Q4 2024 aTyr Pharma Inc Earnings Call
Speaker Change: Good afternoon ladies and gentlemen and welcome to the ATyr Pharma 4th quarter in full year 2024 conference call. At this time all participants are in a listen only mode.
Speaker Change: Later, we will conduct a question and answer session and instructions will be given at that time. As a reminder, this conference is being recorded for replay purposes.
Speaker Change: It is now my pleasure to hand the conference call over to Ashley Dunston, attires Senior Director of Investor Relations and Public Affairs, Ms. Dunston, you may begin.
Speaker Change: Thank you, and good afternoon, everyone. Thank you for joining us today to discuss A Tired, Fourth Quarter and Full Year 2024, Operating Results and Corporate Update. We are joined today by Dr. Sanjay Shukla, our President and CEO , Ms. Jill Broadfoot, our CFO , and Dr. Leslie Nangle, Vice President of Research.
Speaker Change: On the call, Sanjay will provide an update on our corporate strategy, including our clinical program for F. Sofitamon. Leslie will discuss our research and discovery programs while Jill will review the financial results and our current financial position, before handing it back to Sanjay to open up the call for any questions.
Speaker Change: Before we begin, I want to remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the Safe Harbor provision of the Private Securities litigation reform act of 1995.
Speaker Change: These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements.
Speaker Change: Please see the forward-looking statement disclaimer in the company's press release, issued this afternoon, as well as the risk factors in the company's SEC filings and included in our most recent annual report on Form 10K, subsequently filed quarterly reports on Form 10Q and in our other SEC filings.
Speaker Change: Under-reliance should not be placed on our forward-looking statements, which speak only as if the date they are made as facts and circumstances underlying those forward-looking statements may change. Except as required by law, a Tyr Pharma disclaims any obligation to update these forward-looking statements to reflect future information events for circumstances.
I will now turn the call over to Sanjay.
Thank you Ashley.
Sanjay Shukla: Good afternoon everyone and thank you for joining us for our fourth quarter and full year 2024 Results Conference call.
Sanjay Shukla: At A-Tire, we are on a mission to translate TRNA's synthetase biology into new therapies for fibrosis and inflammation.
Sanjay Shukla: or Lead Therapy to Candidate of Sofitamod is the first in class biologic immunomodulator that selectively modulates activated myeloid cells via Neural Philan II or NRP II.
Sanjay Shukla: to resolve inflammation without immune suppression and potentially prevent fibrosis progression.
Sanjay Shukla: We're developing F-sofutamide as a treatment for patients with interstitial lung disease or ILD, a group of rare immune mediated disorders that can cause chronic inflammation and fibrosis of the lungs.
Sanjay Shukla: 2024 was an important year for A-Tyr as we completed enrollment in our Global Pivotal Phase III Episodeship Study of Episodeship Pharma in patients with pulmonary circuitosis in major form of ILD that is our lead indication.
Sanjay Shukla: This is the largest interventional study ever conducted in Palais, Surgadosis.
Sanjay Shukla: and we look forward to releasing top line data from this study in the third quarter of this year.
dose intravenously monthly for a total of 12 doses.
Sanjay Shukla: The study enrolled 268 patients at 85 centers in nine countries.
Sanjay Shukla: The trial design incorporates a four-stereoid taper with steroid reduction as the primary endpoint of the study.
Sanjay Shukla: Secondary endpoints include measures of sargadosis quality of life and lung function.
Sanjay Shukla: Patients who complete the study in which to receive treatment with Epsilon Pharma outside of the clinical trial are eligible to participate in an individual patient expanded access program or EAP.
Sanjay Shukla: The EAP was implemented primarily based on feedback from multiple study principal investigators of PIs whose patients requested to continue treatment once they completed this study.
Sanjay Shukla: These patients will receive 5 milligrams per kilogram out of sulfidamod while in the EAP.
Sanjay Shukla: However, PI's, patients, and the company remain blinded to the F. Sofit Tremis assignments of these EAP patients.
Sanjay Shukla: Additionally, we have now held four positive data and safety monitoring board for DSMB reviews for this study.
Sanjay Shukla: All of which have identified no safety concerns and recommended that the study continue unmodified.
Sanjay Shukla: The most recent pre-planned, independent review indicates that the study continues to track well from a safety standpoint.
We remain confident in the favourable.
Safety profile we have seen for us so for a month to date, which we believe is the key value proposition of the drug.
Sanjay Shukla: And finally, we'll get our first look at the blinded baseline demographic and disease characteristics of the patients enrolled in the study at the upcoming American thoracic study conference for ATS.
which is scheduled to take place mid-May in San Francisco.
in a poster we will be.
Sanjay Shukla: Able to get a sense for the profile of the patients enrolled, including baseline steroid dose and background immunomodulator use.
Sanjay Shukla: As part of our planning for the Phase 3 readout for SOFIT, we recently held a Type-C meeting with the US Food and Drug Administration, or FDA.
Sanjay Shukla: The main objective of this meeting was to discuss the statistical analysis plan or SAP for the study, including how the primary and secondary endpoints are assessed statistically.
Sanjay Shukla: For the primary end point, we determined how storied reduction will be analyzed in the
Sanjay Shukla: As we previously discussed, we initially proposed that we measure steroid reduction based on calculating the average daily steroid dose between week 12 and week 48, which is the protocol specified post steroid taper period.
Sanjay Shukla: We viewed this as a conservative way of measuring steroid reduction in the study.
Sanjay Shukla: Based on FDA feedback, we will now measure steroid reduction as the absolute change from baseline to week 48.
Sanjay Shukla: We feel this change creates a more simplified assessment to capture potential sterile delta between groups.
Sanjay Shukla: The statistical powering for the study remains intact and we are pleased with the clarification around how we will measure steroid reduction.
Sanjay Shukla: With limited clinical studies in sargadosis as a benchmark, we are pioneering a path forward to measure how we can potentially improve the lives of these patients.
Sanjay Shukla: While we brought you up to date on FSOFIT, I want to take a few minutes to provide you with critical insights into the pulmonary circuitosis landscape in the US that have emerged from some of our early pre-commercial activities.
Sanjay Shukla: We believe these findings support a potentially larger market opportunity for FSO Phytomod and Sargerosis.
Sanjay Shukla: pulmonary circuitosis is a disease characterized by the formation of granulomas, or clumps of immune cells predominantly in the lungs.
Sanjay Shukla: The current standard of care is oral court of steroids which may help improve symptoms in the short term, become with serious side effects.
with long-term news.
Sanjay Shukla: And despite the use of steroids and other off-label immunospers of agents, many patients have disease that progresses.
Sanjay Shukla: with around 20% developing long fibrosis, which can lead to organ failure and death.
Sanjay Shukla: There remains a lack of safe and effective treatments available for these patients.
Sanjay Shukla: It is typically reported that Sargedosis affects close to 200,000 people in the US with 90% of patients having lung involvement.
Sanjay Shukla: A third-party claims analysis, which we conducted late last year, confirms that number and shows that the number of patients diagnosed with lung involvement similar to the population in role in our phase 3 trial is 30% higher than previously estimated.
Sanjay Shukla: Since the US epidemiology numbers most frequently referenced were published nearly a decade ago, we were not surprised that the population has grown.
Furthermore, when we looked at treatment practices,
Sanjay Shukla: such as the number of patients that require any treatment and those that are prescribed steroids, we saw that nearly 75% of diagnosed patients are prescribed steroids, which is well above previous estimates in the U.S. and at the upper range as to what is reported globally.
Sanjay Shukla: Furthermore, the claims also showed significant mortality in hospitalization rates, which speak to the high and medical need for this disease.
Sanjay Shukla: When it comes to pricing through additional payer research that we conducted, we continue to see positive feedback from payers regarding their willingness to reimburse for an on-label biologic in circuitoses.
Sanjay Shukla: We are encouraged by the reimbursement landscape we've seen recently where some rare disease product launches have included steroid reduction as part of the label and are priced at a premium.
Sanjay Shukla: In some, we believe the findings from these recent activities support the patients and physicians need and strong desire for a product like F. Sofutamot.
Sanjay Shukla: We view SOFIDAMOT as a potential frontline steroid-reducing agent in patients with moderate to severe disease, which could address 50 to 75% of all socketosis patients.
Sanjay Shukla: We've here previously stated that we estimate a total global market opportunity for Epsilon so for a mod in ILB at $2 to $5 billion.
Sanjay Shukla: and our updated research supports a market where Saga dosis represents a significant portion of that range.
Sanjay Shukla: Eric brings a wealth of experience in launching high-value pharmaceuticals, including, most recently, a product for a rare disease that has a steroid reduction component as part of its phase three clinical trial and FDA approval package.
Sanjay Shukla: We anticipate his contributions will be highly valuable, as we advance Esophidomon to a commercial product.
Sanjay Shukla: Now let's turn to our second indication for episode Pharma, ILD related systemic sclerosis or SSC, which is also known as Clare Durma.
Sanjay Shukla: As a C is a form of connected tissue disease where ILD commonly occurs and is a leading cause
Sanjay Shukla: Current treatment options for SSCILB are limited, and like Sarkadosis, they do not treat the underlying disease or improve quality of life.
Sanjay Shukla: AppsoConnect is a phase two randomized double-blind placebo controlled proof-of-concept 28-week study to evaluate two fixed doses of absent Pharma, 270 milligrams or 450 milligrams compared to placebo.
Sanjay Shukla: Patients and dose intravenously monthly for a total of six doses.
Sanjay Shukla: This study is currently enrolling patients with limited and diffused SSCILD at multiple centers in the US.
Sanjay Shukla: The primary endpoint of the study is long function that is measured by force-wide of capacity, and key secondary endpoints include symptom control and skin assessments.
Sanjay Shukla: We expect to release interim data from the study in the second quarter of this year. The interim data will focus on skin assessments.
Sanjay Shukla: measured at baseline in week 12 for approximately eight patients, including patients on drug and placebo.
Sanjay Shukla: We plan to present findings for skin histopathology, including immune biomarkers, and the modified rodent skin score, which will provide insight regarding potential changes in skin tissue.
Sanjay Shukla: Skin Manifestations in SSC highly impact the quality of life for these patients, and others that there be showing improvement in these measures that are limited to no success.
Sanjay Shukla: This interim data may provide us with an early signal related to skin changes.
Sanjay Shukla: and may help inform the clinical development strategy for this indication.
Sanjay Shukla: Because we plan to evaluate skin assessments in the interim data, and we do not plan to include any data related to lung function, we see limited read-through from this data to the face-to-face top-line data in pulmonary circuitosis.
that we will present later this year.
Speaker Change: I will now turn the call over to Leslie Nangler, Vice President of Research, to discuss our research and discovery programs.
Leslie Nangle: Thank you, Sanjay. While we have focused quite a bit on esophidimod in the clinic, it will be useful to comment on esophidimod unique mechanisms action or MOA, as this is truly a first in-class drug candidate.
Leslie Nangle: Since we started this program, we have greatly enhanced our mechanistic understanding of
Leslie Nangle: and we are pleased to report that just yesterday we published an extensive manuscript in the journal Science Translational Medicine which outlines the MOA and all of the pre-clinical generations for SFNMOD from concept to clinic.
Leslie Nangle: The article describes the foundational science, detailed preclinical studies and discovery work behind F.F.Idomon. This includes how it is engineered from a spice variant of the T.E.R.N.A.S. in the T.E.R.S. Hars, which is enriched in human lung tissue and upregulated by inflammatory cytokines in lung and immune cells.
Leslie Nangle: It also describes its specific and selective binding to NRP-2, which is a cellular receptor highly expressed by myelin cells in active sites of inflammation.
Leslie Nangle: Through this finding, it inhibits the expression of permanent planetary receptors and cytokines thereby down-regulating and planetary pathways in macro features.
Leslie Nangle: This mechanism can subsequently disrupt the cycle of chronic inflammation and fibrofish.
Leslie Nangle: This type of top-tier peer-reviewed journal requires extensive vetting by the broader scientific community, with multiple independent reviewers performing a comprehensive audit of all of the work that we've generated. This process itself demands the utmost transparency in our work.
Leslie Nangle: Therefore, we believe this publication validates the immune regulatory properties and extra solidarily mediated mechanism we have demonstrated for FSA Pharma as it relates to reducing
Leslie Nangle: Furthermore, it can considerably reinforces the basis for the application of FSA Phytomon in chronic inflammatory conditions.
Leslie Nangle: It strengthens the scientific rationale for our clinical program in ILD, as well as encourages the potential development of other taryons and case-based therapeutics for disease prevention.
Leslie Nangle: We are very proud that the novel science that drives us to Pharma is being recognized on the world stage. To publish this extensive body of work in such an esteemed journal is a momentous accomplishment for our research team and speaks to the nature of the high quality work that each hire produces.
Leslie Nangle: While we have focused much of today's conversation around as the phytomod, I want to remind you that the Spice variant that forms the backbone of us as the phytomod comes from a robust intellectual property estate, covering domains from all 20 human tionic sentences.
Leslie Nangle: and we utilize our platform and unique drug discovery process as an engine to generate U-Pipeline Candidate.
Leslie Nangle: With us, Joseph Pantginis and Hars, we have demonstrated that this taryons and base fragment has a previously undiscovered extra cellular function and we continue to interrogate other taryons and base fragments to identify roles they may play in cellular response and altered disease state.
Leslie Nangle: We currently have two preclinical candidates from other tiering spaces where we have identified their interactions with targets and therapeutic areas where they may play a role.
Leslie Nangle: Both of these candidates, A-Tyr O-101 and A-Tyr O-750 interact with receptors that affect fibrosis.
Leslie Nangle: We are exploring ATIR01 in both lung and kidney fibrosis, where we recently presented data at a keystone symposia that shows its ability to induce myofibroblasts apoptosis through a novel anti-phabiotic mechanism.
Leslie Nangle: We are exploring a Tyrosim 50 in liver disorders based on the strong connection to its target, which is FGFR-POR.
Leslie Nangle: We are really proud of the innovative work that we have done with SFITAMON and the advancement of the program to date. We look forward to replicating that process with some of our current and yet to be discovered candidates.
Leslie Nangle: I will now turn it over to our Chief Financial Officer, Jill Broadfoot, to review our financial results.
Jill Broadfoot: Thank you, Leslie. We ended 2024 with 75.1 million in cash, restricted cash, cash and investments.
Jill Broadfoot: Subsequent to the end of the fourth quarter 2024, we raised approximately 18.8 million and gross proceeds from our at-the-market or ATM offering program.
Jill Broadfoot: Collaboration and license revenue related to the Curen agreement was 0.2 million for the year ended 2024, which consisted of drug product material sold to Curen for the Japan portion of that socket.
Jill Broadfoot: Kiran is our partner for the development and commercialization of F-soaked mod for ILD in Japan and we now have received over 20 million under this agreement to date.
Jill Broadfoot: including milestones, where we are eligible to receive up to $155 million in additional milestone payments.
Jill Broadfoot: which are primarily geared towards the regulatory and commercial milestones for Sarkway
Jill Broadfoot: Research and development expenses were $54.4 million for the year ended 2024, which consisted primarily of clinical trial costs.
Jill Broadfoot: for the FSOFIT and FSOF Connect Studies, Manufacturing Costs for the FSOFITAMOD Program and Research and Development Costs for the FSOFITAMOD and Discovery Programs.
Jill Broadfoot: General and administrative expenses for $13.8 million for the year-end in 2024.
Jill Broadfoot: Based on our current cash position, we have updated our financial guidance and believe our cash runway is expected to be sufficient to fund the company's operations through one year following the phase three of subject readout.
Jill Broadfoot: We view this runway as important as it covers key upcoming inflection points for the company, including the Phase III, SFIT, Readout, and a potential filing of a Biologics License Application for SFIT Ahmad in Pulmonary Zarqueidosis.
Jill Broadfoot: In addition to extending our cash runway, we plan to use some of the ATM proceeds to help fund our commercial readiness plan.
Sanjay Shukla: Now I'd like to turn the call back over to Sanjay before we open it up to Q&A.
Thanks Jill.
Jill Broadfoot
Speaker Change: When we assess our current position, we feel incredibly pleased with our SOFIDAMOT program and our enthusiastic about the future.
Speaker Change: for poised to seize an extraordinary opportunity and park sightment for the rest of 2025 is unmatched.
Speaker Change: Our latest validating publication in Science Translational Medicine confirms our understanding of Epsophiromod's mechanism of action.
Speaker Change: Our Phase 3 Circuitosis Trial has progressed through four successful DSMB reviews, bolstering our confidence in the therapy safety profile.
Speaker Change: and new claims data from socketosis patients suggesting growing multi-billion dollar market.
with little competition.
Speaker Change: Our journey began with our innovative biology platform which advanced from research to clinical stage through transparent seamless execution while upholding a high level of scientific and medical rigor.
A groundbreaking advancement for Sargadosis, maybe within our reach.
Speaker Change: One that could greatly enhance the company's trajectory and elevate A-tire to new heights in the biotechnology sector.
Speaker Change: We greatly appreciate your interest. At this time, we'll be happy to take your questions.
Speaker Change: Thank you to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.
Speaker Change: And our first question comes from Derek or Chilla with Wells Fargo. Your line is open.
Derek Archilla: Hey there, thanks for taking the questions and congrats on all the progress. So just the first question that I just...
Speaker Change: Maybe Sanjay, can you shed some light on how measuring the absolute change in steroid reduction at baseline now to week?
Speaker Change: 48 versus the current way that you had set it up in terms of the average cumulative steroid dose. How does that impact the trial? I know you noted the powering remains intact, but I guess maybe just remind us, you know, the powering of the trial and I have a follow up.
Speaker Change: Sure, Derek. So previously, as I mentioned, we were looking at the average steroid dose in that week 12 through week 48 period, basically taking the patient diary, information from every single day they report their prednisone and dividing by the number of those.
Speaker Change: A fairly conservative way of looking at all the peaks and valleys combined with our steroid taper and that protocol that's occurring simultaneously to that treatment period.
Speaker Change: But after some feedback and discussions with the FDA, the view was to look at just the change from week zero to week 48.
Speaker Change: This is something that we're very happy with. I think in many ways this allows us to simplify.
the manner in which we analyze our data.
It allows us to look simply at the...
Speaker Change: Starting dose, essentially, and the ending dose. Remember, during this period we're trying our best to taper patients and continue to retapre to zero.
Speaker Change: The assumption now is many of those peaks and valleys by the time the study ends should allow us to potentially maximize the steroid delta that we see in these patients.
Speaker Change: With regard to powering, it remains over 90%, 90% power that either 3 or the 5mg dose shows a stat sig.
Speaker Change: Stairward reduction compared to placebo that has not changed and with focusing now on the absolute change, as opposed to percent change, we think that's also a better framework that's more relevant to patients and providers.
Speaker Change: Super-helpful. And then, just a follow-up here. I know you highlighted in the prepared comments. There was investigator and patient enthusiasm for the EAP. So, just wanted to ask, you know, if you have any idea in terms of the percent of the patients who are in the trial rolling over into the expanded access or, you know, a new program there. Thanks.
Speaker Change: Yeah, it's a common question I get. How many patients? What's the percent? And I want to start by saying start by saying we have seen continued interest growing interest.
Speaker Change: But the issue really here is that not all countries and not all centers can participate based on their local regulatory requirements. I've said this before, countries like Japan, for example, do not have a pathway to participate in an EAP type program.
Speaker Change: So you'd have to subtract out all of those regions that aren't involved and then try to come up with a quote unquote crude measure of response, which is but I think a lot of investors want to do here.
Speaker Change: What I can say is the interest is still very robust. I was just with about 30 experts recently this past weekend. There continues to be more and more interest to participate in the EAP.
We have committed.
to helping patients who are performing well in the trial.
Speaker Change: site-by-said site decision because of course we are not any former formal open label type extension, so.
Very pleased with the progress.
Speaker Change: I think it's a great signal, a great interim biomarker if you will.
Speaker Change: and we're going to continue to support those patients to move into that EAP.
Speaker Change: All of these patients are on placebo, that they have been able to taper more or less off their steroids and And then and it doesn't have anything to do with the drug so people know me to be rather conservative in my messaging I just think it's a great signal to see that patient who are
Speaker Change: Finishing a trial, want to remain in the trial. That to me as a former clinician speaks very powerful to what's something is happening during the trial.
Got it. Understood. Very helpful. Thanks, Andre.
Speaker Change: And the next question will come from Yasmeen Rahimi with Hypersandler. Your line is open.
Speaker Change: Was it the market research around managing patients with shared reduction that led to engage with the agency to make this change from up?
from a sort of clinical perspective.
Speaker Change: Just maybe we could kind of shed light how that meeting came about and why that change, the change makes absolute sense, but maybe the question would be why implemented now and the rationale behind it.
Speaker Change: That's sort of question one and question two is really exciting to see the baseline demographics from the study here upcoming at ETS
Could you maybe help us understand?
Speaker Change: What we should be looking for, obviously that it's a tremendous study with.
Speaker Change: Globally, lots of work went into it, so just kind of help us framework on what are some of the measures that we should be looking closely to in terms of the station population and I'll jump back in the queue.
Sure, yes.
Speaker Change: Three questions I will love. Take the first one and say that
Sanjay Shukla: The market research is not necessarily really connected to this type of meeting. This is a little inside baseball biostatistics that typically before you lock your database, you want to have solve the rules set up with the biostat's division. And as a biostatistician
Sanjay Shukla: It's important that we really agree to all the pre-hawk analysis.
Speaker Change: I think far too many times in biotech, we implement rules and then after data comes out we start to do post-talk analysis and cherry pick and cut and slice the data and I wish more biopharmas wouldn't do that so we're very rigorous.
Speaker Change: And I like to be very rigorous around. Hey, let's get everything pre-hawk organized down to the details exactly how do you want us to program and even look at some of this steroid reduction that we have proposed something that I viewed as
Speaker Change: A fairly conservative way of looking at steroids and the average daily steroids upon interacting with the FDA here. Their view was this approach.
Speaker Change: Would be fine, not the suggested approach where we're looking at just a simplified change from baseline.
Speaker Change: I'm not going to disagree with that. I'm going to go ahead and implement that approach because, as I said, I can this actually allows us to potentially maximize a signal at the end of the trial. Remember, there's a four steroid taper component.
Speaker Change: So, civil patients will get the benefit of that reduction of the poor steroid tipper. But now...
Looking at the end of the trial.
Speaker Change: The clinical team and I view this as potentially a way to maximize a signal here because as I pointed out, all those peaks and valleys that occur over the course of the trial now should be adequately
Speaker Change: Handled, observed, and now we'll have a true measure at the end of the trial.
Speaker Change: Your second question was really around the baseline demographics. It's important to put this out. The community is really interested. They want to see data as quickly as possible. Many of our PIs have said can we take a look at background. We're going to take a look at background.
Speaker Change: Immunomodulator Use. We just want to see the data. We like to see what the average daily steroid doses, duration of disease, things of that nature. So these are all important things for us to
Speaker Change: to show to the community. And we already have that data. It's just baseline data. So why not put it out at a major medical conference? The important thing for investors to pay attention to is that...
Speaker Change: that average prednisone dose. I'll remind everyone in the last trial, the phase 2 trial.
Speaker Change: We had an average of somewhere in that 11 to 13 range.
Speaker Change: This trial where we're enrolling patients with a slightly lower basement dose of seven and a half milligrams, I expect that prednisone dose maybe, maybe a little bit a little bit lower but we want to take a look at that and then that helps with all.
Speaker Change: All the investors that want to do the modeling with regards to how much sterile delta you want to see there so it's important to get this baseline data out there. Make sure we're more or less enrolled per the IE criteria in our trial.
Speaker Change: Thank you so much. They're very much looking forward to it.
Speaker Change: And our next question will come from Faisal Kershed with Learing Partners, your line is open.
Faisal Khurshed: Hey, Sanjay. Thanks for taking the question. That's to be on the call with you guys. Just want to ask who in terms of the placebo arm, I guess with the stereotyping in general, I think in the past you said that, you know, patients would have to cry to tap the zero three times over the course of this 48 weeks. So with this change now, like what happens if a patient is mid taper at week 48 like is that mean that they'll kind of [inaudible]
Speaker Change: Have a steroid level that's sort of being impacted by this force taper for what you're measuring for the primary endpoint?
Speaker Change: Unmask their disease and not only unmasked the disease, but have as you point out several rounds of trying to basically retaper them. So we still we still are going to continue with that protocol in that manner.
Speaker Change: Now, you point out an example, I would say maybe an extreme example, that what if a patient in that last?
Speaker Change: Dosing Period is actually trying to be retapred. So again, this is a very, very specific question for a specific circumstance, but typically when you look at a change from baseline, it's not that you're looking at the point estimate on that day of that visit.
Speaker Change: Typically, what you're looking at is a trailing average of, say, 28 days.
Speaker Change: So that's like kind of very wonky bio stats and programming question that you pass there. So in that case, if somebody is in an active paper, we have a look back there of those 28 days. That's occurring for all of the patients there.
My view is, most patients will have reached their
What I would call resting dose
Speaker Change: as a placebo patient and their resting dose of a potential absolute treated patient, and we'll know that over the course of those last 28 days.
Speaker Change: That's why we believe that this allows us to potentially maximize the differences you may see from change from baseline within each cohort.
Does that help?
Speaker Change: Yeah, super helpful. Thanks for clarifying. And then if I could ask just in terms of the, how should we think about the durability of the drug impact now that you're kind of doing the analysis in a way that really emphasizes the end of the study?
Speaker Change: Oh, I love that you asked that question because we were talking about this this week durability is going to be really important with this trial and this is one way that it signals a potential durable response.
Speaker Change: I would say things like time to relapse and time to clinical worsening are other ways that you can look at it I'll remind everyone that from our last data the pooled analysis showed that these two treatment doses
Speaker Change: kept people 93% of the patients in that small data set from relapsing in six months.
Where's
Feast of 55% of the sub-deer, pediatric and placebo patients relapse.
So as a comparison,
Speaker Change: This is the way we're mentioning this endpoint is certainly going to allow us a clue to see if the drug is actually has durable response, but we're also going to be looking at time to relapse as a tertiary analysis. Many of the experts are, you know, they really care about that.
Speaker Change: So that's something that also I think we can potentially see a statistical win on albeit it's not a primary or secondary end point but definitely durability is something that we're bullish on right now with a therapy. [inaudible]
Great, thank you for taking the questions.
Speaker Change: And our next question will come from Packer Agarwal with Cantor. Your line is open.
Packer Agrawal: All right. Thank you for bringing my questions and congrats on the progress who firstly,
Packer Agrawal: I think in the phase one, two, for the five milligram per kg dose, the 1.6 milligram per day steroid reduction that was seen was during the post-tapal period. So if you can remind us, what would you see in the world?
Packer Agrawal: Overall time period based on the new definition here. That's my first question. And the second question maybe you mentioned that the powering remains intact, but did the powering decrease force of the initial assumption that may have been very conservative to begin with?
Packer Agrawal: and lastly, if you can comment on what did the FDS say on FVV1 in the Type-C meeting? Or was there any discussion around that? Thank you so much.
Speaker Change: Yeah, I'll take the last part first. A little to no discussions on PFTs.
I think this speaks to a much greater interest in
Speaker Change: in in steroid reduction and and frankly the King's sarcoidosis. So I with regard to FEV1 specifically
Speaker Change: You know, that is a important PFT for obstructive disease and many of these patients, of course, have obstructive disease. We'll look at that again as a tertiary endpoint.
but my general sense is.
Speaker Change: I'm going to probably have to set some time aside with you in our biostatistician.
Speaker Change: The powering remains the same, over 90% powered. We may in fact be able to...
Speaker Change: I've said before looked for a three and three and a half milligram percent absolute difference, excuse me, not percent. Now I think it's probably skewing closer to three milligrams. So even with the same powering assumptions.
Speaker Change: This new way of analyzing the data may allow us to, as I said, potentially maximize the difference here, maybe not even as high a bar, slightly lower.
Speaker Change: We'll confirm. And again, I want to keep the powering here at 90%. Your first part of the question that Picard was...
Can you just repeat that again?
Speaker Change: Yeah, so I think in the phase one, two, for the high dose, the one point, for the sky reduction was for the post-caper period. So if you apply the same definition as the new endpoint, if you can remind us what would you see there?
Speaker Change: Right, so we haven't analyzed it in that manner. What I can tell you is the placebo population of the benefit of the forced steroid reduction in that trial.
So if you just sort of qualitatively think about this.
Speaker Change: If you remove that and just focus at the end of the trial, we knew that over 50% of the patients in those subterputic doses were not doing well at the end of the trial. They were have been rescued and managed at a much higher dose.
so
Speaker Change: Just from a qualitative standpoint, given the fact that we held the line and did pretty well with our three and five milligram doses and placebo got worse over time, I think you can see that that number would grow, but we haven't gone back and back calculated that.
Speaker Change: It's a good question, but I can qualitatively you could probably understand that that delta would be certainly larger than 1.6.
Speaker Change: And our next question will come from Gregory Renza with RBC Capital Market, your line is open.
Gregory Rinza: Hey, good evening, Sanjay and team, a congrats on the progress and thanks for taking my question.
Gregory Rinza: Sanjay, maybe just spinning to FSO Connect and sclerodera ILD. It's nice to see the detail on the the eight patients on the data that you'll be showing on on drug and placebo.
Speaker Change: Fit, of course, I just wanted to have you come in a bit on what you are looking for, what do you want to learn from the data set? And especially as you talk about the
Gregory Rinza: The white space with EPSO and other fibromatic diseases, to what extent could this data help guide the directionality there? Thanks so much.
Speaker Change: Sure Greg, thanks for the question. So absolutely, I think that the focus on skin as you can imagine, we're not really looking so much really at all for skin for psychedelosis.
Speaker Change: The skin readouts represent an extremely high bar. Let me first start by saying, I'm wearing a skirt or a mildly patient's.
Speaker Change: The primary morbidity that they really complain about and care about, unfortunately, have not been able to address with any of the therapies is improving skin.
Speaker Change: None of the approved therapies made a dent in helping with clinical symptom or quality of life.
Speaker Change: So, we take this seriously. We also know it's a very high bar. Why do we think it's worth looking at skin pathology? Well, we saw a lot of norepine expression.
Speaker Change: and even our paper from Science TM that just came out has experts in other areas of inflammatory disease with refractory therapies very much interested.
Scleroderma is an area where we see norepine expression in those skin plaques.
Speaker Change: So it makes sense for us from an experimental point of view to really interrogate what's happening there.
Speaker Change: Do we see any pathology benefit? Do we see any kind of impact? Again, no therapies being able to move the needle at all? Can we see something there with immune biomarkers?
Speaker Change: Now, with that as a context, it's okay then in my mind to look at a small data set.
Speaker Change: because if we do see something, I think it would be...
Speaker Change: It'd be pretty amazing, and I think it could open up EFSO's potential in a number of other systemic diseases.
Speaker Change: which is where experts continually ask me, can this be used outside of the lung?
Speaker Change: With our recent paper that just came out, it has attracted more interest from other areas in rheumatology and dermatology This is something that could be quite exciting for the therapy.
Speaker Change: So, as of now, we're really focused on the lung, as a franchise with Epsil Phutamon, but you can start to see with the mechanistic relegation.
Leslie Nangle: that we Leslie outlined in the Science TM paper, this really looks like an opportunity that how do you best position that so fit a mod and this is the first step looking at skin perhaps in scleroma patients.
Bum.
So I think it's a fair...
Speaker Change: I'm off here fight right now to take a look here. See if we can actually move the needle. It may actually impact where we want to go with
Speaker Change: and we're also competing with some rather large players right now in that space but we feel as though we can go toe-to-toe with them regardless of how big they are from a pharmaceutical perspective. Thank you.
Speaker Change: That's great sound. I really appreciate it. Look forward to the data.
Speaker Change: And our next question will come from Joe Pantginis with HC Wainwright, your line is open.
Speaker Change: Everybody good afternoon. A couple questions if you don't mind. So first Sanjay, the later part of your comments.
Speaker Change: What is the potential to see steroid reductions or even going to zero without therapeutic interventions?
Speaker Change: That's a great question, Joanne. I think what we are now really uncovering and want to...
Speaker Change: I really think about what the CIP is, as patients start to get into longer term.
Speaker Change: Therapy with Epsilon Phydemont. Again, I don't know what they were on during the trial, but now I know they're receiving 5 milligrams per kilogram.
Speaker Change: And as I continue to remain in the EAP, the question becomes, are we inducing things more than just management of active inflammation, is there, are we inducing any signs of
Speaker Change: So this is a different study. It's quite exciting to those patients
Speaker Change: But for them to be off steroids many times for the first time and maybe a decade this is just a welcome relief to them. So the CAP is something that I'm really proud of as we look to get more patients in the CAP. How do we then?
Speaker Change: potentially if our drug is successful with the readouts, how do we then morph that into a more formal AAP or a registry? This is going to answer some of those questions where you, where you start to
Speaker Change: Start to say, okay, what is it doing long term? It's that durability question.
Thank you.
Speaker Change: I think it's both exciting, but it also opens up some questions around once we get into the 2018 or 24 months.
of good management of these patients.
Speaker Change: What are the implications for a drug like ours? How does it impact pricing?
Speaker Change: and how do we, as a company, prepare ourselves for what seems to be a larger market than anyone ever anticipated. So, both exciting, challenging
Speaker Change: But I think it's something that we look forward to knowing once we unlock and unblind from this current trial.
Speaker Change: Got it, thanks for that. And then maybe from a reminder standpoint can you let us know about your current manufacturing readiness, not only for, you know, development indications, but also for potential early commercialization and the early on needs.
Speaker Change: Yeah, we invested a significant capital a few years ago ahead of time to prepare for a commercial readiness strategy with our drug supply, a launch readiness plan.
Speaker Change: and we made those changes from a clinical group-grade partner to a commercial-grade partner.
Speaker Change: We remain on track. That's going to be an important component to our submission. It's something the FDHCMC Division, CEMC Group, certainly keeps tabs on where we are.
Speaker Change: Because if we have good data, we want to have drug ready for these patients. As I told you, 20% of these patients upwards to 20%
Speaker Change: Have significant morbidity and potential mortality rate in certain age groups that are even higher than that. So these patients can't wait.
Speaker Change: So for us to be ready as a biopharma, we made those investments.
Speaker Change: If anything right now we have to look at this new appy data and say do we have to be ready to have this as a bigger opportunity.
We know, I can tell you that...
Speaker Change: And I've said this to many of you, the interest from strategics, for example, is the highest that's ever been because I think the market, even with some of those potential strategics, we talked to, they are realizing it's a much larger market. We've had a hand in that.
Speaker Change: by leading the way in circuitosis. We've opened up people's eyes.
more data.
Bye.
Equals More Publications, More Understanding
Speaker Change: We can continue to lead that way with this claims database that
Speaker Change: We'll have some data around and the treatment landscape poster at ATS. This is going to fundamentally start to establish a burgeoning market of which we're really the world wide reader right now without so.
Thanks for the color.
Speaker Change: And our next question will come from Leon Chang with Jeffrey. Your line is open.
Speaker Change: Good afternoon. Thank you for taking all questions. This is Jan for Roger. So, I just want to start to back to the statistical plan change. So, wondering if you can give us any color on, what are the drivers for the ASI to change that statistical analysis plan to, you know, the current one, anything, you know, more you see from your phase one, too, that's more, you know,
supporting V-blast, Turing Blast.
Speaker Change: Well, I'm probably not going to comment what exactly is in the FDA's head because if I knew that, I'd have another career, but I think it's really about simplification.
and if anything...
Speaker Change: conservative, as I said, lacking in bias approach. A simplified assessment will certainly always on the table. But when you sit down with the FDA and specifically the biostat reviewers, you listen to what...
they guide you towards. [inaudible]
Speaker Change: and sometimes you take it quickly, and I'll say that. So this is an approach I think again as we are trailblazing here, creating a new path, some of this is working closely with the regulators there.
Speaker Change: So, we may have ways in which we are thinking about analyzing things from an academic or a clinical point of view make sense to us.
Speaker Change: but they're going to provide a little bit of that regulatory color. And again, if something is a little bit more simplified for them
Speaker Change: Like I said, we're going to go ahead and take that win and we do see this as a more streamlined approach, that as I said, we think it can help us.
Speaker Change: Absolutely. Thank you. Thank you very much. Maybe one more question on the you know upcoming in terms and analysis for the growth of a program. So
Speaker Change: Understand that there will be like eight patients. So what's the distribution between different doses and placebo? And you know how I understand that will be focusing on you know high high-barred skin analysis. So...
We just wonder how would that result effect your ongoing plan?
Speaker Change: Yes, I imagine, you know, I don't have obviously the treatment assignments for these patients as of yet. We'll do that when we take, when we pull down on these 8-4-8 patients, but I anticipate they will include...
Treated Hand for Civil Patients [inaudible]
Speaker Change: and how should we think about the, you know, the result regarding any change on your ongoing
Speaker Change: Any change? You're saying what are the assessments we'll look at with those
Yeah, it's going to largely to impact.
Speaker Change: Right, right. Well, again, these are patients. These skin samples will look at histopathology to see if there's any kind of fibiotic improvement. We'll be looking at immune biomarkers.
Speaker Change: We've seen, of course, in animals that the drug performs quite well, but now we have access.
Speaker Change: at the cellular level to potentially see things. You know, the one thing with Sargerosa is not having the ability to biopsy the granulomas that wouldn't be ethical in the trial.
Speaker Change: This allows us in this trial to really look at what's happening right there.
at the site of inflammation with these patients.
Speaker Change: So having the access to the skin samples allows us to see if things are really moving right there in these patients. And of course, there's also some clinical sub-scoring with something called the Rodman skin score. Again, that's something that no approved therapies have been approved.
Speaker Change: So this is why those rheumatologists in particular are really interested to see if Epsofidamod moves and heal at all in the samples. If it does, I think, as I said, it unlocks.
Speaker Change: A number of other potential systemic opportunities in the rheumatology space.
Got it, thanks
Dev Prasad: And our next question will come from Dev, Prasad with Lucic Capital Market, your line is open.
Dev Prasad: Hey everyone, congrats on the progress and thank you for taking my caution. I have a couple of questions one on.
Dev Prasad: expanded access program and wondering whether you plan to use the data in BLA in any ways and secondly I liked it.
Dev Prasad: Will you have significant data from AAP prior to BLA submission?
Dev Prasad: Okay, so the first question answers the second. The first thing is we
Dev Prasad: We're not slowing down our BLA timelines by wanting to really take a look at this data. Now, this is outside of our trial.
Dev Prasad: Pulled together, Investigator initiated trial. That could be a possibility. I mean discussions with some of them about potentially what would that look like. Again, that's.
Dev Prasad: would sit outside of our trial, so I don't want everyone to understand. Not slowing down the BLA timelines. And again, we updated our guidance today that we preserved not only the readout or BLA timelines but now.
Effectively have more than a year of cash.
Dev Prasad: Come on, read out, our phase three read out. So we don't want to slow anything down. Will there be any meaningful?
Analysis from those EIP patients. Again, that's...
Depends on whether or not investigators.
Dev Prasad: I want to have some data out whether anecdotally or bundled together with some of the sites there so. [inaudible]
Dev Prasad: Stay tuned for that. I would love to actually have some data.
come out in parallel.
Dev Prasad: I think it could potentially really help our BLA discussions if we show in fact long-term durable effects.
Dev Prasad: of ASSO and then of course from a safety perspective it doesn't hurt to even have some more data. So stay tuned, I do think that's something that could potentially really benefit us in 2026.
Speaker Change: Great, just one more. If you can talk about the next pipeline product and potential I&Ds, do you plan to evaluate as soon other ILD diseases or the path will be to bring next program, like 101 or 750 into clinic? Thank you.
I think right now we're-
Speaker Change: We're enthusiastic to do both. I think Epsilon Pharma, clearly mechanistically now, could have relevance in a number of other IODs.
Speaker Change: And as I pointed out here, we're talking about upwards to a $5 billion market when you get outside of circuitosis
Square Dremel [inaudible]
Speaker Change: ILD, R.A., MyocytociledD, these are all markets that incrementally, there's no therapy out there that would be considered above ours if we are successful here with sarcanosis. There's a lot of legacy products, biologics, other immunosuppressive agents.
So, I'm continually
for example
Speaker Change: In discussions with those autoimmune ILD experts, how can we move into these areas?
Big Area.
that so could potentially work from a mechanistic standpoint.
Speaker Change: With a rather pipeline, O101 has produced some rather outstanding effects as an anti-fibrotic and what I would consider a true anti-fibrotic in that it is initially looking like it modulates my fibroblast.
Speaker Change: So, our goal would be to expand F. Sofidamat, look at other indications. I think there would be a significant demand.
Speaker Change: in other ILDs, certainly, and then with regard to our pipeline.
We clearly have a first class [inaudible]
Speaker Change: Research Team here that can generate outstanding discoveries, some moving O101 and O750 into areas like lung fibrosis, kidney fibrosis, liver disorders. That would certainly be in the cards here and it's why I think
Speaker Change: This is a real big inflection moment for us as a company with this phase 3 readout.
Got it. Thank you.
Unidentified Moderator: I show no further questions at this time. I would now like to turn the call back over to Sanjay for closing remarks.
Sanjay Shukla: Well, I want to thank everyone for a number of great questions today. A lot of enthusiasm and interest that I can hear on the...
Sanjay Shukla: Other side of the line. We certainly appreciate everyone's interest. It has been a journey for us.
We're really proud of the work we've done.
Sanjay Shukla: I'll just highlight one last thing here. Again, I go back to that publication.
You know, as a company here with-
Sanjay Shukla: 20 to 25 researchers. We're competing with companies, for example, like Roach and Novartis, places I've worked with thousands in research departments and to have a publication and science TM. I think this is our second one in the last five years.
thousands of publications.
Sanjay Shukla: over the last five years in that journal. I can only count five companies.
Sanjay Shukla: who had had two major publications, and we made the cover this time with these discoveries.
Sanjay Shukla: And of those five, we're talking about major big pharma players with thousands of people so a big shout out to our research team here in San Diego.
Sanjay Shukla: 2020-25 folks here strong under the leadership of Leslie, and we're producing discoveries and insights and really fulfilling the mission.
Sanjay Shukla: of translating this rather unique biology into meaningful medicine. So, really, really proud of the work we've done here. I'll end with that. Look forward to seeing all of you, many of you on the road, as we get closer here to phase three readouts later this year. So, thank you all for your interest.
Unidentified Moderator: This does conclude today's conference call. Thank you for participating. You may now disconnect.