Good morning and welcome to the Larimar Therapeutics Conference Call. All participants are now in a listen-only mode. There'll be a question-and-answer session at the end of this call. If you'd like to ask a question, you may press star one on your telephone keypad to be placed in the question queue. You may press star two to remove yourself from the queue. Please be advised that this call is being recorded at the company's request, and a replay will be available on the company's website. I'll now turn the call over to Alexandra Folias of Westside Advisors. Please go ahead.
Thank you, Operator, and thank you all for participating in today's conference call. Before we start, I would like to point out that there is a slide deck that accompanies today's presentation. It can be viewed using the webcast link provided on the investors' page of the Larimar Therapeutics website. Also posted on this webpage is a news release issued earlier today. Before passing it off to company management for prepared remarks, I would like to remind everyone that some of the information disclosed on this conference call contains forward-looking statements that are based on the company's beliefs and assumptions and on information currently available to management.
These statements include, but are not limited to, statements regarding expectations and assumptions regarding the future of the company's business, the company's plans, and ability to develop and commercialize Nomlabofusp, formerly referred to as CTI-1601, and other matters regarding the company's plan, clinical trials, business strategies, use of capital, results of operations, and financial position. These forward-looking statements involve risks, uncertainties, and other factors that may cause actual results, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements.
These risks, uncertainties, and other factors include, among others, the success, cost, and timing of the company's product development activities, non-clinical studies, and clinical trials, including Nomlabofusp clinical milestones and continued interactions with the FDA, that earlier non-clinical and clinical data and testing of Nomlabofusp may not be predictive of the results or success of later clinical trials and assessments, and that clinical trial data are subject to differing interpretations and assessments. The company's ability to raise the necessary capital to conduct its product development activities and other risks described in the filings made by the company with the Securities and Exchange Commission and available at www.sec.gov. These forward-looking statements are based on a combination of facts and factors currently known by the company and its projections of the future, about which it cannot be certain and, as a result, may not prove to be accurate.
The company assumes no obligation to update any forward-looking statements except as required by law. Speaking on today's call will be Dr. Carole Ben-Maimon, President and CEO of Larimar Therapeutics. In addition, Larimar's Chief Financial Officer, Mike Solano, will be available during the question-and-answer session following the prepared remarks. With that, I will now turn the call over to Carole.
Thank you, Alex, and good morning, everyone. We are excited to share some critical regulatory updates for our Nomlabofusp program, which we believe represent truly exciting developments for both Larimar and the Friedreich's Ataxia community. Nomlabofusp is the generic name for CTI-1601, and I will be using the generic name in this presentation. We are thrilled to announce that we have received recommendations from the FDA reflecting their thoughts about the size of the safety database. We now have clarity on what is recommended to support a BLA submission pursuing accelerated approval. Specifically, the FDA recommended that Larimar evaluate safety data from a total of at least 30 participants who had continuous study drug exposure for six months and a subset of at least 10 participants who had continuous study drug exposure for one year.
The large majority of the safety data should be from participants receiving the 50 mg dose. These recommendations were provided to us after the FDA's complete review of a briefing package containing all the safety data and exposure data collected in the Nomlabofusp study trial. Based on the safety database, recommendations by FDA to submit with 10 patients with continuous exposure for one year, with the large majority of the data in patients on the 50 mg dose, and our plan to request approval for a broad patient population, including adults, adolescents, and children. We will be moving our guidance on the timing of the BLA submission, seeking accelerated approval to the second quarter of 2026. Recall, in our December update, we announced that patients had begun transitioning from the initial 25 mg dose to the 50 mg dose.
That transition was completed in the first quarter of this year, and those patients are expected to complete one year of dosing in the first quarter of 2026. Therefore, to analyze and incorporate the data into the BLA, we plan to submit the BLA in the second quarter of 2026. With this update, we believe we now have written recommendations from the FDA on the critical elements of the BLA submission seeking accelerated approval, including the use of skin frataxin concentrations as a reasonably likely surrogate endpoint. Here, we have outlined critical elements of the BLA seeking accelerated approval, and we are very excited to say we have clarity from FDA on expectations across these key elements. We appreciate the collaborative nature of the interactions with the FDA and look forward to continuing to collect the data to support the submission.
As we reported in March, the FDA has provided written correspondence that the agency is open to the use of skin frataxin concentrations as a reasonably likely surrogate endpoint and acknowledged that the submitted data appear to support a relationship between increased skin frataxin concentrations and relevant tissues such as the heart, dorsal root ganglion, and skeletal muscle. Acceptability of increases in skin frataxin concentrations for accelerated approval will be decided during future BLA review. As we discussed in the previous slide, we now have FDA recommendations on the safety database to achieve our near-term submission goals. For our clinical data package, we plan to include clinical data from our successfully completed and ongoing clinical trials, including our completed single ascending dose and multiple ascending dose phase II studies, which support the safety and tolerability of Nomlabofusp.
This package will also include our phase II dose exploration study. Lastly, data from the ongoing open-label extension study will also be included and will provide the data supporting long-term increases in skin frataxin concentrations and long-term safety in adults, adolescents, and children. Our global phase III study is ongoing with the identification and qualification of sites in the U.S., as well as sites in the EU, U.K., Canada, and Australia. The phase III study is expected to be underway at the time of BLA submission and is currently intended as the confirmatory study to verify clinical benefit as required by FDA's accelerated approval pathway. The trial will evaluate clinical outcomes measuring measures, including upright stability and MFARS.
Across our studies, we continue to see consistent findings, including that Nomlabofusp has been generally well tolerated and dose-dependent increases in tissue frataxin levels in skin have been seen following treatment. For our pharmacology and toxicology elements, we plan to submit all of our non-clinical studies that support the use of frataxin as a novel surrogate endpoint, a complete toxicology package, including a juvenile toxicology study, and data from clinical studies supporting improvements in patient lipid profiles and gene expression. Lastly, for our chemistry, manufacturing, and controls, or CMC elements, we will include the required data supporting the lyophilized drug product, which is stable at room temperature, data on batches manufactured at a commercial scale, and analytical methods and proposed specifications. Overall, we are very pleased with our progress.
We are now confident that with these written recommendations in hand, we are well positioned to submit our planned BLA seeking accelerated approval in the second quarter of 2026. With that discussion of today's exciting news, I'd now like to take a step back to provide an overview of Larimar and the Nomlabofusp program. For those less familiar with the Larimar story, Larimar is a clinical-stage biotechnology company with a novel protein replacement therapy platform with first-in-class potential. Our lead program is being developed for the treatment of Friedreich's Ataxia, or FA, a rare, progressive, and systemic disease with neurologic deterioration. It is caused by a genetic defect on both alleles that prevents production of the critical mitochondrial protein frataxin, resulting in low tissue frataxin levels.
On average, most patients with FA only produce about 20%-40% of the frataxin levels seen in homozygous healthy people. Not having enough frataxin leads to a myriad of debilitating symptoms, including unsteady posture and frequent falling. Patients will often present before the age of 14, and symptoms are progressive, typically causing patients to be wheelchair-bound 7-10 years after the initial diagnosis. The symptoms of FA include loss of musculoskeletal function, blindness, deafness, an inability to speak clearly, and diabetes. Unfortunately, patients with FA have a life expectancy of only 30-50 years, with the most common cause of death being heart disease. In 2023, omaveloxolone was approved by the FDA as the first therapy indicated for FA, and it was a critically important breakthrough for patients.
Omaveloxolone has no impact on frataxin levels, and currently, there are no approved therapies designed to increase frataxin and address the deficiency underlying FA's horrible symptoms. Because of this, key opinion leaders, patients with FA, and advocates have made it clear that there is still a pressing unmet need for novel therapies to treat the underlying cause of FA. To address the needs of patients with FA, Larimar is developing Nomlabofusp, the first potential disease-modifying therapy designed to systemically address the underlying frataxin deficiency in FA. Nomlabofusp is a recombinant fusion protein designed to directly address the root cause of the disease, frataxin deficiency. We do this by attaching a cell-penetrating peptide to the frataxin molecule, allowing the delivery of the protein across the cell membrane and into the mitochondria. Now let's turn to our clinical program.
Our open-label extension study is currently evaluating the long-term safety and tolerability, the pharmacokinetics, and the ability of Nomlabofusp to increase tissue frataxin levels over longer periods of time following daily administration of Nomlabofusp. Participants initially received the 25 mg dose. In November of 2024, we began transitioning participants to the 50 mg dose, with the transition being completed in the first quarter of 2025. Currently, all patients are receiving 50 mg daily. Enrollment of the remaining adult patients who participated in prior studies, as well as enrollment of the 14 adolescent patients who participated in the PK run-in study, is ongoing. In December of 2024, we presented initial positive data for the 25 mg dose, and I would now like to briefly review some of that data.
Recall, following 25 mg daily administration of Nomlabofusp, we showed increases in both skin and buccal cell frataxin levels, with skin frataxin levels shown here on the left. We also demonstrated that skin frataxin levels as a percentage of healthy volunteers are higher at day 90 compared to baseline. These data support the potential of Nomlabofusp to increase frataxin levels in tissues and address the protein deficiency leading to FA's devastating clinical course. Encouragingly, we observed early trends towards improvement across a number of clinical outcomes following long-term 25 mg daily Nomlabofusp. Decreased values indicating early trends towards improvement were observed in modified Friedreich's Ataxia Rating Scale, or MFARS, MFARS activities of daily living, modified fatigue impact scale, and the nine-hole peg test at day 90 relative to baseline.
These data support the potential that Nomlabofusp administration and resultant increases in tissue frataxin concentrations may lead to clinical benefit across a broad spectrum of patients with FA. To date, we have reported data showing increases in frataxin in three independent clinical studies, trends towards normalization in gene expression and lipid profiles, and early trends in clinical outcomes. Thus, the totality of the data continues to support the therapeutic potential of Nomlabofusp. Looking at safety, Nomlabofusp continues to be generally well tolerated in our open-label extension study, which includes some participants on treatment for up to 15 months. The most common adverse events were local injection site reactions, with most being mild, brief in duration, and self-limited. No participant has withdrawn from the study due to a local injection site reaction. Anaphylaxis has been deemed an adverse drug reaction likely related to Nomlabofusp by the Larimar safety team.
This is common to proteins and biologics. Participants with prior exposure who have been off treatment for some time seem to be more likely to develop an allergic reaction. Premedication with antihistamines starting five days prior to the first dose and continuing for the first month is being administered to patients who have participated in a prior Nomlabofusp study. Although data is not available at this time, we are hopeful that these medications will mitigate some of these reactions. As we further advance our open-label extension study, we have made several recent updates to the study design, including introducing the lyophilized drug product formulation intended to be used for commercialization. This formulation is stable at room temperature, making use much more convenient for patients. As mentioned, we also amended the protocol to include antihistamine premedication for patients who participated in a prior Nomlabofusp study.
To further broaden the program, we will be enrolling eligible adolescents from the PK run-in study, as well as patients with FA who have not participated in a prior Nomlabofusp trial. Note that due to the inclusion of patients who have not participated in a prior Nomlabofusp clinical trial, we will now refer to the open-label extension study as the open-label study. The significant clinical and regulatory progress we have achieved for our Nomlabofusp development program has been expedited through our participation in the START pilot program, which has been incredibly valuable and continues to help us further advance efficiently. The START pilot program, Support for Clinical Trials Advancing Rare Disease Therapeutics, is a new pilot milestone-driven program launched by the FDA in September of 2023. It is designed to accelerate the development of novel therapies for rare diseases.
We are very proud to have been one of seven programs selected for participation by the FDA. FA is a devastating and progressive neurodegenerative disease with high unmet needs, and we are focused on bringing Nomlabofusp to a broad range of patients around the world. As outlined earlier, following FDA's recommendations on key BLA elements, we are excited now to have clarity on our potential path towards BLA submission seeking accelerated approval using skin frataxin concentrations as a novel surrogate endpoint. We expect to submit our BLA seeking accelerated approval in the second quarter of 2026 and are planning a U.S. launch of Nomlabofusp in early 2027. For our open-label study, we continue to enroll patients with FA on 50 mg of Nomlabofusp daily. We are also beginning to introduce the lyophilized dosage form, making it easier for patients.
We are expanding the study to include patients who have not participated in a prior Nomlabofusp trial, and we are considering enrolling children two to eleven years of age directly into the open-label study. This decision will be made after discussions with the FDA and our DMC. We continue to monitor safety data regularly in this ongoing open-label study and plan to provide data from the next formal data cut in September. This will include data from 30-40 participants who received at least one dose of Nomlabofusp. We expect to share skin frataxin concentrations and clinical outcomes data, provide a full safety update, as well as an enrollment update for the study.
For our adolescent PK run-in study, dosing of 14 adolescents, 12 - 17 years of age, for seven days at a weight-based dose expected to match the PK of adults receiving the 50 mg dose is complete. In September, we expect to report data from the 14 participants, some of whom were on placebo, including safety and pharmacokinetic data. Eligible participants are currently transitioning into the open-label study. Lastly, we have started to expand the Nomlabofusp clinical trial to ex-U.S. geographies with our global phase III study, following feedback from both the FDA and EMA on the study protocol. Activities are ongoing, including identification and qualification of sites in the U.S., Europe, U.K., Canada, and Australia. The global study will be a double-blind placebo-controlled study with one-to-one randomization of 100-150 ambulatory patients that are more heavily weighted to younger patients.
The study will include patients two to 40 years of age. We are particularly excited by the prospect of generating data in pediatric patients, as the only approved treatment for FA is not indicated for use in those under 16 years old. Nomlabofusp will be evaluated following 18 months of dosing in the phase III study. Primary outcome measures will include upright stability and MFARS. As you heard today, we believe we have clear recommendations from FDA on key elements for our BLA submission seeking accelerated approval for a broad population, including adults, adolescents, and children, and are advancing Nomlabofusp towards BLA submission in the second quarter of 2026 for the treatment of FA. This progress has reinforced our confidence in the differentiated potential of Nomlabofusp to deliver meaningful benefits to a broad population of patients with FA.
Current treatments for FA do not address the root cause of the disease, and high unmet needs remain. Nomlabofusp is designed to directly increase tissue frataxin concentrations to address the root cause of FA. Supported by the clinical and non-clinical data generated to date, Nomlabofusp is poised to potentially change the treatment paradigm as the first potential disease-modifying therapy for FA. Our clinical program continues to advance as we further collect long-term data, broaden our program to younger patients, new geographies, and those new to our studies. Importantly, we have several near-term catalysts, including long-term data from the open-label study and PK and safety data from our PK run-in study expected in September of 2025. On the regulatory front, we have clear FDA recommendations on the path towards submission.
Now, with FDA alignment on key elements in hand, including the potential use of skin frataxin concentrations as a surrogate endpoint and the recommendations for the safety database, we plan to submit our BLA seeking accelerated approval in the second quarter of 2026 and are targeting a U.S. launch of Nomlabofusp in early 2027. With this clear path for Nomlabofusp and our strong, maturing clinical dataset demonstrating a differentiated mechanism of action, we believe we are well positioned as we seek to address the urgent unmet needs of the FA community. Before I conclude, I would like to thank our clinical trial participants and their families. Addressing the unmet needs of individuals with FA remains our key source of inspiration, and I commend their bravery and dedication.
I would also like to thank the FDA for their engagement throughout the regulatory process thus far, as well as our talented and dedicated Larimar employees and our partners, clinical trial investigators, and patient advocates at the Friedreich’s Ataxia Research Alliance, all of whom helped Nomlabofusp get to this exciting point in its development. With that, I'd like to now move on to today's Q&A session, where I'll be joined by our Chief Financial Officer, Mike Solano. We will now open the line for questions.
Certainly. When I'll be conducting a question-and-answer session, if you'd like to be placed in the question queue, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue.
For participants using speaker equipment, it may be necessary to pick up your handset before pressing star one. Our first question today is coming from Yatine Sanejo from Guggenheim. Your line is now live.
Hey, guys. Thank you for taking my question. I have a couple. First one is on this on the BLA submission. I mean, could you do a rolling BLA submission where you can submit the other modules first? And then if, you know, I mean, you know, in the past, you had given a guidance of BLA submission by year-end. The question is, how does this safety requirement line up with your initial expectation, keeping in mind that, you know, earlier you were expecting it to be submitted this year? I do have a question on OLE. I'll ask after you answer these questions.
Sure. Hi, Yatine. Thanks for the question.
We have not yet started conversations with the agency about a rolling submission. It is clearly a possibility. Right now, we're planning for the second quarter because of the safety data that we need to collect, specifically the one-year data. Ten patients out of a year on 50 is really the challenge. I want to make sure we highlight the fact that I think the agency has shown real flexibility and has been really, I think, acknowledged that this is a rare disease and there is a significant unmet medical need by only asking for ten patients. That said, we had thought the one-year data could include the 25 mg, but clearly they made it very clear that they would like to have the large majority on the 50 mg dose.
Since we did not complete switching patients until the first quarter of this year, it is going to take us a little more time. Rolling submission is something that we are thinking about and considering.
Okay. Helpful. Could you also give us a sense of the average duration we should expect for these 30-40 patients that you will be announcing data on in September? For clarification, that 30-40, does that include the 14 adolescent patients? Maybe finally, would you be or are you willing to present the lipid profile and gene expression data for the 25 and 50 mg OLE in September or sometime this year?
Yeah. I cannot really give you the average duration because the data is still being collected. Remember, this is an ongoing study.
Until we do a formal data cut, we really do not have totally clean data. Obviously, we look at safety on an ongoing basis. Other than that, we really need a formal data cut before we can provide that. What I can tell you is we dosed our first patient in that study last March, March of 2024. Some of these patients are out 15 months. They just, remember, had started on 25 mg and then were switched. It will be a combination of duration, will be a combination of 25 and 50 for some people. Clearly, people are coming up on six to nine months' worth of data on the 50 mg.
With regard to the lipid and gene expression data, that probably will not be part of the September update, mostly because we have to run all those samples and we're dependent on an academic center to do that. That data will probably be provided in a later update, potentially prior to BLA submission, but in a later update.
Thank you.
Thank you. Next question is coming from Joe Schwartz from Lyric Partners. Your line is now live.
Great. Thanks so much and congrats on all the progress. I guess my first question is, given that there have been a lot of changes at the FDA as recently as last week with the departure of Mick Colverton, can you discuss how much buy-in you feel you have behind or beyond these former leaders and how high up within the new CBER regime has this plan been discussed?
First of all, Joe, nice to talk to you, but we are not in CBER. We are actually in CDER. And so we actually, you know, have not had very much change, quite honestly. I was actually down at the meeting in Washington, D.C., actually at FDA, with Dr. McCarry, the first meeting with the industry that they had. He's very engaged. He's very focused on rare disease. He's very focused on expediting rare disease. We have been getting all of our responses in a timely fashion. The comments, the recommendations we got from them were in writing. They were on time to their commitment. I think START's been a huge help, the START program. They seem to be meeting their timelines. They seem very focused on rare diseases. I think when you look at this dataset, they showed the flexibility and the acknowledgment that this is a rare disease.
We're actually feeling very good and very optimistic about that.
Excellent. Great. Thanks for the clarification. We noticed the statement you made that acceptability of increases in skin frataxin for accelerated approval will be decided during future BLA review or NDA review. Can you help us understand what would be or likely be viewed as adequate data on that front by the FDA?
Yeah. How this all works is, you know, we submit data packages, which are our interpretation of the data. It's, you know, we provide data, obviously, but we don't actually submit the raw data when you're submitting a briefing package. Whenever the FDA agrees to something, they always leave their out that it's a review issue.
As of now, we know that they have put in writing for us that they do believe that they are open to the data that we have already submitted, and they have reviewed the briefing package, and they are open to considering skin frataxin concentrations as a novel surrogate endpoint. When they talk about that, it's an issue for review, they reserve the right, obviously, that when we actually submit the raw data, they could come to a different conclusion than us. I can tell you that we feel very comfortable. The conversations have been incredibly candid. We have provided them everything that they've asked for. I don't usually like to disclose conversations with the agency, but they've even made the comment that you've pretty much done all the work. We are very confident that the use of skin frataxin levels will be acceptable.
Now with the dataset where it's at, we're actually very confident that we know what they want from the standpoint of the safety data.
Sounds good. Thanks for the insight.
Thanks, Joe.
Thank you. Next question is coming from Joon Lee from Truist Securities. Your line is now live.
Hey, thanks for the updates and for taking our questions. For the September update from 30-40 patients, is it fair to assume that all will be on 50 mg for at least 90 days? And if so, why do you need to expand the study?
Yes, it is fair to assume that they will all be on 50 for 90 days, unless, of course, somebody dropped out. The data, like I said, it's an ongoing study. You know, anything can happen. Yes, you can assume that they would all be on 50 for 90 days.
The reason for expanding the study is a couple of reasons. First, we want to make sure we have a broad population. You know, we need data on our adolescents as well as on our children in order to be able to get an indication that is, you know, that is in all populations. That is one reason. The second reason is to allow patients who may not be eligible for other trials. Remember, our phase III study is going to be all ambulatory patients, right? We have certain ages in that trial, 2-40, I think we said. By expanding to patients who may not be eligible for the phase III trial and have not participated in prior trials, it gives options to patients who may not be able to participate in other clinical trials.
Remember, all the phase III trials to date have been in ambulatory patients. That leaves out a huge population of patients, those who can't walk or who may be more debilitated.
Carole, I may have misunderstood Jens' question, but his question, I think, was in September, will all 30-40 patients be on 90 days?
No, they will not. They will all be on 50, but they may not be on 90 days.
All right. Thanks for the clarification. I have a quick follow-up. No, will the start of phase III now, I mean, still on track for sometime mid-year, or is the timing changed given the shift in timing for the BLA as well?
No, it's still on track.
It's actually still on track, and it's actually a good thing because remember, the agency requires that the phase III be enrolling before they will give an accelerated approval. The further along we are with that study, the better. We are going to continue at the same pace, and hopefully we'll just have more patients by the second quarter than we have in the first quarter.
Great. Thank you so much.
Thank you. Our next question is coming from Samantha Simenko from Citi. Your line is now live.
Hi, good morning, and thanks very much for taking the questions. A couple from me. Just first off, do you view the regulatory update as a delay for the program as it relates to the timing of a potential launch? Is that also expected to be pushed out?
And then secondly, can you remind us just on your cash balance? I think it's to Q2. Is that going to be sufficient to support operations through BLA filing? And are there any opportunities to further extend that runway? I have a follow-up.
I'll respond to the launch question, and I'll let Mike talk to the cash balance. We had always intended to launch in the first quarter of 2027, so the launch has actually not been delayed at all. That is because we, you know, we have to make enough product to be able to supply the market. The launch has not changed.
Yeah. Sam, as of March 31, we have $158 million of cash, which is runway into the second quarter of 2026.
From a financing perspective, you know, we'll be continuing to be opportunistic, ensuring that what we do is in the best interest of the shareholders. We are actively considering and evaluating non-dilutive financing alternatives, including royalty financing, which we believe is very possible given our proximity to the BLA submission.
Got it. Thank you for those additional details. Just on the, I guess, the open-label study now, as you call it, has FDA reviewed any of the efficacy data, specifically the skin frataxin data from patients that have been on 50 mg for a reasonable amount of time, or is the alignment on skin frataxin driven almost primarily by the 25 mg data? Thank you.
Thanks. We have not done a data cut, a formal data cut for the 50 mg dose yet. They have relied mostly on the 25 mg.
A lot of what they reviewed was the data actually. First of all, the lipid data was very impressive to them, and they were very interested in that because it's obviously not effective. There wouldn't be any placebo effect. It's a biochemical marker. They also had a lot of animal data. All of the animal data that we submitted, they were able to look at the exposures of the 50 mg dose that were generated out of the dose exploration study. I think what made them comfortable, and it's hard for me, I don't really want to speak for them, but we did provide them with blood levels both in animals and in people and in patients at 50 mg. They overlap dramatically.
They acknowledged in their written responses and in the minutes that they actually were happy to see that the concentrations that were achieved in the animals that showed adequate distribution were at the same exposures as in the patients. That is the data that they have seen. By the way, we will be publishing the animal data, hopefully over the next couple of weeks, if not a couple over the summer for sure. The publication has been accepted in a peer-reviewed journal, so it is just a matter of when it comes out.
Thank you. Next question is coming from Miles Minter from Williams Leary. Your line is now live.
Hi. Thanks for taking the questions. First one is just on if the FDA is going to require any sort of functional data in this BLA filing for accelerated approval. Obviously, we have alignment on safety.
We've got the questions on frataxin expression in skin, but is a functional outcome important there given your peer gene therapy company that appears to be going both on Frataxin expression and a cardiac functional improvement measure there? That's the first one. The second one is, was there any sort of breakdown between the number of adolescent and adult patients from the safety database that you'd need out to six months or potentially even a year to secure an accelerated approval in both adolescent and adult populations, or is it just 30 patients as you get them at six months and 10 patients as you get them at a year? Thanks.
Yep. So we obviously will be submitting functional data. Thanks, Miles, by the way. We will be submitting functional data as we're collecting it every 30 days, every three months.
There has not been any discussion as it's we don't need to be P vals, right? This is an open-label study. We would like to see some trends, but I do want to remind people, I think it's important to remember, more than half of our patients in this trial currently, now that may change as we get more, you know, more patients in, but even so, I think most of our patients coming in are going to be further progressed than a lot of other studies. When half of these patients are in wheelchairs, I think it's not realistic to expect that these patients are, you know, going to get up and walk or that they're going to improve by all that much. What we're hoping is we halt the deterioration and we stop them from getting worse.
If you talk to patients, that's a huge thing. If they can continue to swallow better, if their speech is maintained and they don't lose the ability to speak, those are really things that have a significant effect on their quality of life. I think, you know, we will be providing functional data. Obviously, we're also following the data in the Vacom's database and looking at how best to present that. We will be doing, you know, matches, creating a synthetic arm when we're finally, we'll be submitting to the FDA. I think what we're trying to do is maintain function. Yes, I think they will want to look at it, whether there's any requirements or not. They specifically called out Phospholipids.
They have specifically in correspondence called out the fact that if we can show correlations with changes in lipid levels, that would be of interest to them. That is data we pretty much have already. We are actually presenting at a conference in Bordeaux, France this week, I think, where we are presenting some data with the key opinion leader who is at Montreal Heart Institute and is working on all of this with us. She had asked that one of our employees go with her and talk about, you know, the industry side of the whole thing. She is actually presenting some of the data. You asked about adolescent safety data. There was no breakout. They do know the studies. Obviously, we have submitted all of our studies. We have conversations with them all the time.
I think the advantage of submitting, quite honestly, in the second quarter is that we'll have quite a bit of data on the adolescents. The adolescents are actually transitioning as we speak. They should be coming into the study, or most of them should be coming into the study over the summer. We should have quite a bit of data on the adolescents.
Makes sense. Thanks very much.
Thank you. Next question today is coming from Andrea Sagarides from Oppenheimer. Your line is now live.
Hi, good morning. This is Echo on behalf of Andrea. Congratulations on today's update, and thanks for taking our question. One quick one. Biogen is initiating a pediatric study in 255 children.
I want to ask, do you have an idea of what this overlap is going to be for the sites and how this is going to impact enrollment in your studies concurrently? Thank you.
No worries. Andrea, it is a very good question. It is a lot of patients. The sites do have overlap, but as we've been activating and looking at sites for the 301 study for our phase III study, we've also started looking at different sites for that study. We have a lot of interest from investigators. They clearly believe that getting at the root cause of the disease is a critical thing to do. I think they are very interested in participating. I can tell you we haven't had a lack of interest from patients at all.
We even have identified, you know, some children two to eleven who want to be in the study. And they all know that they can't be in two studies at one time. It's a pretty sophisticated population. So I don't think there's going to be a huge effect. I do think where the effect that we've already seen is these sites are really busy and they have limited capacity. And it's not only because of omaveloxolone or even studies in FA. They may be doing studies on other ataxias, and that takes, you know, takes not, it creates resource issues, study coordinators, et cetera. That's why we're looking to open more sites aggressively and looking at sites that are also not in the U.S., but are in Europe and other parts of the world.
That's helpful. Thank you. And if I may ask one more question.
For the phase III primary endpoint, have you decided on MFARS or upright stability, or is it possible to use both?
It may be both, and it may be different in different parts of the world. We're actually watching the PTC story. As you know, PTC submitted their NDA even though they did not meet their primary endpoint for MFARS, but they did meet upright stability. They have been very public about the fact that the EU has not been as open to that. There is a good possibility that it will be upright stability in the U.S. and MFARS in the EU. We will see what happens in other parts of the world. Our preference is to do upright stability wherever we can.
Thank you very much.
Thank you. Next question today is coming from Cory Jubinville from LifeSight Capital. Your line is now live.
Hey, thanks for taking our questions, and congrats. It's really great to get this level of clarity. As it relates to the adolescent PK run-in patients who are enrolling into the open-label extension, can you comment on the duration of drug holiday between completion of the PK study and restarting Nomlabofusp in the OLE? You mentioned that the adolescent patients are screening and enrolling, but have any of these patients been dosed in the OLE yet? And have you observed any additional cases of allergic reactions either in the adolescent population or any newly enrolling OLE patients?
We announced, if you recall, that we started the PK run-in study early this year and that we finished the first at the end of March, essentially. We are now enrolling them, so you can do the math of, you know, what the hiatus has been.
Obviously, these studies are still ongoing. What I can say is we have not seen anaphylaxis in the PK run-in study. I can't say more than that because the studies are still ongoing. I would like to take the opportunity to make one other comment. One thing that made us so pleased about what the agency agreed to for the safety database was the fact that they clearly aren't concerned about the safety data. They've seen everything. They clearly have bought into the potential for a benefit here that we are getting at the root cause. They seem actually very comfortable with the safety profile. I can't speak for them, obviously, but based on their agreement to what is a relatively limited database, granted it is a rare disease, but it is a relatively limited database, they've, you know, shown quite a bit of flexibility.
You know, they seem to be as comfortable as we are.
That is really helpful. Earlier, when you say the large majority of patients or exposure should be at the 50 mg dose, what does that mean qualitatively? Is there a certain perception they are looking for or duration, et cetera?
I do not, honestly, that is their wording. I think it is going to be somewhat of a judgment call and a discussion with them as we move on. It obviously, a large majority is more than half. That is why we think we really need to look at those patients who were switched earlier and make sure that we have the numbers that we need, you know, that we need in the long term.
I do not, I mean, what really seems to happen here is as the patients continue on the drug, we have more and more compliant, they are more and more compliant. We have less and less issues with number one safety and less and less issues with dropouts. That is a very encouraging sign because patients, you know, who do not perceive any benefit, you know, may very well not want to take an injection every day. You know, again, it is an open label extension, so we have to make sure we put all those caveats in, but we are very optimistic about the way things are going.
Very helpful. Thank you.
Thank you. Next question today is coming from John Wolvin from Citizens. Your line is now live.
Hey, Carole, thanks for hosting the call and taking the questions. A couple for me.
Can you remind us when you reached steady state for drug and for frataxin at the 25 mg dose and if there was a similar timeframe for the 50 mg? Any sense of how many naive patients you expect to enroll in the open-label study?
We reached steady state around, within, let's put it this way, within two weeks. It may be sooner than that, but surely within two weeks. Sorry, it appears to be the same both for the 50 and the 25. They appear to behave well. We haven't really decided how many naive patients we're going to accept at this point. I think it'll depend on how much interest we have. You know, we'll try and accommodate as many patients as we possibly can.
This population is, you know, is really needy and has, you know, it's important that they have access to clinical trials.
One more. Is it fair to assume that you won't be pursuing approval of the 25 mg dose as well, just the 50 mg based on the FDA feedback?
Yes.
Got it. Okay. Thanks, Carole.
Thank you. Next question is coming from Laura Chico from Wedbush Securities. Your line is now live.
Hey, good morning. Thanks very much for taking the questions. Just a couple of clarifications, Carole. For the regulatory submission in 2Q 2026, I just wanted to clarify. This is simply due to the need to reach the proper duration on exposures in that longer term, that one-year 10-patient bucket. I guess, are there any other gating factors that could impact the timing of the submission?
The reason I'm asking, I'm trying to clarify if the enrollment of the participants not previously in a trial, is that also impacting timing? And what was the rationale here by the agency for the request for the naive, I guess, patients? Sorry if I missed that earlier.
I'll start with the last one. It was not the agency that requested. We decided to open it. It had nothing to do with the FDA. We just think it's the more patient data we can get in the, you know, in more people, the better it will be for a review. It also, like I said, gives patients access to clinical trials and to drugs that they wouldn't have access to. It was not a request by the agency.
With regard to exposure at one year, I do not think there is any kind of issue with PK or anything like that. It is just, I mean, remember the ICH guidelines are 100 patients for a year. They are asking us to give them 10. It is just a matter, I think, of having patients that are on drug for a long enough period of time that they feel that they have adequate information to be able to, you know, draft a label and that there is not something that is happening later in the course of their disease or later in the course of therapy that they are missing. It is not a matter of, you know, PK for frataxin levels or anything like that. It is a matter, I think, of just having appropriate exposure.
Just to follow up to that, in terms of the submission then, are there any other items or gating factors that could impact timing at this point? It does not sound like it, but just wanted to clarify.
Not that I can anticipate right now. I mean, there is, you know, there is always something that can happen that you do not anticipate. Based on everything I know, we are very confident with those dates.
Okay.
You and I have talked about it at other times that, you know, we needed to, the one thing that could really have an impact was the safety database. Now that is out of the way. We know that they are willing to accept skin frataxin levels, at least to review the data, the detailed data. They have seen a lot of it.
We feel very good now that we've checked most of the boxes.
Okay. Last question here is just what would be the timing for understanding the dosing in the 2 to 11-year-old population? I think that that would be started later in the phase III s tudy, but just trying to understand what additional information do you need to migrate to that population? Thanks.
Yeah. They will be in the phase III study, but we will also, we're now thinking about whether, remember the original PK run-in study, the original design was to do the adolescents and then to do the kids 2 to 11 as a cohort to confirm exposures and then put them in the open-label extension.
We're actually reconsidering that now because we think it's better for them to go into the, you know, 2 to 11-year-olds, putting them through a PK study that they may not need to be in doesn't seem to be very smart. So we're actually working with FDA now and their DMC to amend the protocol to allow the 2 to 11-year-olds to come directly into the open label extension because we do PK in the open label extension. And we saw the data from the PK run-in study in the adolescents, which looked really good. So, like I said, we still need confirmation from FDA and the DMC that they'll be comfortable with that, but that is sort of the plan that we're transitioning. That won't happen until much later this year.
Thanks very much.
Thank you. Our next question today is coming from Catherine Novack from Jones. Your line is now live.
Oh, hi, morning. Thanks for taking the questions. I just want to get a sense from you, how firm is the FDA guidance on the safety database? You know, is there any risk that later they say they want all patients on 50 mg or that they want more patients at one year? Just trying to assess, you know, what level of risk there still is in the FDA timelines.
Yeah, I think the risk is limited, Catherine. There's always a risk. I mean, we could have some unexpected, unanticipated adverse event or something that, you know, that gets their attention. They, you know, they're hesitant to put in writing things that they don't follow through on.
Unless there is something unexpected that happens, and remember, like I said, we do have patients out for quite a bit of time. Unless something unexpected happens, I do not think that their request will change. You know, it is a regulatory agency. They always have the right to change their minds until they do not, right? Even after an approval, they have a right to change their minds if something pops up. Like I said, we have now written correspondence and all the key elements. That obviously is not written in stone, but it is much more firm than not having that. I feel very comfortable. I think it also, like I said earlier, shows their comfort level with what they are seeing.
Just wondering, can you speak to turnover on the review team since you've started working on the BLA with the FDA? You know, is the original team still in place? Have new people been appointed or, you know, removed without being replaced? What has that looked like from your perspective?
I can tell you that the Head of the Office, the Head of the Division, and our lead reviewer are all people that were at our pre-BLA meeting like six years ago. They are, and now they've been promoted. They were not the Head of the Office and Head of the Division at the time, but they've been with us from the beginning. They are very interested in the program, and we have not seen any effective turnover at all. I can tell you at the FDA meeting, Dr.
Makari basically said they are hiring reviewers, and they are even hiring back some of the people that were let go. We have not seen that because we just have not, we have not experienced any people leaving the team. Okay, great.
That is very helpful. Thanks for taking my questions.
Thank you. Next question is coming from Joel Beatty from Baird. Your line is now live.
Good morning, Carole. Good morning, Mike. This is Chris on for Joel. I just had a couple of questions. First on dosing, in terms of the adolescent study, you mentioned, you know, it is weight-based. Is there a chance based on weight that, you know, some of these adolescents will get more than the 50 mg dose? And then just follow up on that last question on FDA. Can you clarify if you had discussions with Dr.
Makari regarding this and the new regime and kind of maybe some clarity on that? Thanks.
The weight-based dose is capped at 50, Chris. Nice to talk to you. Nobody can get over 50. I do not really want to say what I talked to Dr. Makari about, but what I can tell you is that during the meeting, what I spoke about was the value of the START program. They gave everybody an opportunity, all 75 of us or 76 of us, to speak, believe it or not. I really cannot believe they are actually going to do five of these because they hear the same thing over and over again. I wanted to impress, there was a lot of discussion on communication and being able to get, you know, quicker feedback than the type A, B, C, D meetings allow for.
What I tried to make the point was that the START program really has been spectacular and really has helped to solve a lot of those problems. He was very receptive to that.
Real quick, you were part of that after the roundtable a couple of weeks ago, you were part of those 75 people who were able to talk to them right after that roundtable?
Yeah. They did the roundtable in the morning, and then in the afternoon, they did these listening sessions, which they're doing in other parts, right? They're doing one in Boston, one in New York, one in San Diego, one in San Francisco. This was the first one.
Thank you. Next question is coming from Ramsaraju from, I'm sorry, Raghuram Selvaraju from H.C. Wainwright. Your line is now live.
Thanks very much for taking our questions.
Firstly, I was wondering if you could provide some clarification on the extent of long-term stability that you currently have on existing produced batches of Nomlabofusp?
We have a lot. I honestly don't know off the top of my head, but it's well over two years. And it is on the lyophilized drug product as well and the drug substance.
With respect to the phase III study as planned, can you comment on whether it might be reasonable to expect final top-line results from this study before the end of 2028, obviously depending upon the pace of enrollment?
I do not think that you will get final results before 2028. It's 18 months of dosing, as I said. If you figure, it might be close.
If you figure a year to 18 months to enroll and then 18 months of dosing, you're talking about three to four years, I would think. That's not guidance. That's just a calculation off the top of my head.
Understood. Thank you.
Thank you. We reached the end of our question and answer session. I'd like to turn the floor back over for any further closing comments.
I just want to thank everybody for participating, and the questions were great, and we're very excited and look forward to moving this program forward.
Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.