ACELYRIN - Q3 2024

Executive Summary

• Cash, cash equivalents and short-term marketable securities were $562.4M; management reiterated cash runway to at least mid-2027 and expects to initiate Phase 3 lonigutamab in TED in Q1 2025.
• Year-end cash guidance was updated to $435–$450M (from $420–$450M) following resolution of manufacturing commitments and receipt of a $35.7M credit voucher; restructuring charges in Q3 totaled $10.8M.
• Topline data from the Phase 2b/3 izokibep uveitis trial (96 patients) is expected in December 2024; management will decide on further development based on data and explore potential accelerated pathways given orphan dynamics.
• FDA EOP2 meeting for lonigutamab was positive, with alignment on Phase 3 design (size, endpoints, dosing approach); dosing to 52 weeks planned in both active and inactive TED populations, with MRI introduced to assess proptosis in Phase 2.
• Street consensus comparisons via S&P Global were unavailable for SLRN in Q3, so no formal beat/miss is presented (S&P Global estimates unavailable).

What Went Well and What Went Wrong

What Went Well

• “We are executing on our refocused pipeline strategy and are excited by the near-term catalysts… advance subcutaneous lonigutamab into Phase 3… next quarter” — CEO Mina Kim, highlighting EOP2 alignment and Phase 3 initiation timing.
• Lonigutamab dosing strategy refined with Cohort 4 at 70–100mg Q4W; MRI assessments added to strengthen proptosis measurement ahead of Phase 3; narrative emphasizes rapid efficacy with appropriate PK window.
• Manufacturing commitments for izokibep were favorably resolved: $42.9M payment paired with a $35.7M manufacturing credit voucher that can offset future lonigutamab supply costs; year-end cash guidance tightened higher.

What Went Wrong

• Company remains pre-revenue and recorded a Q3 net loss of $48.5M; restructuring charges of $10.8M impacted the quarter.
• Persistent investor focus on hearing safety versus Tepezza requires clear Phase 3 audiologic strategy; management deferred specifics to early-2025 investor event, potentially an overhang until detailed data are shared.
• An ATM facility was established to provide future capital flexibility, which can be perceived as a dilution overhang until program value is crystallized by uveitis topline and Phase 3 initiation.

Transcript

Operator (participant)

Good afternoon and welcome to the ACELYRIN, Inc. third quarter 2024 financial results and company update conference call. This conference call is being recorded today, November 13th, 2024. I would now like to turn the call over to Tyler Marciniak, Vice President of Investor Relations and Corporate Affairs. Tyler.

Tyler Marciniak (VP of Investor Relations and Corporate Affairs)

Thanks, Victor. Good afternoon, everyone, and thank you for joining us for ACELYRIN'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. 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 ability to commercialize our product candidates.

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 and which is also available on our website at ACELYRIN.com, along with today's press release, which identifies certain factors that could cause our actual results, performance, and events to differ materially. 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.

Mina Kim (CEO)

Thanks, Tyler, and thanks, everyone, for joining us today. The first nine months of 2024 were transformative for ACELYRIN, and we're pleased with the progress we've made refocusing our pipeline and corporate strategy. In August, we announced the strategic reprioritization of our pipeline to focus our efforts on developing our lead product candidate, lonigutamab, for which we are in late-stage development as a treatment for thyroid eye disease, or TED. Today, we will review our progress with lonigutamab, as well as our anticipated upcoming milestones for both that program and our ongoing phase II-B3 trial of izokibep in non-infectious, non-anterior uveitis. First, I'd like to review our progress on lonigutamab, our subcutaneously delivered humanized IgG1 monoclonal antibody targeting IGF-1R, which is the only approved mechanism of action for the treatment of TED.

TED 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 the eyelids. Double vision, or diplopia, can also occur, as well as the potential for compression of the optic nerve, which can lead to blindness. TED is a progressive, chronic inflammatory disease impacting more than 100,000 people in the U.S. alone. Earlier this year, we shared positive proof-of-concept data for a subcutaneously delivered lonigutamab 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. 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.

In selecting a dose, we're focused on maintaining a narrow therapeutic window that stays above a certain Cmin to drive efficacy of the kind that we have observed with lonigutamab, and which is in line with other anti-IGF-1R agents and minimizes Cmax in an effort to mitigate the safety liabilities, especially hearing-related events that are evident with these same agents. We've now completed cohorts two and three through 12 weeks of dosing and 12 weeks of follow-up. As a reminder, Cohort 2 included a loading dose of 50 mg, followed by 25 mg weekly, and Cohort 3 tested 50 mg monthly with no loading dose. We previously announced that we were adding a fourth dosing cohort to our phase II trial. That dosing cohort was expected to be 70 mg, either Q3W or Q4W. We started this cohort at 70 mg Q4W, but have now shifted to 100 mg Q4W.

We are using this cohort primarily to confirm PK we've used to model a loading dose. For example, cohort two used a loading dose, and that cohort demonstrated rapid achievement of steady-state Cmin, which we think could deliver faster patient benefit. Cohort 4 is also the first cohort where we are using MRI assessments to measure proptosis in addition to Hertel measurements. We think this early experience with MRI assessments will help ensure smooth execution in the phase III program. 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 III program design and timelines.

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 III program in the first quarter of 2025. The TED patient data presented so far for lonigutamab has been met with excitement from both the physician and patient communities, and during the third quarter, we're presented at multiple international medical congresses, including ASCRS, ESCRS, and AAO. 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, 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. We also recently completed a positive end-of-phase II meeting with the FDA. The goal of the meeting request was to achieve alignment on important elements of the phase III registrational program, including design, size, primary and secondary endpoints, and proposed phase III dose. We were pleased with the feedback received, too, and in alignment with our proposed differentiated approach to developing lonigutamab in TED. 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. We look forward to sharing further details at our upcoming investor event in early 2025.

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 lonigutamab into phase III clinical development. But before that milestone occurs, we also expect to announce top-line results for our phase II-B3 trial of izokibep in uveitis in December. As with our earlier decision to discontinue internal development of izokibep in HS and PSA, we will make a decision about the future development plans for uveitis after we see the data. The development path for uveitis as a standalone 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.

This materially changes the potential opportunity for uveitis, especially if our data demonstrate improved patient outcomes compared to the currently approved treatments. We look forward to providing the uveitis top-line data along with an update on the entire izokibep program in December. With that, I'll turn it over to Shep to walk you through the uveitis program in more detail.

Shephard Mpofu (Chief Medical Officer)

Thank you, Mina. Uveitis is a complex disease that is characterized by ocular inflammation. It is heterogeneous, and the pathophysiology varies greatly. Although the exact cause of uveitis remains multifactorial, aberrant immune insults can 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. Unfortunately, demographically, the most at-risk population in developing uveitis is the working-age group, with ages 20-50 years. 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. As noted above, there is a high unmet need in both the diagnosis and treatment of uveitis. In terms of treatments, patients really only have two approved options: corticosteroids and Adalimumab.

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. Adalimumab is the only approved biologic, and approximately half of patients fail treatment on Adalimumab and half lose efficacy due to antidrug antibodies. Thus, there is an unmet medical need for the treatment of uveitis. 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, secukinumab, a monoclonal antibody targeting 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 Adalimumab. However, when the trials were run using 300 mg of secukinumab delivered subcutaneously, the signal was lost.

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. Izokibep, 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. In preclinical study, we have shown izokibep to be significantly more potent than secukinumab, and they have also shown that izokibep can penetrate the blood-retinal barrier in a dose-dependent manner. Further, we have shown that due to its higher potency and smaller size, izokibep 160 mg delivered subcutaneously every week can deliver drug exposure similar to 10 mg per kg every other week of IV secukinumab. In May, we completed enrollment of our phase II-B3 trial in uveitis with 96 patients, randomized one-to-one, active treatment versus placebo.

The trial primary endpoint is designed to be similar to the adalimumab VISUAL I study, that is, time to treatment failure. In addition, as was done with VISUAL I, in our top-line results, the treatment failure rates will be read out at a landmark endpoint of 24 weeks. In VISUAL I, adalimumab demonstrated a 20% benefit over placebo at 24 weeks. As we look forward to our data readout, we will be looking for a clinical outcome that is superior to that of adalimumab. Should the upcoming phase II-B3 data be positive, our best guess is that one additional phase III trial of approximately 200-250 patients will be required for registration.

However, given the high unmet need and the FDA's acknowledgment of uveitis as an orphan disease with the associated potential for orphan drug-like pricing, we would certainly look to confer with the health authorities on any potential accelerated pathway to approval. 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 (CFO and Chief Business Officer)

Great. Thank you, Shep. Today, we reported our financial results for the quarter ended September 30, 2024. 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. Research and development expenses were $31.6 million for the quarter, as compared to $74.6 million for the same period in 2023. The decrease was primarily a result of reduced clinical development activity, as the phase III trials for izokibep in PSA and HS are substantially complete. For the third quarter, general and administrative expenses were $12.3 million compared to $19.9 million for the same period in 2023. The decreases were primarily a result of lower stock-based compensation expense.

As we recently reported in an amended Form 8-K filed on November 5th, we are very pleased to have fully resolved outstanding manufacturing commitments for izokibep that we identified last quarter as part of our restructuring. Our team was successful in transforming a significant contractual liability to a net expense of only $7.2 million. This net expense consists of a payment to the manufacturer of $42.9 million, together with an accompanying $35.7 million credit voucher. This credit voucher can be directly applied towards any future manufacturing services, including lonigutamab supply, where we are already actively working on the manufacturing front to advance this program into phase III development in Q1 2025. 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.

With this, we have incurred substantially all of our expenses associated with the restructuring announced in August of this year. In August, we guided to a 2024 year-end cash position of $420 million-$450 million. With the manufacturing commitments resolved, we are now updating year-end cash guidance to $435 million-$450 million. This year-end cash guidance includes the anticipated $31 million license option payment in Q4 to acquire all global rights to lonigutamab from our licensing partner. As we stated last quarter, our current cash position gives us operational runway to at least mid-2027. This runway projection includes the entire phase III development program for lonigutamab, including both development and manufacturing activities through to a potential BLA filing, but does not include any new investments in izokibep including uveitis.

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. 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. Our focus heading into 2025 will remain on disciplined capital allocation, efficiency, and high-quality execution. I will now turn the call back to Mina for closing remarks.

Mina Kim (CEO)

Thanks, Gil, and thanks, Shep. We're proud of the progress we're continuing to make with both lonigutamab in TED and izokibep in uveitis. And I want to thank our entire team for their continued hard work. 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. 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.

Operator (participant)

Thank you. And to ask a question, you will need to press star one one on your telephone and wait for a name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. One moment for our first question. Our first question will come from the line of Tyler Van Buren from TD Cowen. Your line is open.

Tyler Van Buren (Managing Director and Senior Equity Research Analyst)

Hey, guys. Good to see progress with the clinical programs and the decreased operating expenses and improved cost controls in particular. I have a couple for you on lonigutamab. 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 three cohorts, or did they see partial data from Cohort 4? I guess I'm trying to understand how you could propose a dose for phase III if they didn't see the Cohort 4 dose or four data. And the second question is just, is it fair to say that the pivotal TED will likely include a dose somewhere in the 70 mg-100 mg range being tested in Cohort 4?

Mina Kim (CEO)

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? What was part of that end of phase II meeting? And then the second was, what's the 70 mg and that 100 mg, the Cohort 4, right? What's kind of the purpose of that, or what role are they going to play, right, in the program? Is that fair?

Tyler Van Buren (Managing Director and Senior Equity Research Analyst)

Yep.

Mina Kim (CEO)

Okay. Yeah. So maybe on the end of phase II meeting, right? I mean, we had the pretty typical end of phase II meeting with the FDA where we showed them what we had, right? As you know, this is an open-label trial with data that's maturing over time. And what we've been testing really in those first three cohorts is doses from 25 mg-100 mg, right? And sorry, that includes Cohort 4 with that 100 mg and with regimens that are weekly to monthly, right, with data kind of maturing along the way. So that's a pretty narrow band, right, in which to do dose ranging. And we have a molecule that's very well-behaved, right, where the data, frankly, has been very consistent with our modeling. And so that is helpful, right, and is obviously a pretty important input here.

And so we've taken the totality of the data that we had, and we took that to the end of phase II meeting, and we aligned with them on sort of an approach to dosing and how we're thinking about it. And so the totality of that informed that decision. Like I just said in the script, the 70 mg and the 100 mg in the Cohort 4, we're really thinking about as a loading dose, 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 provide patient benefit faster? And so that's really how we're thinking about that Cohort 4 dose. And so it does have a fairly narrow role, right, as we think about dosing.

Tyler Van Buren (Managing Director and Senior Equity Research Analyst)

Thank you.

Operator (participant)

One moment for our next question. Our next question will come from the line of Akash Tewari from Jefferies. Your line is open.

Hey, this is Manoj in for Akash. Thanks for taking our question. Just one question. What do you see a confidence that efficacy in uveitis is Cmax-driven? If the molar exposure of 160 mg izokibep comes, let's say, slightly lower than secukinumab 10 mg per kilogram, 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 secukinumab 10 mg per kilogram, IV? Thanks.

Mina Kim (CEO)

Hey, thanks for the question. Hey, I just want to make sure we're hearing the question and answering the right question. I think you're curious about, I guess, the potency, sort of equivalency to secukinumab, and how do we think about the 160 mg relative to other programs? Okay. Yeah. And sort of what does that mean in terms of potential clinical benefit, right, that we could see in the uveitis program? Yeah? Okay. I'm actually going to ask Shep to take that one.

Shephard Mpofu (Chief Medical Officer)

Yeah. No, thanks for the question. So we have done a significant amount of work as we started the program on izokibep 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 to secukinumab. So 10 mg/kg IV every two weeks of secukinumab equates in all our modeling and some of our datasets across the autoimmune indications we've started to 160 mg subcu every week. In uveitis, we are very fortunate that we have done primate studies with the various exposures subcu that have enabled us to find the presence of izokibep within vitreous humor. So we know this is possible because it's 10 times smaller than secukinumab, so therefore, it's able to penetrate the blood-retinal barrier, so it gets into the eye.

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 dataset. We hope to see something much improved, mainly because of the notion that a big monoclonal antibody like secukinumab in uveitis 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.

Operator (participant)

Thank you. One moment for our next question. Our next question will come from the line of Yasmeen Rahimi from Piper Sandler. Your line is open.

Hey, team. This is Jung-gyu for Yas. Thanks for taking our questions. Given the base case for a phase III 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?

Gil Labrucherie (CFO and Chief Business Officer)

Yeah. Thanks for the question. This is Gil. I'll certainly take the first piece of that question. So as I mentioned in my prepared remarks, with our runway out to mid-2027, we haven't given any specific estimates around the uveitis study. We won't probably do so until we have data in hand if we decide to take that forward. But we do have significant flexibility within our runway to further develop uveitis 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.

Mina Kim (CEO)

Yeah. And maybe I'll take the timing one. I don't think we're ready to give any kind of specific guidance, right, around timelines. But obviously, it's a molecule in a program that we know really well. And I think, as Shep said, our base case, right, is that we're going to need another trial with 200, 250 patients, right, something like that. But we would certainly go and talk to the FDA about potential acceleration paths if the data warrant that. So 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. Yeah. Thank you so much.

Operator (participant)

Thank you. One moment for our next question. Our next question will come from the line of Derek Archila from Wells Fargo. Your line is open.

Adam Ahn (Analyst)

Great. Hey, team. This is Adam Ahn for Derek. Thanks for taking our questions this evening. Maybe just one on izokibep in 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.

Mina Kim (CEO)

Yeah. Hey, maybe I'll just start. 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. 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 clinical profile compared to adalimumab.

Gil Labrucherie (CFO and Chief Business Officer)

Yeah. And maybe just to add on the market front, this is a very significant population. And as Mina just said, there's really an unmet need. There's not much here right now. So when we think about izokibep within the orphan pricing framework, we see this as a market with significant potential to have patient benefit and associated economics with that benefit.

Adam Ahn (Analyst)

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

Mina Kim (CEO)

Yeah. And so we have not announced the pivotal dose, right? What we have said is that we have dosed in a range that's 25 mg-100 mg, right? And that 100 mg is new in that Cohort 4, and again, really to test a potential loading dose. And the regimens we've tested are weekly to monthly. So it will be in that kind of envelope, but we have not announced yet the pivotal dose. And we'll do that when we announce the data and provide details on the phase III program.

Adam Ahn (Analyst)

Got it. Thank you.

Mina Kim (CEO)

Thanks.

Operator (participant)

One moment for our next question. Our next question will come from the line of Emily Bodnar from H.C. Wainwright. Your line is open.

Emily Bodnar (VP of Equity Research)

Hi. Thanks for taking the question. I guess for lonigutamab, 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 timeframe? And then just to clarify, for the phase III in the first quarter, are you planning to initiate phase III studies for chronic and active TEDs? Thanks.

Mina Kim (CEO)

Yeah. And so maybe I'll start. So 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 testament, I think, to the dosing work that we've been doing in patients, right, to show that these anti-IGF-1R agents can be both effective but could potentially come with an improved safety profile at the same time. And so we do think that gives us the ability to look at dosing out to 52 weeks in both the active and inactive TED populations. And so that's how we're thinking about the phase III trial design. Like I said, I think we'll provide sort of a complete picture of what is that development program and timelines, right, in early 2025, right?

But those are sort of the parameters that we're using to think about the development program.

Shephard Mpofu (Chief Medical Officer)

Yeah. Maybe just to also add, in keeping with the real-world evidence on 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. And given the potential safety considerations in the exposures we are having in these patients, as Mina mentioned, ranges of 25 mg-100 mg, which we know are multiple-fold lower exposures than current therapies or including approved therapy, we believe the FDA saw a very good rationale to really address what is currently a dysregulated immune pathway in a chronic autoimmune disease 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.

Emily Bodnar (VP of Equity Research)

Okay. Thanks, and just on the active and TED phase III are both expected in the first quarter?

Mina Kim (CEO)

We haven't provided sort of that level of detail. Like we said, we're going to be testing in both populations, right? We'll provide details about the phase III program design in early 2025.

Emily Bodnar (VP of Equity Research)

Okay. Got it. Thank you.

Mina Kim (CEO)

Thanks.

Operator (participant)

One moment for our next question. Our next question will come from the line of Vikram Purohit from Morgan Stanley. Your line is open.

Vikram Purohit (Biotechnology Small and Midcap Research Analyst)

Great. Good afternoon. Thanks for taking our questions. So we have two. First, on lonigutamab, apologies if this was asked and we missed it. But for the next data cut and then the eventual pivotal data as well, what would you consider a clinically meaningful hearing impairment benefit versus TEPEZZA in terms of the number of events and their severity? And then secondly, on izokibep in 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.

Mina Kim (CEO)

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.

Gil Labrucherie (CFO and Chief Business Officer)

Yeah. Vikram, yeah. On the BD front, on the program for izokibep, we're going to have the data in hand on uveitis coming up here very shortly in December. I think at that time, we can provide a more fulsome update on the program. I would just remind you that in my runway guidance that we've talked about earlier, we have not included any assumptions around partnering or new investments in izokibep.

Shephard Mpofu (Chief Medical Officer)

Yeah. And on the hearing, I think Mina alluded to how we have been really calibrating a dose which also mitigates 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, be able to share with you how we are approaching hearing. As you might be aware, more and more, all phase III studies currently are assessing patients' audiogram at baseline to really quantify objectively whether patients are having sensorineural hearing impairment or just subjective changes that do not impact objective assessments. And therefore, we'll be able to share data with you how we are approaching this hearing and what we are expecting in different subpopulations.

Let's not forget that 40%-50% of patients 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.

Vikram Purohit (Biotechnology Small and Midcap Research Analyst)

That's helpful. Thank you.

Operator (participant)

Thank you. One moment for our next question. Our next question will come from the line of Samantha Semenkow from Citi. Your line is open.

Samantha Semenkow (VP and SMid Biotech Equity Research Analyst)

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 better than HUMIRA? And I have a follow-up, please.

Mina Kim (CEO)

Yeah. Yeah. Let me start. I think it is, right? I mean, obviously, look, data always tells a complicated story, and you look at the whole package. So 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 is this something that patients need? And so we will think about that. But like I said, I do think that Adalimumab is the bar, right? And so we would, I'd say, in general, look for a profile that is better.

Samantha Semenkow (VP and SMid Biotech Equity Research Analyst)

Got it. That's very helpful. And then just thinking about the study design, I believe you're allowing patients that are biologically experienced, meaning they've seen HUMIRA previously, into the study. I'm just trying to think about how that could impact the data and how that, because biologically experienced patients in a lot of other indications potentially do worse. And when you look at the VISUAL I study, obviously, those patients were biologically 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.

Mina Kim (CEO)

Yeah. For sure. So let me start, and then I'll turn it over to Shep. So you're correct, right? So the Adalimumab trial, 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 who are in our trial. And so let me start there. And then I can turn it over to Shep for any further comments.

Shephard Mpofu (Chief Medical Officer)

Yeah. No, it's an important question. And thank you for that. 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, an understanding of that subpopulation, how are we doing versus the naive patients. As you would expect in these trials 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 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 izokibep on patients that have failed adalimumab as well in the study. So more to come.

Operator (participant)

Thank you, and with no more questions, I'll turn it over to Tyler to conclude today's call.

Tyler Marciniak (VP of Investor Relations and Corporate Affairs)

Thank you, Victor. And thank you, everyone, for joining our call today. 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 Jefferies Conference in London, as well as sharing with you the phase II-B3 top-line results for izokibep in uveitis by the end of the year and hosting our lonigutamab investor event in early 2025. Thank you for your continued interest in ACELYRIN and with that, we will conclude today's call.