinic in that indication.
Great. Thank you.
This concludes our question and answer session I would like to turn the conference back over to Carson Braun for any closing remarks.
Yes. Thank you operator, and thank you to everyone, who joined US This morning stay safe and healthy and this concludes today's call. Thank you.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.