Acelyrin Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 14, 2023

There are 9 speakers on the call.

Operator

Corporate updates. This conference call is being recorded today, August 14, 2023. I would now like to turn the conference call over to Tyler Marciniak, Vice President of Investor Relations, Communications and corporate operations for Acelaren. Tyler?

Speaker 1

Thank you. Good afternoon, everyone, and thank you for joining us. Before we begin, I'd like to remind the audience that this conference call will contain forward looking statements such as those related to our development milestones, pipeline and program potential of IZAKIRAV and our ability to commercialize our product candidates. These forward looking statements involve risks and uncertainties factors that could cause our actual results and events to differ materially from those contained in such statements. We urge you to review the Risk Factors section of our quarterly report filings on Form 10 Q for the quarter ended June 30 filed with the SEC and also available through the Investor Relations section of our website at acelerant.com.

Speaker 1

Along with statements contained in today's press release and our slide presentation, which identify certain factors that could cause our actual results, performance and events to differ materially from those contained in such forward looking statements. Additionally, these statements are based on information available to us today, August 14, 2023, and we undertake no obligation to update them as circumstances may change. Quarters. Joining us on today's call are Doctor. Shao Lee Lin, our Founder and Chief Executive Officer Doctor.

Speaker 1

Paul Peloso, our Chief Medical Officer and Gilda Broussery, our Interim Chief Financial Officer. I will now turn the call over to Doctor. Lin. Shao Lee?

Speaker 2

Thank you, Tyler, and good afternoon, everyone, and thank you for joining us for AcelRent's first quarterly earnings call as a public company. Accelerate is a late stage clinical biopharma company focused on identifying, acquiring and accelerating the development commercialization of transformative medicines. We are driven by our sense of urgency to bring life changing therapies to patients globally, core value that we refer to as courageous care. And our initial focus is on the treatment of immunologic diseases, an area where our team brings industry leading expertise. We acquired our portfolio of product candidates with the intent to develop and commercialize novel therapies that we believe may provide the opportunity to offer clinically meaningful differentiated benefit for patients.

Speaker 2

Our strategy is to identify candidates we believe are diamonds in the rough. Where based on molecular characteristics, our collected experience and expertise and the evolving scientific and medical understanding, we can establish development plan that tests whether or not our hypotheses are correct. And if so, then what the potential benefits could be for patients. Since our founding in 2020, we have created a robust portfolio. This includes our lead program, Izakayvep, which is a small therapeutic protein with high potency and small molecular size, we believe can drive clinically meaningful differentiated benefit for patients across multiple indications, truly a potential pipeline and program.

Speaker 2

Beyond the ZikaVE, we're also advancing our earlier clinical stage programs, onezutumab SLN-five seventeen, initially being developed with thyroid eye disease and chronic urticaria, respectively. We have previously shared some of the compelling data with isekaiwa across 2 indications, hidradenitis suppurativa and psoriatic arthritis. Each of these and even more so, but both together have supported our original hypothesis that the small size and high potency imizakiva could offer the potential clinical trials for clinically meaningful differentiated therapeutics. Later in the call, I look forward to sharing with you more context for our clinical progress, including new data related to improvements in training tunnels from the open label Part A of our Phase IIbIII trial of isacibank in HS. In addition to continuing to advance our leading immunology portfolio, we continue to build an exceptional team of experienced biopharma leaders with proven track record key areas of building strong, innovative and diverse teams across the healthcare industry.

Speaker 2

Most recently, we had the pleasure of welcoming veteran immunology sales and marketing leader, Ken Locke, to our team as Chief Commercial Officer. This is a key leadership position for us as we advance isakayebev toward commercialization. Ken brings decades of commercial leadership expertise in dermatology and rheumatology, and we are looking forward to his contributions to our ongoing success. Also, we previously announced that Marty Deere, Chief Financial Officer and Chief Business Officer, had resigned. Marty served with us during important times in the company, and we thank her for her contributions and wish her well in her future endeavors.

Speaker 2

I am pleased that Gil Labroucherie has agreed to join us as Interim CFO. Gil previously served as CFO of the company from July until November of 2022 when he left Biotech to address personal family matters. His availability at this time enables seamless continuity of ongoing activities, and he will address our financials in greater detail later on this call. However, I do want to make one more comment related to the financials, and that is to reiterate our strong financial position from which we plan to deliver on key milestones across several indications. Following our successful upsized IPO in May, We are fortunate to be operating from a position of strength with more than $820,000,000 at June 30.

Speaker 2

We continue to build a leading sustainable biopharmaceutical company with the goal of serving multiple large global markets clinically differentiated new medicines in immunology and beyond. We are incredibly grateful to all of our investors, new and existing, for their continued support and confidence in our ability to deliver on our ambitious mission. Given this is our first earnings call, I'd like to spend a little time diving deeper into the exciting and rapid progress we continue to make with our clinical programs. Today, I will review our lead program, isacaybev, across its multiple indications. And then I will turn the call over to Chief Medical Officer, Paul Poloso, for a review of our promising earlier stage programs with Lonagutumab NSR-five seventeen.

Speaker 2

Recall that Intacaybev is a small protein therapeutic designed to inhibit IL-17A with high potency Through tight binding affinity, the potential for robust tissue penetration due to a small molecular size, about oneten the size of a monoclonal antibody and an albuminibining domain that extends half life. And we have hypothesized that this high potency and small size can lead to clinically meaningful differences in efficacy relative to the market in monoclonal antibodies against this target and without the introduction of new safety liabilities. We are pursuing late stage development of viscovec across a number of indications where IL-seventeen inhibition has been validated. These include HS, PSA, uveitis and axial spondyloarthritis. Let me begin with the progress we've made with our HS program.

Speaker 2

HS is a chronic inflammatory disease characterized by skin abscesses, inflammatory nodules, draining tunnels, scar tissue, malodor and pain, quarters, often resulting in permanent disfigurement and social stigma and all of this contributing to poor quality of life. HS affects more than 300,000 patients in the U. S. With more than half of these patients considered moderate to severe. There is currently only one FDA approved treatment for HS significant need remains for new medicines that provide more rapid and complete resolution of disease.

Speaker 2

We've long known that drug exposures in HS quarters are lower compared to other inflammatory conditions and had hypothesized that the high quality of isotype 2i-17a as well as the small molecular size, again about a tenth of the size of a monoclonal antibody, could generate deep levels of clinical response due to robust tissue penetration and potent target engagement. We designed our Phase IIbIII trial with a Part A and a Part B. Part A was an open label study of 30 patients that we conducted to test our hypothesis. Our benchmark for success in Part A was to determine if we could demonstrate clinical response as good as or better than the leading data available and without introducing new safety liability relative to the safety profile of the marketed IL-17A inhibitors. We presented results from Part A during a late breaker podium session at AAD earlier this year and reported high orders of efficacy responses at 12 weeks, including achievement of highscore100 response in a third of patients.

Speaker 2

Highscore100 is a stringent measure of disease resolution in HS as it requires the same individual to achieve both abscess and nodule resolution without formation of new draining tunnels. Today, we also announced additional analysis from Part A of the Phase IIbIII trial in HS from patients with at least 1 draining tunnel at baseline. It is important to note that this analysis is based off of a small data set numbers of patients in the high single to low double digits. In this data, treatment with LINZESS Kayvek resulted in improvement of at least 1 draining tunnel as early as week 4 in 2 thirds of continuing patients. Week 4 was the first time point assessed and this percentage remains consistent to continuing patients through LEAP 12.

Speaker 2

Furthermore, half of continuing patients improved by at least 2 draining tunnels by week 8, which remained consistent through week 12. This is an exciting development for patients because of the speed of response, its ultimate magnitude and consistency over time. The combination of the high score 100 results as presented at AAD and today's data on numbers of draining tunnels are encouraging. We believe that the full control of active inflammation is important to enable the early improvements observed in the number of training tunnels. As a reminder, Part B of the Phase IIbIII trial is a double blind placebo controlled randomized trial of more than 170 patients intended to serve as part of the registrational package for isotypebib in HS.

Speaker 2

Enrollment of Part B completed ahead of schedule, accelerating anticipated top line results into the Q3 of 2023 from the end of 2020. In Part B, participants were randomized to receive either 160 milligrams of isotype up weekly or every other week for placebo. An independent data monitoring committee conducted a preplanned review of unblinded efficacy and safety data from Part B and confirmed the dose of 160 milligrams weekly for the 2nd Phase 3 trial of HS. Consistent with the understanding that higher exposures enabled by the high potency and small size of isatyma are required for greater efficacy in HS. With the dose confirmed in May, we initiated and dose the first patient in the 2nd Phase III trial in June, and that trial continues to actively enroll.

Speaker 2

As in other chronic inflammatory conditions, maintaining therapeutic exposures has been demonstrated as critical to maintaining or improving disease control over time. For Xicago, this has been validated in PSA with our Phase 2 positive results at week 16 that continue to deepen out commercial studies. Turning now to our late stage program in PSA, where we are evaluating isekaipt in a Phase IIbIII clinical trial. Psoriatic arthritis is a chronic inflammatory disease with multiple clinical manifestations, including arthritis, psoriasis, spondylitis, bactylitis and importantly, emphyseitis, which is an inflammation of the strong dense poorly vascular tissues that anchor our ligaments and tendons to both. Emphasize impacts the majority of moderate to severe PSA patients and has been historically very difficult to treat.

Speaker 2

It is a marker of disease severity and a source of residual pain and physical dysfunction that impact the quality of life for patients. There are approximately 1,600,000 PSA patients in the U. S. And about 60% of those are considered moderate to severe. Here again, as with HS, more complete and more rapid resolution At EULAR in June of 2022, we presented 16 week placebo controlled data from our Phase II trial in PSA showing that isotype F demonstrated clinically meaningful benefits across these manifestations, including 52% achieving ACR50 response, a marker arthritis improvement, 85% achieving PASI-seventy five response and 88% achieving resolution of emphyseitis, which Well, not head to head, to our knowledge is a level of resolution that has not previously been reported for any other agent.

Speaker 2

As in HS, this also validates our hypothesis that the high potency and small size of isacaybe could make a difference in difficult to treat tissues. In April of this year, we were excited to report 46 week results from the Phase II trial in PSA that showed continued deepening improvements beyond 16 weeks across key manifestations of the disease. Of participants receiving isocciabab 80 milligrams every other week, 79% achieved ACR50 response versus 52% at week 16. And even higher orders of clinical response, including resolution of disease, were observed with 50% achieving ACR 70 response, 71% achieving PASI 100 response and 89% achieving endocitis resolution. As a rheumatologist, these are exciting results all contributing to even greater improvements in quality of life for PSA patients.

Speaker 2

Internal modeling has suggested that the magnitude of clinical response will continue to increase with longer duration of treatment as has been demonstrated. The model also predicted further differentiation may be achieved with increasing dose levels. Supported by that modeling and as a result of the Phase 2 data at 16 weeks last year, we accelerated the initiation of a Phase 2bthree trial in psoriatic arthritis evaluating a range of doses, including higher doses than the completed Phase II trial. Enrollment in this trial has been complete, accelerating anticipated top line results into Q1 2024 from mid-twenty 24. The totality of evidence across these two independent data sets of HS and PSA continues to support the hypothesis The high potency and small molecular size of isoclonal fat can lead to clinically meaningful differentiated benefits for patients.

Speaker 2

In HS, high school 100 responses in 33 percent of patients at week 12 and improvements in draining tunnels within the 1st month of therapy. And in PSA, resolution of important manifestations of disease, including joints, skin and endocytes, all associated with residual pain and severity of disease We are also planning to initiate a Phase 3 program evaluating it isitagib for the treatment of axial spondylaraphritis in 2024. Emphyseitis is a central feature of axolotl and we believe the rates of emphyseitis resolution demonstrated in Phase 2 psoriatic arthritis trial suggest the potential for clinically meaningful differentiated benefits for patients with this disease as well. Finally, a Phase IIbIII clinical trial of vizakayve as a treatment for uveitis is enrolled. Previously reported data for secukinumab delivered have validated the inhibition of IL-17A as a potential therapeutic approach for uveitis.

Speaker 2

A clinical dose response demonstrated with IV levels of secukinumab exposure. However, that response was lost with lower levels of exposure when delivered subcutaneously, leading to discontinuation in development of secukinumab in uveitis. Based on its high potency and small size, isletribec can achieve secukinumab IV levels of closure with a single subcutaneous injection. We believe this provides the potential to unlock this mechanism as an approach to treating uveitis will review our opportunities with our earlier stage clinical programs, lonabutumab and 517. Paul?

Speaker 3

Thank you, Shao Lee, and good afternoon, everyone. As Shao Lee noted earlier, we've added 2 promising programs to our portfolio earlier this quarters and have quickly advanced these product candidates into important clinical studies to accelerate their development in areas of critical unmet need for patients. Lonagutumab is a humanized IgG-one monoclonal antibody against IGF-1R With up to 75 fold higher potency than teprotumumab and it's currently under investigation for the treatment of thyroid eye disease TED is a potentially vision threatening progressive chronic autoimmune disease in which the eye muscles, eyelids, tear glands and fatty tissue behind the eye become inflamed and enlarged. It's estimated there are more than 100,000 chronic TED patients in the United States. Recent studies have demonstrated that the inhibition of IGF-1R is effective in patients with both acute as well as chronic thyroid eye disease.

Speaker 3

There is currently a single FDA approved therapy for TED that is administered intravenously and is a fixed 6 months course. As such, opportunities remain for improved efficacy, safety and more convenient administration. As a chronic inflammatory illness, a fixed course dosing regimen is insufficient for some patients, safety considerations, including hearing impairment and hearing loss also remain a concern for the current standard of care recent updates from the FDA to the warnings and precautions of the teprotumumab label highlight hearing impairment as a serious, potentially permanent side effects. Hearing impairment may be directly related to targeting IGF-1R IGF-one functions to regenerate cells of the inner ear subsequent to auditory insults. Finally, The need for intravenous infusion complicates care between patients and facilities, which we avoid with patient administered subcutaneous delivery.

Speaker 3

We hypothesized That the characteristics of Lonagunumab can optimize efficacy by maintaining minimum drug levels needed to achieve improved depth and durability of response, limit safety liability including hearing impairment and hearing loss, Potentially associated with high maximum drug concentrations and maximize patient convenience through single injection subcutaneous delivery. While teprotumumab dosing requires 3 to 5 doses to achieve optimal minimum drug levels, lonigutumab may achieve these minimal drug levels with the first dose with the potential to better control disease earlier. There is potential for more complete control throughout the disease course with chronic dosing beyond 6 months facilitated through the potential for at home subcutaneous injections. Our goal is to treat patients to complete and lasting resolution of signs and symptoms. Furthermore, we believe that the characteristics of lonigutumab that enable subcutaneous delivery also allow for the reduction of the maximum serum concentrations incurred with current intravenous therapy As decreasing these maximum concentrations limits the potential for an anti IGF-one therapy to cross the blood labyrinth barrier and inhibit the normal function of IGF-one to regenerate the cells of the inner ear.

Speaker 3

Finally, based on published exposure response modeling of teprotumumab and the relative potency of lanagutumab As well as our completed single ascending dose trial, Lonagutumab achieved targeted exposures when given as a single subcutaneous injection. The Phase III proof of concept trial Uplonogutumab delivered subcutaneously in thyroid eye disease patients is ongoing and we expect to announce top line results by late 2023, early 2024. FLRN-five seventeen is a monoclonal antibody targeting cKIT, the inhibition of which can reduce mast cell proliferation and activity in various allergy and inflammatory diseases. With FLRN-five seventeen, we are aiming to address SLRN517 is a fully human IgG1 monoclonal antibody With no agonistic activity that is no mast cell degranulation demonstrated high potency against targets across binding and functional assays and therefore has the potential for low subcutaneous volume injections. The fully human nature of SLRN-five seventeen should also limit its potential for immunogenicity and therefore the potential for acute reactions.

Speaker 3

Additionally, Its high potency and relatively short half life of approximately 16 days allows for rapid depletion of mast cells, While limiting opportunity for the adverse effects of cKIT inhibition on spermatogenesis, hair color hematopoietic cells including neutrophils. In addition to our initial focus In chronic urticaria, SLRN-five seventeen also has the potential to address several other mast cell driven disorders, including prurigo nodularis, bolus pemphigoid and eosinophilic esophagitis. The Phase onetwo proof of concept trial of SLRN-five seventeen is ongoing and will include healthy volunteers and chronic urtic carrier patients. We expect top line results in the second half of twenty twenty four. With that clinical overview, let me turn the call over to Gil for a review of our financials.

Speaker 3

Gil? Thank you, Paul, for that overview of our earlier stage clinical programs, and good afternoon, everyone. First of all,

Speaker 4

I could not be more pleased to reunite with the team in Accelerant, a very talented and experienced team that I thoroughly enjoy working building a business I know well. As you just heard from Chiao Lee and Paul, it has truly been a transformative year for Aceleren, On the financial front, in early May, we were delighted to close an upsized initial public offering, which included the full exercise of the underwriters option at $18 per share, which was at the high end of the pricing range. The IPO generated $621,000,000 in gross proceeds for Accelerant. At June 30, cash and cash equivalents and short term marketable securities totaled $823,000,000 Research and development expenses were $30,000,000 for the 2nd quarter as compared to $12,700,000 for the same period 2022. Comparing 2023 to 2022, the company has undergone significant growth, including the expansion of the Isoquaybevac program across multiple indications and the addition of 2 programs in 2023, both of which are now in clinical stage development.

Speaker 4

General and administrative expenses were $12,700,000 for the Q2 as compared to $2,200,000 for the same period in 2022. This increase in expenses was primarily a result of expanding our organizational capability to support the development and commercialization Q2 of 2023 compared to $14,500,000 for the Q2 of 2022. And now I would like to turn it back to Shao Lee. Shao Lee?

Speaker 2

Thank you, Gil. As you've heard, it's been a tremendous year for Celera. We've had much to look forward to as we continue to execute on our vision to accelerate the development commercialization of transformative medicines for patients. Our lead program is a kind of that is a true pipeline in the program with potential across multiple indications representing multibillion dollar opportunities in the aggregate. We now have meaningful evidence in 2 independent data sets In HS and PSA, supporting our hypothesis, the high potency and small size of ezocaipt can lead to clinically meaningful differentiated benefits for patients, including resolution of important manifestations of each disease associated with residual pain, severity of disease as well as physical function, quarters.

Speaker 2

Both londegugumab and ECELLRIM-five seventeen continue to progress through early clinical stage trials and we believe have potential similar to isekaipt to address significant unmet efficacy, safety and convenience needs in thyroid eye disease, chronic urticaria and beyond. These programs are expected to collectively deliver multiple important data readouts through the end of 2024 that include HS Phase IIbIII trial, which was previously shared as expected in Q3 that was accelerated from the end of the year. The PSA Phase 2bthree trial, which is now expected in Q1 accelerated from mid-twenty 24, both of which These are ambitious goals, and we feel confident we will achieve them, thanks to our experienced team, the right pipeline and strong financial foundation to enable our execution. We have created a culture designed to foster robust innovation at all stages of drug development And one that encourages collaborative teams and harnesses the power of inclusion and diversity to fuel creative solutions. You have seen the results of this incredible culture, and we look forward to continuing to deliver our promise for patients and for our shareholders.

Speaker 2

Finally, before I open the call to your questions, I want to thank all of our patients, investigators, investors and employees who are partnering with us on this mission to accelerate the development and delivery of transformative new medicines

Speaker 1

and

Operator

questions. Our first question comes from the line of Tyler Van Buren from TD Cowen.

Speaker 5

Hey, guys. Good afternoon. Congrats on all the progress. Great to see the new HS data and the PSA pivotal accelerated to Q1. I have a couple for you guys on HS given all the near term focus.

Speaker 5

The first one is for the new Draining Tunnel HS data from Part A that you disclosed that focuses on improvement In at least 1 or 2 draining tunnels, can you help us put that into context with the Moon Lake sunilocumab data recently reported, which focuses on change in DT counts or DT-one hundred and or any data that bimekizumab has presented? And then The second question is for the upcoming Phase IIbIII HS data readout. What is the ultimate goal in terms of efficacy? Is it to show a placebo adjusted high score 75 rate that is equivalent or better than what Vimy and That's okay, put up in Phase 2 or on top of this, is it also to demonstrate high score 100 responses in a meaningful percentage of patients? Thanks.

Speaker 2

Thanks for those questions, Tyler. Really appreciate it and great to be here today with everybody. So in terms of the draining tunnel counts, we're super excited to be able to share that with you today. I think the most important new development there is to our knowledge, this is the first report of improvement in training trials As early as 1 month into treatment sort of across the therapeutics to our understanding. You asked for some comparison relative to what solanilocumab Phase 2 showed recently as well as bimekizumab data.

Speaker 2

To our knowledge, I don't think bimekizumab has shared any change in branitumab data to date. From a somnolikumab perspective, I'd say it's It's been a little bit more difficult to tease out. There's a high placebo response within the context of that data set in the middle in the mid-20s, I think. So a little bit tougher to make a clear comparison. I think, what we would like to highlight within the context of what we've seen and why we're so excited is again as early as a month in any patients.

Speaker 2

So that's I think we've reported now 20 or sorry, 2 thirds of patients by week 4 with 1 draining tunnel. I'll add that it's on the order of a third of patients with 2 draining tunnels as early as a month and then going up to 50% of those patients by week 8 and then that number continuing out to week 12. So we're very excited about these in terms of the consistency from week to week, in terms of the speed, the magnitude improving over time as well. And we think that the reason that we're seeing this happen As early as we are, it's because of the frankly the achievements in terms of high score or abscess and nodule 100 caps, Which is what my tour is defined as without any new training tunnels. And I think it really requires this level of active control over the abscesses and nodules and resolution of that inflammation that is allowing us to see this kind of early quants in that typical to treat tissue.

Speaker 2

So I think your second question, Tyler, was around what expectations or how we would guide folks to think about the upcoming Part B randomized control Phase 2bthree data, Appreciate that question. Our goals are actually no different at this juncture than when we started out asking ourselves Whether or not the high potency and small size of isicayvev could make a difference, a meaningful meaningfully differentiated difference in this disease state that really requires inherently to the disease itself a great deal more exposure and has such difficult to penetrate tissues. We saw in our open label Part A experience that we were reaching and I'll confess what even surprised us at the time, high score 100 levels of response in as many as a third of patients as early as week 12. Granted that was a small data set and exactly what that point estimate ends up being within the context of the larger Part B is to be determined. But from our perspective, and especially given now that we have 2 datasets that are suggesting the ability to approach the potential for resolution of disease.

Speaker 2

We're laser like focused on that concept And that this molecule has the potential to really bring us to something that may be more paradigm shifting for patients across these indications. So we've always talked about being at least as good as, if not better than whatever we consider the best agent out there to be without any new safety liability. We think that we've been consistent with that to date. We are going to hold ourselves to that same standard moving forward. And We think that all eyes really on the potential to continue to talk about resolution of disease for patients.

Speaker 5

Thanks very much.

Speaker 2

Thank you, Tyler.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Yasmeen Rahimi from Piper Sandler.

Speaker 6

Hi, this is Jung Gu on for Yaz at Piper. Thank you for taking our questions. Given that enrollment completion Part B was announced on May 1, investors are wondering if you could provide any color on timing of top line and whether it could be in the first half or second half of September. 2nd, congrats on the PSA data coming out in 1Q 2024. Could you help us understand how this data set will provide read through into uveitis and axial spondyloarthritis studies?

Speaker 6

And last, what do you hope to see in Phase 1 for Celeron-five seventeen to move forward into Phase 2b and make differentiation clear? Thank you so much.

Speaker 2

Okay. That was a lot. Let me take them piece by piece. I might ask Paul to help me with 5 17 on the end. And I'll take certainly the guidance with regards to the HS Phase IIbIII study that we accelerated from Q4 or end of year into Q3.

Speaker 2

That still sits firmly within Q3 and it's probably the extent of the guidance that I'd like With regards to the PSA data now having completed enrollment in the 2b3 study, also being accelerated and that primary endpoint top line readout will now be in Q1 of 2024 instead of mid-twenty 24. Obviously, very, very excited about that as well. We've talked about both the Phase 2 primary endpoint data that read out last year as well as the 46 week data that we shared earlier this year, with outsized benefits and even the concept of resolution in the context of that disease state as well. And so we think your specific question was around the read through to additional indications, AKFA, uveitis, potentially even others will say that we're excited about the read through. We talked about the totality of evidence across HS and PSA Really enabling us to talk about the concept of the potential for evolution of disease.

Speaker 2

We and so we think that there's read through there with regards to What this means from a technology and platform perspective. For axSpA in particular, emphyseitis is tremendously central to that disease, perhaps even more central in a lot of ways than it is in PSA. Axial spondyloarthritis, as the name suggests, is All about inflammation of the spine. There are ligaments up and down, the front and back of our clients that are connected at every single vertebral level or spinal level by emphasizing by tiny little bits of tissue that Their whole job is to connect our ligaments and tendons to bone. They're incredibly strong and poorly And when they get inflamed, it's really, really tough to resolve that inflammation.

Speaker 2

And what we're seeing within the context of our Phase 2 PSA data set, We think it's the first time that we've been able to have this kind of magnitude of resolution of quarters. That's a manifestation of disease that is associated with residual pain, severity of disease, core physical function and therefore, of course, impacting quality of life. Given that, and again, we're talking about resolution of enthesitis on the order of 80% 90% at this juncture. But historically, it's been it's not even approached that. We think that the implications for EXPAREL, given the neutrality of enthesitis to EXPAREL is going to be very, very important and we're going to be excited to advance that program as well.

Speaker 2

And then as we said for uveitis, another difficult to penetrate tissue, the back of the eye, already derisked With regards to, secukitinib having shown dose response with efficacy there with very high exposures from an IV perspective, Losing that response, when it went down to subcu levels of exposure and therefore discontinuing that program. We think that this high potency and small size of delivered in a single test tube injection is going to enable us to unlock this mechanism for uveitis patients. And so obviously a lot more to come there.

Speaker 6

All right. Thank you so much. Very helpful.

Speaker 2

Paul is going to cover the 517.

Speaker 3

Yes. I believe the question was related to what we expect to see in the proof of concept studies. We have launched single ascending dose studies already. And we do know that For this mechanism, we have a great biomarker in terms of tryptase. And also that the tryptase levels in healthy go down in a way that's very similar to the triptase levels in patients with chronic spontaneous urticaria.

Speaker 3

So we'll start in healthy And we'll move on to chronic spontaneous urticaria. And our belief is given the greater potency that we will be able to achieve meaningful suppression of triptase and therefore meaningful suppression of disease activity measured by itch and urticaria in a low volume subcutaneous injection and that's ongoing. We're exactly where we expect to be and We'll look forward to seeing those triptase responses across a variety of doses.

Operator

Our next question comes from the line of Akash Tewari from Jefferies.

Speaker 7

Hey, thanks so much. So just want to go into the high score 75 expectations for weeks.

Speaker 2

Sorry, we're having trouble hearing, you Akash.

Speaker 7

Can you hear me now?

Speaker 2

Now I can, yes. But I think Highscore 75 and nothing after that.

Speaker 7

Okay. Sorry about that.

Speaker 2

So Just in

Speaker 7

terms of the bar for Highscore75 at week 16, I think previously when we've spoken about some of the Moon Lake data, The bar the data that they showed in HS seems to be kind of doable, but not a bar that ease of Quebec couldn't actually hit. If they showed about 28% at week 16 and we know that from week 12 to 16, there's about a 2% to 4% benefit, Just with longer duration, would it be fair to say that your expectation for your drug at week 16 on high score 75 is between 30% to 35%? And kind of circling back on a question that came up earlier, do you feel like highscore75 would be somewhere where your drug could differentiate versus the Moon Lake compound or the UCB compound? Or will that really be high score 100 that we should be thinking about? And then just maybe finally on you mentioned that your DSMB allowed you to move forward with your weekly subcu dose And it looked at both safety and efficacy consistent with the idea that higher exposure is a better is something that you want to pursue.

Speaker 7

Can you give a little more color on what your kind of protocol looked at to recommend that weekly dose, specifically on ISRs, dropouts and then efficacy for both your biweekly and weekly dose? Thanks so much.

Speaker 2

That was a mouthful, gosh. Thank you. So let me take this bit by bit. So with regards to HEIGHT Score 75 quarters. Our data from our open label study had a high score point estimate 75 point estimate of 57%.

Speaker 2

That was obviously a small and open label experience. Our understanding of kind of historical placebo response rates high score 75 are in the range of 10% to 15% or thereabouts. So it's It's pretty straightforward math. I think that could we be within the range that you've described? The short answer is yes.

Speaker 2

Is that our goal? I would say, I've described the goal the same way I described it earlier, which is that our mission as a company is about making Transformatively meaningfully different medicines. And so could one continue to differentiate in high score 75? I think that was part of your question? I think the answer to that is yes.

Speaker 2

If we're still in the 50%, 60% range, could we demand to have higher orders of response there. I think the answer is yes. To your question about what we're looking for though again, a, At least as good as, if not better than the best agents out there for a given disease state, I'll even broaden that beyond HS. And then also in the specific case of HS and given the specific molecules that are out there without any additional safety liability relative to that. So that's our goal.

Speaker 2

That said, with regards to the data that we have seen and have been pleasantly surprised by, Pleased with in terms of the high score 90 and even 100 response rates and now trading tunnels happening improving as early as week 4. I would say That again, we hope that we're moving the expectations for what we can offer patients within the context of the HS treatments. And fundamentally, that's what we're going to be focused on evaluating. And then I think your last the last part of your question was about our DMC. We had a preplanned independent our independent data monitoring committees look at our Part B data at an interim look and confirm for us whether or not our expectation of the highest exposure 160 milligrams every week was a reasonable dose to continue to move forward with in our planned second confirmatory HS study.

Speaker 2

Their remit was really to tell us whether or not they felt that there was any safety reasons we shouldn't do that or whether or not there was any efficacy reason we should not do that. And they confirmed for us that neither of those were true. In fact, that we could and from their perspective should move forward with that dose level and that's Why the second study kicked off the way they did. Hopefully that covers your question. Thank you.

Speaker 7

That's really helpful and thanks so much for bearing with me. It's the first earnings call, so you got a little excited.

Speaker 2

Thank you, Akash. Take care.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Vikram Purohit from Morgan Stanley.

Speaker 8

Hi, good afternoon. Thanks for taking our questions. So 2 from our side, one follow-up on the Part B we had expected in 3Q and then one broader commercial question. So first question is what sort of mechanistic read through do you think is fair for people to draw from the Part B data in HS to other indications and development for isokaybep like PSA? And then secondly, On commercial, what do you see as the overall addressable patient population in HS for all biologic therapies?

Speaker 8

And then looking forward a few years, how do you see potentially multiple IL-seventeen targeting agents fitting into the treatment paradigm and what do you think is going to drive preferential use of 1 IL-seventeen versus another? Thanks.

Speaker 2

All right. So thanks very much for that, Vikram. So let's see. The first question Was about if Part B is positive, what's the read through to PSA and potentially other indications, if I heard that right. And I think that I'll reiterate that from our perspective, positive looks like clinically meaningfully differentiated efficacy without any additional safety liability.

Speaker 2

We think that that would be an extremely exciting We think that we have positive PSA Phase 2 data already. So that's just additional confirmation, if you will, about the totality of evidence of the high potency and small size of vizatribeV being able to have a differentiated offerings within the context of these disease states. And I think that the potential read through to other indications we talked about AKSBA already, I think there's some frankly that it brings about the potential paradigm shift to think about the fact that small therapeutics can penetrate these difficult to treat tissues better and that the high potency may allow them once they get in sort of do their business in a more effective way as well. And so from our perspective, that's very exciting not just for isekaiVap And its indications potentially for how we might think about applying that concept more broadly within the context of drug development as well. With regards to the addressable patient population in HS, and kind of the evolution, I guess I'll summarize to say the evolution of the treatment paradigm and how physicians and patients might choose together moving forward.

Speaker 2

The overall population, I think, as we mentioned in our prepared remarks, is on the order of 370,000 patients in the U. S. About half of those are moderate to severe. What we know from a commercial sort of total risk for market size perspective Is that currently that's on the order of 1 plus maybe 2,000,000,000 estimated to grow Between 4 and 5 within the context of now and 2,030. So really a growing market size.

Speaker 2

As we know, with many areas or disease areas where we gain better and better treatments, where We gained an initial even often treatment to begin with that there are more patients that are out there than we previously predict Because we haven't had the agents the medicines before to appropriately have the reason to identify them and therefore have the opportunity What we're seeing within the context of the HS as a field is incredibly exciting. In that, we're moving both the higher orders of response, whether we're talking about high score 75 or high score 90s 100s. I think across the agents that we see in development currently, we're all moving to higher orders of response, which is fantastic for patients. And is the kind of shift that we've seen in psoriasis in the past, for instance, where we can now talk about sort of all Clear Skin Instead of 50% improvements or 75% improvements in terms of clearance of your skin lesions. We hope to get there And we believe that's what we're seeing for hydrant and isopropipa as well.

Speaker 2

And in addition, we're not only talking about that, but we're talking about the ability to improve even on those responses, those 12 to 16 week responses, up through a year of treatment. And we've seen that with a couple of other data sets out there now, secukinumab, bimekizumab, both have demonstrated that continued improvement over time. Given the continued improvement over time that we've seen with in our PSA Phase 2 data sets and even in an outsized way relative to other molecules like secukitumab that have been approved for PSA. We think that the likelihood seeing that for furosemkibeV in HS

Speaker 8

Got it. Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Yasmeen Rahimi from Piper Sandler.

Speaker 6

Hi. Thank you for taking our question. I have another one on. So given that the DMC decision on the 160 milligram weekly in the AITA study was more effective. Are we supposed to infer that this weekly dose is going to be moving forward over the 2 weeks?

Speaker 6

Or could you provide a little bit more color on that as well?

Speaker 2

Yes. No, thanks for that. And sorry if I wasn't clear earlier. Yes. So the choice was made to pick a single dose moving forward into the 2nd confirmatory HS Phase 3 study and that dose is 160 milligrams weekly, Which is the dose we anticipated based on our understanding of the disease state, and why we set up the DMC to help us with that evaluation at clients?

Speaker 2

We set up the first study as 2 dose levels versus placebo because one does need to demonstrate that you core utilizing a minimally effective dose and not potentially overdosing for instance patients for no reason when you have within the context of our registration packages. And so that was the purpose also of ensuring that that's what we were doing for Pershing.

Speaker 6

Thank you so much again.

Operator

Thank you. At this time, I would now like to turn the conference back over to Doctor. Kim for closing remarks.

Speaker 2

Thanks, Gigi. It's Doctor. Lin. Thank you everybody for your engagement and questions today. Really

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Earnings Conference Call
Acelyrin Q2 2023
00:00 / 00:00