Q3 2022 Kymera Therapeutics Inc Earnings Call
Okay.
Good morning, My name is Martin deep and I'll be your conference operator today.
Yeah.
Welcome to the Chimera Therapeutics quarterly conference call, leading the call from management are Nello, <unk>, founder and CEO , Derek Gala, Chief Medical Officer, and Bruce Jacobs Chief Financial Officer.
After management's prepared remarks, we will open the call to your questions to ask a question.
Please press star one on your telephone keypad, if any point you would like to withdraw from the queue. Please press star one again before we get started I would like to remind everyone that some of the comments that management make on this call include forward looking statements as outlined in the press release.
Actual events and results could differ materially from those expressed or implied by any forward looking statements. As a result of various risks uncertainties and other factors, including those set forth in <unk>. Most recent filings with the SEC and any other future filings that the.
We may make with the S E C.
You are cautioned not to place any undue reliance on these forward looking statements and <unk> disclaims any obligation to update such statements.
I will now hand, the call to Nello, <unk> founder President and CEO .
Thank you operator, and thank you everybody for joining US today, we're very excited to share with you. The progress we've made over the last quarter and how it contributes to achieving our mission to build being best in class fully integrated global be Greater Medicine company. We recently completed the patient cohort portion of our key people.
Seven four phase one clinical trial, which concludes the phase one campaign produced drug Jonathan will share more details in his remarks that we have the study completed we are currently in the process of collecting and analyzing all the data.
We plan to share as we always do the data and the analysis of the data with our partner and.
And then we will subsequently share the data publicly on a company webcast on the morning of December 14, 2022, as we have reiterated in the past the objective of the patient cohort is to confirm that PK PD and safety in patients with AIDS. The NHS is consistent with what was demonstrated in the healthy.
Volunteers, the southern <unk> cohort.
As we announced last month, we plan to update investors also on our clinical oncology pipeline under December 14th call. I believe you. All know we have two clinical stage programs the recommended.
<unk> three <unk> hundred 33 and.
One program that we expect to enter the clinic soon which is our MDM to degrade the Kt's 253 with respect to the ongoing trials the KC for one three and 333.
Both in dose escalating stages of our phase one portion as a reminder, the objective in this early dose cohorts is to demonstrate what we call a proof of mechanism, which we define as the ability to degrade the proteins of interest, which obviously start three or $3 33 in port <unk> direct core and even substrates equalized.
<unk> with an advanced <unk> safety profile again, Gerald will share more here as we go into the call.
Along with our clinical progress we continue to work to ensure that we have the resources to build our company in a sustainable way and continue to invest in our clinical programs discovery pipeline platform and team to this end in August we raised an additional $150 million through a private placement equity financing which was.
Led by a broad group of really committed strategically align our long term oriented investors each of which demonstrated their confidence in the team and share our optimism in <unk> future.
As a result, we ended the third quarter and a very solid financial position with approximately $596 million in cash.
Before I turn the call over to Gerald I also wanted to take a moment to recognize the change we announced today on our board of directors as many of you have heard me say, we aspire to build camera into a fully integrated biotech company and to sustain our leadership position in both PPD as well as in biotech.
As we work to achieve this mission, we obviously will continue to build both an employee base as well as the board of directors. They bring all the requisite knowledge and experiences to support our success.
To that end, we're pleased to announce that Dr. Victor Sandor has joined our board of directors for those of you who don't know Victor He has deep expertise in global clinical development of magazines that have significantly impacted lives with patients, especially in oncology. It was most recently the CMO at Ara.
<unk> biopharma prior to its acquisition by Pfizer and is an impressive career in the biopharmaceutical industry.
Importantly at the same time I also would like to recognize and thank another director Don Nicholson, who will be leaving <unk> as director after having served for the past five years and having started just shortly after the company's formation. Don is one of our longest tenured directors and has been an important contributor.
As to <unk> growth and success over the last five years.
We're very thankful for all of these important contributions and wish him the best.
With that said Jerry will now cover in greater details.
Recent progress for each of our disclosed programs before turning the call over to Bruce for a financial update.
I'll, then finish with some concluding remarks before handing the call back to the operator for a Q&A session in which myself and Bruce will be available Jared. Thanks, Noah I am excited to share updates on our three clinical programs.
I'll begin with our Iraq or program.
80, 474, as a potentially first in class oral the greater of Iraq for a key protein involved in inflammation mediated by the activation of toll like receptors and <unk> receptors.
If your profile.
Artsy includes patients with either a moderate to severe hydride and that is separate tivo or atopic dermatitis and is examining the safety pharmacokinetics and pharmacodynamics of Katie 474, while also exploring early signs of clinical activity <unk>.
<unk> received a daily dose of 75 milligrams of K P 474 in the Feds state.
This dose is expected to provide a plasma exposure that is approximately equivalent to that achieved with 100 milligram per day dose and the fastest state and healthy volunteers and the <unk> portion of the trial, which showed maximal or close to maximum degradation and blood and skin and broad disease relevant cytokine inhibition ex vivo.
As previously mentioned the Gulf of this study is to confirm that are PK PD and safety profiled in patients is in line with what we have seen healthy volunteers.
In December we plan to share data on the impact 87, 474 on Iraq, four levels, and BMC and inactive Hs and 80 skin lesions as well as on the expression of current laboratory, Jean transcripts and skin lesions and on plasma biomarkers of information.
We are also undertaking an exploratory assessment of early impact on clinical endpoints, including eczema area and severity index or easy for a.
Total assets and inflammatory nodule counts four Hs as well as symptoms scores and global assessments of disease severity for both 80 and H S.
As we have noted in the past is important to consider that this is an open label study without placebo and a small number of patients and one in which we do not expect to reach steady state direct word degradation and skin until the second half of the four retail some period.
And as a result, the data on early signs of clinical activity should be viewed that lens.
It will also be following safety and Tolerability artsy.
And as a reminder, and our Saturday and Emma Studies K E 474 demonstrated no serious adverse events and only a few mild to moderate adverse events.
Ah December update will include a safety analysis, including whether the modest non adverse Q T. Prolongation that we observed with multi dosing and healthy volunteers then plateaued. After seven days continues to show evidence that it is self limited, but in this case out to 28 days.
Before I conclude my remarks, I will update everyone on our disclosed oncology pipeline, which includes our staff three Ah recommend and MDM too to greater as the first two of which are in the dose escalation stage of their ongoing phase one trials.
As mentioned in our December webcast will include an update pipeline.
As a quick reminder, staff three is a transcription of regulator that has been linked to numerous cancers and other inflammatory and autoimmune diseases.
Our phase one clinical trial is evaluating K E 333, as potential and Hematological malignancies and solid tumors.
Specifically the trial of evaluating the safety Tolerability P. K P. D in clinical activity of K T 333 in adult patients with relapsed and or refractory lymphomas in solid tumors.
We have been recruiting broadly in phase one a dose escalation across solid and liquid tumors in order to reach pharmacologically active doses as soon as possible before then focusing on patient populations, where we expect to see clinical activity.
Either as a mono therapy or in combination with other agents.
The trials second stage will consist of four phase when the expansion cohorts to further characterise safety Tolerability Kpd, an anti tumor activity of K T 333, and relapse <unk> refractory peripheral T cell lymphoma cutaneous.
Loma large granular lymphocytic leukemia and solid tumors in.
In September K T 333 was granted second orphan drug designation by the U S food and drug administration for the treatment of cutaneous diesel lymphoma. Following its orphan drug designation for peripheral T cell lymphoma earlier this year.
Our our recommend program K E 413 is a novel hetero by functional the greater that targets degradation of both Iraq, four and the image substrate. It grows in ilo's with a single small molecule.
84, three was designed to address both the <unk> and the type one interferon pathways synergistically to broaden activity against my the 88 piece of malignancies.
80, 413 is on a similar timeline in step three and is currently in the dose escalation stage of the phase one trial evaluated the safety Tolerability PK PD and clinical activity of K P 413 in patients with relapsed indoor refractory b cell non hodgkins lymphoma is similar to the strategy.
Subscribed for the K T 333 phase one we are enrolling a broad population of visa lymphoma patients after which we will focus on patients that when we expect to see the most substantial clinical activity.
Typically the second stage will consist of two phase when the expansion cohort and <unk> to further characterized safety Tolerability PK P. D anti tumor activity of Katie 413, and relapse refractory <unk> 88, mutants and Mighty 88 Wildscape Bcl.
Finally, a Casey 253 hour MDM too to greater has completed IMD, enabling studies and is on track to achieve any clearance by year N.
<unk> is the crucial regulator of the most common tumor suppressor, 53, which remains intact and more than 50% of cancers.
Prime era is developing a highly potent MBM through the greater that unlike small molecule inhibitors has been shown preclinically to have the ability to suppress the MDM to feedback loop and rapidly as a pup doses, even with brief exposures.
80, 253 has the potential to be effective in a wide range of hematological malignancies, and solid tumors with functioning or wild type you 53.
We look forward to updating investors on our pipeline in December .
I will now hand, the call to Bruce Jacobs, our Chief Financial Officer, who will share. Some brief comments on our financial results for the first quarter Bruce Thanks, Jarod for the quarter, we recognized $9.6 million of revenue total that reflects revenue recognized pursuant to our sanity and vertex collaboration.
At the end of the quarter are deferred revenue total on the balance sheet was approximately $77 million that reflects the partnership revenue we expect to recognize over the next several years, excluding the receipt of any future potential milestones with respect to operating expenses R&D for the quarter was $43 9 million about $4 $9 million of that represented non-cash.
Stock based comp the adjusted cash R&D span of $39 million, which again it excludes the stock based comp reflects a 7% increase from a comparable amount in the June quarter with respect to G&A spending for the quarter was 10.6 million of which $4 $2 million represented non-cash stock based top that adjusted cash TNA span of six.
$4 million again, excluding Saturdays comp reflects a 5% decrease from a comparable amount and the June quarter, we exited the second quarter with the cash and equivalents balance of approximately $596 million recall that we do not include in our cash runway any payments for milestones that we have not yet achieved our guidance for cash runway of at least into 2025 <unk>.
Corporate's the completion of our 150 million dollar pipe, but we do plan to update this runway guidance in particular, the specifics around the extent of runway extension driven by the financing closer to year and with that I'll turn the call back to know for some concluding remarks.
Bruce and as we look forward to providing a clinical update on our December webcast. It's clear that came era successfully transition into a new phase.
One in which we can observe are signs in auctions in patients.
We are excited to begin to assess the impact that three of our programs may have in patients with cancer and immunological conditions and to demonstrate the advantages of our platform over traditional medicines.
We'd also progress made this quarter. We're just getting started in addition to three clinical programs. We're on track to clear 94, MDM two degrees of <unk>. This year and we're advancing several earlier programs with clear degree the rationale insignificant commercial opportunities.
So with a productive partnerships and plays with <unk> with a recent financing we continue to maintain an array of pipeline investment opportunities to maximize the potential of our best in class platform and discovery engine.
At this point I would like to thank the <unk>.
Well as our partners <unk>.
The patients were participating in a clinical trials and finally all of you for participating in this call and I look forward to your questions.
I will now hand, the microphone back to the operator, so we can take your questions. Thank you again.
At this point, we will open the call for questions to ask a question. Please press star one on your telephone keypad. If at any point you would like to withdraw from the queue. Please press star one again, we will take a moment to render a roster.
Your first question comes from the lineup Brad Keno.
From Stifel. Your line is open.
Good morning, Uhm first can you tell us when you expect to deliver the data package to Tennessee in relation to that December 14th date, each setup and will the package will be based on the 28 days data cut or include the two extra weeks a follow up.
No I want to go back to your R&D. They last year, you said ambitious suite of goals for 2022, which included the first tissue restricted <unk> enabled program and development can you just update us on that status and perhaps share any comments regarding the critical decision points remaining for the target and <unk> selection for that first candidate.
Thank you.
Great. Thanks breath. The two great question. So one at a time so the first one so we plan to deliver to sign up feed the complete data package. So obviously that will include most of the follow up period of the extra two weeks of observation that seek today, we're seeing and I saw some the gleneagles.
Trial Dot Gov that we have completed that phase as well. So that's when we see the study is completed we mean that every patient has gone through also the two weeks of full law. What we've also said today.
We're still collecting and analyzing data so that the face of data collection is not completed yet.
As soon as we complete that fees, we will share the totality of the data.
With our partner.
So we haven't said.
When that will happen because to be honest, we haven't completed.
We're doing internally, maybe the only thing I would add we've always had a very close relationship of communication with dishonesty team. So.
So we try and BSF will as possible. So in this time when we're sued collecting data to to make sure that we we share anything meaningful as we as we collect things.
To your second question.
So so we as a.
As I said, we have several programs in the preclinical stage.
Many of which are actually closed to entering preclinical development.
And one of one of those programs entail the use of an eatery leg is that the restricted expression in the body that will allow us to actually overcome the.
Those limiting toxicity of the well known.
Oncology target I think our plan, although we haven't firmed up yet is to provide an update.
Some point.
Next year.
Where are those programs are maybe will disclose will see one or two of them, depending on which stage of development. They are so I guess, it's not super satisfying, but stay tuned as more information will be shared on that.
Operator can we go to the next question. Please.
Your next question comes from the lineup, Chris Chablis Tani from Goldman stocks. Your line is open.
Thank you very much good morning, just to be clear in terms of the optionality per cent at the end the decision that they'll make we may hear from them that they would.
With both programs, one or sequentially. The way that you have struck drink a relationship there just so that we can find the the different scenarios that could play out that would be helpful. And secondly on the <unk> 333, there is scientific premise for pursuing indications outside of on caller.
G any thinking there in terms of how you would pursue that would that be with partnerships and Tennessee have any opportunity to explore that as well. Thank you.
If you can stay on the line for one more second can you clarify your your first question. When you said two programs I'm not sure I fully understood the question.
Yeah, No just thinking about the two indications for a D and H S and so perhaps clarifying that we shouldn't be thinking that decision from Santa fee is singular in binary but that there's several options yet.
Yeah, Yeah <unk>.
I Miss that so thank you so ah so going back to Europe to the question then.
So as you know we are in in this part in partnership with sign up fee on Iraq for Degraders outside of oncology and immunology, that's actually the the spirit of the contract and boats <unk> Mara had large ambitions, we believe that these.
Macanese has potential to be one is not.
He'd been small molecule anti inflammatory drugs in in in a wide variety of diseases in August .
Obviously, we'll have to generate data to support our beliefs here, but that's that's what we're doing so when sign up fee will make the decision to transition.
If and when make the decision to transition <unk> into <unk> into a we call. The late development <unk> decision to invest into the global development of the drug.
And so it is not indication bays, but it's in the in the late late developments, we as a partnership we've always been a line that the reason for <unk> and camera to partner is to use and benefit the least from primary point of view benefit from the broad both clean.
Nickel and commercial footprint that benefit is built in immunology and as they say publicly that they want to be the number one immunology company in the world and so the spirit of the collaboration has always been to try and pursue several indications, but obviously, we would like to.
Look at the data and then with <unk> decide how to prioritize indications going forward.
I would say their decisions and global development of.
We hope to be multiple indications.
Great and.
<unk>, yeah, yeah, sorry, if that three outside of oncology. So we have been talking about this program for a couple of years. We've released data indifferent confidence is this is something we're very keen on and I think we'll share some data as we <unk>.
Sure.
Kind of.
Clinical strategy around this asset.
For now this is something that came out or are you bleeding independently from any other existing or any potential new partner, but obviously time will tell if things go in different ways.
Thank you we look forward to December 14th.
Thanks.
Your next question comes from the line of <unk> rail from Cowen and company.
Line is open.
Good morning. This is Debbie <unk>. Thanks for taking my question, we have one on the oncology program and then why not T. T 474, So just for the on call your programs what what data can we expect at the R&D day, and then could you remind us what level of degradation you would expect to see to translate into clinical activity.
And then for 474.
Put that part see now completed I know that you guys are giving some analysis and that got it.
Ongoing but is there anything outside of lines that still needs to be generated before presenting the data package to Tennessee. This quicker.
Right to judge you you Wanna take the oncology sure Yeah for for both oncology program. The aim is for us to be able to show will be called proof of mechanism, which is knocked down of the intended targets.
To a level that hopefully is associated with preclinically anti tumor activity and to show that we can accomplish that knocked down at doses that are safe and well tolerated at your question around what are are the target levels of knocked down for the various programs for the Rachmat program, we've seen that knocked down of Iraq or in the image.
Substrates that grows in Iowa, and the 60% to 80% range is sufficient to give us activity and it might be 88 mutated <unk>. So that the level of knock on that ultimately we'd like to see in that program.
For Stat, three we have shown in century dependent lymphomas that greater than 90% knockdown maintain for several days is sufficient to also do significant tumor regression in that context. So those are the sort of benchmarks that we'd like to ultimately see but from the standpoint of what we will be presenting it R&D date.
Hopefully that will be through enough dose levels to be able to show initial group of mechanism at doses that are safe and well tolerated.
And maybe the other I'll take the other questions on first of textures on 474.
Would it be take the opportunity to remind what.
What was the purpose of this study was and is and it's really too to demonstrate that transitioning from has to volunteer to patients were able to maintain.
A good votes P. D P. K P D relationship and safety profile to advance the dragged into phase two.
So that means that our our key goal is to actually collect data to demonstrate that there is it continue to be a strong relationship between exposure MPD that can inform our face do those selection.
The P. B is now defined let's say a direct towards the gradation in blogs and skin that'd be the results into impact on.
Disease relevant pathway irrelevant chemo.
Chemo kinds are cytokine that we believe will create that new now correlation given that it has people and see if we were unable to do that so correlation between.
We call it let's see target engagement and something that is this is relevant that as as the Biomarkers and then as we said just so that I, obviously, Don Don dismiss it completely and we also said that we will be collecting clinical endpoints with the goal of trying to establish a potential correlation again with.
BB.
Some biomarker and anything that can be tied to a clinical endpoints that obviously would be highly exploratory given the size.
And the design of the study now going back to your question sorry, we are actually still collecting data. So there is some data that you can imagine these.
Easily accessible in an open label study.
And then there is some data.
Especially with regards to <unk> that is actually takes weeks to generate so we are generating data, we're not just analyzing data and so he would take us more.
More time to fully collect all the data and that's the only reason for.
For having in December call, because we want to have the <unk>.
Holiday of the data in hand.
Before sharing it again, both with Sanofi to get their approval to share the data and then with with with all of you.
That's helpful. Thank you.
Your next.
Question comes from the line of Joseph Eric from J P. Morgan Your line is open.
Thanks, Good morning, Sir Joseph J P. Morgan.
No I'm, assuming that some of the additional data gathering is perhaps the the intermittent dosing data and healthy volunteerism added this additional cohort looking at Bi-weekly or.
Every other day dosing is that.
Specifically the data that you're gathering and I guess, what should we expect those data to be presented at December 14th and then I guess can you just talk about the rationale for evaluating.
Evaluating that that regiment, specifically with 474.
Yeah, Thanks, Eric for bringing that up actually.
So the answer to your first question is no I mean, we were focused on the patient cohort and maybe you know as I said, just maybe to be even more transparent in this study.
You can get initial read on safety and clinical and volume quickly. There is obviously a data lock in a clean up that takes time, even to do that and what is taking longer S. As it does in as is done in the past is generating all the BB and biomarker data. These are not simple as the fact that these are.
R.
Cutting edge things that we're doing an industry I don't believe other companies I've ever done what we're doing in Hs in the basement and I have to thank Jared and his team for all the work that they've done and actually designing and executing and hopefully eventually generating the data with regards to the.
In frequent those do you guys have said in the past this was it.
PK PD experiment that we wanted to run.
Before the eventual transition of the program to <unk>, where we will lose the ability to run clinical studies and this was a study that we wanted to learn not just <unk> learning given that in decides we learned that had to extend the degradation. After a single dose. So we wanted to learn.
How far and how reliable would be dosing less frequently but also for US was a big platform question, but.
But I don't expect that that will be a part of our disclosure as it would be focused on I'd like to read anything relevant to that to the development of the program, but we'll be focused on the patient data and how hopefully that will be informing further development.
Okay, Great I appreciate that let me just to follow up on the.
Policy programs.
And thanks for.
Sitting here.
Here.
Oh excuse me now yeah.
Again.
Okay. Good thanks for just a follow up on the oncology programs and thanks for framing expectations into December 14th I'm, just wondering whether.
As part of the presentation you might be.
At a point, where you can detail.
Recommended phase two dose.
How neat.
How close a website that you have on when you might start the enrolling the expansion cohorts.
For 333 and 430.
Yeah, I I think it's.
First of all at this point is appropriate or not appropriate for us to comment. So we might comment on this in December but what I would say we're still in the in the dosage escalation phase and we're focused on US too. So just maybe to take a step back.
<unk> of this technology and the reason why many of US there here is because it allows you to do drug development in a completely different way allows you to do a data driven drug development, where you know at any given point in your clinical trials. If you design them right where are you versus your expectations.
Versus your prediction or or your data driven expectation of what kind of degradation do you need.
To achieve the type of efficacy that you're looking for so.
The ability that we have in dose escalation instead of blindly escalating to and MTV, we have an opportunity to.
Scully learning, where we are versus our expectations on the level of degradation needed to achieve efficacy. So the goal of this year is really to see is the translation of the P. K P. B S.
You know, let's say as good as we've seen with K T 474, where we degrade the protein.
Reliable predictable dose responsive way and the safety that goes with the degradation profile is in line with what we see preclinically because if that is the case, we will have really bullish prospect on the potential clinical success of these drugs because the mechanism.
Well known oncology and here is really getting the <unk> right for both of these drugs in oncology and I think if we can show that I think it will be a large derisking event for this program moving forward now I don't want to dismiss your question I think we will comment on there but I.
I suspect that next.
Next year, we will continue to do both some escalation in some expansion at the time that maybe we will discuss more in December .
Your next question comes from the line of Vitrum <unk> E for Morgan Stanley . Your line is open.
Hi, good morning, Thanks for taking my questions. The following up on K 2474.
I just wanted to see if there had been any more exploratory work done.
On the palpitation in Q T C signals that you reported earlier with the healthy volunteer data set and if so if there's any update to communicate out here on anything you more you might've learned versus your prior update on.
But the the mechanistic rationale for the findings can be and then secondly on the same program going.
Going back to your prepared remarks, you mentioned that you won't be seeing steady state degradation until the second half of the the dosing interval in parts C. So given that how would you advise people to interpret.
Difficulty data here versus some other 20th a dermatologist datasets that are available in the space.
Great. Thanks, Vikram, maybe if you want to comment on the first question, but the only thing I would say maybe before.
Sinking onto Jarrett, we have never.
Draw a line of correlation between palpitation in Q T. So, but I'll, let jess comment on anything else that.
We want to share on our understanding of that mechanism. Yeah <unk>, Yeah, I think what we have done what we've described previously right based on our in vitro data is that with Ips.
IPSA Cardiomyocyte, so we have been able to see.
In effect on current that's consistent with a mild you know hurt effect in high concentrations.
That is somewhat delayed and that is sort of consistent with a sort of effect that we saw in the clinic, where we have a delayed effect that's not in the clinic anyway, doser exposure dependent and appears to plateau. After day seven and then remained steady until the end of dosing period.
At 14 days and so we don't really have anything new to report on those lines in terms of our understanding mechanistically of what's going on I think what would be important for us and parts C. As to really as we continue to observe now out to 28 days of dosing past 14 days that we did in part B do we continue to see sort of a plaid towing.
Q T effect, and I think that will further inform us as to.
What sort of.
Clinical impacted any of their is of this subclinical not adverse cutie effectively Saddam heartbeat.
It may be too then to get back to you on the efficacy question I mean.
The question you asked this really why we continue.
To say that <unk>.
Expecting.
Clear.
You can see read on from this study is I think.
Kind of unfair for how we've designed this study and the purpose of this study and it's really difficult for.
For us kind of scientifically to take the eventual dataset and compare it to other agents given that this is a different macanese new pathway.
A small numbers no placebo and again for a new macanese relatively very short time.
But I think what we what.
We want to be able to do as possible and again, we will have to generate the data and see.
To see if there is if there are any trends between what.
What we see in terms of TB in biomarker changes any early signs of.
Differences in clinical in clinical endpoints.
It would be really hard if not impossible for us one way or the other to say that.
The drug.
Works or doesn't work you can adjust the based on comparison with other studies just because this is a different study.
Your next question comes from the line of early Merril from UBS financial Your line is open.
Hey, <unk> I'm I'm damn <unk>, maybe if you could just elaborate on why a potential national trial.
Like any commentary on <unk>.
Awful.
I was hoping I could.
Let's see.
Yeah.
And then also just in terms of the biology, hi, you're thinking about what.
And.
<unk> <unk> <unk> <unk> <unk> <unk> <unk>.
Oh.
Thanks, Ellie enjoy talking about also other programs in our pipeline. So for MDM too. We have you know we're really excited about this program.
Obviously, not more or less than others, but it's really I think another program that we build to demonstrate that this technology can be used to do things that other technologies cannot do and is so hopefully you would that everybody I appreciate that has been <unk>.
In terms of target selection, all the time and when we disclose our next three or four programs that are you know.
Really good stage Preclinically, you'll see that philosophy continues to be true. So we'd MDM too. This is not a super small molecules. This is just a different biological intervention that pathway.
This is look into eventually and finally replicated the the cancer genetics data shows that absence of MBM too.
Generates high level of sensitivity <unk> tumors, which is not what has been seen with small molecule inhibitors and as we said the one way that we are able to do is because we removed the protein quickly we have overcome.
This feedback loop and we drive sales of choices in a way the small molecules are not able to do.
So I'll, let Jared comment on the clinical trials design I'll go with something that we haven't fully disclosed, but maybe you can give you a high level overview, but what I would say our strategy. There is too focused on indications, where we see a.
A very rapid antiapoptotic responds that allows us to maximize <unk> was this mechanism.
And what I will say that we have several indications in both live with tumors in solid tumors.
That have this type of response and I believe today are ash abstract design I believe at nine am highlighting a bit more work on AMM.
Which will be one of the indications of interest.
Maybe just a high level.
Yeah, definitely just give a high level overview and just as a reminder, that because of the mechanism of action of degrading.
Those too.
Just small molecule inhibition, we're able to sort of dose intermittently. So we're planning on bringing in a intermittent Ivy does things are infrequent Ivy dosing I ended up phase one and the trial design it will be sort of a standard days one dose escalation followed by faith won't be expansion, but importantly, the phase when they will be able to set us up to understand and safety.
<unk> ability and PD, both and he malignancies as well as in solid tumors, and we will have opportunities to put on.
Indications of particular interest both and he malignancies in solid tumors.
Within phase one a and then eventually what we do.
Come up with a either recommended phase two dose or maximum maximum tolerated dose of them bring that interface on the expansion that will likely involve expansions in malignancies, especially AML above essentially others, including Obama as well as in solid tumors.
Thanks.
Your next question comes from the line of Jeff medium from Bank of America. Your line is open.
Hi, all this is Joe on for Jeff Meacham. Thanks for taking the question on K T. 253 are you hoping to achieve a tumor agnostic label and can you provide any additional information on patient selection and your breakdown between liquid and solid tumors. Thank you.
Yeah. That's a great question. We unfortunately are not in the position to comment on the specifics but.
Rest assured that the that is one of.
Our ongoing translational.
Being able to potentially get to that type of tumor agnostic.
Development and approval, but we're not in the position right now to comment on where we are and do something we hope to share at different meetings.
Hopefully next year I know the team is working on obviously generating data and also identifying the right medical meetings to start to discuss what are translational strategies.
Your next question comes from the line of Rich law from Credit Suisse. Your line is open.
Which are you there.
Oh, Yeah, sorry, I was on mute yeah. Thanks for taking my question can you comment on what were the stopping booth in place for parts C and can we blew out all great 344 adverse effect.
Also a follow up question is that you mentioned earlier that your.
<unk> can you confirm that and if you haven't seen any of the data yet there was no piecewise data or wheel safety day that they were that they already saw when the study was ongoing.
What was the first part.
So we I think we've said it in the past we.
We can't really comment on the specifics obviously, if there were events that that impacted the study success. We would we would obviously had to share them.
With regards to sign up the.
We really are not in the decision to share what we have or haven't shared with them.
Again as I said earlier, you can assume that we are in constant communication as we've been throughout the collaboration so I'll leave it at that.
Your next question comes from the line of Michael Smith from Guggenheim. Your line is open.
Hey, guys. Good morning, just a couple of from us.
K T 333, which is three program.
Other than odd target degradation and Nfa's. One study are there any other P.
P D markers related to staff three that that you're looking at that.
Potentially further validate this target.
Yeah, I do want to take that one thanks, Michael Yeah. Thanks for the question Michael Yes.
So in addition to looking at Stat. Three yes. We are also looking at the impact of statuary degradation on the actual statute pathway will have the best opportunity to look at that and cereal tumor biopsy is where we can look at the impact either looking at <unk> was that three or looking at gene expression profiles for statuary pathway activation.
And so that will give us an opportunity to show not only that we can hit the target, but that by hitting the target we're able to impact.
The pathway itself will also be doing.
Typing.
Of these patients in order to see whether specific genotype for examples battery mutations or other mutations affecting the pathway.
Correlate at all with critical responses as we get into higher doses. When we can start to assess the clinical responses and where we can start to bring on the target patient population, especially those patients with T cell malignancies.
So expect that to be part of the kinds of our global assessment of.
Comprehensive phase one study of this fee is not something that we can do in every patient.
Alright got it and then a question on here MDM to program. It sounds like you are focusing on <unk> and then perhaps other solid tumors as well and you know I know, but this class of.
Trucks, there has been some on target.
Success. It in particular model oppression and I was just wondering what the decorator mechanism and I think you mentioned the intermittent dosing.
<unk> looking at.
Just given the the P. K P D. Iran. Degradation do you think you can avoid some of those safety issues that have.
Associate with some of the other drugs in the class.
Yeah, So just to clarify Michael.
Email is one of the indications of interest.
Not not domain indication is just one that we've generated let's see we're sharing data.
And obviously as we said be part of our clinical.
Clinical strategy going back to your question I mean, that's the point the second part of your question. That's the point that I was trying to make before we want to use protein degradation to do things that the small molecules or antibodies or RNA eyes or <unk> technologies.
Cannot do in this case.
Actually heavy as safe and effective therapy.
At least.
That much more effective than you can do with other agents in the in the let's see the trick there is really too.
Heavy.
A very profound effect.
Very early on very very quickly, which again small molecules could not have and then allow for recovery. So Jared mentioned, we do frequently so we those once every three weeks.
And we have seen that that's enough to lead to.
Tumor cells through extremely rapid doses and we also see healthy cells being able to recover because they're obviously less sensitive to cancer cells.
And so we have a.
Able to manage the.
Safety with maximizing efficacy in a way, although not not not exactly similar but how will developing a raccoon me then how we're managing neutropenia with the image part is.
Theoretically philosophically exactly the same way and this is why we build these drugs to be those the infrequently did a drag to have been designed at the molecular level to add extended PD.
So that you can does that mean frequently but also with the dosing paradigm that will allow recovery of non cancer cells. So that so what we're doing okay marriage, not just pushing the envelope of protein degradation in immunology, but we're trying to show is that you actually you can push the envelope.
On cancer biology through probably very very thoughtful drug development.
Using the technology to change the paradigm on how one can think about affecting the biology.
In tumor.
Your next question comes from the line of Kelly C from Jeffries. Your line is open.
Thank you for taking my questions for last question regarding.
Regarding the advocacy laid out at 5757.
So how many lines of a prior biologics actually allowed to ask like a child.
According to <unk> and do you expect and most of the patients had a prior to kick Santana awesome your accent.
<unk> patients and effectively.
Two Friday authenticated Africa interpretations.
The defense after <unk>.
Can I, if I can fall compared to like either.
H as tax thank you.
Yeah. Thanks for the question.
We actually did not restrict number or type of prior treatments for either your agents patients. So the party of the.
Phase one allowed patients either who had not received prior therapy prior systemic therapy as well as patients who had received prior therapy, including biologics a patient had received any prior systemic therapies.
Acquired a wash out period before coming onto the studies. So we did not allow concurrent therapy, along with the greater that would've confounded the results.
Again, because this is a small <unk>.
Open label study.
We're not trying to control baseline characteristics in terms of prior treatment that would have been difficult to do would probably not appropriate for such a small study and because clinical efficacy is not the primary endpoint apart see we didn't deal with necessary to do that however, when we do look at the results. We will of course, you know pay attention to what the prior tree.
That's it anywhere for patients with either a D or H S and as we interpret results.
Actually exploratory endpoint results, we will certainly keep that in mind.
Yeah, Thanks, Yeah, and just to confirm so we do not expect or do we know that we won't have any impact from previous therapy, because every patient that they're aware of previous therapies would there have been washed up.
And so there would be no previous drug onboard when they received K T 474.
Your next question comes from the line of might Kratzke from SBB Securities. Your line is open.
Hi, everyone. Thanks for taking my question.
Having completed the dosing portion heartbeat can you provide any details on the split between the total number of a T vs. Hidradenitis patients in the study and whether those baseline characteristics are largely consistent with your expectations.
Well I mean, we're not we were close enough to sharing the at this point. So we're just gonna not comment on display I think baseline.
Six judge we've always said moderate to severe right. So I think that is consistent.
Got it.
Thanks.
Your final question comes from Zheng shoe from Bamberg. Your line is open.
Good morning, and thanks for taking the question.
First one I I was wondering if you can tell us more about the the the.
The difference in terms of biology between H as in a D. N. I guess at your December data set or to be able to differentiate the potential to type of disease and provide prioritization at that point and.
And then the second set of questions around the safety given.
You had.
You have banks boring the and the last frequent dosing schedule an ear.
And you'll have you'll enter your mass Daddy can you comment on any <unk>.
Change or any any any safety signal in terms of charity foundation that cohort and finally on that also related to Q T. I can't confirm on the.
For your oncology programs necessary and.
And also Iraqi image at that.
<unk> at the Q T Foundation, a signal should that should not be expected.
Thank you very much.
Thanks, So maybe I'll start from the lost and then maybe Jared if you can come in on the.
The first and DHS and Jose outage, yeah. So it's a bit that the last one is easy we don't expect that Q T has anything to do with the platform. The programs broadly do as we shared already we have characterized for Casey for it to.
And for this this week of Cds or channel that we believe is compounded by.
Hi, higher than expected exposure in in the category of tissues in humans that leads to the now very again as we said very ATB go non dose responds in Nancy Mack Stevens <unk> Foundation that again, we believe no.
Impact.
In our view no impact on clinical development of this drug assuming it stays within the range that we've seen in Nancy volunteers.
We have also say it in the past that we've been able to replicate these change of current in Cardiomyocyte I believe Jared said it even earlier today and wish and we've also share that in that particular assay. We've demonstrated that we can take another Eric for the greater and show that we Don change current so we know it's a molecule specific.
Good thing.
Going back to infrequent dancing and safety, we will say is that if there is anything out of the study that is worth sharing we will share I guess as I've said it in the past the reason why we've never discussed this study's because we had.
Lila no expectation that we will have an impact on the development of K T 474.
It will be informative again for the Dragon would be informative throughout the platform again, if there is data from this study there is worth sharing we would share it.
In December .
Continue to.
Size on guide on low expectation, there and then an H S D.
If you want to comment on the biology sure Yeah in terms of the biology, you know, even though Hs is classically thought of as a th one th 17 disease and a D. As a th two disease and in reality there've been very interesting sort of gene expression analyses of skin lesions showing that the inflammation is actually quite mixed in both of these diseases even in a D.
In addition to th to U C. Th went in th 17 elements and and a chance you could also see some th two elements.
In reality both of these diseases importantly are driven by till like receptor activation you bacterial colonization of the skin with activate until like distributors is important in both diseases in both diseases and also been shown to be driven by multiple different I'll, one family cytokine members and so there's probably more in common hazardous largely between those diseases.
One might suspect and therefore, we think both of these diseases.
Are really prime indications for targeting within Iraq for the greater.
Great. Thank Jared.
So maybe just to conclude thanks, everybody for joining today I Wanna say.
From my <unk> and the whole team. We appreciate the engagements from the community promote our analysts and investors we've had.
Hundreds of meetings. This year. So we appreciate that there is interest in what we're doing as you know we're always available to follow up with the menu view, they're interested in understanding.
The facts and design it came era, we're excited about what we're doing I think that the sky's the limit for the technology and it's really our responsibility to develop drugs and to build a company that can really capitalise on the power of it. So we look forward to seeing.
You hopefully all of you in December .
Some of you may be that confidence where it would be present in the next few weeks.
This concludes today's conference call you may now disconnect.
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