On November 13, 2024, Acelyrin, Inc. (ticker not provided) conducted its Third Quarter 2024 Earnings Call, led by CEO Mina Kim and CFO Gil Labrucherie. The call centered on the company's strategic shift towards advancing lonigutamab, a promising treatment for thyroid eye disease (TED), and the anticipated results from the Phase 2b/3 trial of izokibep for noninfectious uveitis.
Financial highlights included a decrease in R&D expenses and an update on year-end cash guidance, with a focus on disciplined capital allocation and an operational runway extending to mid-2027.
Key Takeaways
- CEO Mina Kim announced a strategic reprioritization towards lonigutamab for TED, with positive data and a Phase 3 program planned for Q1 2025.
- Top-line results from the Phase 2b/3 trial of izokibep for noninfectious uveitis are expected in December 2024.
- Acelyrin ended Q3 with $562.4 million in cash, and year-end cash guidance is updated to $435 million to $450 million.
- The company is preparing to acquire global rights to lonigutamab for $31 million.
- An investor event for lonigutamab is planned for early 2025, with further updates on thyroid eye disease and related hearing impairments.
Company Outlook
- Acelyrin is focused on high-quality execution with an operational runway extending to mid-2027.
- Upcoming data and strategic decisions regarding uveitis development will be guided by trial results.
Bearish Highlights
- The company reported a decrease in cash from the previous quarter, with R&D expenses down due to reduced clinical activity.
- A net expense of $7.2 million was incurred due to the resolution of manufacturing commitments for izokibep.
Bullish Highlights
- Positive proof-of-concept data for lonigutamab show rapid improvements in TED patients within three weeks.
- The company anticipates izokibep to demonstrate superior efficacy compared to the current standard treatment, adalimumab.
Misses
- Specific capital commitments for the anticipated Phase 3 study of izokibep in uveitis have not been disclosed.
- The timeline for initiating the pivotal study for izokibep is pending, awaiting data evaluation.
Q&A Highlights
- The company is considering potential partnerships related to izokibep for other conditions.
- Discussions included the efficacy of izokibep compared to adalimumab and the importance of superior clinical profiles.
- The outcomes of thyroid eye disease and related hearing impairments are being explored, with more updates expected in early 2025.
Acelyrin, Inc. has emphasized its commitment to addressing unmet medical needs through its pipeline, with a keen focus on the development of treatments for thyroid eye disease and noninfectious uveitis. The company is poised to make significant strides in these areas, pending the evaluation of upcoming trial data and the initiation of Phase 3 programs. Investors and stakeholders are looking forward to the top-line results from the izokibep trial and further developments in the company's strategic initiatives.
InvestingPro Insights
Acelyrin, Inc. (SLRN) is navigating a critical phase in its development, with its strategic focus on lonigutamab for thyroid eye disease and the anticipated results for izokibep in noninfectious uveitis. This aligns with several key insights from InvestingPro.
According to InvestingPro data, Acelyrin's market capitalization stands at $596.85 million, reflecting investor interest in the company's potential. The company's Price to Book ratio of 1.05 suggests that the stock is trading close to its book value, which could be attractive to value-oriented investors considering the company's pipeline prospects.
InvestingPro Tips highlight that Acelyrin holds more cash than debt on its balance sheet, which supports the company's statement about having an operational runway extending to mid-2027. This financial stability is crucial for a biotech company advancing multiple clinical programs. Additionally, the tip indicating that liquid assets exceed short-term obligations aligns with the company's reported strong cash position of $562.4 million at the end of Q3.
However, it's important to note that Acelyrin is not currently profitable, with an adjusted operating income of -$423.82 million over the last twelve months. This is consistent with the company's stage of development and its focus on R&D for potential breakthrough treatments. The InvestingPro Tip that Acelyrin is "quickly burning through cash" underscores the importance of the company's disciplined capital allocation strategy mentioned in the earnings call.
On a positive note, Acelyrin has seen a strong return over the last three months, with the stock price showing a 47.29% total return. This could reflect investor optimism about the upcoming trial results and strategic initiatives.
For investors seeking a more comprehensive analysis, InvestingPro offers 7 additional tips that could provide further insights into Acelyrin's financial health and market position.
Full transcript - ACELYRIN Inc (SLRN) Q3 2024:
Operator: 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 13, 2024. I would now like to turn the call over to Tyler Marciniak, Vice President of Investor Relations and Corporate Affairs. Tyler?
Tyler Marciniak: 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 (TASE:PMCN) 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: Thanks, Tyler, and thanks, everyone, for joining us today. The first 9 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 2b/3 trial of Izokibep in noninfectious non-interior 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 3 weeks after the first dose. Our adaptive Phase 2 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 3 registrational program. In selecting a dose, we’re focused on maintaining a narrow therapeutic window that stays above a certain cement 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 2 and 3 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 mgs monthly with no loading dose. We previously announced that we are adding a fourth dosing cohort to our Phase 2 trial. That dosing cohort was expected to be 70 mgs 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 the model loading dose. For example, Cohort 2 used a loading dose and that cohort demonstrated rapid achievement of steady-state Cmax, 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 3 program. We are 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 time lines. Given this last cohort is really being used to confirm a loading dose we have now largely completed our dosing exploration with the first 3 cohorts. And with FDA alignment on our dosing strategy, we’re confident in our ability to start our Phase 3 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, were presented at multiple international medical congresses, including ASOPRs, ESOPRS 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 3 trials in a timely manner. We also recently completed a positive end of Phase 2 meeting with the FDA. 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. We were pleased with the feedback received to 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 3 clinical development. But before that milestone occurs, we also expect to announce top line results for our Phase 2b/3 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 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. 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. And with that, I’ll turn it over to Shep to walk you through the uveitis program in more detail.
Shephard Mpofu: 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 most at-risk population in developing uveitis is the working age group with ages 20 to 50 years. These patients are at risk of retinal detachment, cataract, glaucoma and macular edema. Loss of vision is a key concern and often leads to blindness in 5% to 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 2 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 failed 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 innovation 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 milligrams 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 one-tenth the size of a monoclonal antibody. In preclinical study, we have shown izokibep to be significantly more potent than secukinumab and 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 milligram 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 2b/3 trial in uveitis with 96 patients randomized 1:1 active treatment versus placebo. The trial primary endpoint is designed to be similar to the adimumab 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 VVISUAL I, adimumab 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 2b/3 data be positive, our best guess is that one additional Phase 3 trial of approximately 200 to 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: 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 the 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 3 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 5, 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 3 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. And 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 to $450 million. With the manufacturing commitments resolved, we are now updating year-end cash guidance to $435 million to $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 3 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: 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’ll 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: [Operator Instructions] Our first question will come from the line of Tyler Van Buren from TD Cowen. Your line is open.
Tyler Van Buren: Hey, guys. Good to see progress of 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 2 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 3 if they didn’t see the Cohort four dose and four data. And the second question is just, is it fair to say that the pivotal TED trial will likely include a dose somewhere in the 70 mg to 100 mg range being tested in Cohort 4?
Mina Kim: Yes. So, yes, Tyler, thanks for the questions. 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 2 meeting? And then the second was what’s the 70 and that 100, the cohort 4, right? What’s the kind of the purpose of that or what role are they going to play, right, in the program? Is that fair?
Tyler Van Buren: Yes.
Mina Kim: Okay. Yes. So maybe on the end of Phase 2 meeting, right? I mean we had a 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 with data that’s maturing over time. And what we’ve been testing really in those first 3 cohorts is doses from 25mg to 100 mg, right and that – 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 2 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 and 100 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: Thank you.
Operator: Our next question comes from the line of Akash Tewari from Jefferies. Your line is open.
Unidentified Analyst: This is [indiscernible] in for Akash. Thanks for taking my question. Just one question, what gives you confidence that efficacy in UA is Cmax driven if the Molar exposure 160-milligram izokibep comes, let’s say, slightly lower than secukinumab 10-milligram 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 milligram per kilogram IV? Thanks.
Mina Kim: Hey, thanks for the question. 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 relative to other programs?
Unidentified Analyst: Yes.
Mina Kim: Okay. Yes. And sort of what does that mean in terms of potential clinical benefit, right, that we could see in the uveitis program?
Unidentified Analyst: Yes.
Mina Kim: Yes, okay. I’m actually going to ask Shep to take that one.
Shephard Mpofu: Yes. 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 equally potent to secukinumab. So 10 mg per kg IV every 2 weeks of secukinumab equates in all our modeling and some of our data sets across the autoimmune indications we have studied to 160-milligram subcu every week. In uveitis, we are very fortunate that we have done primate studies with the various exposure subcu that have enabled us to find the presence of izokibep within vitreous humor. So we know this is possible because it’s 10x 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 data set. 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.
Unidentified Analyst: Yes. That’s really helpful. Thanks.
Operator: Thank you. [Operator Instructions] Our next question will come from the line of Yasmeen Rahimi from Piper Sandler. Your line is open.
Unidentified Analyst: Hey team. This is John Hjelm [ph] on for Yas. Thanks for taking our questions. 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 the pivotal study following top line data in December?
Gil Labrucherie: Yes. Thanks for the question. This is Gil. I will take the – 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: Yes. And maybe I will take the timing one. I don’t think we are 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. And I think as Shep said, our base case, right, is that we are 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 path if the data warrants 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 will update you guys on timing at the right time.
Unidentified Analyst: Got it. Thank you so much.
Operator: Thank you. [Operator Instructions] Our next question will come from the line of Derek Archila from Wells Fargo (NYSE:WFC). Your line is open.
Unidentified Analyst: Hey team. This is Adam on 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: Yes. Hey. Maybe I will just start. We are thinking about, if you are thinking about clinical benefit, there is high unmet need, right, in uveitis, it’s steroids and then there is 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.
Shephard Mpofu: Yes. And maybe just to add on the market front, this is a very significant population. And as Mina just said, there is 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.
Unidentified Analyst: Got it. And then maybe just one on lonigutamab’s proposed Phase 3 dosage, I believe previously, you have disclosed that the go-forward dose for Phase 3 was going to be 70 milligrams. Can you confirm that this is – remains to be the case? And any color on the dose regimen proposed if where you are in that? Thank you.
Mina Kim: Yes. 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 to 100 mg, right. And that 100 mg is new in that cohort four and again, really to test a potential loading dose and the regimens we have 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 will do that when we announce the data and provide details on the Phase 3 program.
Unidentified Analyst: Got it. Thank you.
Mina Kim: Thanks.
Operator: [Operator Instructions] Next (LON:NXT) question comes from the line of Emily Bodnar from H.C. Wainwright. Your line is open.
Emily Bodnar: Hi. Thanks for taking the questions. I guess for loni, you mentioned for the Phase 3, you are looking at 52 weeks instead of 24 weeks. So, maybe can you just talk about how you are thinking about durability of response and what you would kind of hope to see beyond that 24-week timeframe? 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 TED?
Mina Kim: Yes. And so maybe I will 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 testament, I think to the dosing work that we have 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 are thinking about the Phase 3 trial design. Like I said, I think we will provide sort of a complete picture of what is that development program and timelines, right, in early ‘25, right, but that – those are sort of the parameters that we are using to think about the development program.
Shephard Mpofu: Yes. Maybe just to also add, in keeping with real-world evidence on thyroid eye disease, it’s very clear that current therapies do not fully address the unmet need. There is 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 milligram to 100 milligram, 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: Okay. Thanks. And just on the active and TED Phase 3 are both expected in the first quarter?
Mina Kim: But we haven’t provided sort of that level of detail. Like we said, we expect to – we are going to be testing in both populations, right. And we will provide details about the Phase 3 program design in the – in early ‘25.
Emily Bodnar: Thank you.
Mina Kim: Thanks.
Operator: [Operator Instructions] Our next question comes from the line of Vikram Purohit from Morgan Stanley (NYSE:MS). Your line is open.
Vikram Purohit: Great. Good afternoon. Thanks for taking my questions. So, we had 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 has been any interesting BD discussions, and if you feel like this is something that could be actioned in the near to mid-term? Thanks.
Mina Kim: Okay. Hey. Thanks for the question. Maybe let’s start with the BD question, and I will turn it over to Gil and then we can hit hearing.
Gil Labrucherie: Yes, Vikram, on the BD front, on the program for Izokibep, we are 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 talked about earlier that we have not included any assumptions around partnering or new investments in Izokibep.
Shephard Mpofu: Yes. 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 investor – at our Research Day in early ‘25, 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 sensor neuro hearing impairment or just subjective changes that do not impact objective assessments. And therefore, we will be able to share-case with you how we are approaching this hearing and what we are expecting in different subpopulations. Let’s not forget that 40% to 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 of those important considerations, so more to come in early ‘25.
Vikram Purohit: That’s helpful. Thank you.
Operator: Thank you. [Operator Instructions] 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 am 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: Yes. Let me start. I think it is, right. I mean obviously look, data is always tells a complicated story and you look at the whole package. So, we will – when we have the data in the same way that we did with HS and PSA, we will 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 would say, in general, look for a profile that is better.
Samantha Semenkow: Got it. That’s very helpful. And then just thinking about the study design, I believe you are allowing patients that are biologically experienced, meaning they have seen Humira previously into the study. I am just trying to think about how that could impact the data and how that because biologically experienced patients and a lot of other indications potentially do worse. And when you look at the VISUAL-1 study, obviously those patients are biologic naïve, I believe, given there are 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: Yes, for sure. So, let me start, and then I will turn it over to Shef. So, you are 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 are in our trial. And so let me stop there, and then I can turn it over to Shep for any further comments.
Shephard Mpofu: Yes. No, it’s an important question and thank you for that. And we have in our protocol mature, 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 naïve patients. As you would expect in these trials, where you have patients previously failing 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 naïve 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 failed adalimumab as well in the study, so more to come.
Operator: Thank you. And with no more questions, I will 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. 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 2b/3 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.
Operator: 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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