Q3 2024 Acelyrin Inc Earnings Call

November 13, 2024

Speaker Change: Shephard Labrucherie, Shephard Mpofu, Mina Kim Shephard Labrucherie, Shephard Mpofu, Mina Kim

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Good afternoon and welcome to the Accelerant, Inc. 3rd Quarter 2024 Financial Results and Company Update Conference Call. This conference call has been recorded today, November 13th, 2024. I would now like to turn the call over to Tyler Marciniak, Vice President of Investment Relations and Corporate Affairs. Tyler?

Tyler Marciniak: Thanks, Victor. Good afternoon, everyone, and thank you for joining us for Accelerin's third quarter 2024 conference call. With me today are Mina Kim, our Chief Executive Officer, Gil Labrucherie, our Chief Financial Officer and Chief Business Officer, and Shephard Mpofu, our Chief Medical Officer.

Tyler Marciniak: We issued a news release earlier detailing our third quarter financial results and important corporate updates. And before we begin today's call, I'd like to remind the audience that our remarks may contain forward-looking statements such as those related to the progress of our clinical trials, our future financial operating results and investments, and our future financial

and our ability to commercialize our product candidates.

Tyler Marciniak: We urge you to review the risk factors section of our Form 10-Q for the quarter ended September 30, 2024, which was filed today with the SEC.

Tyler Marciniak: along with today's press release, which identifies certain factors that could cause our actual results, performance, and events to differ materially.

Tyler Marciniak: Finally, our statements are based on information available to us today, November 13, 2024, and we undertake no obligation to update them as circumstances may change. I would like to now turn the call over to Mina. Thanks, Tyler, and thanks everyone for joining us today.

Mina Kim: The first nine months of 2024 were transformative for It's Sovereign, and we're pleased with the progress we've made refocusing our pipeline and corporate strategy.

Mina Kim: In August, we announced the strategic reprioritization of our pipeline to focus our efforts on developing our lead product candidate, monogutamab, for which we are in late-stage development as a treatment for thyroid eye disease, or TED.

Mina Kim: Today, we will review our progress with Onagutumab, as well as our anticipated upcoming milestones for both that program and our ongoing Phase 2b3 trial of izakibab in non-infectious, non-anterior uveitis.

Speaker Change: First, I'd like to review our progress on monogutamab, our subcutaneously-delivered, humanized IgG1 monoclonal antibody targeting IGF-1R, which is the only approved mechanism of action for the treatment of TAD.

Speaker Change: TADD is a vision-threatening autoimmune disease in which there is both inflammation as well as expansion of the tissues behind the eye, resulting in eye bulging known as proptosis and the subsequent inability to close eyelids.

Speaker Change: Double vision or diplopia can also occur, as well as the potential for compression of the optic nerve, which can lead to blindness. TET is a progressive chronic inflammatory disease impacting more than 100,000 people in the US alone.

Speaker Change: Earlier this year, we shared positive proof-of-concept data for a subcutaneously delivered lonigutimab in TED patients, a first for the anti-IGF-1R MOA, demonstrating rapid improvements in proptosis and clinical activity scores within three weeks after the first dose.

Speaker Change: Our Adaptive Phase II Dose Finding Trial now continues with multiple cohorts to establish both a minimum effective dose and optimal dose level and dose regimen for the Phase III Registrational Program.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: In selecting a dose, we're focused on maintaining a narrow therapeutic window that stays above a certain semen to drive efficacy of the kind that we have observed with Lonegutimat and which is in line with other anti-IGF-1R agents.

Speaker Change: and minimizes TMAX in an effort to mitigate the safety liabilities, especially hearing-related events that are evident with these same agents.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: We've now completed Cohorts 2 and 3 through 12 weeks of dosing and 12 weeks of follow-up.

Speaker Change: As a reminder, Cohort 2 included a loading dose of 50 mgs, followed by 25 mgs weekly, and Cohort 3 tested 50 mgs monthly with no loading dose.

Speaker Change: We previously announced that we were adding a fourth dosing cohort to our Phase 2 trial. That dosing cohort was expected to be 70 mgs either Q3W or Q4W.

Speaker Change: We started this cohort at 70 mg Q4W, but have now shifted to 100 mg Q4W.

Speaker Change: We are using this cohort primarily to confirm PK we've used to model loading dose. For example, Cohort 2 used a loading dose and that cohort demonstrated rapid achievement of steady-state semen, which we think could deliver faster patient benefits.

Speaker Change: Cohort 4 is also the first cohort where we are using MRI assessments to measure proptosis in addition to Hertzau measurements.

Speaker Change: We think this early experience with MRI assessments will help ensure smooth execution in the phase three program.

Speaker Change: We're continuing to enroll Cohort 4, and this cohort may not be fully enrolled at the time that we announce the full results from the first three cohorts, as well as detailed Phase 3 program design and timelines.

Speaker Change: Given this last cohort is really being used to confirm a loading dose, we have now largely completed our dosing exploration with the first three cohorts. And with FDA alignment on our dosing strategy, we're confident in our ability to start our phase three program in the first quarter of 2025.

Speaker Change: The TED patient data presented so far for LongitudeMap has been met with excitement from both the physician and patient communities, and during the third quarter were presented at multiple international medical congresses, including ASOPers, ESOPers, and AAL.

Speaker Change: We're encouraged by the response from the KOL and patient communities and believe this response demonstrates the need for even better treatment options for TED patients, which deliver the right risk-benefit profile.

Speaker Change: One that delivers the efficacy seen with IGF-1R agents, but also with a potentially improved safety profile. This response also gives us confidence in our ability to enroll the Phase III trials in a timely manner.

Speaker Change: We also recently completed a positive end-of-phase 2 meeting with the FDA.

Speaker Change: The goal of the meeting request was to achieve alignment on important elements of the Phase 3 Registrational Program including design, size, primary and secondary endpoints, and proposed Phase 3 dose.

Speaker Change: We were pleased with the feedback received, too, and in alignment with our proposed differentiated approach to developing Montegutu map in TED.

Speaker Change: We have also aligned with the agency on our approach to dosing patients beyond 24 weeks and out to 52 weeks in both active and inactive TED patients.

Speaker Change: We look forward to sharing further details at our upcoming Ambassador event in early 2025.

Shephard Labrucherie, Gilbert Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Finally, we recently established a Scientific and Patient Advisory Board that brings together world-class clinicians and patient advocates to provide important strategic input, clinical expertise, and patient perspectives as we prepare to advance Montegutumab into Phase III clinical development.

Speaker Change: But before that milestone occurs, we also expect to announce top-line results for our Phase 2b3 trial of Isaac HiBab in uveitis in December.

Speaker Change: As with our earlier decision to discontinue internal development of isokaibevin HS and PSA, we will make a decision about the future development plans for uveitis after we see the data.

Speaker Change: The development path for uveitis as a stand-alone indication, and not one tied to HS and PSA, presents a very different opportunity. Importantly, we are now thinking about uveitis as a potential orphan indication in a patient population with very high unmet need.

Speaker Change: This materially changes the potential opportunity for uveitis, especially if our data demonstrate improved patient outcomes compared to the currently approved treatments.

Speaker Change: We look forward to providing the UVI-DISC top-line data, along with an update on the entire ISOC-HIPAD program in December. And with that, I'll turn it over to Shep to walk you through the UVI-DISC program in more detail.

Shep: Thank you, Mina. UVI is a complex disease that is characterized by ocular inflammation. It is heterogeneous and the pathophysiology varies greatly.

Shep: Although the exact cause of uveitis remains multifactorial, aberrant immune insults can

Shep: cause ocular tissue damage and cytokine imbalances play a key role. So it is not surprising that there are significant challenges in diagnosis and management of this disease.

Shep: Unfortunately, demographically most at-risk population in developing UVITs is the working-age group with ages 20 to 50 years.

Shep: These patients are at risk of retinal detachments, cataracts, glaucoma, and macular edema. Loss of vision is a key concern and often leads to blindness in 5-20% of cases in developed countries.

Shep: As noted above, there is a high unmet need in both the diagnosis and treatment of uveitis.

Shep: In terms of treatments, patients really only have two approved options, corticosteroids and adenlymab.

Shep: The well-established first-line treatment for uveitis consists of corticosteroids, which cannot be maintained long-term as it is associated with systemic side effects.

Shep: Adenomab is the only approved biologic, and approximately half of patients fail treatment on adenomab and half lose efficacy due to anti-drug antibodies. Thus, there is an unmet medical need for the treatment of uveitis.

Shep: In thinking about future innovations for these patients, there is an interesting scientific rationale for the potential role of interleukin-17A inhibition as a treatment for uveitis.

in previous clinical trials.

Shep: Sekikinumab, a monoclonal antibody target in IL-17A demonstrated proof-of-concept response in uveitis with IV dosing of 10 mg per kg and 30 mg per kg, showing a response rate that was approximately 15% better than Adlimumab.

Shep: However, when the trials were run using 300mg of Seiki Kinmab delivered subcutaneously, the signal was lost.

Shep: It is hypothesized that reduced drug exposures, when moving from IV to subcutaneous, combined with the relatively large size of a monoclonal antibody, contributed to this loss of efficacy.

Shep: Isocubate, on the other hand, is a small protein therapeutic designed to inhibit interleukin-17A with high potency and small molecular size, approximately a tenth the size of a monoclonal antibody.

Shep: In pre-clinical study, we have shown isocupeb to be significantly more potent than cecukinumab, and have also shown that isocupeb can penetrate the blood-retinal barrier in a dose-dependent manner.

Shep: Further, we have shown that, due to its higher potency and smaller size, Isocubep 160 mg delivered subcutaneously every week can deliver drug exposure similar to 10 mg per kg every other week of IV-seq kinemab.

Shep: In May, we completed enrollment of our Phase 2b3 trial in uveitis with 96 patients, randomized one-to-one, active treatment versus placebo.

Shep: The trial primary endpoint is designed to be similar to the ADLIMUMA Visual 1 study. That is, time-to-treatment failure.

Shep: In addition, as was done with Visual One in our top-line results, the treatment failure rates will be read out at a landmark endpoint of 24 weeks. In Visual One, ADWMAP demonstrated a 20% benefit over placebo at 24 weeks.

Shep: As we look forward to our data readout, we will be looking for a clinical outcome that is superior to that of Adlimumab.

Shep: Should the upcoming Phase 2b3 data be positive, our base case is that one additional Phase 3 trial of approximately 200-250 patients will be required for registration.

Shep: However, given the high unmet need and the FTS acknowledgment of uveitis as an orphan disease with the associated potential for orphan drug like pricing

Shep: We would certainly look to confer with the health authorities on any potential accelerated pathway to approval.

Shep: I hope that overview of uveitis has been helpful and we look forward to sharing with you the top-line results from our trial this December. Now let me turn the call over to Gil for a review of our third quarter financial results.

Gil Labrucherie: Great, thank you Shep. Today we reported our financial results for the quarter ended September 30, 2024.

Gil Labrucherie: We remain in a very strong financial position and continue to execute on schedule with a pipeline prioritization plan we laid out in our August conference call. We ended the third quarter with $562.4 million in cash.

Gil Labrucherie: Research and development expenses were $31.6 million for the quarter, as compared to $74.6 million for the same period in 2023.

Gil Labrucherie: The decrease was primarily a result of reduced clinical development activity as the phase 3 trials for Azokibep in PSA and HS are substantially complete.

Gil Labrucherie: For the third quarter, general and administrative expenses were $12.3 million compared to $19.9 million for the same period in 2023.

Gil Labrucherie: The decreases were primarily a result of lower stock-based compensation expense.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Gil Labrucherie: As we recently reported in an amended Form 8K filed on November 5th, we are very pleased to have fully resolved outstanding manufacturing commitments for Isochibep that we identified last quarter as part of our restructuring.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Gil Labrucherie: Our team was successful in transforming a significant contractual liability to a net expense of only $7.2 million.

Gil Labrucherie: This net expense consists of a payment to the manufacturer of $42.9 million together with an accompanying $35.7 million credit voucher.

Gil Labrucherie: This credit voucher can be directly applied towards any future manufacturing services, including Wanagut and MAP Supply, where we are already actively working on the manufacturing front to advance this program into Phase 3 development in Q1 2025.

Gil Labrucherie: We expect to utilize this credit in 2025 and the first quarter of 2026 to directly offset what would otherwise have been cash outflows.

We are very pleased with this outcome.

Gil Labrucherie: And with this, we have incurred substantially all of our expenses associated with the restructuring announced in August of this year.

Gil Labrucherie: In August, we guided to a 2024 year-end cash position of $420 to $450 million.

Gil Labrucherie: With the manufacturing commitments resolved, we are now updating year-end cash guidance to $435 to $450 million.

Gil Labrucherie: This year-in-cash guidance includes the anticipated $31 million license option payment in Q4 to acquire all global rights to Lada Guttmach from our licensing partner.

Gil Labrucherie: As we stated last quarter, our current cash position gives us operational runway to at least mid-2027.

Gil Labrucherie: This runway projection includes the entire Phase 3 development program for Lanagut Mab, including both development and manufacturing activities through to a potential BLA filing.

Gil Labrucherie: but does not include any new investments in IsoKibep, including uveitis.

Gil Labrucherie: While we are not changing our cash runway guidance at this time, the $35.7 million manufacturing credit voucher gives us even more flexibility to engage in selective pipeline expansion in 2025, which could also include further development of uveitis pending our review of the upcoming data.

Gil Labrucherie: Our focus heading into 2025 will remain on disciplined capital allocation, efficiency, and high-quality execution.

Mina Kim: I will now turn the call back to Mina for closing remarks.

Mina Kim: Thanks Gil and thanks Shep. We're proud of the progress we're continuing to make with both Lana Gudumab and Ted and Isaac Kaibab and Uveitis and I want to thank our entire team for their hard work.

continued hard work.

Mina Kim: We have a number of important updates to share in just the next few months, and we continue to make disciplined and capital-conscious decisions, and to maintain a strong financial position from which to achieve our clinical and corporate goals for the remainder of this year and into 2027.

Mina Kim: We appreciate your continued support as we work to bring these potentially transformative new treatments to the patients who need them. And with that, we're ready to take questions.

Speaker Change: Thank you. And to ask a question, you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. One moment for our first question.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Our first question will come from the line of Tyler Van Buren from TD Callen. Your line is open.

Speaker Change: Hey guys, good to see progress of the clinical programs and the decreased operating expenses and improved cost controls in particular.

Speaker Change: I have a couple for you on Lonagutamab. So, can you help us better understand what data the FDA saw during the end-of-phase 2 meeting? Was it just data from the first phase?

Speaker Change: three cohorts or did they see partial data from cohort four? I guess I'm trying to understand how you could propose a dose for phase three if they didn't see the cohort four dose and or four data. And the second question is just

Speaker Change: Is it fair to say that the Pivotal Tetra will likely include a dose somewhere in the 70 to 100 mg range being tested in cohort 4?

Speaker Change: Yeah, so hey Tyler, thanks for the questions. Okay, so I want to just make sure I'm answering. I think you had two questions in there. One was what did we show the FDA? You know, what was part of that end of phase two meeting? And then the second was what's the 70 and that 100, the cohort four, right? What's the kind of the purpose of that or what role are they going to play right in the program?

Speaker Change: It's not fair? Okay. Yeah, so maybe on the end of phase 2 meeting, right, I mean we had the pretty typical end of phase 2 meeting with the FDA where we showed them what we had, right? As you know, this is an open label trial.

Speaker Change: with data that's maturing over time. And you know what we've been testing really in those first three cohorts is doses from 25 to 100 mg.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Right where the data frankly has been very consistent with our modeling and so that is helpful right and it's obviously a pretty important input here

Speaker Change: And so we've taken, you know, the totality of the data that we had, and we took that to the end of phase two meeting.

Speaker Change: and we aligned with them on sort of an approach to dosing and how we're thinking about it. And so, you know, so the totality of that informed that decision. Like I just said in the script, the 70 and the 100 in the cohort 4 we're really thinking about as a loading dose.

Speaker Change: Right. And again, that's just to, is there an opportunity for us to get to faster responses, right, to get to that narrow therapeutic window in a shorter period of time to try to prove, provide patient benefits faster?

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Thank you.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

One moment for our next question.

Speaker Change: Our next question comes from Akash Tiwari from Jefferies. Your line is open.

Hey, this is Manoj in for Agas.

Thanks for taking our questions, just one question.

Speaker Change: What gives you confidence that efficacy in UV-AIDS is C-Max driven? If the molar exposure of 160mg iso-T becomes, let's say, slightly lower than 60mg, 10mg, kg, let's say like 80-90%, will that be enough to bring a significant clinical benefit? And are you expecting to see a similar efficacy to 60mg, 10mg per kg IV? Thanks.

Shephard Labrucherie, Gilbert Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Hey, thanks for the question. Hey, I just want to make sure we're hearing the question.

Speaker Change: and answering the right question. I think you're you're curious about um I guess the potency sort of equivalency to Zecchia kinemap and how do we think about the 160 relative to other programs? Okay yeah and and sort of you know what does that mean in terms of potential clinical benefit right that we could see in the uveitis program?

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Okay, I'm actually going to ask Shep to take that one.

Shep: Yeah, no, thanks for the question. So, we have done a significant amount of work.

Speaker Change: as we started the program on Isocubat based on its potency. And if you look at some of our presentations for psoriatic arthritis and HS.

We derived a very clear understanding of the exposure.

that is commensurate equipotent.

Speaker Change: to Psyche KineMAP. So 10 mg per kg IV every two weeks of Psyche KineMAP equates in all our modeling and some of our data sets across the autoimmune indications we've studied to 160 mg sub-Q every week.

In UVI-T's

Speaker Change: We are very fortunate that we have done primate studies with the various exposure sub-Q.

that have enabled us to...

Speaker Change: find the presence of aizokibep within vitreous humor. So we know this is possible because it's ten times smaller than sechikinemab. So therefore it's able to penetrate the blood retinal barrier. So it gets into the eye.

Speaker Change: And in terms of potential outcomes, in terms of the therapeutic impact in uveitis, you asked a question whether we expect to see the same data set.

Speaker Change: We hope to see something much improved, mainly because of the notion that...

a big monoclonal antibody like cecukinamide and uveitis.

Speaker Change: abrogate inflammation peripherally, systemically, and we have the opportunity to do dual abrogation systemically and also locally, given that we permeate the eye and are present there. So we hope to see something better than what was demonstrated.

Yeah, that's really helpful. Thanks.

Thank you. One moment for our next question.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Our next question will come from Yasmeen Rahimi from Piper Sandler. Your line is open.

Speaker Change: Hey team, this is Jungu on for Yaz. Thanks for taking our questions.

Speaker Change: Given the base case for a phase 3 study in uveitis, what would the capital commitment look like? And secondly, how soon would you be able to kick off a pivotal study following top-line data in December?

Shephard Labrucherie, Gilbert Labrucherie, Shephard Mpofu, Mina Kim

Gil Labrucherie: Thanks for the question. This is Gil. I'll certainly take the first piece of that question. As I mentioned in my prepared remarks,

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Gil Labrucherie: with our runway out to mid-2027. We haven't given any specific estimates around the Uganda study. We won't probably do so until we have data in hand if we decide to take that forward. But we do have...

Gil Labrucherie: significant flexibility within our runway to to further develop Louviatus if that's the right decision for us. So we feel really good about where we are and the options that we have to take it forward with the existing resources on hand.

Speaker Change: Yeah, and maybe I'll take the timing one. I don't think we're ready to give any kind of guidance, specific guidance, right, around timelines, but obviously it's a molecule in a program that we know really well.

Speaker Change: So, you know, I think it makes sense for us to take a look at the data, right, figure out what we think is the right path forward, and then we'll update you guys on timing at the right time.

Got it. Thank you so much.

Thank you. One moment for our next question.

Speaker Change: Our next question will come from Derek Achilla from Wells Fargo. Your line is open.

Speaker Change: Great. Hey team, this is Adam on for Derek. Thanks for taking our questions this evening. Maybe just one on ischial buprenorphine and uveitis. Can you remind us what constitutes a clinical meaningful benefit in this patient population and how are you currently thinking about the market opportunity there given the entry of Humira biosimilars into the market?

Thank you.

Yeah, maybe, hey, maybe I'll just start.

Speaker Change: You know, we are thinking about, if you're thinking about clinical benefit, there is high unmet need, right, in uveitis. It's steroids, and then there's adalimumab, and we do think, as Shep noted, right, adalimumab is not a perfect answer. Many patients do fail, so there is room for improvement there. That said, we are certainly going to look at adalimumab as a primary reference point for us as we think about just the data, you know.

Speaker Change: is it differentiated? Is it going to offer patients increased benefit? And so that will be the bar, and as Shep said, we are going to look for a superior, you know, clinical profile compared to Adalimumab.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: And maybe just to add on the market front, you know, this is a very significant population and as Mina just

Speaker Change: said that there's really an unmet need. There's not much here right now, so when you when we think about isokibep within the orphan pricing framework, you know, we see this as, you know, a market with significant potential to have patient benefit and associated economics, you know, with that benefit.

Shephard Labrucherie, Gilbert Labrucherie, Shephard Mpofu, Mina Kim

Thank you for watching. Bye-bye.

Speaker Change: Got it. And then maybe just one on Montegutumab's proposed phase 3 dosage. I believe previously you disclosed that the go-forward dose for phase 3 was going to be 70 mg.

Speaker Change: Can you confirm that this remains to be the case, and any color on the dose regimen proposed?

where you are on that. Thank you.

Speaker Change: Yeah, and so we have not announced the pivotal dose, right? What we have said, you know, is that we have dosed in a range that's 25 to 100 mg, right? And that 100 mg is new in that cohort for, and again, really to test

Got it. Thank you.

Thanks.

One moment for our next question.

Speaker Change: Our next question comes from Emily Bodar from H.E. Wainwright. Your line is open.

Emily Bodar: Hi, thanks for taking the questions. I guess for Lonnie, you mentioned for the Phase 3, you're looking at 52 weeks instead of 24, so maybe can you just talk about how you're thinking about durability of response and what you'd kind of hope to see beyond that 24-week time frame, and then just to clarify, for the Phase 3 in the first quarter, are you planning to initiate Phase 3 studies for chronic and active TEDs?

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Shephard Labrucherie, Gilbert Labrucherie, Shephard Mpofu, Mina Kim

Emily Bodar: Yeah, and so maybe I'll start. So we are, we have alignment with the FDA on the ability to dose out to 52 weeks. And we do think that that's a real differentiator for us. Right? It's a test that I think.

to the dosing work that we've been doing in patients.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Emily Bodar: Right, but that those are sort of the parameters that we're using to think about the development program

Emily Bodar: thyroid eye disease. It's very clear that current therapies do not fully address the unmet need. There's a high rate of recurrence and relapse of disease.

Post Fixed Dose Treatment

Emily Bodar: and given the potential safety considerations in the exposures we are having in this patient, as Mina mentioned, ranges of 25 to 100 milligrams, which we know are multiple fold lower exposures than current therapies or including approved therapy.

Emily Bodar: We believe the FDA saw a very good rationale to really address what is currently a dysregulated immune pathway in a chronic autoimmune disease.

Emily Bodar: in a way where patients might have enough exposure with a safe dose and be able to arrive at disease resolution, if not modification, over time.

The End

Speaker Change: Okay, thanks. And just on the active end, TED Phase 3 are both expected in the first quarter.

Speaker Change: We haven't provided sort of that level of detail you know like we said we expect to we're going to be testing in both populations right and we'll provide details about the the phase 3 program design in the in early 25

Okay, got it. Thank you.

Thanks. One moment for our next question.

Speaker Change: Next question comes from Vikram Purohit from Morgan Stanley. Your line is open.

Speaker Change: Great, good afternoon. Thanks for taking our questions. So we have two.

Speaker Change: First, on Lonagutamab, apologies if this was asked and we missed it, but for the next data cut...

Speaker Change: and then the eventual pivotal data as well. What would you consider a clinically meaningful hearing impairment benefit versus TIPEZA in terms of the number of events and their severity?

Speaker Change: And then secondly, on Izakailipin, HS, and PSA, I know you previously mentioned that you would be open to finding a partner there, so I just wanted to see if there's been any interesting BD discussions, and if you feel like this is something that could be actioned in the near-to-midterm. Thanks.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Okay, hey, thanks for the question. Maybe let's start with the BD question and I'll turn it over to Gil and then we can hit hearing. Yeah, Vikram, yeah, on the BD front, on the program for Isochiba, we're gonna have the data in hand on uveitis.

Speaker Change: coming up here very shortly in December. I think at that time, you know, we can provide a more fulsome update on the program. I would just remind you that in my runway guidance that we talked about earlier, that we have not included any assumptions around partnering or new investments.

and Aizel Kaibab.

Speaker Change: Yeah, and on the hearing I think Mina alluded to how we have been really calibrating a dose which also mitigates

Speaker Change: You know, the overexposure that's associated with potential hearing impairment on this pathway. So as you asked the question around percentages of what we are expecting

We will at our research day in early 2025

Speaker Change: be able to share with you how we are approaching hearing, as you might be aware, more and more all phase 3 studies currently are assessing patients' audiogram at baseline to really quantify objectively whether patients are having

Speaker Change: Sensor Neural Hearing Impairment or just subjective changes that do not impact objective assessments.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: with thyroid eye disease also have issues pertaining to hearing impairment of various nature. So we will have to explore outcomes based on all those important considerations. So more to come in early 2025.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

That's helpful. Thank you.

Thank you. One moment for our next question.

Speaker Change: Our next question will come from the line of Samantha Semenkow from Citi. Your line is open.

Samantha Semenkow: Hi, good afternoon and thanks for taking the questions. I'm just following on a prior question. Is it the right way to think about it if the uveitis data comes sort of in line with Humira? Does that make it less interesting for you to take forward? Is the bar for success in your mind really, you know, better than Humira?

And I have a follow-up, please

Speaker Change: Yeah, let me let me start. I think it is, right? I mean, obviously, look, you know, data is always.

Speaker Change: tell the complicated story and you look at the whole package. So we'll, you know, when we have the data in the same way that we did with HS and PSA, we'll look at the totality of that data to really think about what is the potential clinical sort of benefit, right? And, you know, is this something that patients need?

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: got it that's very helpful and then just thinking about the study design I believe you're allowing patients that are biologic experience meaning you know they've seen Humira previously into the study

Speaker Change: I'm just trying to think about how that could impact the data and and how that

Speaker Change: you know, because biologically experienced patients and a lot of other indications that potentially do worse. And when you look at the visual one study, obviously those patients were biologic naive, I believe, given there were no other approved biologics at that time. So just trying to think through that dynamic and how that might impact your study results. Thanks very much.

Speaker Change: So let me start and then I'll turn it over to Shep. So you're correct, right? So the Adalimumab trials, that was not the case and we are different and it is a different patient population now, right? Because Adalimumab is now approved and so we do include some of those patients are in our trial.

Speaker Change: So let me start there and then I can turn it over to Shep for any further comments.

Speaker Change: Yeah, no, it's an important question and thank you for that.

Speaker Change: We have in our protocol made sure obviously at randomization we stratify for these patients so that we have equal numbers on drug and placebo to be able to ascertain to your point

Speaker Change: and understanding of that sub-population. How are we doing versus the naive patients? As you would expect in these trials.

Speaker Change: where you have patients previously failing a TNF blocker like we have seen in PSA or HS, usually this is a small fraction of the overall population. So for sure, we will take the data in consideration of...

Speaker Change: What would have been a naive population result and also a total population including those patients and be able to have an understanding of the impact of ISO on patients that have felt Adlimumab as well in the study. So, more to come.

Shephard Labrucherie, Gilbert Labrucherie, Shephard Mpofu, Mina Kim

Thank you.

Speaker Change: And with no more questions, I'll now turn it over to Tyler to conclude today's call.

Tyler Marciniak: Thank you, Victor, and thank you, everyone, for joining our call today.

Tyler Marciniak: As noted in our press release, we look forward to participating in one-on-one meetings with many of you and a fireside chat at the upcoming Jeffries Conference in London.

Tyler Marciniak: as well as sharing with you the Phase 2b3 top-line results for Isochiba and uveitis by the end of the year and hosting our Lana Gudumab Investor Event in early 2025.

Tyler Marciniak: Thank you for your continued interest in Acelerin, and with that, we will conclude today's call.

Speaker Change: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone have a great day.

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Shephard Labrucherie, Shephard Mpofu, Mina Kim

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Tyler Marciniak: We issued a news release earlier detailing our third quarter financial results and important corporate updates.

Tyler Marciniak: And before we begin today's call, I'd like to remind the audience that our remarks may contain forward-looking statements such as those related to the progress of our clinical trials, our future financial operating results and investments, and our ability to commercialize our product candidates.

Tyler Marciniak: We urge you to review the risk factors section of our Form 10-Q for the quarter ended September 30, 2024, which was filed today with the SEC.

along with today's press release.

Tyler Marciniak: which identify certain factors that could cause our actual results, performance, and events to differ materially.

Speaker Change: Finally, our statements are based on information available to us today, November 13, 2024, and we undertake no obligation to update them as circumstances may change. I would like to now turn the call over to Mina.

Thanks, Tyler, and thanks, everyone, for joining us today.

Mina Kim: The first nine months of 2024 were transformative for It's Sovereign, and we're pleased with the progress we've made refocusing our pipeline and corporate strategy.

Mina Kim: First, I'd like to review our progress on monogutamab, our subcutaneously-delivered, humanized IgG1 monoclonal antibody targeting IGF-1R, which is the only approved mechanism of action for the treatment of TAD.

Mina Kim: TADD is a vision-threatening autoimmune disease in which there is both inflammation as well as expansion of the tissues behind the eye, resulting in eye bulging known as proptosis and the subsequent inability to close eyelids.

Mina Kim: Double vision or diplopia can also occur, as well as the potential for compression of the optic nerve, which can lead to blindness.

Mina Kim: Ted is a progressive chronic inflammatory disease impacting more than 100,000 people in the U.S. alone.

Mina Kim: Earlier this year, we shared positive proof-of-concept data for a subcutaneously-delivered lonagutamab in TED patients, a first for the anti-IGF-1R MOA, demonstrating rapid improvements in proptosis and clinical activity scores within three weeks after the first dose.

Mina Kim: Our Adaptive Phase II Dose Finding Trial now continues with multiple cohorts to establish both a minimum effective dose and optimal dose level and dose regimen for the Phase III Registrational Program.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Mina Kim: In selecting a dose, we're focused on maintaining a narrow therapeutic window that stays above a certain semen to drive efficacy of the kind that we have observed with Lonegutamab and which is in line with other anti-IGF-1R agents.

Mina Kim: and minimizes CMAX in an effort to mitigate the safety liabilities, especially hearing-related events that are evident with these same agents.

Mina Kim: We've now completed cohorts two and three through 12 weeks of dosing and 12 weeks of follow-up

Mina Kim: As a reminder, Cohort 2 included a loading dose of 50 mgs, followed by 25 mgs weekly, and Cohort 3 tested 50 mgs monthly with no loading dose.

Mina Kim: We previously announced that we were adding a fourth dosing cohort to our Phase 2 trial. That dosing cohort was expected to be 70 MIGs, either Q3W or Q4W.

Mina Kim: We started this cohort at 70 mg Q4W, but have now shifted to 100 mg Q4W.

Mina Kim: We are using this cohort primarily to confirm PK we've used to model loading dose. For example, Cohort 2 used a loading dose, and that cohort demonstrated rapid achievement of steady-state semen, which we think could deliver faster patient benefit.

Mina Kim: Cohort 4 is also the first cohort where we are using MRI assessments to measure proptosis in addition to Hertzau measurements.

Mina Kim: We think this early experience with MRI assessments will help ensure smooth execution in the Phase III program.

Mina Kim: We're continuing to enroll Cohort 4, and this cohort may not be fully enrolled at the time that we announce the full results from the first three cohorts, as well as detailed Phase 3 program design and timelines.

Mina Kim: Given this last cohort is really being used to confirm a loading dose, we have now largely completed our dosing exploration with the first three cohorts. And with FDA alignment on our dosing strategy, we're confident in our ability to start our phase three program in the first quarter of 2025.

Mina Kim: The TED patient data presented so far for Longitude Map has been met with excitement from both the physician and patient communities, and during the third quarter were presented at multiple international medical congresses, including ASOPers, ESOPers, and AAL.

Mina Kim: We're encouraged by the response from the KOL and patient communities and believe this response demonstrates the need for even better treatment options for TED patients, which deliver the right risk-benefit profile.

Mina Kim: One that delivers the efficacy seen with IGF-1R agents, but also with a potentially improved safety profile.

Mina Kim: This response also gives us confidence in our ability to enroll the Phase III trials in a timely manner.

Mina Kim: We also recently completed a positive end-of-phase II meeting with the FDA.

Mina Kim: The goal of the meeting request was to achieve alignment on important elements of the Phase 3 Registrational Program including design, size, primary and secondary endpoints, and proposed Phase 3 dose.

Mina Kim: We were pleased with the feedback received, too, and in alignment with our proposed differentiated approach to developing Lonagutumab and TED.

Mina Kim: We have also aligned with the agency on our approach to dosing patients beyond 24 weeks and out to 52 weeks in both active and inactive TED patients.

Mina Kim: We look forward to sharing further details at our upcoming Ambassador event in early 2025.

Mina Kim: Finally, we recently established a Scientific and Patient Advisory Board that brings together world-class clinicians and patient advocates to provide important strategic input, clinical expertise, and patient perspectives as we prepare to advance Lonegut and Mab into Phase III clinical development.

Mina Kim: But before that milestone occurs, we also expect to announce top-line results for our Phase 2b3 trial of Isaac HiBab in uveitis in December.

Mina Kim: As with our earlier decision to discontinue internal development of isokaivebin HS and PSA, we will make a decision about the future development plans for uveitis after we see the data.

Mina Kim: The development path for uveitis as a stand-alone indication, and not one tied to HS and PSA, presents a very different opportunity. Importantly, we are now thinking about uveitis as a potential orphan indication in a patient population with very high unmet need.

Mina Kim: This materially changes the potential opportunity for uveitis, especially if our data demonstrate improved patient outcomes compared to the currently approved treatments.

Speaker Change: We look forward to providing the UV-ITIS top-line data, along with an update on the entire Isaac HyPADS program in December. And with that, I'll turn it over to Shep to walk you through the UV-ITIS program in more detail.

Shep: Thank you, Mina. UVI is a complex disease that is characterized by ocular inflammation. It is heterogeneous and the pathophysiology varies greatly.

Shep: Although the exact cause of uveitis remains multifactorial, aberrant immune insults can

Shep: cause ocular tissue damage and cytokine imbalances play a key role. So it is not surprising that there are significant challenges in diagnosis and management of this disease.

Shep: Unfortunately, demographically most at-risk population in developing UVITs is the working age group with ages 20 to 50 years.

Shep: These patients are at risk of retinal detachment, cataracts, glaucoma, and macular edema. Loss of vision is a key concern and often leads to blindness in 5-20% of cases in developed countries.

Shep: As noted above, there is a high unmet need in both the diagnosis and treatment of uveitis.

Shep: In terms of treatments, patients really only have two approved options, corticosteroids and adalimab.

Shep: The well-established first-line treatment for uveitis consists of corticosteroids, which cannot be maintained long-term as it is associated with systemic side effects.

Shep: Adlimumab is the only approved biologic and approximately half of patients fail treatment on Adlimumab and half lose efficacy due to anti-drug antibodies.

Shep: Thus, there is an unmet medical need for the treatment of uveitis.

Shep: In thinking about future innovations for these patients, there is an interesting scientific rationale for the potential role of interleukin-17A inhibition as a treatment for uveitis.

in previous clinical trials.

Shep: Seki Kinumab, a monoclonal antibody target in IL-17A demonstrated proof-of-concept response in uveitis, with IV dosing of 10 mg per kg and 30 mg per kg, showing a response rate that was approximately 15% better than Adlimumab.

Shep: However, when the trials were run using 300 milligrams of Sexy Kinmap delivered subcutaneously, the signal was lost.

Shep: It is hypothesized that reduced drug exposures, when moving from IV to subcutaneous, combined with the relatively large size of a monoclonal antibody, contributed to this loss of efficacy.

in preclinical study.

Shep: We have shown Isocubep to be significantly more potent than Sequicinimab and have also shown that Isocubep can penetrate the blood-retinal barrier in a dose-dependent manner.

Shep: In May, we completed enrollment of our Phase 2b3 trial in uveitis with 96 patients, randomized one-to-one, active treatment based on placebo.

Shep: The trial primary endpoint is designed to be similar to the ADLIMUMA Visual-1 study. That is, time-to-treatment failure.

Shep: In addition, as was done with Visual One in our top-line results, the treatment failure rates will be read out at a landmark endpoint of 24 weeks.

benefit over placebo in 24 weeks.

Shep: As we look forward to our data readout, we will be looking for a clinical outcome that is superior to that of Adlimumab.

Shep: Should the upcoming phase 2b3 data be positive, our base case is that one additional phase 3 trial of approximately 200-250 patients will be required for registration.

Shep: However, given the high unmet need and the FTS acknowledgment of uveitis as an orphan disease

with the associated potential for often drug-like pricing.

Speaker Change: I hope that overview of uveitis has been helpful and we look forward to sharing with you the top-line results from our trial this December. Now let me turn the call over to Gil for a review of our third quarter financial results.

Gil Labrucherie: We remain in a very strong financial position and continue to execute on schedule with a pipeline prioritization plan we laid out in our August conference call.

We ended the third quarter with $562.4 million in cash.

Gil Labrucherie: Research and development expenses were $31.6 million for the quarter, as compared to $74.6 million for the same period in 2023.

Gil Labrucherie: The decrease was primarily a result of reduced clinical development activity as the phase 3 trials for Ezokibep in PSA and HS are substantially complete.

Gil Labrucherie: The decreases were primarily a result of lower stock-based compensation expense.

Gil Labrucherie: Our team was successful in transforming a significant contractual liability to a net expense of only $7.2 million.

Gil Labrucherie: This net expense consists of a payment to the manufacturer of $42.9 million, together with an accompanying $35.7 million credit voucher.

Gil Labrucherie: This credit voucher can be directly applied towards any future manufacturing services, including Lanagut and MAP Supply, where we are already actively working on the manufacturing front to advance this program into Phase 3 development in Q1 2025.

Gil Labrucherie: We expect to utilize this credit in 2025 and the first quarter of 2026 to directly offset what would otherwise have been cash outflows.

We are very pleased with this outcome.

Gil Labrucherie: And with this, we have incurred substantially all of our expenses associated with the restructuring announced in August of this year.

Gil Labrucherie: In August, we guided to a 2024 year-end cash position of $420 to $450 million.

Gil Labrucherie: With the manufacturing commitments resolved, we are now updating year-end cash guidance to $435 to $450 million.

Gil Labrucherie: This year-in-cash guidance includes the anticipated $31 million licensed option payment in Q4 to acquire all global rights to Lada Guttmach from our licensing partner.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Gil Labrucherie: As we stated last quarter, our current cash position gives us operational runway to at least mid-2027.

Gil Labrucherie: This runway projection includes the entire Phase 3 development program for Lanagut Mab, including both development and manufacturing activities through to a potential BLA filing.

Gil Labrucherie: but does not include any new investments in Isokaibep, including uveitis.

Gil Labrucherie: which could also include further development of uveitis pending our review of the upcoming data.

Gil Labrucherie: I wanted to make one administrative note for the quarter. Like most biotechs who are eligible to do so, today we put in place an ATM facility as part of our corporate infrastructure to provide for future capital flexibility.

Gil Labrucherie: Our focus heading into 2025 will remain on disciplined capital allocation, efficiency, and high-quality execution.

Speaker Change: I will now turn the call back to Mina for closing remarks.

Mina Kim: Thanks Gil and thanks Shep. We're proud of the progress we're continuing to make with both Lana Gudumab and Ted and Isaac Haibab in uveitis and I want to thank our entire team for their hard work.

continued hard work.

Mina Kim: We appreciate your continued support as we work to bring these potentially transformative new treatments to the patients who need them. And with that, we're ready to take questions.

Speaker Change: Thank you. And to ask a question you will need to press star 101 on your telephone and wait for your name to be announced. To withdraw your question please press star 101 again. Please stand by while we compile the Q&A roster. One moment for our first question.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Our first question will come from the line of Tyler Van Buren from TD Callen. Your line is open.

Speaker Change: Hey guys, good to see progress of the clinical programs and the decreased operating expenses and improved cost controls in particular.

Speaker Change: I have a couple for you on Lonagutamab, so can you help us better understand what data the FDA saw during the End of Phase II meeting? Was it just data from the first...

Speaker Change: Is it fair to say that the Pivotal Tetra will likely include a dose somewhere in the 70 to 100 mg range being tested in cohort 4?

Speaker Change: Yeah, so hey Tyler, thanks for the questions. Hey, so I want to just make sure I'm answering. I think you had two questions in there. One was what did we show the FDA, you know, what was part of that end of phase two meeting? And then the second was what's the 70 and that 100, the cohort four, right? What's the kind of the purpose of that or what role are they going to play, right, in the program?

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: And so we've taken, you know, the totality of the data that we had, and we took that to the end of phase two meeting.

Speaker Change: We aligned with them on sort of an approach to dosing and how we're thinking about it. And so, you know, so the totality of that informed that decision. Like I just said in the script, the 70 and the 100 in the cohort 4 we're really thinking about as a loading dose.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Thank you.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

One moment for next question

Speaker Change: Our next question will come from the line of Akash Tiwari from Jeffries. Your line is open.

Speaker Change: Hey, this is Manoj for Agus. Thanks for taking our question. Just one question.

Speaker Change: What is your confidence that efficacy in UVA-ATC C-Max driven, if the molar exposure of 160 mg isoKB comes, let's say, slightly lower than 60 mg, 10 mg, kg, let's say like 80-90 percentage, will that be enough to bring a significant clinical benefit? And are you expecting to see a similar efficacy to 60 mg, 10 mg per kg IV? Thanks.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Hey, thanks for the question. Hey, I just want to make sure we're hearing the question.

Speaker Change: and answering the right question. I think you're curious about, I guess, the potency, sort of equivalency to Zecchia kinemap, and how do we think about the 160 relative to other programs? Okay, yeah, and sort of, you know, what does that mean in terms of potential clinical benefit, right, that we could see in the uveitis program?

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Yeah, okay. I'm actually going to ask Shep to take that one.

Shep: Yeah, no, thanks for the question. So, we have done a significant amount of work.

Speaker Change: as we started the program on Isocubat based on its potency. And if you look at some of our presentations for psoriatic arthritis and H.S.

Speaker Change: We derived a very clear understanding of the exposure that is commensurate, equipotent, to psychokinemab. So 10 mg per kg IV every two weeks.

Speaker Change: of SecChinMap equates in all our modeling and some of our datasets across the autoimmune indications we've studied to 160 mg sub-Q every week.

In uveitis,

Speaker Change: We are very fortunate that we have done primate studies with the various exposures sub-Q.

that have enabled us to...

find the presence of aizokibep within vitreous humor.

Speaker Change: So, we know this is possible because it's 10 times smaller than psachichinema. So, therefore, it's able to penetrate the blood retinal barrier. So, it gets into the eye.

Speaker Change: and in terms of potential outcomes in terms of the therapeutic...

Speaker Change: impact in uveitis? You asked a question whether we expect to see the same data set.

Speaker Change: We hope to see something much improved, mainly because of the notion that

A big monoclonal antibody like Seki-Kini might be Neuviitis.

Speaker Change: abrogates inflammation peripherally, systemically, and we have the opportunity to do dual abrogation systemically and also locally, given that we permeate the eye and are present there. So we hope to see something better than what was demonstrated.

Yeah, that's really helpful. Thanks.

Thank you. One moment for our next question.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Our next question will come from Yasmeen Rahimi from Piper Sandler. Your line is open.

Speaker Change: Hey team, this is Jungu Amfaryaz. Thanks for taking our questions. Given the base case for our phase 3 study in uveitis, what would the capital commitment look like? And secondly, how soon would you be able to kick off a pivotal study following top-line data in December?

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Gil Labrucherie: Thanks for the question. This is Gil. I'll certainly take the first piece of that question. As I mentioned in my prepared remarks,

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Gil Labrucherie: significant flexibility within our runway to to further develop lubeitis if that's the right decision for us. So we feel really good about where we are and the options that we have to take it forward with the existing resources on hand.

Speaker Change: I think it makes sense for us to take a look at the data, figure out what we think is the right path forward, and then we'll update you guys on timing at the right time.

Got it. Thank you so much.

The End

Thank you. One moment for our next question.

Speaker Change: Our next question will come from Derek Achilla from Wells Fargo. Your line is open.

Speaker Change: Great. Hey team, this is Adam on for Derek. Thanks for taking our questions this evening. Maybe just one on Isocopepin uveitis. Can you remind us what constitutes a clinical meaningful benefit in this patient population and how are you currently thinking about the market opportunity there given the entry of Humira biosimilars into the market? Thank you.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Yeah, maybe, hey, maybe I'll just start.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: and maybe just add on the market front you know this is a very significant population and as Mina just

Speaker Change: said that there's really an unmet need. There's not much here right now. So when you when we think about isokibep within the orphan pricing framework, we know we see this as you know a market with significant potential to have patient benefit and associated economics you know with that benefit.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Got it. And then maybe just one on Montegutumab's proposed phase 3 dosage. I believe previously you've disclosed that the go-forward dose for phase 3 was going to be 70 milligrams. Can you confirm that this remains to be the case? And any color on the dose regimen proposed?

where you are on that, thank you.

Speaker Change: Yeah, and so we have not announced the pivotal dose, right? What we have said, you know, is that we have dose in a range that's 25 to 100 mg, right? And that 100 mg is new in that cohort for, and again, really to test

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Got it. Thank you.

Thanks.

One moment for our next question.

Speaker Change: Our next question comes from Emily Bodar from H.E. Wainwright. Your line is open.

Emily Bodar: Hi, thanks for taking the questions. I guess for Lonnie, you mentioned for the Phase III, you're looking at 52 weeks instead of 24, so maybe can you just talk about how you're thinking about durability of response and what you'd kind of hope to see beyond that 24-week time frame? And then just to clarify, for the Phase III,

Emily Bodar: In the first quarter, are you planning to initiate Phase III studies for chronic and active TUDs? Thanks.

Speaker Change: Yeah, and so maybe I'll start. So we are, we have alignment with the FDA on the ability to dose out to 52 weeks. And we do think that that's a real differentiator for us, right? It's a test that I think

to the dosing work that we've been doing inpatient.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: And so we do think that gives us the ability to look at dosing out to 52 weeks in both the active and inactive.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Right, but that those are sort of the parameters that we're using to think about the development program

Speaker Change: thyroid eye disease. It's very clear that current therapies do not fully address the unmet need. There's a high rate of recurrence and relapse of disease.

post fixed dose treatment

Speaker Change: and given the potential safety considerations in the exposures we are having in this patient, as Mina mentioned, ranges of 25 to 100 milligrams, which we know are multiple fold lower exposures than current therapies or including approved therapy.

We believe the FDA saw a very good rationale

Speaker Change: to really address what is currently a dysregulated immune pathway in a chronic autoimmune disease.

Speaker Change: in a way where patients might have enough exposure with a safe dose and be able to arrive at disease resolution, if not modification, over time.

Speaker Change: Okay, thanks. And just on the active end, TED Phase 3 are both expected in the first quarter.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: We haven't provided sort of that level of detail, you know, like we said, we expect to, we're going to be testing in both populations, right? And we'll provide details about the, the phase three program design in the, in early twenty five.

Okay, thank you.

Thanks. One moment for our next question.

Speaker Change: Next question comes from Vikram Purohit from Morgan Stanley. Your line is open.

Vikram Purohit: Great, good afternoon. Thanks for taking our questions. So we have two.

Vikram Purohit: First, on Lonegutamap, apologies if this was asked and we missed it, but for the next data cut...

Vikram Purohit: and then the eventual pivotal data as well. What would you consider a clinically meaningful hearing impairment benefit versus TAPEZA in terms of the number of events and their severity?

Vikram Purohit: And then secondly, on azathiopin, HS, and PSA, I know you previously mentioned that you would be open to finding a partner there, so I just wanted to see if there's been any interesting BD discussions, and if you feel like this is something that could be actioned in the near-to-midterm. Thanks.

Vikram Purohit: Okay, hey, thanks for the question. Maybe let's start with the BD question, and I'll turn it over to Gil, and then we can hit hearing. Yeah, Vikram, yeah, on the BD front, on the program for Isochiba, we're going to have the data in hand on uveitis.

Gil Labrucherie: coming up here very shortly in December. I think at that time, you know, we can provide a more fulsome update on the program. I would just remind you that in my runway guidance that we talked about earlier, we have not included any assumptions around partnering or new investments.

and Aizel Kaibab.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: Yeah, and on the hearing I think Mina alluded to how we have been really calibrating a dose which also mitigates

Speaker Change: you know, the overexposure that's associated with potential hearing impairment on this pathway.

Speaker Change: So, as you asked the question around percentages of what we are expecting,

We will at our research day in early 2025

be able to share with you how we are approaching

Speaker Change: hearing. As you might be aware, more and more, all phase 3 studies currently are assessing patients' audiogram at baseline to really quantify objectively whether patients are having

Speaker Change: Sensor Neural Hearing Impairment or just subjective changes that do not impact objective assessments.

Speaker Change: and therefore we'll be able to share case with you how we are approaching

Shephard Labrucherie, Shephard Mpofu, Mina Kim

That's helpful, thank you.

Thank you. One moment for our next question.

Speaker Change: The next question will come from the line of Samantha Semenkow from Citi. Your line is open.

Samantha Semenkow: Hi, good afternoon and thanks for taking the questions. I'm just following on a prior question. Is this the right way to think about it?

Samantha Semenkow: If the uveitis data comes sort of in line with Humira, does that make it less interesting for you to take forward? Is the bar for success in your mind really, you know, better than Humira? And I have a follow-up, please.

Speaker Change: Yeah, yeah, let me let me start. I think it is right. I mean, obviously, look, you know, data is always.

Speaker Change: tells a complicated story, and you look at the whole package. So we'll, you know, when we have the data in the same way that we did with HS and PSA, we'll look at the totality of that data to really think about what is the potential clinical sort of benefit, right, and, you know, is this something that patients need?

Speaker Change: Shephard Labrucherie, Shephard Mpofu, Mina Kim Shephard Labrucherie, Shephard Mpofu, Mina Kim

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Speaker Change: For sure. So let me start and then I'll turn it over to Shep. So you're correct, right? So the Adalimumab trials, that was not the case and we are different and it is a different patient population now, right? Because Adalimumab is now approved.

Speaker Change: and so we do include some of those patients are in our trial.

Speaker Change: So let me start there and then I can turn it over to Shephard.

Any further comments?

Speaker Change: I know it's an important question and thank you for that.

Speaker Change: and we have in our protocol made sure obviously at randomization we stratify for these patients so that we have equal numbers on drug and placebo.

to be able to ascertain to your point.

Speaker Change: and understanding of that sub-population, how are we doing versus the naive patients, as you would expect in these trials.

Speaker Change: What would have been a naive population result and also a total population, including those patients and be able to have an understanding of the impact of ISO on patients that have felt Adlymumab as well in the study. So, more to come.

Shephard Labrucherie, Shephard Mpofu, Mina Kim

Thank you.

Speaker Change: And with no more questions, I'll now turn it over to Tyler to conclude today's call.

Tyler Marciniak: Thank you, Victor, and thank you, everyone, for joining our call today.

Tyler Marciniak: As noted in our press release, we look forward to participating in one-on-one meetings with many of you and a fireside chat at the upcoming Jeffries Conference in London, as well as sharing with you the Phase 2b3 top-line results for Isocaibep and uveitis by the end of the year and hosting our Lana Gudumab Investor Event in early 2025.

Tyler Marciniak: Thank you for your continued interest in Acelerin, and with that, we will conclude today's call.

Speaker Change: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone have a great day.

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