Q4 2024 Kymera Therapeutics Inc Earnings Call
Good day, everyone.
Megan: My name is Megan and I will be your conference operator today. At this time, I would like to welcome you to the Chimera Therapeutics fourth quarter 2024 results call. All lines have been placed on mute to prevent any background noise.
Megan: After the speaker's remarks, there will be a question and answer session.
Megan: If you would like to ask a question during this time, and if you have joined via the webinar, please use the raise hand icon which can be found at the bottom of your webinar application.
Speaker Change: If you have joined by phone, please dial star 9 on your keypad to raise your hand. At this time, I would like to turn the call over to Justine Koenigsberg, Vice President of Investor Relations.
Speaker Change: Good morning and welcome to Chimera's quarterly update. As you will notice, we have moved to video format, which we hope you will enjoy. Joining me this morning are Nello Mainolfi, our founder, president, and CEO, Jared Gollob, our chief medical officer, and Bruce Jacobs, our chief financial officer.
Speaker Change: Following our prepared remarks, we will open the call to questions, where we will take questions from our publishing analysts on video. To be sure we have enough time to address everyone's questions, we ask that you please limit your questions to one and a relevant follow-up.
Speaker Change: Before we begin, I would like to remind you that today's discussion will include forward-looking statements about our future expectations, plans, and prospects.
Speaker Change: These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected.
Speaker Change: A description of these risks can be found in our most recent 10-K filed with the SEC. Any forward-looking statements speak only as of today's date, and we assume no obligation to update any forward-looking statements made on today's call. With that, I will now turn the call over to Nello.
Nello Mainolfi: Thank you, Justine. Welcome, everybody. We're excited to have you with us today as we transition our quarterly financial updates to a video format.
Nello Mainolfi: I believe this reflects our continued commitment to transparency, open communication, and deeper connections with our stakeholders. We will have lots of data updates this year, so it will be productive to have videos and slides.
Nello Mainolfi: We'll use today's call to briefly reflect on our achievements of 2024, which positions us for what I anticipate will be a very exciting 2025. Stepping back, we start the 2024 with our R&D day, where we shared our expanded focus on immunology.
Nello Mainolfi: with the goal of developing therapies that have the potential to deliver biologic-like efficacy.
with the convenience of an oral daily pill.
Nello Mainolfi: There, we introduced STAT6 and TIC2, which exemplify programs we believe have the potential to disrupt conventional treatment paradigms and expand access to millions of patients around the world.
Nello Mainolfi: As we mentioned at the time, the strategic effort was years in the making, but it has materialized rapidly with the recent clinical progress.
Nello Mainolfi: Our team executed exceptionally over the past year and successfully delivered on all of our key priorities.
Nello Mainolfi: Here's a quick recap of what we did last year. For Step 6, we completed IND-enabling studies for KT621, 5 in IND, and initiated the Phase 1 Healthy Volunteer Study. Now we're completing the final MAD cohorts.
Nello Mainolfi: This is the first STAT6-targeted agent to enter clinical development. While the attractiveness of STAT6 is a target,
Nello Mainolfi: and the strong validation of our preclinical work has attracted many others to the space. We believe we are the unquestioned leader, a position on which we intend to build.
Nello Mainolfi: With TIC-2, progress continued as well. Since the first introduction in January, again, of last year, we named and advanced a novel development candidate, KT295, and are now completing IND-enabling studies.
Nello Mainolfi: Regarding IREC4, we continue to support our partner Sanofi in their efforts to progress the two ongoing Phase IIb studies in HS and AD.
Nello Mainolfi: Importantly, following an interim analysis in the middle of last year, Sanofi expanded the studies to accelerate the overall development timelines on path to pivotal trials.
Nello Mainolfi: Finally, while less visible to investors, we progressed our early pipeline of novel immunology programs to the point where we're poised to soon share our new exciting immunology target.
Nello Mainolfi: So with all the progress that I just discussed, which reflect really a year of truly outstanding accomplishments, we're positioned to an even more productive 2025.
where we'll have several clinical advancement across our immunology pipeline.
To summarize, here is what you can expect this year.
Nello Mainolfi: Starting with Stat 6, we're on track to report KT621 phase 1 data this year for both the Healthy Volunteer trial, which will happen in June,
Nello Mainolfi: and the Phase 1B trial in AD, which will happen in the fourth quarter of 2025. And we also initiate two Phase 2B studies. AD will start in the later part of 2025, and asthma will start in early 2026.
Nello Mainolfi: For TIC-2, we're on track to advance KT295 into the clinic next quarter with Phase I healthy volunteer data before year-end.
Nello Mainolfi: Stay tuned in May as we plan to unveil our next program, a previously undrug transcription factor that has the potential to be first-in-class agent for multiple rheumatic as well as other old immune diseases.
Nello Mainolfi: Importantly, we will not stop here. Our goal remains to deliver at least one new IND per year, so you should expect more exciting new developments to be disclosed at a consistent pace.
Nello Mainolfi: I want to finish my comments here, where we started this call, which is with our drug development principles and strategy. Khmer is deeply committed to developing an industry-leading immunology pipeline, featuring innovative oral small molecule therapies.
Nello Mainolfi: We're determined to ensure that patients won't have to choose or make trade-offs between efficacy, safety, convenience, and cost. We believe that if we achieve this we will expand the choices available to patients and transform how patients are treated in immunology.
and potentially beyond.
Nello Mainolfi: Transition traditional small molecules have always offered convenient benefits by delivering powerful pharmacology compared with biologics has been elusive. We believe our oral medicines can provide a differentiated and potentially better solution. Oral drugs with biologics like efficacy.
and we're dedicated to making this a reality.
Nello Mainolfi: Our work to deliver on the promise continues. We look forward to delivering on and sharing multiple data readouts in the next 12 to 18 months.
Nello Mainolfi: that we believe will validate our strategy and put us that much closer to addressing many important markets with next-generation oral drugs.
Speaker Change: Before handing the call over to Jared, I'd like to take a moment to thank Lee Morgan, who has been a director at Chimera for the last three years.
Nello Mainolfi: As you may have seen in the filing today, she has decided not to stand for re-election at our upcoming annual shareholder meeting in June. I would love to personally thank her.
Nello Mainolfi: for all the contributions she's made at Chimera over the last several years, which has been much appreciated. With that, let me pause here so Jared can give you more details on our clinical strategy plans and data.
Jared Gollob: Thanks Nello. This is an exciting time for Chimera from a development perspective.
Speaker Change: We are well positioned to achieve multiple clinical data readouts that will further validate our approach and strategy.
So, let's go ahead and jump in.
Speaker Change: Last month we laid out our accelerated development strategy for the STAT-6 program which starts with Phase 1, Phase 1B, and parallel Phase 2B trials that enable subsequent registrational Phase 3 studies across multiple indications.
Speaker Change: Each of these trials serves a distinct and unique purpose in our clinical development strategy for KD621.
Speaker Change: I'll walk you through some details on each of these trials today, but I want to first start at a high level.
Speaker Change: So starting with the Phase 1 Healthy Volunteer Study, our primary goal there is to demonstrate STAT6 degradation and safety.
Speaker Change: In addition, we will also take an early look at several Th2 biomarkers.
Speaker Change: Now, while we will look at biomarkers in the Phase 1a, the Phase 1b study will be a much more relevant and meaningful opportunity to assess the impact of stat6 degradation on multiple Th2 biomarkers in blood and skin.
Speaker Change: And that study will also take an early look at any clinical efficacy signals.
Speaker Change: After these two Phase I studies, the parallel Phase IIb trials in AD and asthma are intended to measure the clinical activity in two key indications and enable dose selection for registrational studies in multiple indications.
Speaker Change: In terms of the specifics on some of these activities, our Phase 1 Healthy Volunteers study is ongoing and is evaluating single and multiple ascending doses of KT621 versus placebo.
Speaker Change: The primary objective is to show that we can robustly degrade STAT6 in blood and skin, which we define as a reduction of 90% or more at doses that are safe and well tolerated.
Speaker Change: Given all the human genetics data, the preclinical data we have generated, and the pathway validation, we believe that if we can demonstrate this, it will largely de-risk the program and increase the probability of success once we move into patients.
Speaker Change: As we've shared in the past, in Healthy Volunteers, we expect to see some impact on several Th2 biomarkers, such as TARC and IgE.
Speaker Change: Our expectation entering the trial is that the effect would likely be comparable to what has been reported for dupilumab, though, as we have said, we believe the best opportunity to show effect on a variety of Th2 biomarkers will come in patient studies, for these are greatly elevated at baseline.
Speaker Change: In terms of the trial status, we are recruiting the last remaining cohorts and we're on track to report results in June.
Speaker Change: As we approach the start of the Phase 1b trial next quarter, we want to take a moment and provide a few more details about the study.
Speaker Change: The Phase 1b trial in moderate to severe atopic dermatitis will be a relatively small single-arm open-label trial with dose selection optimized based on Phase 1 healthy volunteer results.
Patients will be administered KD621 once daily for four weeks.
The trial is expected to include approximately 20 patients.
Speaker Change: The key study aim is to show that robust static degradation in blood and skin by KT621 has a dupilumab-like effect on reducing multiple Th2 biomarkers in the blood, such as
Speaker Change: Eotaxin, TARC, Triostin, IgE, and others, and on the transcriptome of active AD skin lesions.
Speaker Change: This study will also assess KT621 effect on AD clinical endpoints such as EZ and PRITIS-NRS.
Speaker Change: We decided to make this a streamlined, biomarker-focused study to transition quickly into Phase 2b, which is on critical path to Phase 3 initiation and eventually registration.
Speaker Change: In the fourth quarter, we'll read out the Phase 1b data and also initiate the first Phase 2b placebo-controlled dose range finding trial in moderate to severe atopic dermatitis.
Speaker Change: In the first quarter of 2026, we will start a second Phase IIb trial in moderate to severe asthma.
Speaker Change: This initial parallel development strategy is intended to accelerate late-stage development across multiple Th2 dermatological, gastrointestinal, and respiratory indications.
Speaker Change: So turning now to TICC2, this is another program where we believe we can mimic the human genetics TICC2 loss-of-function profile and achieve biologics-like activity with an oral drug.
Speaker Change: We're on track to start the KT295 Phase 1 Healthy Volunteer Study in the second quarter.
Speaker Change: The primary goal is to demonstrate safety and full TIK2 degradation in blood and skin, which if achieved, we believe, would be the first time an oral small molecule was able to show complete blockade of TIK2 sigmoid.
Speaker Change: And we expect data will be shared in the fourth quarter of 2025.
Speaker Change: And to round out our immunology franchise, I'll wrap up with IRAC-IV.
Nello Mainolfi: As Nello mentioned, last year Sanofi took steps to accelerate the overall KT474 development timeline.
Speaker Change: The decision to expand the Phase II program was to structure the hydradenitis separativa and atopic dermatitis trials with the necessary regulatory perspective to enable dose selection and advancement directly to pivotal Phase III studies, ultimately with a meaningfully shorter development timeline.
Speaker Change: To support this strategy, the size of the studies increased with additional doses planned for evaluation in both trials.
There are no changes to the Phase II Study Endpoint.
Speaker Change: With the planned expansion of the trials, the primary completion dates were adjusted to the first half of 2026 and mid-2026 for HS and AD, respectively.
Speaker Change: The progress made by our team in 2024 sets us up to execute in 2025.
Speaker Change: Importantly, within our immunology franchise, we believe KT621, our first and we believe best-in-class oral spastic degrader, has the ability to transform the treatment of Th2 inflammatory diseases.
Speaker Change: And we look forward to sharing phase one data and healthy volunteers next quarter and advancing the program into patient studies while also initiating the TIC2-KT295 phase one trial next quarter and sharing data by year end.
Nello Mainolfi: And, as Nello mentioned, we're excited to introduce our next immunology program, which aligns perfectly with our pipeline portfolio strategy.
Nello Mainolfi: We're planning to host a company webcast in early May to unveil the new Target and we'll share more information as we get closer.
Nello Mainolfi: I should point out that the KT621 Phase 1 Healthy Volunteer Data, which we expect will be reported in June, will be its own, separate event.
Nello Mainolfi: I'll now turn the presentation over to Bruce for a review of the fourth quarter and full-year financials. Bruce?
Bruce Jacobs: Thanks, Jared. As I review our fourth quarter 2024 financial highlights, please reference the tables found in today's press release.
Speaker Change: Revenue in the fourth quarter of 2024 was $7.4 million. All of that was attributable to our Santa Fe collaboration.
Speaker Change: With respect to operating expenses, R&D for the quarter was $71.8 million. Of that, approximately $6.8 million represented non-cash, stock-based compensation.
adjusted cash R&D spend of $65 million.
Speaker Change: excluding that stop-base comp, reflects a 23% sequential increase from the third quarter.
Speaker Change: G&A for the quarter was $16.3 million, of that approximately $7 million was non-cash stock-based comp, and adjusted cash G&A spend of $9.3 million, again, excluding stock-based comp, was up 13% sequentially.
Speaker Change: Our cash balance at the end of 2024 was $851 million. Our cash balance is expected to provide a runway into mid-2027, and that will enable us to execute on multiple data readouts you've heard today, including several important Phase II trials across our programs.
Speaker Change: So this concludes our prepared remarks. If you just give us a moment to assemble in our conference room, we'll be happy to address any questions you have there. Thanks very much.
We will now move to our question and answer session.
Speaker Change: At this time, if you would like to ask a question, please click on the raise hand button, which can be found on the black bar at the bottom of your screen.
Speaker Change: You may remove yourself from the queue at any time by lowering your hand.
Speaker Change: When it is your turn, you will receive a message on your screen asking to be promoted to a panelist.
Speaker Change: Please accept, wait a moment, and once you have been promoted, you will hear your name called and you may unmute your video and audio to ask your question. As a reminder, we are allowing analysts one question and a relevant follow-up. We will now pause a moment to allow the team to gather and assemble the queue.
Speaker Change: Our first question will come from Faisal Khurshid with Learing Partners. Please unmute your audio and video and ask your question.
Speaker Change: Hey guys, it's good to literally see you and congrats on all the updates. Just a quick one for us, what supports your view that the 28 dosing in the atopic derm phase 1b is enough time to show robust biomarker activity? And then could you also comment a little bit on how you've kind of thought about the inclusion-exclusion criteria for that phase 1b?
Jared Gollob: Good morning, good to see you as well. Jared, why don't you take this one? Sure. It's an important question. We know from prior dupilumab trials, where there have been 16-week endpoints in AD, in moderate to severe AD,
Jared Gollob: that when you look at the time course of what's happening, they don't just look at six weeks, they also look at earlier time points. And looking at four weeks, it was shown that there was a clear, you know, very clear impact on TH2 biomarkers, as well as on clinical endpoints, like EZ and pruritus NRS.
Jared Gollob: I think we're very confident that 28 days of treatment using an optimal dose selected from phase 1a should allow us to see a clear impact on Th2 biomarkers, which is the primary objective of the study, and to also give us an opportunity to see an impact on clinical endpoints.
Jared Gollob: In terms of eligibility criteria, I think here it's going to be very important that we have
Speaker Change: you know, stringent criteria that make sure that we're getting, number one, patients that definitely have AD.
and secondly, patients that have moderate to severe disease.
Speaker Change: I think that's very important in trying to minimize any sort of placebo effect is to pay close attention to those particular eligibility criteria. That's going to be a very important part of the study. Maybe just mentioning a few other things that are important to reduce or minimize placebo effect. The one is, you know, having a rigorous approach to site selection and making sure we bring on sites.
Speaker Change: that are able to select the right AD patients for the study and have personnel that can perform the clinical assessments in a rigorous manner and to also make sure that we're closely monitoring for drug compliance on the study and also making sure that patients are not taking any other comments.
Maybe if I can just add one thing.
Speaker Change: Obviously, hopefully it's appreciated that I think we have not only an amazing opportunity with this drug, but I also think we have a unique responsibility
Speaker Change: to do the right type of drug development. And so there's also another reason for the 28-day study, besides being long enough to measure, and actually the study's powered enough for 28 days to measure strong biomarker changes, is that what's a critical path is going into a dose-ranging phase two P study, which is on path to go to phase three in registration. So what we don't want to do is spend time unnecessarily in early clinical development
but not critical.
Speaker Change: Yeah, and then Greg, just to kind of clarify on the choice to not have a placebo arm in the phase 1b, especially given kind of like what's been seen in other atopic term studies.
Greg: Yeah, maybe, Jared, maybe I'll start. It kind of goes back to what I just said. So the goal of the study, as Jared said, is to demonstrate a biomarker profile in blood and skin that we believe
Greg: will be robust and be compared to, for example, the Dupilumab for weak data.
Greg: And that's for that type of study. Actually, we don't believe we need the placebo. We know that biomarkers do not move.
Greg: substantially in the placebo arm of these studies. And again, if we had to run a placebo-controlled study for four weeks powered to demonstrate a difference on clinical endpoints, this would be a much larger and longer study. And again, this does not...
Greg: fulfill our drive, which is to go into phase two, be a city.
God, that's super helpful. Thank you guys so much.
Our next question is connecting. One moment.
Andy Chen: Our next question will come from Andy Chen with Wolf Research. Please unmute your audio and video and ask your question.
Andy Chen: Hi, nice to see you in person. So the phase 1b is designed to be single arm, so we won't be able to see dose response on biomarkers. Do you think the Th2 biomarker data is going to be so clean that we won't need to see dose response across different doses to be comfortable with the data? Just curious if we're going to have enough data to answer additional questions about efficacy by Q4. Thank you.
Yeah, so maybe I'll start and Jared can add more.
Andy Chen: specific point. So, thanks, Andy. I think this is a great question. So, our goal is to take into phase 1B study
Andy Chen: has demonstrated in Healthy Volunteer the type of profile that we're looking for, and as we said, at least 90% degradation in blood and skin. We have shown pre-clinically that that type of profile leads to extremely robust biomarkers effect.
in a plethora of readouts.
Andy Chen: So, our development is based on our understanding of the biology.
both in terms of all the preclinical data we've...
we've amassed as well as on human genetics.
Andy Chen: So we expect that a dose with that profile will have a dupilumab-like effect, and that's really what we want to show.
if we were not certain.
Andy Chen: And if this was really an exploratory Phase I B study,
Andy Chen: to show an early proof of concept, we'll probably design it differently. But we're designing this study with expecting a successful outcome based on all the experience that we've built internally and all the data we've generated so far.
Andy Chen: And maybe just to add, you know, the opportunity for being able to see the impact on, you know, both TA2 biomarkers and clinical endpoints.
Nello Mainolfi: to see a dose response that will come from phase 2B, where that will be a true dose range finding study, and that will give us a strong opportunity to do that. And as Nello said earlier, the key really is for us to use phase 1A information to select the doses for the dose range finding phase 2B study and to get to phase 2B as quickly as possible. And then phase 2B becomes a great platform for us to show, you know, perhaps differences in impact on THQ biomarkers and clinical endpoints depending on the doses that we select for phase 2B.
Nello Mainolfi: And that will ultimately allow us to pick the optimal bills for the Phase 3 Registrational Studies.
Thank you, Nello. Thank you, Jared.
Speaker Change: Next question. Our next question will come from Michael Schmidt with Guggenheim.
Speaker Change: Michael Schmidt with Guggenheim. Please unmute your audio and video and ask your question.
Speaker Change: Hey guys, thanks for taking our question. This is Paul on for Michael Schmidt.
Speaker Change: Just on the STAT6 program, what do we know currently about the potential bioavailability of KT621 in tissues of interest, for example, skin versus lung tissue or others that might be disease-relevant down the line? How predictive are the preclinical models there? Is there any opportunity to look into that in the early Phase 1 or 1b? Thank you.
Thank you.
Speaker Change: Yeah, so obviously I can't speak to the phase one healthy volunteer data, but I can speak to the preclinical data that we generated. And we generated extensive data across all species that you can imagine, mouse, rat, dog, non-human primate.
Speaker Change: and others where we've been able to demonstrate that KT61 not only is orally bioavailable, but it's actually highly active at low oral doses and distributes evenly across
Speaker Change: all tissues of interest. We've shown in non-human primates equal distribution and degradation in blood, skin, spleen, lungs.
And so our expectation is that the preclinical...
profile will translate.
Speaker Change: equally inhuman, and a way to measure that, obviously, we can't take.
Speaker Change: you know, lung and spleen, but obviously we can take blood and skin as we've done for other programs. And so we believe that those are great surrogate tissues to show not only hopefully the desired degradation that we
expect to have, but also a consistent degradation across
Speaker Change: multiple tissues. I would just go back to what we've been saying, you know, for the past years, I would say, that, you know, we've been fortunate...
that all of our programs are translated.
Speaker Change: impeccably I would say between preclinical and clinical so we hope and expect that six to one will follow suit on that on that particular front.
Speaker Change: Great, and if I could just have a quick follow-up on the plan design for the Phase 2 AD study. Is the sort of ongoing IRAC-IV study a reasonable comp, you know, three different doses plus placebo? Any meaningful differences in the type or severity of AD patients you might recruit there?
Speaker Change: I'm going to save Jared on this one. I think at this point we're not going to comment. Hopefully you guys appreciate that we're sharing the relevant information when when it's the right time, as we're doing today for the Facebook. We promise you that when it's the right time we will share that kind of information as well.
Great, thanks very much.
Thank you both.
Speaker Change: Our next question will come from Ron Finer with J.P. Morgan. Please unmute your line, your video, and ask your question.
Hi, guys.
Speaker Change: You will be evaluating only one dose in this Phase 1b for AD, and how does the FADMAD data so far from the Healthy Volunteers trial kind of give you information on the effective range, at least from a PD perspective?
Speaker Change: Yeah, I mean, unfortunately, we can't go into the answer, but what I think I can say, Jared has already said it, but I'll say it again, the beauty of protein degradation, unlike any other technology out there,
Speaker Change: that you can measure target engagement both in a dose-responsive manner as well as in a time-responsive manner so you know what is the level of degradation of your target at different doses at different time points.
Speaker Change: And so we have designed a really comprehensive Phase I Healthy Volunteer Study that is looking at a range of doses that will allow us to understand
as well as we can.
Speaker Change: the relationship between those PK and degradation involved in skin. With that set of data, as we said in clinicaltrials.gov, we expect up to 120 subjects on the study, so we'll have...
Speaker Change: a really large data set, we will be able to have enough to confidently select the, let's say, three doses for the phase II B studies.
Speaker Change: And we don't believe, and we've already shown with IRECT4 that there is a really strong translation of degradation between healthy and disease.
Speaker Change: patients in terms of degradation profile. And so we believe that everything that we've designed, going from a very comprehensive phase 1 healthy, going into 1B, to really demonstrate that
Speaker Change: One of the doses that likely will be taken into phase two is given the type of profile that we expect in patients, let's say, confirmatory study, and then run.
Speaker Change: go into a face-to-face SAP. I think we feel very confident about our plan right now. And so, you know, again, we look forward to sharing the data along the way and then, you know, get to the end of the year with those big studies.
Speaker Change: Thanks, and then just maybe if I can try on the new program, are you guys geared more towards staying in the teach-to space or have anything additive or orthogonal to the current programs or is it going to be completely new?
Speaker Change: TLR activity. If you look at TIC-2, it's a, you know, I-23 type 1 interferon. If you look at STAT-6
Speaker Change: It's a classical, maybe the best, PH2 target, I would say, and so these are all complementary pathways that actually one can imagine could be synergistic in a combination one day, and so you should expect these other targets to be a complementary pathway.
to the ones that we've shared so far.
Thanks.
Jeff Jones: Our next question will come from Jeff Jones with Oppenheimer. Please unmute your audio, video, and ask your question.
Good morning, guys, and thanks for taking the question.
Speaker Change: You know, I think we've asked a lot on Stat. 6.
Speaker Change: Curious to get your view on the TIC-2 program from a similar perspective as we think about biomarkers and tissue penetration.
Speaker Change: how we should think about looking at that data, which at the healthy volunteer data, which is obviously some way out.
Speaker Change: So can you share how you're going to be looking at...
Speaker Change: not only safety, but efficacy signals there from a perspective of TIK2 and biomarkers.
Jared Gollob: Jared, do you want to take this one? Yeah, I think for the TIK2 program, you know, I think we have a unique opportunity to show pharmacology, you know, that is differentiated from what's out there for typical TIK2 small molecules, and that's why we believe this program can eventually
Jared Gollob: attain biologics like activity, hopefully, which has not really been attained by the small molecules. And to do that, it's important, we believe, that for the pharmacology to show that we can fully degrade TIK2, 95 plus percent, and keep that degradation level 24-7, sort of around the clock, in order to give us that full pathway blockade that would be the equivalent of what you can get with an injectable upstream biologic. So I think when we look at the Phase I study, just as we've done in Staff 6, we're going to have a very detailed look at
Jared Gollob: the impact on tick-2 levels in blood and in skin in healthy volunteers, looking over time, looking at different dose levels in SAD as well as in MAD, and that's going to really give us a very good idea as to whether our pharmacology can really achieve
Jared Gollob: on TIC-2, and if we're able to see that sort of impact.
Jared Gollob: I think that will be very encouraging for us and our plan then is the next step after phase one is to then do
Jared Gollob: a Phase II proof-of-concept study, probably a placebo-controlled study that might be in a disease like psoriasis, where there we want to be able to bring, you know, optimal dose or doses from that phase when they study into Phase II and really demonstrate there that we have biologics like activity, for example, that we have sclerosi-like effect on PASI-90 and psoriasis. And that would be the key inflection point.
Jared Gollob: for us to then say, okay, here we have, you know, a compound that is clearly differentiated from small molecule inhibitors. It has biologics like activity, and then we would want to move it forward potentially across multiple potential different indications that are both interferon properties, you know, such as lupus, IBD, in addition to psoriasis.
Great, I appreciate that.
Speaker Change: And just one quick follow-up, and as you mentioned, the possibilities in phase two, you know, how do you think about, in terms of patient selection, you know, patients who have prior exposure to, say, Ducra or one of the biologics?
impacting the L23 pathway.
Speaker Change: Maybe it's a bit too early, Jeff, to discuss it. Obviously, you know, let's say we end up going in psoriasis, there is, you know, lots of patients that
Speaker Change: that are available to us to ask the question in a way that is not influenced by, you know, failures on, let's say, pathway agents. So we'll obviously be very thoughtful about the patient selection, but we'll share more of that as we get in closer to the study.
Thanks, guys. Thank you.
Speaker Change: Our next question comes from Kelly Shea with Jeffries. Please unmute your audio, video, and ask your question.
Speaker Change: Hi, thank you for taking my question. This is Yifan on behalf of Kelly from Jefferies.
Another question on step six.
Speaker Change: So, for the biomarker analysis in the MAD portion, how long is the follow-up going to be? Can we expect data from IHG and the TARC?
Speaker Change: at multiple time points across the dosing period. And after 14 days of dosing, or we may only expect one or two time point. And also wondering how would this biomarker data in Health Volunteer guide your decision on those levels in phase 1B and phase 2 trials in patients? Thank you.
Speaker Change: Maybe I'll start. This is a great question, actually. So, the first part, it's obviously CT, yes, we will have several time points, both during doses and post-dosing.
Speaker Change: period. The second question is, actually it's a great question because it allows us to touch on a very important point.
which is if you look at the Dupilumab
Speaker Change: Healthy Volunteer Studies, where we now have it in our tax sometimes to show to investors what their data look like.
Speaker Change: instead of just talking about numbers, actually looking at the totality of the Dupilma data, you will actually see that in most cases, if not in all cases, there is actually a lack of dose response between the different doses. So if you actually chose...
the Healthy Volunteer biomarker data for dose selection.
Speaker Change: for Dupuy-Lemans. Let's talk about Dupuy-Lemans. You would probably pick the wrong those.
to go into phase two or phase three.
Speaker Change: But, obviously, how we're going to select these doses is by looking at the totality of the data, right? For us, the key information is, can we degrade STAT-6 robustly, and by that, we mean 90 percent or more in blood and skin? Is that safe and well-tolerated?
Speaker Change: And that's really what we're going to use to make a dose selection, but we will also look at the totality of the data and obviously share it with you at the right time.
Thank you.
Speaker Change: Our next question will be coming from Brad Canino with Stifle.
One moment as he connects.
Speaker Change: Brad Canino, please unmute your audio video and ask your question.
Brad Canino: Right, good morning. So look, I think you've done a really good job previewing the STAT6 Healthy Volunteer data, and I can see how the target profile will allow you to move into patients with conviction. You can marry that to the preclinical outcomes.
Speaker Change: It's an outstanding question, and you started to touch on this in some of the prior responses, is how you see the Phase 1B building on that conviction?
Speaker Change: a 20-patient study, short four-week treatment. How do you really see that being a useful tool to shape the view of the profile potential, even though it's not designed to be a definitive assessment of the drug ambitions?
Brad Canino: Yeah, so look, Brad, our view is that this is going to be...
Brad Canino: you know, I don't know what we want to call it, the drug of the decade or the drug of the century. So we have to be really thoughtful about the study designs along the way.
Brad Canino: And we have to really ask the right question in each study, otherwise we end up creating confusion instead of clarity. The questions for our studies are very well thought out, and I think we're going to get the right questions.
Brad Canino: in the right study. So for healthy volunteers, the question is, I'm going to keep saying it, can we degrade the target well?
Brad Canino: robustly, I should use the same word, and is that safe or well-tolerated? To me, to us, this is a hugely risky step. This is the first time that StatSix has ever been tried.
Brad Canino: So, this is paramount type of information. We will collect the biomarkers. I expect that they will look like the pilumab, in healthy, I was talking about. And then, the study is really designed for us to move into Phase IIb ASAP.
Brad Canino: Now, why are we running the Phase 1 Beach Study? First of all,
The main goal is really to generate...
Brad Canino: data, especially around biomarkers, that will allow us to, I think, close the circle on, is a Statsix degrader a DUPI-like agent?
Brad Canino: We really cannot do it in Healthy Volunteers, for all the reasons we discussed. These biomarkers don't move enough, there is a lot of noise, in many cases you don't even see a dose respond. It's more of a yes or no. Do they move? Can we change them?
Brad Canino: I expect, right? But in patients, we have a plethora of chemokines, cytokines in blood and skin. And in four weeks...
Brad Canino: we can actually see a big window that we should be able to reduce robustly with our drugs.
Brad Canino: And to me, that's really what we're trying to show in that study. That study is telling, you know, potential...
Brad Canino: investigators and patients on our Facebook page. This study is local.
Brad Canino: This is a drug that is safe and well-tolerated, degrades the target well, and actually also shows that has a duplic-like effect in biomarkers.
Brad Canino: And I'm confident that that will translate into a beneficial clinical effect in these patients so that we can power up the studies and recruit fast our Phase I-B studies. That's really what we're trying to do. I think the Phase I-B, it's in a luxury. It's not a critical path study, but we believe it's a powerful study to really demonstrate everything that we've been saying for the past year and a half.
Brad Canino: on the STAT-6 to be a 2p in a pill. I think that that data will clearly demonstrate that. Without the need of other doses of placebo because biomarkers don't lie.
Thank you.
Speaker Change: Our next question comes from Mark Frame with TD Cohen. Please unmute your audio video and ask your question.
Mark Frame: Hey guys, thanks for taking my questions. Let me just start off with one clarifying question on some of the enrollment criteria you mentioned earlier for the Phase I-B, just take the
Speaker Change: Obviously, no concomitant meds, but will you be requiring people to be biologic and jack therapy naive, or could there be a patient or two that end up in this trial that have at some point seen some of these more modern agents?
And now I'll have a follow-up after that.
Speaker Change: Yeah, yeah, that's a good question, Mark. No, I mean, we will allow patients, you know, who have had prior systemic therapy or biologics, you know, that could include Doopey or could include a JAK inhibitor, as long as they responded to it. So, there will be those patients enrolled onto the study as well as patients who are biologics-naive.
Speaker Change: Okay, thanks. And then just on the Phase 2Bs that you're planning in AD and asthma, you can pick and have a kind of a range of, a handful of different kind of dosing paradigms depending upon the indication.
Speaker Change: Do you think those trials will ultimately give you enough information about dosing to go to phase 3 for kind of across the board of...
Speaker Change: the IL4-STAT6 pathway, or are you expecting that you'll ultimately need more phase 2b's and some of these other indications as well to help select those for the different indications?
Speaker Change: And if so, should we expect to see those trials done in parallel to AD and asthma or are you going to really wait for AD asthma data until you would open up any more?
So, as we said in the...
Speaker Change: in the last discussion around our healthcare conference early in the year.
Our development plan is based on
Speaker Change: previous experience of other pathway agents in this phase in Th2 where eventually they were able to select a dose from let's say AD to go a phase 3 dose
Speaker Change: in AD to go into other skin indications and a phase 3 dose from asthma to go into the other respiratory indications.
Speaker Change: And so we have a high degree of confidence that this would be the only Phase IIb studies that we will run that will allow us to go into seven, eight, or more Phase III programs.
Speaker Change: But obviously, just to be absolutely clear, that will have to be demonstrated also along the way. Obviously, we think that can happen, but we'll have to go through the studies to make sure that will happen.
Speaker Change: And then lastly, as you get that more robust efficacy readout from these phase 2Bs, you know, obviously the goal is to every bit match dupixent. It may be even potentially exceeded a little bit. But.
Speaker Change: If that isn't the case and you end up being a bit lower on efficacy, is that accessible? And how close do you think you need to be to justify the expensive late-stage trials?
Speaker Change: Yeah, so first I'd like to say, I'd like to clarify our expectations, I hear yours Mark. So, our expectation is that based on the biology and what we've seen preclinically that
Speaker Change: We should have an effect in PH2 diseases that is similar to dupilumab.
Again, we've shown some numerical...
Speaker Change: superiority preclinically but you know well I think for us our expectation is that it will look to be like you know we to be honest are not expecting that we will have lesser on effect
Speaker Change: we have talked to and others have done calls with KOLs in the space that have made the case that a less active drug
Speaker Change: that is oral and safe and well-tolerated could be also extremely successful. So, we believe that the bar for success is not Dupuy-like, but our bar is that we're going to be Dupuy-like.
Okay. Super helpful. Thank you.
Speaker Change: Our next question will come from Ellie Merle with CBS Securities. Please unmute your audio video and ask your question.
Hey guys, congrats on all the progress.
Speaker Change: Maybe just in terms of dose selection, how are you thinking about how the doses you plan to study in phase 2b will compare between atopic derm and asthma? I guess do you expect to study the same doses in each indication? And then kind of a broader question about stat 6.
Speaker Change: as it relates to dose selection. How does STAT6 expression potentially differ across indications or maybe between patients? Thanks.
Jared Gollob: So I'll let Jared answer the question. I just want to add one thing to address the later part of your question. So we have seen, and I can only speak about preclinical data, that expression levels of sub-seqs have no effect on our degradation kinetics.
Jared Gollob: So, which means that our expectation is no matter the expression levels, we'll be able to degrade it.
Jared Gollob: to the level that we need to, or we want to, which pre-clinic may be 90% plus. But, Jared, do you want to speak to those issues? Yeah, Eli, you know, in our pre-clinical models, and we have, I think, good pre-clinical models for both asthma and atopic dermatitis, you know, we've shown in both those models.
Jared Gollob: that doses of 6-2-1 that give us at least 90% degradation lead to sort of optimal activity or doobie-like effect.
Jared Gollob: I think our expectation, therefore, is that the doses that we choose for Phase 2B coming out of Phase 1A will be similar doses for both the Phase 2B asthma study and the Phase 2B AD study.
Jared Gollob: Then the question could be, is the phase 3 though is going to be different? I think it's unlikely, but that's the point of the phase 3 study.
I asked if a lot already early, so...
Okay, great. Thanks, guys.
Speaker Change: Our next question comes from Parth Patel with Morgan Stanley. Please unmute your line and ask your question.
Hi guys, can you hear me?
Let's go.
Parthon: Sorry, my video is not working. This is Parthon for Vikram. So just a question on 621.
Speaker Change: So following the phase two studies in AD and ASWA, how expansive of a phase three development program would you expect to initiate for KT621? And how would you prioritize indications given the broad potential you've laid out for the molecule?
Speaker Change: Okay, I'm going to take this and we're going to try more quickly because I hear we have many questions and limited time so So what we've said is that we want to develop this drug with two key goals in mind that are actually not mutually exclusive. One is pace and path registration
Speaker Change: and breadth of opportunities. And so we're going to run these important face-to-face studies to inform face-to-face selection for potentially eight different indications.
Speaker Change: and we're going to run parallel phase 3 campaigns for several of those indications. I think it's too early for us to say which and how many, but you can expect that if you look at 2P, the red map market where now asthma...
Speaker Change: Asma and Debi account for more than 80% of the revenues.
Speaker Change: I would add that once COPD picks up, it'll probably be another important pillar of the revenues for the drug. I would expect that we will definitely prioritize those three, and then we have to, you know, we have to, between now and phase three campaign start.
Speaker Change: decide whether we want to add additional campaigns in parallel versus slightly staggered.
Okay, thank you.
Yep. Thanks.
Speaker Change: At this time, we will only be taking one question and no follow-up. Our next question comes from Kripa Derevaconda with Truer Securities. Please unmute your audio video and ask your question.
Speaker Change: Hey guys, thank you so much for taking the question. This is a really interesting format.
Thank you.
Speaker Change: So, you mentioned this before, but in terms of degradation levels, do you expect to see, similar to what you've seen in the preclinical studies, degradation levels similar in different tissues, skin and plasma, I know you're measuring it in healthy volunteers, and do you expect that to be, to follow through into patients as well? Like, what you see in healthy volunteers, would you expect similar degradation levels in patients as well?
Speaker Change: Yeah, so again, preclinically, we've seen robust degradation. If you look at our studies, we were able to show more than 90% degradation in all species. We've also seen, as I mentioned, we have non-human primates. We also have other species that we haven't shared data for, but where we've seen consistent degradation across tissues.
Speaker Change: So we do expect to see robust degradation, again, 90% or above, in healthy volunteers. And yes, based on...
Speaker Change: both statics preclinical data where we've done, let's say, had the
healthy
Speaker Change: animals versus disease models where we haven't seen changes of degradation profile, but I would probably speak more about, for example, IRAC-4.
Speaker Change: where we haven't seen any difference of degradation between healthy and AD, which is relevant, obviously, for STAT6 in a way. Yes, we expect all of that. Obviously, we'll have to show it, and that's the point of some of these studies that are ongoing or will be ongoing.
Speaker Change: Our next question comes from Derek Arquilla with Wells Fargo. Please unmute your video and audio and ask your question.
Speaker Change: Hey guys, this is Yvonne for Derek. Thanks for taking our questions. A quick one from us. So you mentioned biomarkers, you know, for the STAT6.
Speaker Change: that they should be comparable to DUPI. So could you provide a little bit more color on what this means in terms of like the TH2 biomarkers and just remind us like what did we see for DUPI here? Thanks.
Speaker Change: Well, yeah, thank you. So if you're talking about hectic volunteer studies, so if you look at data from
publication from Regeneron, they showed, for example, that
Speaker Change: to Pilumab, in a dose-response manner, both IV and Sub-Q with multiple doses, we're able to show, within the first two weeks, right, we need to compare the first two weeks.
Speaker Change: effect, a maximal effect in TARC around I believe 35% actually peaked early and then started to be less already by week two.
Speaker Change: Again, it was not really dose-responsive, so it seemed a bit stochastic in nature, but there was a clear reduction for one of the doses. And then for IgE, for the first few weeks, we really don't see much. I think if you
Speaker Change: If you draw a line, it's probably 5, 6, 7 percent. I haven't actually done the calculation myself yet. So, for the first week, IG,
Speaker Change: because those are, you know, again, noisy and, for example, for IgE, pretty close to baseline.
Okay, thanks.
Speaker Change: Our next question will come from Eric Wong with Goldman Sachs. Please unmute your audio and ask your question.
Speaker Change: Hi, this is Eric Wong on for Chris Shibutani. Thank you for taking the question. Just a quick one for me. So just thinking beyond the Sanofi collaboration, how are you thinking about strategic partnerships to accelerate development or de-risking programs? I guess, particularly in oncology, can you elaborate on the criteria you'll be using to select partners and how you intend to maximize the value of those assets and potential deals?
Speaker Change: Yeah, so I would start maybe with most of the general answer, so you know, I think the biopharma industry can thrive by creating win-win partnerships, and it has done so for decades.
Speaker Change: So, we are part of this ecosystem and we will continue.
to think about
Speaker Change: where are the win-win opportunities? As we said clearly for our immunology pipeline, we don't believe.
Speaker Change: their partnering in this point will add any value or accelerate our program.
So, for those reasons...
Speaker Change: We are continuing to advance our immunology pipeline independently and we're building the team. Jared is building a great team of immunology development that I believe, you know, is and will be even more so best in class at doing what we're doing.
Speaker Change: So with regards to the oncology, but again, in immunology at some point that might happen right as we get closer to
Speaker Change: phase three registration, and if we're amazingly successful across the whole pipeline, it is possible, if not likely, that, you know, there could be some partnership for a program or another. For oncology, as we said clearly last year now, that we had decided to
Speaker Change: continue those programs through the end of phase one and then advance it beyond only in partnerships. And so, you know, in order for us to partner program it will have to be a win-win for both parties. The company that takes the program on and us and, you know, the criteria are simple. I don't know that I need to go through the details but obviously a company that is
Speaker Change: driven interest and has the capability to do justice to those programs.
Next question.
Speaker Change: Our next question will come from Jeet Mukherjee. Please unmute your audio and your video and ask your question.
Jeet Mukherjee: Great, thanks for taking the question. So, just given the novel nature of STAT6 as a target, you know, thoughts on its potential in the post-Dupixent setting, and if this is an area you plan to evaluate in a more fulsome manner, considering the Phase 1b will enroll some biologic experienced patients, as you just mentioned. Thanks.
Jeet Mukherjee: Yeah, I just want to clarify, so the biologically experienced would have to...
Jeet Mukherjee: would be enrolled only if they didn't fail for kind of lack of response, right? So, it might be that they discontinued for other reasons, vulnerability, or they just got tired of injecting themselves, for example, which we know happens. So, I would say, look, the potential for sub-60s...
Jeet Mukherjee: to be the Ph.D. drug and to be the first option for every patient.
Buh-bye!
Ph.D. in Inflammation, whether it's asthma, A.D.
Jeet Mukherjee: COPD or EOE, etc. So, yes, is there an opportunity for post-DUPI? Sure, but I don't think that's really the problem we're solving. I think the problem we're solving is getting these millions of patients that are not on DUPI, that either can't get it, can't get the green births, they don't like the needles.
to actually have an effective drug.
Jeet Mukherjee: And I'm sure we will recruit enough patients as we continue the development.
Jeet Mukherjee: to also look at what that will look like, but I would say, honestly, it's not really where I think this drug will be positioned for. That's not the problem we're trying to solve. The problem is patient access to an amazing drug that solves a lot of problems.
Speaker Change: Thank you. Our last question comes from Sudan Loganathan with Stevens. Please unmute your audio and ask your question.
Sudan Loganathan: Yes, thank you for taking the questions and being on video today. So mine is going to be just on the R&D and the spend. I'm just kind of curious on, you know, as you're ramping up 2025 in those two trials for 295 and 621, you know, how do you expect that to be the R&D expenses to be allocated between two programs? And then can we anticipate any expense profile changes as, you know, depending on?
Speaker Change: the progress of those two trials over the next one or two years.
Speaker Change: Thanks again. I thought I was going to escape talking on this call, but I guess not, or at least on the Q&A part. So just, you know, obviously we have $850 million. That runway takes us into the middle part of 2027. If you just do the math over that, you know, 10 quarters, obviously our cash burn will increase. I'd say that...
Speaker Change: some of the clinical trial activity really kicks into higher gear and then maybe rises at a slower rate into 2027. Hopefully that gives you a little perspective, but you know obviously the important point is that we are well capitalized to get us through many of these important readouts that we discussed on the call today.
Speaker Change: Maybe the only thing I'd add is you should expect the StatSix portion of it to be dramatically superior to the TIC-2 portion of expenses, especially as we continue in the next two to three years.
Good, thank you. Yeah, appreciate it.
Nello Mainolfi: There are no more questions at this time. I'd now like to turn the call over to Nello for closing remarks.
Nello Mainolfi: Well, great. I want to thank everybody for joining us today.
Nello Mainolfi: I also hope the new video format is appreciated. I assure you the background is real, it's not fake.
Nello Mainolfi: And, you know, we, as you all know, we're available for any follow-up. We'll be at the Cowen conference in Boston, finally a conference in Boston, next week, and happy to, again, take any questions offline. Thanks again, and see you again.