Acelyrin Inc. has reported a strategic refocusing and positive clinical trial results in its latest earnings call held on August 13, 2024. The biopharmaceutical company announced successful Phase 3 results for its drug izokibep in the treatment of hidradenitis suppurativa (HS) and is planning to extend its cash runway to mid-2027. Acelyrin is shifting its focus to the development of lonigutamab for thyroid eye disease (TED), with a Phase 3 trial expected to commence in the first quarter of 2025. In a bid to streamline operations, the company has also reduced its workforce by 33% and halted the development of SLRN-517, an anti-c-KIT program.
Key Takeaways
- Acelyrin's Phase 3 trial for izokibep in HS met its primary endpoint, showing compelling response rates.
- The company will not initiate new trials for izokibep but will complete ongoing studies in HS and psoriatic arthritis (PsA).
- Acelyrin is continuing the Phase 2b/3 trial of izokibep in uveitis and is confident in patient enrollment despite competition.
- The company has stopped development of SLRN-517 and reduced its workforce by 33% as part of restructuring.
- Future capital investment will be focused on lonigutamab for TED, with a Phase 3 trial starting in Q1 2025.
- Acelyrin reported a cash position of $635 million as of June 30, 2024, and is open to partnering options for izokibep.
- The company is evaluating lonigutamab's development program to potentially accelerate the Phase 3 trial.
Company Outlook
- Acelyrin plans to use its capital to focus on the development of lonigutamab for TED.
- The company projects a cash runway until mid-2027, which includes completing ongoing studies and development programs.
Bearish Highlights
- Acelyrin has ceased the internal development of its anti-c-KIT program, SLRN-517.
- A 33% reduction in workforce has been implemented as part of an organizational restructuring.
Bullish Highlights
- Positive Phase 3 trial results for izokibep in HS could indicate a strong potential for the drug in the market.
- The development of lonigutamab is proceeding, with promising early trial results and a Phase 3 trial on the horizon.
Misses
- There are no specific mentions of misses in the provided context.
Q&A Highlights
- Acelyrin is open to partnering with larger organizations to advance the izokibep program for HS and PsA.
- The company has not factored any potential financing or partnership proceeds into their cash runway guidance.
- Lonigutamab's Phase 2 program data will be reviewed after an FDA meeting later in the year, with the potential to adjust the dose and regimen.
- No notable hearing impairment or sensorineural hearing loss was observed in the lonigutamab trials.
- It is too early to speculate on the pricing for uveitis treatment with the new drug, despite the presence of cheaper alternatives like HUMIRA.
Acelyrin Inc. (Ticker: ACEY) has made significant advances in its drug development programs, as discussed in their recent earnings call. With a clear strategy to focus on promising treatments and extend their financial resources, the company is positioning itself to meet unmet medical needs while navigating the challenges of the biopharmaceutical landscape. Investors and patients alike will be watching closely as Acelyrin moves towards pivotal trials and seeks to bring new therapies to market.
InvestingPro Insights
Acelyrin Inc. has been navigating a challenging period, as reflected in the recent strategic refocusing and workforce reduction. Despite these efforts, the company's financial health and stock performance provide additional context for investors considering Acelyrin's future prospects.
InvestingPro Data highlights a market capitalization of $471.37 million, indicating the size and scale of Acelyrin within the biopharmaceutical industry. The company's Price to Book ratio, as of the last twelve months leading up to Q1 2024, stands at 0.73, suggesting that the stock may be undervalued compared to the company's book value. Additionally, the one-year Price Total Return as of the same period shows a significant decline of -81.0%, reflecting the market's reaction to the company's performance and outlook.
InvestingPro Tips for Acelyrin reveal that the company holds more cash than debt on its balance sheet, which is a positive sign for financial stability and could support the company's operations and drug development programs. However, it is also noted that Acelyrin is quickly burning through cash and has not been profitable over the last twelve months. This could raise concerns about the company's ability to sustain its operations without additional financing or partnerships.
As part of the InvestingPro service, there are additional tips available for investors seeking deeper insights into Acelyrin's financial health and stock performance. For instance, there are currently six more InvestingPro Tips available that could provide further guidance to investors evaluating Acelyrin's potential.
Investors interested in Acelyrin Inc. can find a comprehensive analysis and additional InvestingPro Tips at https://www.investing.com/pro/ACEY, which could prove invaluable in making informed decisions about the company's stock.
Full transcript - ACELYRIN Inc (SLRN) Q2 2024:
Operator: Good afternoon, and welcome to the ACELYRIN INC. Conference Call to discuss the company's second quarter 2024 financial results and other corporate updates. This conference call is being recorded today, August 13, 2024. I would now like to turn the conference call over to Tyler Marciniak, Vice President of Investor Relations and Corporate Affairs. Tyler?
Tyler Marciniak: Thank you, Carmen. Good afternoon, everyone, and thank you for joining us. Before we begin, I'd like to remind you that this conference call may contain forward-looking statements such as those related to progress of our clinical trials and anticipated data readouts, our future financial and operating results and projected cash runway, and our ability to commercialize our product candidates. These forward-looking statements involve risks and uncertainties that could cause our actual results and events to differ materially. We would urge you to review the Risk Factors section of our Form 10-Q for the quarter ended June 30, 2024, and additional Form 8-K that we filed with the SEC, both of which are also available on our website at acelyrin.com along with today's press release and our slide presentation. Additionally, these statements are based on information available to us today, August 13, 2024, and we undertake no obligation to update them as circumstances may change. The agenda for today's call is on the screen. We will review the corporate strategy updates announced in our press release, as well as positive top-line data from the Phase 3 trial of izokibep in hidradenitis suppurativa. We will also provide an update on the lonigutamab program in TED and close with a financial update highlighting our projected three-year cash runway covering multiple anticipated milestones. Joining us on today's call are Mina Kim, our Chief Executive Officer; Dr. Shep Mpofu, our Chief Medical Officer; and Gil Labrucherie, our Chief Financial Officer and Chief Business Officer. I will now turn the call over to Mina.
Mina Kim: Thanks, Tyler, and thanks everyone for joining us today. Earlier today, we announced positive Phase 3 results for izokibep in hidradenitis suppurativa, as well as details of a refocused pipeline strategy and plan designed to extend our cash runway to mid-2027. We'd like to provide more details on this call. First, we're very pleased to have achieved a positive Phase 3 readout for izokibep in HS. We met the primary endpoint of HiSCR75 and are especially pleased with the compelling response rates in HiSCR90 and HiSCR100 within 12 weeks of treatment, an effect we believe has not been previously observed by other agents. While the primary endpoint was measured at 12 weeks, we continued dosing patients in a placebo-controlled manner through week 16. We have data from two-thirds of the trial participants who completed week 16 and these preliminary data further demonstrate deepening of responses over time. These data follow the positive PsA Phase 2b/3 readout we announced earlier this year and which were presented in the late-breaking session at EULAR in June. Collectively, the data in HS and PsA further validate our longstanding view that izokibep has the potential to be an effective therapy that is approvable in multiple indications. As we have previously stated, we will make disciplined and capital-conscious decisions. We've determined that a program of this breadth and size is best brought to market by a larger organization with more resources and an existing footprint in the therapeutic areas of interest. Over the past several months, we've been evaluating where to prioritize investments to maximize the success of our pipeline, including lonigutamab, which we believe has the potential to improve on clinical response and convenience versus the standard of care in thyroid eye disease. We plan to complete the ongoing trials of izokibep in HS and PsA, but we will not start new trials in these indications. We do plan to continue the ongoing Phase 2b/3 trial in uveitis through to its primary endpoint with top-line data expected in the fourth quarter of 2024. There's high unmet need in uveitis and a compelling scientific rationale for the IL-17 axis. Should the upcoming Phase 2b/3 data be positive, we anticipate one additional Phase 3 trial of roughly 200 patients to 250 patients would be required for registration. The ongoing trial is fully enrolled with approximately 100 patients. In addition to these izokibep updates, we've decided to stop internal development of SLRN-517, our early anti-c-KIT program. Data from healthy volunteers demonstrated molecular activity, but we have made the decision to deprioritize this program. Finally, this refocused pipeline also requires a different organizational structure and we are executing an approximately 33% reduction in force. I want to take a moment to pause and thank our colleagues who were impacted by this restructuring. They played an important role in our growth and I wish them the very best in the future. While these decisions are difficult, we're confident that they are the right ones to enable ACELYRIN's long-term success. We remain committed to high-quality execution that's disciplined and capital-conscious. These program decisions as well as the organizational restructuring enable us to move forward aggressively to develop lonigutamab and extend our cash runway to mid-2027. By focusing future capital investment on lonigutamab, we will be well-positioned to fund our ongoing and planned TED trials through BLA submission. Shep will review our overall strategy and ongoing activity for lonigutamab in a moment, but I did want to make a few comments on the program. In terms of development strategy, the original plan had included a Phase 2b/3, but with the additional dose-ranging that we are completing in patients in the ongoing Phase 2 trial, we will be able to go directly into Phase 3 program, potentially with concurrent trials. We're currently planning to start the Phase 3 program in the first quarter of 2025. Additionally, we plan to meet with the FDA later this year and then host an investor presentation to provide additional Phase 2 data and details for the planned Phase 3 program. With that, I'd like to turn the call over to Shep.
Shep Mpofu: Thank you, Mina and hello, everyone. I'm very pleased to share with you today positive Phase 3 data of izokibep in hidradenitis suppurativa or HS and provide a program update on lonigutamab in thyroid eye disease. Let me start with HS. Dysregulated interleukin-17a activity plays a pivotal role in hidradenitis suppurativa pathogenesis. Multidomain disease resolution is underachieved with available current therapies. An unmet need exists for therapies demonstrating efficacy across multiple disease manifestations, including abscesses, inflammatory nodules, and draining tunnels. Izokibep is a small protein therapeutic designed to selectively inhibit interleukin 17a with high potency through tight binding affinity. The small molecular size of izokibep attains the size of a monoclonal antibody may enable tissue penetration, and its albumin-binding domain prolongs its half-life and may enhance targeting to sites of inflammation in HS. Here you see the design of our global Phase 3 trial of izokibep in HS, which we expect will be the first of the two pivotal trials needed for registration in this indication. 258 patients were randomized one-to-one to receive either izokibep 160 milligrams weekly or placebo. The inclusion criteria and design is similar to other Phase 3 studies with a primary endpoint here for the first time in a Phase 3 of HiSCR75 at week 12. At week 16, placebo patients were switched to receive izokibep 160 mg weekly in the active treatment blinded period. As Mina mentioned, two-thirds of trial participants have available week 16 data and will present those preliminary data today as well. Here, we see patient demographics and baseline characteristics which were well balanced between izokibep treatment group and placebo typical of a patient population with moderate-to-severe HS and comparable to other global Phase 3 pivotal trials. 103 patients on the izokibep arm and 112 patients in the placebo arm completed the study through week 12, thus having approximately 20% on izokibep arm and approximately 13% on placebo arm discontinuing treatment with a delta of around 7% between the two groups. Please note, the most common reasons leading to discontinuation on izokibep were mild AE and there were no notable differences between izokibep and placebo in terms of loss to follow-up and withdrawal of consent rates. In this trial, izokibep had a rapid onset of action associated with clear evidence of improvement within two weeks, achieving statistical significance as early as week four. As mentioned, the study met its primary endpoint with 33% of izokibep patients achieving a HiSCR75 response, that is a 75% reduction in abscess and inflamed nodules versus 21% for placebo. Looking at the two-thirds of patients with week 16 data, we can observe an increase in response up to 40% on izokibep versus 20% on placebo. When we look at higher orders of response, looking at HiSCR90 and HiSCR100, izokibep again achieved statistically significant responses at week 12 versus placebo, with approximately one in four patients on izokibep achieving these deeper responses versus placebo. Notably, the delta for HiSCR90 and HiSCR100 were maintained at week 16. Here you see the response across the continuum of HiSCR50 to HiSCR100 as depicted from left to right on the slide. As expected, we observe a consistent trend with placebo response decreasing as the efficacy hurdle increased at week 12. Clinical meaningful reductions in skin pain and improvements in DLQI were seen -- observed versus placebo at week 12 and also at week 16. The safety findings of izokibep were consistent with those observed in previous trials, with the most common adverse events being mild-to-moderate injection site reactions in around 65% of patients on izokibep versus 8% in the placebo arm. You also note not much differences for other events like headache happening in 10% versus 9% and 7% of nasopharyngitis in both arms. Notably, there were no cases of candida on izokibep with only three cases showing in placebo. There was no IBD, liver toxicity, suicidal ideation behavior in the izokibep treatment arm. In conclusion, izokibep's safety is in line with our past experience and Izokibep appears to have the optimal to offer deep clinical responses across multiple HS domains including skin pain and patient-reported outcomes. We are very pleased to have successfully delivered this positive Phase 3 trial for izokibep in HS, which builds on the Phase 3 data released in PsA earlier this year. Now, turning our attention to lonigutamab, which we are developing as a subcutaneous treatment for thyroid eye disease. Thyroid eye disease is an autoimmune disorder characterized by progressive inflammation that can lead to irreversible damage to tissues around the eye, threatening vision. Patients present with proptosis, diplopia, and a variety of disabling eye symptoms. It affects greater than 100,000 patients in the U.S. A high unmet need persists in thyroid eye disease, a multifaceted disease whose impact extends beyond the well-recognized visual disfigurement. Patient quality of life is markedly impacted by TED. A therapy that provides rapid, deeper disease-modifying effects that are durable across TED manifestation and results in improved patient quality of life, safety and convenience will be important for patients. Lonigutamab is a next-generation recombinant humanized IgG1 monoclonal antibodies against human IGF-1 receptor being developed to treat severe manifestations of TED. As shown in the middle cartoon on the slide, lonigutamab binds IGF-1 on a unique binding site, which we call an epitope and does not compete with IGF-1 binding. It does this with high affinity, with a kilodalton affinity measured around 30 picomolar and its specificity which triggers rapid internalization and degradation within minutes of the IGF-1 receptor, thus eliminating it from the surface of the IGF-1 expressing cells with potential to maintain IGF-1 within homeostatic levels. IGF-1R internalization prevents downstream signaling in orbital fibroblasts from patients with TED and has been associated with therapeutic benefit in TED. The rapid and efficient suppression of IGF-1 receptor signaling in TED with lonigutamab could potentially improve clinical outcomes for patients by providing lower doses of exposure to achieve robust clinical response, as we saw in our proof-of-concept with 40 milligrams Q3W having responses at early time points when we assessed at three weeks after a single dose. There's potential for deep and durable responses with chronic dosing and ability to minimize safety risk by choosing an optimal, convenient dose regimen. As I mentioned, we completed the Phase 1 proof-of-concept portion of our ongoing lonigutamab trial earlier this year and we are now embarking on a dose-ranging Phase 2 portion across four-dose-group levels, as you can see depicted on the right part of the slide projected. The Phase 2 trial was designed with the flexibility to test multiple dose levels and regimens in order to, number one, establish what we call a minimum effective dose when we are focusing on assessing the Cmin and, number 2, to enable establishment of an optimal dose selection for Phase 3 program within the optimal therapeutic window that you can see labeled on the y-axis on the left part of the slide and making sure that we don't have a Cmax that results in overexposure and therefore really calibrating an opportunity to minimize safety which might be associated with high and overexposure. We are using the totality of this data to calibrate to an optimal dose level and convenient dose regimen. We recently initiated the final dose group with a dose level of 70 mg administered every three to four weeks in this Phase 2 trial to confirm the dose we will take to Phase 3. We believe our Phase 2 approach is unique, in that it's patient-centric, designed comprehensively to address the ongoing unmet needs of thyroid eye disease patients and really balance benefit-risk to define an optimal dose level and a regimen that proffers a robust therapeutic impact across the multifaceted aspects of TED. We are currently planning to start the Phase 3 trial in the first quarter of 2025 and, as Mina mentioned, we are looking forward to meeting with the FDA later this year and sharing more information about the registrational program in TED at a future investor event. Now, I'll turn over to Gil.
Gil Labrucherie: Thank you, Shep and good afternoon, everyone. Today, I'm going to make a few comments on financial highlights from the quarter ended June 30, 2024, and then discuss some of the financial implications of the refocused pipeline and restructuring initiatives we announced today, the key milestones ahead for us and also provide year-end cash guidance. We are fortunate to be in a strong financial position. At June 30th, our cash position was approximately $635 million. For Q2, our R&D expense was $76.4 million as compared to $30 million for the same period in 2023. A substantial majority of our R&D expense, approximately 75%, is related to the izokibep program, where we have been executing three Phase 3 programs this year in PsA, HS and uveitis. General and administrative expenses were $16.6 million for the second quarter as compared to $12.7 million for the same period in 2023. R&D and G&A expense includes stock-based compensation expense of $10.2 million, which increased from $8.5 million for the same quarter in 2023. Today, we made the difficult decision to rightsize our organization in line with our refocused pipeline strategy. I wanted to make a few comments on the financial implications of this decision. We expect to incur approximately $4.5 million in cash-based restructuring charges related to the workforce reduction. Our estimate for the costs associated with the completion of the ongoing uveitis study, HS and PsA studies is expected to range between $30 million to $35 million. With respect to the ongoing izokibep CMC activities and commitments, we expect to incur between $55 million and $85 million. We are actively working with our manufacturing partners with a goal to mitigate these costs. From a financial point of view, our focus will be on efficiently and effectively executing this refocused pipeline strategy and associated restructuring, remaining disciplined and risk-aware with our operational spend, and significantly extending our cash runway out approximately three years to mid-2027 through multiple value-enhancing catalysts. This long-range financial guidance includes adding an additional dose arm to our ongoing lonigutamab Phase 2 trial, as Shep just reviewed, funding two Phase 3 trials for lonigutamab and BLA-enabling activities for that program. In addition, please note that our cash runway guidance does not include any proceeds related to additional financing or partnering. We are very excited about the milestones ahead for ACELYRIN. We remain focused on our core mission to accelerate the development and delivery of transformative medicines in immunology. On this slide, we have outlined some of the important milestones for our development programs and related timing windows. Following our end-of-Phase 2 meeting with the FDA on the lonigutamab program, we plan to hold an investor event focused on the unmet need for thyroid eye disease patients, the detailed rationale underpinning dose selection, the outcome of the end-of-Phase 2 meeting with the FDA, additional data from the ongoing Phase 2, and the design of our Phase 3 development program. In addition, we also continue to project that we'll have top-line results from the izokibep Phase 2b/3 trial in uveitis before year-end. We anticipate rapidly advancing lonigutamab into late-stage development with the start of the Phase 3 program before the end of Q1 2025. We expect the first top-line readout from the registration program in 2026 and to file a potential BLA thereafter. We look forward to sharing more details on our plans for the lonigutamab program at our upcoming investor event. Now, turning to forward-looking financial guidance. We currently project our 2024 year-end cash position will range between $420 million and $450 million. We expect our cash used in operations to increase substantially in the second half of 2024. Remember, in the first half of 2024, we received $37 million from a one-time vendor credit and licensing payments. Conversely, in the second half of 2024, we expect to pay a $31 million option payment related to achieving proof-of-concept with lonigutamab and non-recurring payment for costs related to the restructuring and exiting certain izokibep commitments. As I mentioned earlier, we now project our cash runway to mid-2027, which we anticipate will fully fund the lonigutamab development program through BLA filing while also preserving capital for selective pipeline expansion. And, as I stated earlier, our cash runway guidance does not include any proceeds related to additional financing or partnering. And now, I'll turn the call back over to Mina.
Mina Kim: Thank you, Gil and Shep, and thank you all for joining us on today's call. The decisions we announced today about our go-forward strategy position us to execute on lonigutamab from a position of strength by suspending new investment for izokibep in PsA and HS, discontinuing SLRN-517, and the difficult decision to rightsize our organization, we can now focus on rapidly developing lonigutamab as the potential best therapy for thyroid eye disease. We have an outstanding team, who are positioned to deliver high-quality execution of the pivotal program and we now have a cash runway to take the program through both pivotal trials. We're excited by the opportunity to serve the unmet needs of TED patients. Since taking on the CEO role a few months ago, I've had the opportunity to meet with many, probably more than 100 of our investors, and I appreciate the opportunity to provide this update today. We look forward to providing regular updates on our progress and I hope you will join us for our investor event after our FDA meeting, where we will provide an in-depth and comprehensive overview of the full lonigutamab opportunity and the many reasons why we're so excited to move this program forward. Thanks for joining us today and, operator, with that, we can open up to questions.
Operator: [Operator Instructions] And it comes from the line of Derek Archila with Wells Fargo (NYSE:WFC). Please proceed.
Derek Archila: Hi, thanks for taking the questions. Just three quick ones from us. I guess, first, what's the rationale for adding the 70-mg dose in the ongoing Phase 2 for lonigutamab? Also, the every three-week dosing arm as well, just wanted to also figure out whether this is kind of leading to potentially a loading dose in Phase 3? So that's the first question. Second question, just for IZO, I guess, is the plan to partner this asset right now, or is it just going on the shelf? I just wanted to clarify, in terms of the comments you made around uveitis, is that something you would plan to move forward by yourself if that data looks good? And then third, you noted in terms of the kind of the expanded cash runway and opportunity potentially to expand the pipeline, I guess, is that a near-term priority? And I guess, what stage of development would you be looking for in terms of assets? Thanks.
Mina Kim: Yes, hi, Derek. Hi, thanks for the questions. There's a lot in there, so I'm going to take them in order. Hi, maybe to start with IZO, right, and the partnering question, and then what are we going to do with uveitis or how do we think about uveitis? You know, what I'd say with respect to partnering, and this is what we've been saying, we're going to do what's best for the program, right? We're open to all options. And fundamentally, we want to see HS and PsA, right, bring benefit to patients, and that might be with a larger organization that has existing capabilities and infrastructure, right? So, again, we'll do -- we'll look at all the options and we'll do what's best for the program. I do want to note and reemphasize something that Gil said, which is we have not included any financing proceeds or proceeds from a partnership in our cash runway guidance, right, so that excludes any contribution from a potential partnership. So I think that's the response on the IZO and uveitis questions. With respect to potential BD going forward, look, I mean, we are always going to look at opportunities. We'll be opportunistic. And as Gil said, we have assumed, right, that there could be some pipeline expansion and we have the funding for that, we believe, right? I would say, though, right now it's important for us to focus on lonigutamab and high-quality execution on that program. And that is the focus for now. And so any additional BD, I don't think we're in a hurry, and it's a high bar, right, but we certainly will consider any opportunistic opportunities, right, over time. And then, I think you had questions around the design, right, of the lonigutamab development program? And maybe it's helpful to frame that up a little bit, right, just stepping back, we have spent the last few months evaluating the entire development program, really with two goals. One is how do we de-risk the Phase 3 program, right, and the other is, can we do that at the same time as we try to accelerate the program? And we have been trying to balance both of those things. We do think that adding this additional dose cohort into the Phase 2 program helps us achieve that. First, it allows us to complete dose exploration in the Phase 2 trial rather than in a 2b/3 as originally planned. And what that does is it allows us to move directly into a Phase 3 program and potentially run two Phase 3 trials concurrently, right, rather than sequentially, which obviously has the potential to accelerate that program. And we've added the 70-mg dose. We are looking at it in both three weeks, right, and four weeks, right, to confirm the dose that we're going to take into the pivotal program. I would say, I think it's important to note we think we have our dose, right, but regimen is also important. And again, we want confidence around that dose we take into the program. And the ability to do that in the Phase 2, right, is we think, potentially both de-risking and hopefully does allow us to go more quickly into that Phase 3 program.
Derek Archila: Understood. I guess just to follow up there in terms of like, again, is that being examined for potential loading dose or is the loading dose going to be figured into the Phase 3 program?
Mina Kim: No, I mean, that's not something we're contemplating now. I mean, we do think the 70 is our dose.
Derek Archila: Understood. Thank you.
Mina Kim: Thanks, Derek.
Operator: Thank you. Our next question comes from the line of Tyler Van Buren with TD (TSX:TD) Cowen. Please proceed.
Tyler Van Buren: Hi, guys. Thanks for the updates. It's encouraging to see the rationalization of the pipeline. I want to ask about the Phase 3 uveitis trial readout. So what would compelling data from that trial look like later this year that would lead you to pursue another trial for registration? And the second question is what are your latest thoughts on the market size for uveitis?
Mina Kim: Yes, so maybe I'll start, and then I'll turn it over to the team. I mean, I think we're going to evaluate uveitis in the same way that we have all of our other programs, right? We're going to look at the totality of the data, the market, the unmet need. What I would say maybe to start is there is very high unmet need, right, in uveitis. And so we like that opportunity, right, to address the unmet needs of patients. There is, obviously, very limited -- there are very limited options for those patients, and that will also factor into it. In terms of the trial design and sort of what are the endpoints, I'll turn it over to Shep maybe to just walk you through that.
Shep Mpofu: Yes, no, thanks, Mina. Our trial is designed the same as the HUMIRA trial, which is the only large Phase 3 study that was done in uveitis. We have patients receiving steroids at baseline and then having a regimen to decrease them over 15 weeks. And we have a primary efficacy endpoint at week 24, where we'll be looking at four parameters same as HUMIRA did, looking at inflammation in the back of the eye, chorioretinal inflammation, and then looking at inflammation within the eye, looking at the vitreous haze, anterior chamber as well, and then best corrected visual acuity. So that's the treatment failure. So we'll be looking at a compelling data set that showcases there are more patients on placebo versus drug that achieve this endpoint.
Mina Kim: Tyler?
Tyler Marciniak: Yes, all good. Thank you.
Operator: Thank you. One moment for our next question. And our next question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed.
Yasmeen Rahimi: Thank you so much, team, for sharing these difficult decisions with us and walking us through the rationale. Team, I guess, could you maybe talk about Cohort 3? Cohort 4 has just begun. At what junction -- and what have you seen from that dose cohort so far? When should we be expecting data from it? And then, I guess, and then as we think about Phase 3 design, just maybe parts of the -- you alluded to some innovative approaches, but maybe walk us through who would be the ideal patient? It also seems like TET studies have become quite competitive in terms of enrollment, so appreciate also color and ensuring being able to deliver top-line data in an efficient manner? Sorry, there was too many questions in there, but I guess Cohort 3 and, yes, I appreciate color on that. Thank you. Sorry about that.
Mina Kim: Yes. No, for sure. So let's start with Cohort 3, and then, hey, if we miss anything, just remind us. Just prompt us. Like I just said in our prepared remarks, we are thinking about that Phase 2 program, right, holistically. We think it's most useful to read out the data from that Phase 2 program after we've met with the FDA later this year, right, when we can give a more complete picture. And that more complete picture would be additional data, right, including from Cohort 3, really, from the totality of that across the Phase 2 program, and also how we're thinking about the Phase 3 program. So I think that's a little bit of the timing, and we would expect that to be later this year or potentially early next year, right, but really, when we've got a more complete picture to share with you all, we think that that's most useful. So, I think that's kind of the design. In terms of the patients that we can potentially serve, we do think that there continues to be very high unmet needs, right, in TED patients. And I think we've talked about this before. We are particularly interested in the ability to think about chronic dosing, right? This is a disease that can flare or regress or however you want to describe that. And there is an ongoing need for those patients, right, across many different endpoints. And so, we really want to optimize the dose and the regimen, right, to try to address the totality of the disease. So we think that there, again, continues to be unmet need, and we are very interested in exploring that chronic population. So, what did I miss?
Yasmeen Rahimi: Yes. No, no, no. Just -- yes, that's an enrollment timing, just because it's competitive, like we feel confident to, just because now several test studies will be ongoing concurrently in Phase 3. Appreciate some color there.
Mina Kim: Yes. And look, we feel good about that. I mean, obviously, we're enrolling patients right now, right, into the Phase 2. And we think that that's -- we feel good about that experience and confident going into the Phase 3 trial somewhat based on that experience. So understand that there are more trials going on, but we feel good about that.
Yasmeen Rahimi: Thank you so much. I'll jump back in the queue.
Operator: Thank you. Our next question comes from the line of Akash Tewari with Jefferies. Please proceed.
Phoebe Tan: Hi, this is Phoebe on for Akash. Thank you for taking our question. So I guess more on uveitis, are you targeting more refractory patients like those who are on or after prior biologic use? And additionally, will uveitis be considered an orphan indication? And could you potentially get orphan pricing of around 200,000 per year in this indication? I imagine there might be some pushback from payers for orphan drug pricing given HUMIRA is already approved for uveitis and is much cheaper. So just some color around that would be helpful.
Gil Labrucherie: Yes. Great. Thanks for the question. This is Gil. You know, as Mina was saying earlier, this is an interesting indication there's still a very high unmet need. There's really only a couple treatment options, essentially steroids and HUMIRA, and the current standard of care is really only modestly effective. So we really think there's an opportunity here to drive additional benefits to patients, whether that -- at any line of this. We also think that with the limited therapeutic options as a therapy like IZO may come in here, they'll also have an opportunity to expand the market in a diagnosis of this, with this condition. I think in terms of the pricing question, that's a little early to say that, certainly something that we think about as we go in, but it's a little early to speculate on pricing of the indication.
Shep Mpofu: Yes. And on patients that are coming in the study, these are patients with active, non-infectious uveitis. There will be patients who also have been previously exposed to other biologics, except those biologics that are on the IL-17 pathway.
Phoebe Tan: Understood. Thank you.
Operator: Thank you. Our next question comes from the line of Emily Bodnar with H.C. Wainwright. Please proceed.
Emily Bodnar: Hi, thanks for taking the questions. I guess, some of the clarifying question. In the 70-mg LONI dose, are you enrolling eight patients in total across the three-weekly and four-weekly regimens, or is it eight per regimen? And then kind of follow-up to that, do you think that's a sufficient number of patients to kind of get an idea if that's the appropriate dose to take into Phase 3? And then lastly, if you can kind of confirm that you haven't seen any cases of hearing impacts from any of the cohorts so far? Thank you.
Mina Kim: Yes. Thanks. Let me start and maybe I'll turn it over to Shep on that as hearing. The way that this final cohort is set up, it has eight patients and allows us to try the 70 mg Q3 and Q4. It also gives us the flexibility to go up to 16 patients in that cohort. So it is built with some flexibility. Obviously, those are small numbers, but in totality, right across this Phase 2 program, right, we will have seen inpatient data across multiple doses and regimens. And we think that that's going to be very, again, useful for us in a way to de-risk that Phase 3 program, right? And maybe I'll let Shep address the hearing question.
Shep Mpofu: Yes, no. Thanks for that response. And for hearing, all our dose groups that we have been exploring in the dose range have audiograms done at baseline and throughout the course of the study. None of the patients in any of the dose groups have developed any notable hearing impairment or sensorineural hearing loss. We did report in March in our top-line data that there were three patients in one of the cohorts that had transient tinnitus that resolved, and none of those patients had changes in audiogram. So, so far, no major changes pertaining to audiogram changes in all of our cohorts.
Emily Bodnar: Okay, great. Thanks for taking the questions.
Mina Kim: All right. Thank you.
Operator: Thank you. Our next question comes from the line of Vikram Purohit with Morgan Stanley (NYSE:MS). Please proceed.
Vikram Purohit: Hi, good afternoon. Thank you for taking our questions. We had two. So first, on 517, I was just curious what you might have seen in the early stage of development for that molecule to decide to stop pursuing that any further? And then secondly, for the end-of- Phase 2 meeting with the FDA, just curious, what are the main questions you're hoping to have answered about the Phase 2 development program through that meeting with the agency? Thanks.
Mina Kim: Yes, maybe I'll start with 517. As I said on the call, we did do a healthy volunteer study, and actually, some of that data is up on our website if you want to take a look at that. I think -- in -- really, we've made, again, a strategic sort of prioritization decision and a program decision and so that's -- we are not going to continue development of that program internally, but if you do want to see the data, it is up on the website. Okay. And then I guess on the second question, with respect to the end-of- Phase 2 meeting, maybe I'll turn that over to Shep.
Shep Mpofu: Yes, no, thank you for that question. Our end-of- Phase 2 meeting is principally a traditional end-of- Phase 2, where we would sit with the regulator, FDA, to explore what we have done to date and agree on the benefit-risks that we are showcasing as was discussed dose, and obviously, importantly, the study designs will be at that point in time wanting to proceed with the Phase 3.
Vikram Purohit: Understood. Thank you. And then a quick follow up, and just apologies if this was discussed and we missed it, but the cash runway guidance through '27, exactly what does that contemplate with regards to future development in uveitis?
Gil Labrucherie: Yes. So the cash runway guidance, Vikram, we have included the completion of the ongoing uveitis study as well as the HS and PsA. We have included the completion of the Phase 2 program in lonigutamab, two Phase 3 programs -- two Phase 3 trials, the registrational program for lonigutamab as well as potential BLA-enabling activities.
Vikram Purohit: Okay, understood. Thank you.
Operator: Thank you. And our last question is coming from the line of Samantha Semenkow with Citi. Please proceed.
Samantha Semenkow: Hi, good afternoon and thanks for taking the questions. I just have a couple on LONI. I see in your corporate deck, you have, I think, what's maybe a new slide, just a bit more detail on the tinnitus that you've seen, and you've observed all three cases from just Cohort 1. So the question is why you think this might be the case? Why is it only in Cohort 1 and none of the Cohort 2 patients so far? Is there something common between these three patients? Or is perhaps the loading strategy -- loading dose strategy exporting Cohort 2? Do you think that's driving the difference? Would just love any thoughts you could provide there.
Mina Kim: Yes, look, maybe I would just start with, what we are showing is what we saw in Cohort 2 and I would note that there were none in -- Cohort 1 sorry, there were none in Cohort 2. And then maybe I will turn it over to Shep for some more details.
Shep Mpofu: Yes, no, thanks for the question, Samantha. Number one, we have not seen any reason why these patients had tinnitus in that cohort. If you specifically look at the narratives for each respective patient, you will notice that this was tinnitus that was transient in the majority of those three patients and resolved. If anything, I can comment on one of the patients who had tinnitus at 24 hours after the first injection, and in 24 hours, it resolved and it happened the same. Remember, Cohort 1 only had two injections at week zero and week three. So no relationship to any aspect pertaining to the patient characteristics. And I think, not seeing anything in Cohort 2 give us the confidence that this is not related to any dose exposure and therefore this was just something that happened within the study. And as I mentioned, all patients are having audiograms at baseline over time and to date, we have not seen anything that speaks to sensorineural hearing loss or impairment.
Samantha Semenkow: Great. Thanks so much for taking the question.
Operator: Thank you. And with no further questions in the queue, I will turn it back to Tyler Marciniak for his concluding comments.
Tyler Marciniak: Thank you, Carmen, and thank you all for joining today's call for the opportunity to share with you these exciting corporate updates from ACELYRIN. As noted in the press release, we look forward to sharing more information about our plans for lonigutamab with you during the upcoming investor event, and our management will also participate in multiple webcasted presentations and one-on-one meetings at upcoming investor conferences. So please visit our website regularly for our latest IR calendar. And, of course, please feel free to contact me and the Investor Relations team at any time if we can be of service to you. With that, we'll conclude our call for today. Thank you very much,
Operator: And thank you all who participated in today's conference. You may now disconnect.
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