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spk01: I would now like to turn the conference call over to Tyler Marciniak, Vice President of Investor Relations and Corporate Affairs. Tyler?
spk12: 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 acelerin.com, along with today's press release and our slide presentation. Additionally, These statements are based on information available to us today, August 13th, 2024, and we undertake no obligation to update them as circumstances may change.
spk17: The agenda for today's call is on the screen.
spk12: We will review the corporate strategy updates announced in our press release, as well as positive top-line data from the Phase III trial of Izocaibet and hydrodinitis suppurativa. We will also provide an update on the Lana-Gudimab 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 Meena Kim, our Chief Executive Officer, Dr. Shet Mpofu, our Chief Medical Officer, and Gil Labruchery, our Chief Financial Officer, and Chief Business Officer. I will now turn the call over to Meena.
spk04: Thanks, Tyler, and thanks everyone for joining us today. Earlier today, we announced positive phase three results for Isaac Kaibab and Hydranita Supertiva, 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 III readout for isocibef in HF. We met the primary endpoint of high score 75 and are especially pleased with the compelling response rates in high score 90 and 100 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've 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 2b3 readout we announced earlier this year, and which were presented in a late-breaking session at ULAR in June. Collectively, the data in HS and PSA further validate our long-standing view that isokidab 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 Lana Gutemask. which we believe has the potential to improve upon clinical response and convenience versus the standard of care in thyroid eye disease. We plan to complete the ongoing trials of isocibeb in HS and PSA, but we will not start new trials in these indications. We do plan to continue the ongoing phase 2b3 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 2b3 data be positive, we anticipate one additional phase 3 trial of roughly 200 to 250 patients would be required for registration. The ongoing trial is fully enrolled with approximately 100 patients. In addition to these ISOCIDAB updates, we've decided to stop internal development of SLRN 517, our early anti-CKIP 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 Accelerin'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 Lonigutimab and extend our cash runway to mid-2027. By focusing future capital investment on Lonigutimab, we will be well-positioned to fund our ongoing and planned TED trials through the BLA submission. Shep will review our overall strategy and ongoing activity for Lonigutimab 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 2b3, 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 a 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 three program. With that, I'd like to turn the call over to Chef.
spk23: Thank you, Mina, and hello, everyone.
spk24: I'm very pleased to share with you today positive phase three data of isocubab inhydrodinitis suppurativa, or HS, and provide a program update on lonicultamab in thyroid eye disease. Let me start with HS. This regulated interleukin-17A activity plays a pivotal role in hydradenitis suppurativa pathogenesis. Multi-domain disease resolution is underachieved with available current therapies. An unmet need exists for therapies demonstrating efficacy across multiple disease manifestations, including abscess, inflammatory nodules, and draining tunnels. Isoquibab is a small protein therapeutic designed to selectively inhibit interleukin-17A with high potency through tight binding affinity. The small molecular size of Isoquibab 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 three trial of Isoquibab 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 izocubab 160 mg weekly or placebo. The inclusion criteria and design is similar to other Phase III studies, with a primary endpoint here for the first time in a Phase III of high score 75 at week 12. At week 16, placebo patients were switched to receive Isocubeb 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 Isocubeb treatment group and placebo. typical of a patient population with moderate to severe HS and comparable to other global phase III pivotal trials. 103 patients on the Isocubeb arm and 112 patients in the placebo arm completed the study through week 12, thus having approximately 20% on Isocubeb arm and approximately 13% on placebo arm discontinued treatment. with a delta of around 7% between the two groups. Please note the most common reasons leading to discontinuation on Isoquibab were mild AEs. And there were no notable differences between Isoquibab and placebo in terms of loss to follow-up and withdrawal of consent rates. In this trial, Isoquibab 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 eyes-occupied patients achieving a high score 75 response. That is a 75% reduction in abscess and inflamed nodules, versus 21% for placebo. Looking at the two-thirds of patients' worth of week 16 data, we can observe an increase in response up to 40% on Isoquibab versus 20% on placebo. When we look at higher orders of response, looking at high score 90 and high score 100, Isoquibab again achieved statistically significant responses at week 12 versus placebo, with approximately one in four patients on Isoquibab achieving these deeper responses versus placebo. Notably, the deltas for high score 90 and 100 were maintained at week 16. Here you see the response across the continuum of high score 50 to 100, as depicted from left to right on the slide. As expected, we observe a consistent trend with placebo response decreasing as the efficacy hurdle increases 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 Izoquibab 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 Izoquibab 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 Isoquibab with only three cases showing in placebo. There was no IBD, liver toxicity, suicidal ideation behavior in the Isoquibab treatment arm. In conclusion, Isocubeb's safety is in line with our past experience, and Isocubeb 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 III trial for Isocubeb in HS, which builds on the Phase III data released in PSA earlier this year. Now, turning our attention to Lonigutmab, 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, 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 a rapid, deeper disease-modifying effects that are durable across TERT manifestation and result in improved patient quality of life, safety, and convenience will be important for patients. Lonnie Goodmark is a next-generation recombinant humanized IgG1 monoclonal antibodies against human IgF1 receptor being developed to treat severe manifestations of TERT. As shown in the middle cartoon on the slide, Lonigutma binds IGF-1-ara 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 kilo-delta affinity measured around 30 picomolar, and a specificity which triggers rapid internalization and degradation within minutes of the IGF-1 receptor. thus eliminating it from the surface of the IGF-R1-expressing cells with potential to maintain IGF-1 within homeostatic levels. IGF-1-RI 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 with Lonigutmab 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 one proof of concept portion of our ongoing Lonely GroupMath trial earlier this year, and we are now embarking on a dose ranging phase two portion across four dose groups levels, as you can see depicted on the right part of the slide projected. The Phase II 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 C mean, and number two, to enable establishment of an optimal dose selection for Phase III 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 C-max 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 milligrams administered every three to four weeks in this phase two trial to confirm the dose we will take to phase three. We believe our phase two 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 profiles a robust therapeutic impact across the multifaceted aspects of TED. We are currently planning to start the phase three 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 registration program in TED at a future investor event. Now I'll turn over to Gil.
spk11: Thank you, Shep, and good afternoon, everyone. Today, I'm going to make a few comments on financial highlights from the quarter ended June 30th, 2024, and then discuss some of the financial implications of the refocus 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 ISO-QI-BEP program, where we have been executing three Phase III 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. we made the difficult decision to right-size 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 cost associated with the completion of the ongoing uveitis study, HS, and PSA studies is expected to range between $30 and $35 million. With respect to the ongoing Iso-KyVep CMC activities and commitments, we expect to incur between $55 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 LonagutanMAP Phase II trial, as Shep just reviewed, funding two Phase III trials for LonagutanMAP, 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 Acceleron. We remain focused on our core mission to accelerate the development and delivery of transformative medicines and 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 II meeting with the FDA on the Lonogutimab program, we plan to hold an investor event focused on the unmet need for thyroid eye disease patients, the detailed rationale underpending dose selection, the outcome of the end-of-Phase II meeting with the FDA, additional data from the ongoing Phase II, and the design of our Phase III development program. In addition, we also continue to project that we'll have top line results from the Iso-KyVep Phase 2b3 trial in uveitis before year end. We anticipate rapidly advancing Lonigutimab 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 Lana-Guden MAP 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 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 Lonagutan MAB and non-recurring payment for costs related to the restructuring and actually inserting ISO-CAIDA commitments. As I mentioned earlier, We now project our cash runway to mid-2027, which we anticipate will fully fund the Lawton-Guzman 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 Meena.
spk04: Thank you, Gil and Sheth, 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 lanagutamab from a position of strength. By suspending new investment for isocibev in PSA and HS, discontinuing SLRN517, and the difficult decision to right-size our organization, we can now focus on rapidly developing lanagutamab as the potential best therapy for thyroid eye disease. We have an outstanding team. We're positioned to deliver high-quality execution of the pivotal program, and we now have the 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 Wannagoodamab 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.
spk01: Thank you so much, and as a reminder to our teleaudience, press star 1-1 to get in the queue and wait for your name to be announced. To remove yourself from the queue, press star 11 again. Please stand by for our first question. And it comes from the line of Derek Archela with Wells Fargo. Please proceed.
spk21: Hey, thanks for taking the questions. Just three quick ones from us. I guess first, what's the rationale for adding the 70 milligram dose in the ongoing phase two for longagutamab? 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 three. So that's the first question. Second question, just for Izzo, 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 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.
spk04: Yeah. Hi, Derek. Hey, thanks for the questions. There's a lot in there, so I'm going to take them in order. Hey, maybe to start with ISO, right, and the partnering question, and then what are we going to do with UV, or, you know, how do we think about uveitis? You know, what I say with respect to partnering, and this is what we've been saying, we're going to do what's best for the program. We're open to all options, and fundamentally, we want to see HS and PSA bring benefit to patients, and that might be with a larger organization that has existing capabilities and infrastructure. So again, 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. So that excludes any contribution from a potential partnership. So I think that's the response on the ISO 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 Lonigutimab and high quality execution on that program and that is the focus for now. And so any additional BD, you know, I don't think we're in a hurry and it's a high bar, right, but we certainly will consider any, you know, opportunistic opportunities, right, over time. And then I think you had questions around the design, right, of the Lona Gutimab Development Program. And maybe it's helpful to frame that up a little bit, right? Just stepping back, you know, 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 three 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 2B3 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, you know, obviously has the potential to accelerate that program. You know, 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 two, right, is, we think, potentially both de-risking and hopefully does allow us to go more quickly into that Phase III program.
spk21: Understood. I guess just to follow up there in terms of, like, again, is that being examined for a potential loading dose, or is the loading dose going to be figured into the Phase III program?
spk04: No. I mean, that's not something we're contemplating now. I mean, we do think the 70 is our dose.
spk20: Understood. Thank you.
spk04: Thanks, Eric.
spk01: Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen. Please proceed.
spk13: Hey, guys. Thanks for the updates. It's encouraging to see the rationalization of pipeline. I want to ask about the Phase III 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?
spk04: Yeah, so maybe I'll start and then I'll turn it over to the team. I mean, you know, 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, you know, the market, the unmet need. What I would say maybe to start is there is very high unmet need. Right and so we, we like that opportunity right to address the unmet needs of patients. There is obviously, you know, very limited. They're 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 end points? I'll turn it over to shop. Maybe to just walk you through that.
spk24: Yeah, no, thanks. Mina. Our trial is designed the same as the UMIRA trial, which is the only large phase three 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 UMIRA did. looking at inflammation in the back of the eye, choreoretinal 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.
spk16: Tyler?
spk18: Yep, all good. Thank you.
spk15: Thank you. One moment for our next question.
spk01: And our next question comes from the line of Yasmine Rahimi with Piper Sandler. Please proceed.
spk06: Thank you so much, team, for sharing these difficult decisions with us and walking us through the rationale. Tim, I guess, could you maybe talk about cohort three? Cohort four has just begun. At what junction, 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 three 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 test studies have become quite competitive in terms of enrollment. So appreciate also color and ensuring, you know, being able to deliver top-line data in an efficient manner. Sorry, there was too many questions in there, but I guess cohort three and, yeah. I appreciate color on that. Thank you. Sorry about that.
spk04: No, for sure. So let's start with cohort three, and then if we miss anything, just remind us, just prompt us. You know, like I just said in our prepared remarks, we are thinking about that phase two program, right, holistically. We think it's most useful to read out the data from that phase two 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, you know, cohort three, you know, really from the totality of that across the phase two program and also how we're thinking about the phase three program. So, you know, 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. You know, so I think that's kind of the design. You know, in terms of the patients that we can potentially serve, we do think that there continues to be very high unmet need, right, in TED patients. And, you know, I think we talked about this before. We are particularly interested in the ability to think about chronic dosing, right? This is a disease that, you know, can flare or regress or, you know, 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 sort of the dose and the regimen, right, to try to address the totality of the disease. So we think that there, you know, again, continues to be unmet need, and we are very interested in exploring that chronic population.
spk02: So what did I miss?
spk06: Yes. No, no, no. Just just yeah, that's an enrollment timing just because it's competitive. Like we feel confident to, you know, just because now several test studies will be ongoing concurrently in phase three. Appreciate some color there.
spk04: Yeah, and look, we feel good about that. I mean, obviously, we're enrolling patients right now, right into the phase two. And, you know, we think that that's, we feel good about that experience and confident going into the phase three trial, you know, somewhat based on that experience. So, you know, understand that there are more trials going on, but we feel good about that.
spk05: Thank you so much. I'll jump back in the queue.
spk01: Thank you. Our next question comes from the line of Akash Tiwari with Jefferies. Please proceed.
spk07: 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.
spk11: Yeah, great. Thanks for the question. This is Gil. You know, as Mina was saying earlier, you know, 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, you know, at any line of this. We also think that with the limited therapeutic options, you know, as a therapy, like ISO may come in here, they'll also have an opportunity to expand the market and diagnosis of this condition. I think in terms of In terms of the pricing question, that's a little early to say, but certainly something that we think about as we go in, but it's a little early to speculate on pricing and the indication.
spk24: Yeah, and on patients that are coming in the study, these are patients with active noninfectious UBI teeth. They will be patients who also have been previously exposed to
spk25: other biologics, except those biologics that are on the IL-17 pathway.
spk15: Understood. Thank you. Thank you.
spk01: Our next question comes from the line of Emily Botnar with HC Wainwright. Please proceed.
spk08: Hi. Thanks for taking the questions. I guess just kind of a clarifying question, in the 70-mg LONI dose, are you enrolling eight patients in total across the three-weekly and four-weekly regimens or the 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 three? 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.
spk04: Yeah. Thanks. Let me start and maybe I'll turn it over to Shep on the hearing. The way that this final cohort is set up, it has eight patients and allows us to try the 70 mgs Q3 and Q4. It also gives us the flexibility to go up to 16 patients, you know, in that cohort. So it is built with some flexibility. You know, obviously those are small numbers, but in totality, right across this phase two 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 and a way to de-risk that phase three program.
spk08: Right?
spk04: And maybe I'll let Sheth address the hearing question.
spk24: Yeah, 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 DOS 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 audiograms. So far, no major changes pertaining to audiogram changes in all of our cohorts.
spk09: Okay, great. Thanks for taking the questions.
spk07: Thank you.
spk01: Thank you. Our next question comes from the line of Vikram Purohit with Morgan Stanley. Please proceed.
spk19: Hi, good afternoon. Thank you for taking our questions. We had two, so first on 517, we're 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 II meeting with the FDA, just curious, what are the main questions you're hoping to have answered about the Phase II development program through that meeting with the agency? Thanks.
spk03: Yeah, maybe I'll start with 517.
spk04: As I said on the call, you know, 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. You know, I think, you know, really we made, again, a strategic sort of prioritization decision and a program decision, and so that's, you know, 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 II meeting, maybe I'll turn that over to Chef.
spk24: Yeah, no, thank you for that question. Our end-of-Phase II meeting is principally a traditional end-of-Phase II, where we would sit with the regulator, FDA, to explore what we have done to date and agree on the benefit-risk that we are showcasing, as was discussed, DOS, And obviously, importantly, the study designs will be at that point in time wanting to proceed within phase three.
spk18: Understood. Thank you.
spk19: And then a quick follow-up, then 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?
spk11: Yeah, so the cash runway guidance, Vikram, we have included the completion of the ongoing uveitis study as well as the HSNPSA. We have included the completion of the Phase II program in lanagutamab, two Phase III trials in the registrational program for lanagutamab as well as potential DLA-enabling activities.
spk18: Okay, understood. Thank you.
spk01: Thank you. And our last question is coming from the line of Samantha Semenkov with Citi. Please proceed.
spk07: Hi, good afternoon, and thanks for taking the questions. I just have a couple on money. I see in your corporate deck you have, I think, with 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 one. So the question is, why do you think this might be the case? Why is it only in cohort one and none in the cohort two patients so far? Is there something common between these three patients? Or is perhaps the loading strategy, loading dose strategy, exporting cohort two, do you think that's driving the difference? We'd just love any thoughts you could provide there.
spk04: Yeah, look, maybe I would just start with, you know, what we are showing is what we saw in cohort two, and I would note that there were none in cohort one, sorry, there were none in cohort two, and then maybe I will turn it over to Chef for some more detail.
spk24: Yeah, no, thanks for the question, Samantha. Number one, we have not seen any reason why these patients are 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 24 hours it resolved and it happened the same. Remember, cohort one 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 code, too, gave 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.
spk25: And to date, we have not seen anything that speaks to sensorineural hearing loss or impairment.
spk14: Great. Thanks so much for taking the question.
spk01: Thank you. And with no further questions in the queue, I will turn it back to Tyler Martyniak for his concluding comments.
spk12: Thank you, Carmen. Thank you all for joining today's call, for the opportunity to share with you these exciting corporate updates from Acelerin. As noted in the press release, we look forward to sharing more information about our plans for Lana Gutimab 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.
spk01: And thank you all who participated in today's conference. You may now disconnect. Music Thank you. Thank you. Good afternoon and welcome to the Accelerin, 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?
spk12: 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 acelerin.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.
spk17: The agenda for today's call is on the screen.
spk12: We will review the corporate strategy updates announced in our press release, as well as positive top-line data from the phase three trial of izakaibet and hydradenitis suppurativa. We will also provide an update on the Lana-Gudimeb 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. Shet Mpofu, our Chief Medical Officer, and Gil Labruchery, our Chief Financial Officer and Chief Business Officer. I will now turn the call over to Meena.
spk04: Thanks, Tyler, and thanks, everyone, for joining us today. Earlier today, we announced positive Phase III results for isoCyBev in HydroNIDA SuperTIVA, 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 III readout for Isaac Hiveff in HF. We met the primary endpoint of high score 75 and are especially pleased with the compelling response rates in high score 90 and 100 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 2b3 readout we announced earlier this year, and which were presented in a late-breaking session at ULAR in June. Collectively, the data in HS and PSA further validate our long-standing view that isokidab 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 Lonagutamab, which we believe has the potential to improve upon clinical response and convenience versus the standard of care in thyroid eye disease. We plan to complete the ongoing trials of isokibab in HS and PSA, but we will not start new trials in these indications. We do plan to continue the ongoing phase 2b3 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 2b3 data be positive, we anticipate one additional Phase 3 trial of roughly 200 to 250 patients would be required for registration. The ongoing trial is fully enrolled with approximately 100 patients. In addition to these ISACIBAP updates, we've decided to stop internal development of SLRN 517, our early anti-CKIP 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 Acelerin'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 Lonigutimab and extend our cash runway to mid-2027. By focusing future capital investment on Lonigutimab, we will be well-positioned to fund our ongoing and planned TED trials through the BLA submission. Shep will review our overall strategy and ongoing activity for Lonigutimab 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 2b3, 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 a 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 three program. With that, I'd like to turn the call over to Chef.
spk23: Thank you, Mina, and hello, everyone.
spk24: I'm very pleased to share with you today positive phase three data of isocubab inhydrodinitis suppurativa, or HS, and provide a program update on lonicultamab in thyroid eye disease. Let me start with HS. This regulated interleukin-17A activity plays a pivotal role in hydradenitis suppurativa pathogenesis. Multi-domain disease resolution is underachieved with available current therapies. An unmet need exists for therapies demonstrating efficacy across multiple disease manifestations, including abscess, inflammatory nodules, and draining tunnels. Isocubab is a small protein therapeutic designed to selectively inhibit interleukin-17A with high potency through tight binding affinity. The small molecular size of Isoquibab 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 three trial of Isoquibab 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 izocubab 160 mg weekly or placebo. The inclusion criteria and design is similar to other Phase III studies, with a primary endpoint here for the first time in a Phase III of high score 75 at week 12. At week 16, placebo patients were switched to receive Isocubec 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 Isocubec treatment group and placebo. typical of a patient population with moderate to severe HS and comparable to other global phase III pivotal trials. 103 patients on the Isocubeb arm and 112 patients in the placebo arm completed the study through week 12, thus having approximately 20% on Isocubeb arm and approximately 13% on placebo arm discontinued treatment. with a delta of around 7% between the two groups. Please note the most common reasons leading to discontinuation on Isoquibab were mild AEs, and there were no notable differences between Isoquibab and placebo in terms of loss to follow-up and withdrawal of consent rates. In this trial, Isoquibab 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 eyes-occupied patients achieving a high score 75 response. That is a 75% reduction in abscess and inflamed nodules, versus 21% for placebo. Looking at the two-thirds of patients' worth of week 16 data, we can observe an increase in response up to 40% on Isoquibept versus 20% on placebo. When we look at higher orders of response, looking at high score 90 and high score 100, Isoquibept again achieved statistically significant responses at week 12 versus placebo, with approximately one in four patients on Isoquibept achieving these deeper responses versus placebo. Notably, the deltas for high score 90 and 100 were maintained at week 16. Here you see the response across the continuum of high score 50 to 100 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 Izoquibab 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 Izoquibab 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 Isoquibab with only three cases showing in placebo. There was no IBD, liver toxicity, suicidal ideation behavior in the Isoquibab treatment arm. In conclusion, Isocubeb's safety is in line with our past experience, and Isocubeb 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 III trial for Isocubeb in HS, which builds on the Phase III data released in PSA earlier this year. Now, turning our attention to Lonigutmab, 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, 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 a rapid, deeper, disease-modifying effects that are durable across TERT manifestation and result in improved patient quality of life, safety, and convenience will be important for patients. Learning Good Map is a next-generation recombinant humanized IgG1 monoclonal antibodies against human IgF1 receptor being developed to treat severe manifestations of TERT. As shown in the middle cartoon on the slide, Lonigutma binds IGF-1-ara 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 kilo-delta affinity measured around 30 picomolar, and a specificity which triggers rapid internalization and degradation within minutes of the IGF-1 receptor. thus eliminating it from the surface of the IGF-R1-expressing cells with potential to maintain IGF-1 within homeostatic levels. IGF-1-RI 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 Lonnie Goodmap 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 one proof of concept portion of our ongoing Lonely Group Math trial earlier this year, and we are now embarking on a dose ranging phase two portion across four dose groups levels, as you can see depicted on the right part of the slide projected. The Phase II 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 C mean, and number two, to enable establishment of an optimal dose selection for Phase III 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 C-max 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 milligrams administered every three to four weeks in this phase two trial to confirm the dose we will take to phase three. We believe our phase two 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 profiles a robust therapeutic impact across the multifaceted aspects of TED. We are currently planning to start the phase three 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 registration program in TED at a future investor event. Now I'll turn over to Gil.
spk11: Thank you, Shep, and good afternoon, everyone. Today, I'm going to make a few comments on financial highlights from the quarter ended June 30th, 2024, and then discuss some of the financial implications of the refocus 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 ISO-QI-BEP program, where we have been executing three Phase III 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 cost associated with the completion of the ongoing uveitis study, HS, and PSA studies is expected to range between $30 and $35 million. With respect to the ongoing ISO-QI-VEP CMC activities and commitments, we expect to incur between $55 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 LonagutanMAP Phase II trial, as Shep just reviewed, funding two Phase III trials for LonagutanMAP, 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 Acceleron. We remain focused on our core mission to accelerate the development and delivery of transformative medicines and 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 II meeting with the FDA on the Lonogutimab program, we plan to hold an investor event focused on the unmet need for thyroid eye disease patients, the detailed rationale underpending dose selection, the outcome of the end-of-Phase II meeting with the FDA, additional data from the ongoing Phase II, and the design of our Phase III development program. In addition, we also continue to project that we'll have top line results from the Iso-KyVep Phase 2b3 trial in uveitis before year end. We anticipate rapidly advancing Lonigutimab 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 Lana-Guden MAP 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 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 Lonigut and MAB and non-recurring payment for costs related to the restructuring and actually inserting ISO-CIVA commitments. As I mentioned earlier, We now project our cash runway to mid-2027, which we anticipate will fully fund the Lawton-Guzman 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 Meena.
spk04: Thank you, Gil and Sheth, 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 lanagutamab from a position of strength. By suspending new investment for isocibev in PSA and HS, discontinuing SLRN517, and the difficult decision to right-size our organization, we can now focus on rapidly developing lanagutamab as the potential best therapy for thyroid eye disease. We have an outstanding team. We're positioned to deliver high-quality execution of the Pivotal program, and we now have the 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 Juana Gutemap 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.
spk01: Thank you so much, and as a reminder to our teleaudience, press star 1-1 to get in the queue and wait for your name to be announced. To remove yourself from the queue, press star 11 again. Please stand by for our first question. And it comes from the line of Derek Archela with Wells Fargo. Please proceed.
spk21: Hey, thanks for taking the questions. Just three quick ones from us. I guess first, what's the rationale for adding the 70 milligram dose in the ongoing phase two for longagutamab? 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 three. So that's the first question. Second question, just for Izzo, 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 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.
spk04: Yeah. Hi, Derek. Hey, thanks for the questions. There's a lot in there, so I'm going to take them in order. Hey, maybe to start with ISO, right, and the partnering question, and then what are we going to do with UV, or, you know, how do we think about uveitis? You know, what I say with respect to partnering, and this is what we've been saying, we're going to do what's best for the program. We're open to all options, and fundamentally, we want to see HS and PSA bring benefit to patients, and that might be with a larger organization that has existing capabilities and infrastructure. So again, 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. So that excludes any contribution from a potential partnership. So I think that's the response on the ISO 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 Lana-Gudimab and high quality execution on that program, and that is the focus for now. And so any additional BD, you know, I don't think we're in a hurry, and it's a high bar, right, but we certainly will consider any, you know, opportunistic opportunities, right, over time. And then I think you had questions around the design, right, of the Lona Gutimab Development Program. And maybe it's helpful to frame that up a little bit, right? Just stepping back, you know, 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 three 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 2B3 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, you know, obviously has the potential to accelerate that program. You know, 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 two, right, is, we think, potentially both de-risking and hopefully does allow us to go more quickly into that Phase III program.
spk21: Understood. I guess just to follow up there in terms of, like, again, is that being examined for a potential loading dose, or is the loading dose going to be figured into the Phase III program?
spk04: No. I mean, that's not something we're contemplating now. I mean, we do think the 70 is our dose.
spk20: Understood. Thank you.
spk04: Thanks, Eric.
spk01: Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen. Please proceed.
spk13: Hey, guys. Thanks for the updates. It's encouraging to see the rationalization of pipeline. I want to ask about the Phase III 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?
spk04: Yeah, so maybe I'll start and then I'll turn it over to the team. I mean, you know, 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, you know, 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, you know, 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.
spk24: Yeah, no, thanks, Meena. Our trial is designed the same as the UMIRA trial, which is the only large phase three 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 UMIRA did. looking at inflammation in the back of the eye, choreoretinal 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.
spk16: Tyler?
spk18: Yep, all good. Thank you.
spk15: Thank you. One moment for our next question.
spk01: And our next question comes from the line of Yasmine Rahimi with Piper Sandler. Please proceed.
spk06: Thank you so much, team, for sharing these difficult decisions with us and walking us through the rationale. Tim, I guess, could you maybe talk about cohort three? Cohort four has just begun. At what junction, 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 three 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 test studies have become quite competitive in terms of enrollment. So appreciate also color and ensuring, you know, being able to deliver top-line data in an efficient manner. Sorry, there was too many questions in there, but I guess cohort three and, yeah. I appreciate color on that. Thank you. Sorry about that.
spk04: No, for sure. So, let's start with cohort three, and then, hey, if we miss anything, just remind us, just prompt us. You know, like I just said in our prepared remarks, we are thinking about that phase two program, right, holistically. We think it's most useful to read out the data from that phase two 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, you know, cohort three, you know, really from the totality of that across the phase two program and also how we're thinking about the phase three program. So, you know, 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. You know, so I think that's kind of the design. You know, in terms of the patients that we can potentially serve, we do think that there continues to be very high unmet need, right, in TED patients. And, you know, I think we talked about this before. We are particularly interested in the ability to think about chronic dosing, right? This is a disease that, you know, can flare or regress or, you know, 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 sort of the dose and the regimen, right, to try to address the totality of the disease. So we think that there, you know, again, continues to be unmet need, and we are very interested in exploring that chronic population.
spk02: So what did I miss?
spk06: Yes. No, no, no. Just just yeah, that's an enrollment timing just because it's competitive. Like we feel confident to, you know, just because now several test studies will be ongoing concurrently in phase three. Appreciate some color there.
spk04: Yeah, and look, we feel good about that. I mean, obviously, we're enrolling patients right now, right into the phase two. And, you know, we think that that's, we feel good about that experience and confident going into the phase three trial, you know, somewhat based on that experience. So, you know, understand that there are more trials going on, but we feel good about that.
spk05: Thank you so much. I'll jump back in the queue.
spk01: Thank you. Our next question comes from the line of Akash Tiwari with Jefferies. Please proceed.
spk07: 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.
spk11: Yeah, great. Thanks for the question. This is Gil. You know, as Mina was saying earlier, you know, 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, you know, at any line of this. We also think that with the limited therapeutic options, you know, as a therapy, like ISO may come in here, they'll also have an opportunity to expand the market and diagnosis of this condition. I think in terms of In terms of the pricing question, you know, that's a little early to say, but certainly something that we think about as we go in, but it's a little early to speculate on pricing and the indication.
spk24: Yeah, and on patients that are coming in the study, these are patients with active noninfectious UBI teeth. They will be patients who also have been previously exposed to other biologics, except those biologics that are on the IL-17 pathway.
spk15: Understood. Thank you.
spk01: Thank you. Our next question comes from the line of Emily Botnar with HC Wainwright. Please proceed.
spk08: Hi. Thanks for taking the questions. I guess just kind of a clarifying question, in the 70-mg LONI dose, are you enrolling eight patients in total across the three-weekly and four-weekly regimens or the 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 three? 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.
spk04: Yeah. Thanks. Let me start and maybe I'll turn it over to Shep on the hearing. The way that this final cohort is set up, it has eight patients and allows us to try the 70 mgs Q3 and Q4. It also gives us the flexibility to go up to 16 patients, you know, in that cohort. So it is built with some flexibility. You know, obviously those are small numbers, but in totality, right across this phase two 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 and a way to de-risk that phase three program.
spk25: Right?
spk04: And maybe I'll let Sheth address the hearing question.
spk24: Yeah, 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 DOS 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 audiograms. So far, no major changes pertaining to audiogram changes in all of our cohorts.
spk09: Okay, great. Thanks for taking the questions.
spk07: Thank you.
spk01: Thank you. Our next question comes from the line of Vikram Purohit with Morgan Stanley. Please proceed.
spk19: Hi, good afternoon. Thank you for taking our questions. We had two. So first on 517, we're 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 II meeting with the FDA, just curious, what are the main questions you're hoping to have answered about the Phase II development program through that meeting with the agency? Thanks.
spk03: Yeah, maybe I'll start with 517.
spk04: As I said on the call, you know, 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. You know, I think, you know, really we made, again, a strategic sort of prioritization decision and a program decision, and so that's, you know, 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 II meeting, maybe I'll turn that over to Chef.
spk24: Yeah, no, thank you for that question. Our end-of-Phase II meeting is principally a traditional end-of-Phase II where we would sit with the regulator, FDA, to explore what we have done to date and agree on the benefit-risk that we are showcasing, as was discussed, DOS, And obviously, importantly, the study designs will be at that point in time wanting to proceed within phase three.
spk18: Understood. Thank you.
spk19: And then a quick follow-up, then 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?
spk11: Yeah, so the cash runway guidance, Vikram, we have included the completion of the ongoing uveitis study as well as the HSNPSA. We have included the completion of the Phase II program in lanagutamab, two Phase III trials in the registrational program for lanagutamab as well as potential DLA-enabling activities.
spk18: Okay, understood. Thank you.
spk01: Thank you. And our last question is coming from the line of Samantha Semenkov with Citi. Please proceed.
spk07: Hi, good afternoon, and thanks for taking the questions. I just have a couple on money. I see in your corporate deck you have, I think, with 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 one. So the question is, why do you think this might be the case? Why is it only in cohort one and none in the cohort two patients so far? Is there something common between these three patients? Or is perhaps the loading strategy, loading dose strategy, exporting cohort two, do you think that's driving the difference? We'd just love any thoughts you could provide there.
spk04: Yeah, look, maybe I would just start with, you know, what we are showing is what we saw in cohort two, and I would note that there were none in cohort one, sorry, there were none in cohort two, and then maybe I will turn it over to Chef for some more detail.
spk24: Yeah, no, thanks for the question, Samantha. Number one, we have not seen any reason why these patients are 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 24 hours it resolved and it happened the same. Remember, cohort one 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 code, too, gave 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.
spk14: Great. Thanks so much for taking the question.
spk01: Thank you. And with no further questions in the queue, I will turn it back to Tyler Martyniak for his concluding comments.
spk12: Thank you, Carmen. Thank you all for joining today's call, for the opportunity to share with you these exciting corporate updates from Acelerin. As noted in the press release, we look forward to sharing more information about our plans for Lana Gudimab 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.
spk01: And thank you all who participated in today's conference. You may now disconnect.
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