Longeveron Q2 2025 Earnings Call Transcript

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Provided by Quartr
August 13, 2025

Key Takeaways

  • Positive Sentiment: The company has completed enrollment for its pivotal Phase IIb trial (ALPHACE-2) in single-ventricle congenital heart syndrome (SLHS), and the FDA agreed this trial is pivotal, paving the way for a potential BLA submission in late 2026.
  • Positive Sentiment: Longeveron received an IND approval to move directly into a single pivotal Phase II trial for pediatric dilated cardiomyopathy, a rare disease with ~2,000–3,000 U.S. patients and no approved therapies.
  • Positive Sentiment: After positive Phase IIa ClearMind data and a constructive Type B FDA meeting, the company is actively pursuing a strategic collaboration for its Alzheimer’s disease stem cell program.
  • Negative Sentiment: Q2 revenues fell 31% year-over-year to $700,000, research and development expenses rose 39%, and the net loss widened to $10 million for the first six months, creating reliance on additional financing to fund operations into 2026.
  • Positive Sentiment: To accelerate BLA readiness and manage costs, Longeveron will outsource commercial manufacturing to a third-party CDMO while maintaining in-house capabilities for early-phase work.
AI Generated. May Contain Errors.
Earnings Conference Call
Longeveron Q2 2025
00:00 / 00:00

Transcript Sections

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Operator

Greetings, and welcome to the Longeveron twenty twenty five Q2 Financial Results and Business Update Call. At this time, all participants are in a listen only mode. A brief question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Derek Cole, Investor Relations. Thank you. You may begin.

Derek Cole
Investor Relations at Investor Relations Advisory Solutions

Thank you, operator. Good afternoon, everyone, and thank you for joining us today to review on Chevron's twenty twenty five second quarter financial results and business update. After The U. S. Markets closed today, we issued a press release with financial results for Q2 twenty twenty five, which can be found under the Investors section of the Lung Geron website.

Derek Cole
Investor Relations at Investor Relations Advisory Solutions

On the call today are Wael Hachad, Chief Executive Officer Doctor. Joshua Hair, Co Founder, Chief Science Officer and Chairman of the Board Natalia Agapanova, Chief Medical Officer Lisa Locklear, Chief Financial Officer and Devin Blass, Chief Technology Officer. As a reminder, during this call, we will be making forward looking statements. These statements are subject to certain risks and uncertainties that could cause actual results to differ materially from these statements. Any such statements should be considered in conjunction with cautionary statements in our press releases and risk factors discussed in the company's filings with the Securities and Exchange Commission, which we encourage you to review.

Derek Cole
Investor Relations at Investor Relations Advisory Solutions

Following the company's prepared remarks, we will open the call to questions from covering analysts. With that, let me hand the call over to Wael Hishad, chief executive officer. Wael?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Thank you, Derek. Thank you all for joining us today. We are very excited about our updates for the quarter and the progress we continue to make advancing sensor research in multiple important indications. First and foremost, I am heartened by the team's ability to identify the most expedient, cost effective pathways to advance our technology, develop the corresponding strategy, and effectively implement it. We have made tremendous progress and delivered on multiple important milestones across our pipeline.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

As a reminder, for those of you newer to our story, lonteviron is a regenerative medicine company developing cutting edge cellular therapies. Our stem cell therapy, laromastrocel, has delivered several positive initial results across five clinical trials and three indications. Phase one and two in Alzheimer's disease, phase one and two in aging related frailty, and phase one in haplastic left heart syndrome or SLHS, a rare pediatric and orphan disease. The company's development program for these three initial indications address US market opportunities of approximately 5 plus billion dollars, 4 plus billion dollars, and up to $1,000,000,000 respectively. As we have indicated previously, for 2025, we are focused on three primary operational goals.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Number one, advancing ALPHACE two, our pivotal phase two b study for SLHS. Two, SLHS BLA preparedness and commercialization readiness. Three, pursuing strategic collaboration for Alzheimer's disease program. SLHS is a key strategic priority for us. We believe the SLHS program has a high probability of success and the shortest path to to potential regulatory approval and future commercialization across our pipeline.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

We were very excited to share in June that we have completed enrollment for pivotal office two phase two b study evaluating larametrosol as a potential adjunct treatment to the standard of care for SLHS patients. The determination by the US Food and Drug Administration at our meeting in August that office two is pivotal, significantly accelerate the potential regulatory path for lalanastrozole. And it's supported by data from the clinical trial, we this would allow us to initiate following submission of a biological license application with the Food and Drug Administration in lieu in late twenty twenty six. This would be our first BLA submission, and it would be for an important identification with large unmet need and a significant market opportunity. Now I wanna take a moment to acknowledge and give credit to the Food and Drug Administration and its staff for their diligence, preparation, and professionalism.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

We have had three important interactions with the agency over the past twelve months. While appropriately challenging and demanding, the agency has sought to understand that our development programs and provide input and feedback that has substantially clarified the regulatory pathway for laronextric cell and SLHS, Alzheimer's disease, and now pediatric dilated cardiomyopathy for which we recently received an initial new drug application approval, IND approval. We are grateful for their efforts and appreciate their collaborative approach and the opportunity to reach alignment on our development program. Our success advancing the SLHS and Alzheimer's programs both reinforces our confidence in our science and highlight our strategic plans, risk mitigation through a diversified pipeline. This approach supported by expanding our pipeline to include pediatric dilated cardiomyopathy and license additional novel stem cell technology.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

These expansions to our pipeline build on a focused rare disease where we can potentially make a big difference while completing our existing pipeline and technology. The next twelve to eighteen months are potentially transformational period for launch of our own with multiple critical milestones, and I am thoroughly excited by the opportunity for ladermastuzumab, with patients, ladermastuzumab, and our shareholders. With that, I will turn the call to doctor Agustinova to provide an update on our clinical development program. Natalia?

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

Thank you, Rael, and good afternoon, everyone. Our lead investigational prod product is gloramestrocel, a stem cell therapy derived from culture expanded mutant stem cells or MSCs that are sourced from the bone marrow of young healthy adult donors. As Rael mentioned, our h l h s program is a primary focus for us with a near term pathway to potential approval in an area of clear unmet medical need. The current standard of care for HLHS involves a complicated three stage heart reconstruction surgery over the course of the first five years of patient's life. Despite this surgical reconstruction, only fifty percent of the affected children survive to age 15 without heart transplantation.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

Our laramestrocell program in HLHS is designed to boost, improve the heart function in these children with the goal of potentially enhancing their survival. Altice One, our phase one clinical study evaluating laramestrocel in four months old infants with HLHS, we observed hundred percent transplant free survival for five years in all patients following treatment. This contrast with an approximately twenty percent death in heart transplant observed in historical control data. This translates to a potential number needed to treat a five, which is highly favorable, especially for the rare pediatric disease. We can prevent one death when treat five kids with HLHS.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

We are currently conducting the phase two clinical trial, l p s two, evaluating the potential of laronextro cell to improve right ventricular function and long term clinical outcomes in infants with atrial HS. We completed enrollment of the trial in June, enrolling 40 patients at 12 premier infant and children's treatment institutions across the country. The slight over enrollment of the trial, including two additional patients beyond target enrollment. It's like both. They are met, meet in this area and our commitment to support patients suffering from this devastating condition.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

We are grateful for the participation of the patients, their families, and our investigative sites. This twelve month follow-up period, we currently anticipate top line results from the trial in the 2026. If results from l p s two are positive, we would be positioned to initiate a rolling BLA submission with the FDA in late twenty twenty six. Reaching over to Alzheimer's disease briefing. With the positive results from the phase two a ClearMind clinical trial, the publication of that data in Nature Medicine, and the positive type b meeting with FDA regarding pathway to BLA submission in Alzheimer's disease that yielded alignment on the proposed trial study design, population and endpoints for the single pivotal phase two, three clinical trial.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

That if positive would be acceptable for BLA submission for Alzheimer's disease, we believe we have a strong opportunity to forge collaborations and partnership for the advancement of laramestrocel in addressing Alzheimer's disease. Moving on to our pipeline pipeline expansion to pediatric dilated cardiomyopathy. Dilated cardiomyopathy is a disease that affect the muscle cells of the heart, known as cardiac myocytes. In DCM, dilated cardiomyopathy, this caused the size of the heart chamber to enlarge and the pumping strength of the heart to diminish. Together, these adaptations lead to cardiac failure, diminished blood flow to the body, and overconjunctive heart failure.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

The manifestation of congestive heart failure include a buildup of fluid in the lungs, liver, abdomen, and lower legs, diminished exercise capacity, and death. In a large number of cases, the exact cause of DCM cannot be determined. That's why it's called idiopathic cardiomyopathy. Pediatric cardiomy myopathies affect at least hundred thousand children worldwide. DCM is the most common form of cardiomyopathy in children.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

About fifty to sixty percent of all pediatric cardiomyopathy cases are diagnosed as dilated. According to the pediatric cardiomyopathy registry, DCM is reportedly more common in boys than girls. Although all age group are affected, studies show that DCM is more common in infants before age one than in all the children. Effective treatment options are limited and near forty percent of children with DCM requiring a heart transplant or dying within two years of diagnosis. Current treatment for DCM focuses on managing symptoms, improving heart function, and preventing complications rather than addressing the underlying cause or or causes.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

Many therapeutic adjuncts with non efficacy in adults love the same evidence in children. Our development program in pediatric diabetes cardiomyopathy reinforces lanzivirone commitment to develop an innovative stem cell therapy for rare diseases, particularly for cardiovascular conditions where we believe laramitra cell may have significant potential to improve patient life. As we reported in July, the FDA has approved our IND application for evaluating laramestrocel as a treatment for pediatric dilated cardiomyopathy. We greatly appreciate the positive interaction with the FDA and the extensive discussion of our development plans and the clarity provided on the regulatory pathway. The accepted IND application provides for moving directly to a single phase two pivotal registration clinical trial.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

Moving directly to a pivotal phase two trial is significantly beneficial to the development program and the company. We currently anticipate initiation of pediatric, dilated cardiomyopathy phase two clinical trial in the 2026. That's just to obtain your necessary financing and look forward to providing additional updates as the development program takes shape. I will hand the call over to David Bloss, our chief technology officer. David?

Devin Blass
Devin Blass
SVP & CTO at Longeveron

Thank you, Natalia, and good afternoon, everyone. As we look ahead to the potential BLA submission for HLHS, a key focus this year is our organizational readiness, particularly in industry manufacturing and controls or CMC. We are executing against the strategic plan to ensure that our manufacturing infrastructure and operations are positioned to support both regulatory expectations and future commercial demands. While our GMP manufacturing facility in Miami remains and continues to support our early phase clinical manufacturing, process development and research activities, we've made a deliberate decision to pursue commercial manufacturing through a third party CDMO. This approach allows us to leverage the scale, experience, and compliance infrastructure of a dedicated commercial manufacturer while preserving our internal capabilities for future pipeline programs.

Devin Blass
Devin Blass
SVP & CTO at Longeveron

Our goal is to substantially advance BLA readiness this year ahead of the alpha two data readout so that we can move efficiently towards a BLA submission since the data support it. This includes progressing key activities progressing key activities such as technology transfer, process and analytical method validation planning. We believe this investment in CMC will enable our long term success. I will hand the call over to Josh Hehr, our founder and chief scientific officer. Josh?

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

Thank you, Devin. Good afternoon, everyone. I'm absolutely delighted with the progress we were a we are able to share with you. As Weil mentioned, our stem cell therapy, laramestrocel, has now delivered positive results across five clinical trials in three indications. These include Alzheimer's disease, aging related frailty, and most importantly, HLHS.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

We are on the cusp of pivotal data in HLHS and hopefully our first BLA filing next year, which would be an important step in our mission to help patients and families through the application of stem cell research. We are building on our success thus far, adding to our pipeline with pediatric dilated cardiomyopathy, as Natalia mentioned, and with the licensing of additional stem cell technology from the University of Miami. We believe the timing is right to add this new technology, which represents a major advance to our existing stem cell research. Expanding our therapeutic pipeline expands our effort to multiple new potential applications and is aligned with our core strategic approach. Excellent science, lower required investments, speed to market, lower regulatory hurdles, all addressing important unmet medical needs.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

The composition of matter patents we licensed protect unique induced pluripotent derived cardiomyogenic cells that have widespread therapeutic indications for heart disease. The stem precursor cells protected by this patent are obtained by deriving cells that bear a a cell surface receptor known as the growth hormone releasing hormone receptor or the GHRH receptor. These cells are uniquely able to differentiate into human cardiac muscle cells and have the potential to be safer than existing strategies to derive new cardiac heart muscle cells. This technology provides a solution to one of the most difficult barriers to the implementation of induced pluripotent stem or iPS cell technology in the cardiovascular space. The use of induced pluripotent cells is intended to be able to generate any kind of missing cell lost due to disease or damage.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

Importantly, the technique provides the possibility of generating unlimited supplies of the missing cell, and these cells are developed without using human embryos. However, in current approaches with iPS cells transplant transplanted into the heart, a serious side effect has been observed. The dangerous side effect known as arrhythmia causes a potential life threatening electrical instability of the heart. Our new technology provides an innovative solution to this problem as it develops a new method to select specific cells in the purification process that can form myocytes, heart muscle cells, without causing the arrhythmia. We plan to initiate preclinical studies to develop this technology to the next step of readiness for human use.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

I will now hand the call over to Lisa to review our financial results. Lisa?

Lisa Locklear
Lisa Locklear
CFO at Longeveron

Thank you, Josh, and good afternoon, everyone. This afternoon, we issued a press release and filed our quarterly report on form 10 q, both of which present our financial results in detail, so I will touch on some highlights. Revenues for the six months ended 06/30/2025 and 2024 were 700,000.0 and $1,000,000 respectively.

Lisa Locklear
Lisa Locklear
CFO at Longeveron

This represents a decrease of 300,000.0 or 31 percent in 2025 compared to 2024, driven primarily by a decreased participant demand for our Bahamas registry trial and reduced demand for contract manufacturing services from our third party client. Clinical trial revenue for the six months ended 06/30/2025 was 600,000, which is a decrease of 200,000.0 or 31% when compared to $800,000 for the six months ended 06/30/2024. This decline was primarily a result of decreased participant demand. Contract manufacturing revenue for the six months ended 06/30/2025 was $100,000 from our manufacturing services contract, which is a decrease of approximately 100,000.0 or 35% when compared to the 200,000.0 in contract manufacturing revenue for the six months ended 06/30/2024. General and administrative expenses for the six months ended 06/30/2025 increased to approximately $5,500,000 compared to 4,300,000.0 for the same period in 2024.

Lisa Locklear
Lisa Locklear
CFO at Longeveron

The increase of approximately $1,200,000 or 28% was primarily related to an increase in personnel and related costs in 2025, including equity based compensation. Research and development expenses for the six months ended 06/30/2025 increased to approximately $5,500,000 compared to 3,900,000.0 for the same period in 2024. The increase approximately $1,600,000 or 39% was primarily related to a 1,300,000.0 increase in personnel and related costs in 2025, including equity based compensation in support of ongoing CMC and manufacturing readiness activities as part of our BLA enabling efforts and also $200,000 increase in amortization expense related to patent costs, partially offset by 300,000.0 in lower clinical trial expense resulting from the discontinuation of activities related to the aging related frailty clinical trial following our decision to discontinue trial activities in Japan in Q2 twenty twenty four. Our net loss increased approximately $10,000,000 for the six months ended 06/30/2025 from a net loss of $7,500,000 for the same period in 2024 for the reasons outlined previously. Our cash and cash equivalents as of 06/30/2025 were $10,200,000.

Lisa Locklear
Lisa Locklear
CFO at Longeveron

In August, the company completed a public offering, raising approximately $5,000,000 in gross proceeds with up to an additional 12,500,000.0 of potential aggregate gross proceeds upon the exercise in full of short term warrants. We currently anticipate our existing cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements into the 2026 based on our current operating budget and cash flow forecast. We have been and will remain focused on prudent and efficient capital allocation strategies to advance our development programs, which we believe are highly cost efficient, both intrinsically and relative to other development programs. Following the successful Type C meeting with the FDA in August 2024 with respect to the HLHS regulatory pathway, we began ramping up our BLA enabling activities. We currently anticipate a potential BLA filing with the FDA in late twenty twenty six if the current ELPIS two trial in April is successful.

Lisa Locklear
Lisa Locklear
CFO at Longeveron

With the significant opportunities presented with the potential BLA filing, our operating expenses and capital expenditure requirements are currently expected to increase throughout the remainder of calendar twenty twenty five and in 2026, in a large part to address CMC and manufacturing readiness. We intend to seek additional final financing opportunities, capital raises, as well as nondilutive funding options to support our operating plans. Additionally, following a positive type b meeting with the FDA in March 2025 with respect to the Alzheimer's disease regulatory pathway. We are focused on seeking partnership opportunities and our non dilutive funding for the Alzheimer's disease program supporting a proposed single pivotal seamless adaptive Phase twothree clinical trial. There can be no assurance we will be able to obtain future financing at terms favorable to us or at all.

Lisa Locklear
Lisa Locklear
CFO at Longeveron

In the event we are unable to obtain the financing needed, we will need to materially revise our current operational plan. The relatively near term potential for pivotal clinical trial data for HLHS and possibly our first BLA submission late next year make this an extraordinarily exciting time for Longevron. I will now hand the call back to Wayo.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Thank you, Lisa. Longevron has made tremendous progress advancing stem cell research for important development programs, including HLHS and Alzheimer's disease.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

With the addition of pediatric dilated cardiomyopathy and new stem cell technology licensed from the University of Miami, we are building a robust pipeline with the potential to help patients globally. We are now approaching multiple potentially transformational milestones including completion of pivotal phase two b clinical trial in SLHS, our first potential BLA submission for SLHS and based on the strength of the phase two a clinical data potential partnering for Alzheimer's disease program. I have mentioned before, I'm incredibly proud of our team's effort and accomplishment on behalf of patients and shareholders. Their expertise, industry experience, commitment allow LongeBron to achieve tremendous amount of progress for a company of our size with a smaller team and fewer resources at the moment. We deeply appreciate the support of all of our stakeholders and look forward to continued collaboration and progress in the future.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Operator, we would now like to open the call for questions from covering analysts.

Operator

Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star and then one on a telephone keypad. The confirmation tone will indicate your line is in the question queue.

Operator

You may press star and then 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. The first question we have is from Ram Selvaraju of H. C. Wainwright. Please go ahead.

Raghuram Selvaraju
MD - Healthcare Equity Research at H.C. Wainwright & Co., LLC

Thanks so much for taking my questions, and congratulations on all the progress. Firstly, I wanted to ask a couple of clarificatory questions regarding your activities in rare cardiological conditions. Can you confirm whether or not the target patient populations and indeed target addressable markets in HLHS and pediatric dilated cardiomyopathy are to be considered as roughly similarly sized and therefore, approximately offer the same kinds of dynamics with respect to pricing and overall commercial value, particularly in The United States, or if you believe that there are meaningful differences between the two just in terms of, you know, the total addressable size in terms of number of individuals likely to be afflicted with these conditions?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Thank you, Ram, for for this question.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

I'll I'll take the the the answer to that. So the the overall, the answer is the markets are similar, but not identical from the exact number of population. And I'll explain it just in a minute here. But but both are orphan disease, both are rare disease. And I believe from a pricing strategy standpoint, they should be a comparable, though they may not be identical because they are not going to be administered in the same fashion.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

So one, SLHS, as you know, these injections are given during the Glenn procedure, and they are injected directly into the the the the right ventricle. The for for pediatric dilated cardiomyopathy, that would be an infusion intravenous infusion. So the the the method of administration is gonna be slightly different, not slightly different. But and and and and therefore and also the the big other difference is that on SLHS, it's a onetime use versus the the pediatric dilated cardiomyopathy. The intention is to have a continuous use of the product.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

So it's a chronic utilization. Now in terms of the size the exact size of the population, the incidence of pediatric dilated cardiomyopathy is slightly lower than the than than the SLHS. However, because these patients are many of them live for a longer period of time, the prevalence of the disease is slightly higher than the than the SLHS. So the prevalence is is in the range of about two thousand to three thousand patients in The United States. As you know, the SLHS is about 1,000.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

The incidence is slightly lower. So these are the new born children with with with the condition for pediatric dilated cardiomyopathy. It is lower than one thousand. That's about six hundred patients. So hopefully, that addresses.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

In terms of pricing strategy, we have not finalized any pricing strategy on both, but they should not be that far from each other from a pricing standpoint.

Raghuram Selvaraju
MD - Healthcare Equity Research at H.C. Wainwright & Co., LLC

But it would not be inaccurate to state that because in p c in PDC, you are looking at a different administration paradigm and as you mentioned, you know, longer term administration that in effect, whatever pricing you ultimately establish for HLHS will, in effect, if transferred to PDC, ultimately result probably in higher market penetration because of the ease with which one can conduct an infusion as opposed to direct injection into the heart as well as the fact that you would have more cycles of treatment. Is that is that correct?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Correct.

Raghuram Selvaraju
MD - Healthcare Equity Research at H.C. Wainwright & Co., LLC

And then secondly, just with respect to HLHS regulatory outlook and implications for PDC.

Raghuram Selvaraju
MD - Healthcare Equity Research at H.C. Wainwright & Co., LLC

If we look at the approval criteria for HLHS, the fact that positive results from LPS two are expected to buttress the case for approval of laramestrocel in this disease indication, would it be possible then to infer that a favorable approval decision in HLHS would effectively have some implications for what level of clinical evidence you would need to furnish in order to achieve an approval in PBC. For example, if in HLHS, laramestrocel is adjudicated approvable based upon the results of the OPUS two trial, and as you mentioned in your prepared remarks, you are currently contemplating a phase two study in PBC as well. Then if there are positive results in PBC and we use the larobestrocel approval precedent in HLHS as illustrative or indicative of the regulatory outlook, then positive results from that phase two trial in PBC should ultimately represent an approvable package. Apologies for the the long winded way of saying it. But what I'm trying to say is, is there, you know, direct implications of the regulatory outlook for laramestrocel in HLHS in the PDC indication as well?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Right. So, of course, that's a that's a question ultimately the FDA will have to decide on it, but I will give you my thought. I I do believe if we have a positive data coming out of the SLHS trial that this will definitely help support the case for the pediatric dilated cardiomyopathy when we come to the regulatory review process. However, I I I do believe that the FDA will still want to see the the study results from the pediatric ventilator cardiomyopathy on its own. They wanna see how we perform on the endpoints that we agreed with the agency on it and so on.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

But definitely having a positive outcome from SLHS would would definitely be supportive to the overall regulatory review process. As you know, it's a benefit risk ratio. At least on the benefit on the risk side, that that would be an a big added support from at least that point.

Raghuram Selvaraju
MD - Healthcare Equity Research at H.C. Wainwright & Co., LLC

And then just one very quick question. Sorry. Go ahead.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Yeah. Natalia, do you wanna add anything?

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

I just would like to add one more point, and we communicated this today as well. We already we already reached the agreement with the FDA that that phase two study, which is just designed and submitted and approved IND based on would be sufficient for approval upon the positive results for the for the pediatric dilated cardiomyopathy.

Raghuram Selvaraju
MD - Healthcare Equity Research at H.C. Wainwright & Co., LLC

Okay. Great. That's that's very helpful clarity. Just one quick question for Louisa. If if you look at the phase two study, the proposed phase two study that's envisaged in pediatric dilated cardiomyopathy, can you give us a sense of, you know, relativistically speaking, how much more expensive or whether it is likely to be comparable in expense to the HLHS of this two trial?

Raghuram Selvaraju
MD - Healthcare Equity Research at H.C. Wainwright & Co., LLC

Or is there any point of comparability between those two just in terms of overall budget?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

So so, Ram, I think I think the overall budget we anticipate, and that's why we we prefer to focus on rare diseases because we believe that the budget is is definitely more manageable. The preliminary budget numbers that we have, and I'm saying preliminary numbers, is probably in the range of 15 to $20,000,000 for the entire cost of the trial from a to z. And that is not per year cost. That's the total cost.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

And because this file is is going to span at least four four or five years, the the the whole time period for measuring the efficacy of the drug is thirteen months. So we're we're looking at the start up time, enrollment time, and readout time. We believe that the cost per year could be in the range of about maybe $3,000,000. And as Natalia said, we're also looking for similar to what we did with the Office two is we're looking for non dilutive funding to support that. And and there is a lot of both private and government supported entities that are interested in supporting that type of research.

Operator

The next question No. Just that that's the apologies. Go ahead.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

I'm sorry. I'm wrong. I was just gonna say I'll just say

Lisa Locklear
Lisa Locklear
CFO at Longeveron

that is a preliminary estimate as we're working through the feasibility right now.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Understood.

Operator

The next question we have is from Bhubiland Pataryapan of ROTH. Please go ahead.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

Hi. Good afternoon, everyone. Can you hear me okay?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Yes.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

Hi. Great. So thanks. Few questions from us. So first, with respect to HLHS.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

So you stated you requested it, but BLA filing could occur by year end twenty six. So but if you look at, you know, from a logistic standpoint, at that time, the FSPRV program would have been suspended. Assuming, you know, there is no new developments in that area. So my question to you is, do you still get to keep the RAP pediatric designation and enjoy the associated benefits such as rolling submission and more frequent FDA interactions? And also speaking of the FDA interaction, can you comment on whether there's any leadership changes or, you know, because there's been a lot of trucks at the FDA level, and I wanted to make sure, you know, the offices that you're dealing with are still going to be the same, or do you expect any anyone to be different?

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

The reason I'm asking this question, because I wanted to make sure the chances that the phase two b can still be registration enabling and not a separate phase three study in out of the blue?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

That that those are great questions, Bobalan, as well. So thank you for for those. Let me address the PRB first. As as we have previously disclosed in all of our communications, we realized that the the current PRB was sunset in September 2026 Unless it's reauthorized by the congress and approved by the senate. I can tell you as a member of the board sitting on California Life Sciences, I got the opportunity to meet with a lot of members of the congress from both sides of the aisle of republicans and democrats.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

And there is a significant support for renewal of that, especially it doesn't cost the budget anything because that that is a non budgetary item. Unfortunately, sometimes these type of things gets left out by focusing on other important things that is happening and trade off. But there is a lot of support at least from both sides to do it. I also we we are, as you know, a member of the BIO organization, and there is a lot of efforts that's going also on BIO, and you can see it also on their website that this is one of their top priority. So I'm cautiously optimistic that this will be renewed, but definitely, right now, as we stand, likelihood, it is going to sunset in 2026.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

We have a lot of things that allow us for rolling submission. One of them is that a pediatric disease designation, but also the fast track designation for a cell like that is another way of also supporting the role and submission, and that's why we're gonna move ahead and start to do the role and submission immediately after data readout next year. In terms of your second part of the question, which is the FDA and the changes in the leadership and how this impact. So you're you're correct the fact that we had our HLHS meeting with the FDA last year in the same time as this time, August. And the agreement is mandated, and I do believe that we have very unique things to support our case.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

And I don't believe that the FDA will change, and I will give you multiple reasons for those. Number one, we're doing head to head trial. We're not doing similar to Mesoblast or or Capricor at least the data submitted. We are doing head to head trial, and that is as robust as it gets. The number of patients is considering the the prevalence of the disease or the incidence of the disease is fairly sufficient.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

I mean, we cannot make any larger trial than that. So for all those reasons, we feel confident. So that is that is part one of answering your your question. Part two is actually we have met with the FDA two times over Zoom during the new administration. One in March when we met with them to for the type b meeting, and the second one in June to review the IND for the pediatric dilated cardiomyopathy.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

And and, you know, because we were asking for to move directly to a pivotal phase two pivotal trial with the the FDA requested that we need in of the the in person. So we had those two interaction. And I can tell you, yes, they have asked some challenging appropriately challenging questions. But the spirit of what we have seen was very collaborative and supportive of the development of our program. So I feel confident that we have a good plan.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

The last thing that I would say, and I'm sorry for the long winded answer, is that between now and the data readout, we are planning on several interactions with the FDA as well. And we're gonna be communicating with them around our final SAP. There are a few updates that we need to give them on the CMC and potentiSA. So we are planning on several interactions. And I can tell you if if you have been following the company since since we came, I don't wanna lose leave anything for assumptions.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

We wanna validate everything so there is no surprises when it comes to the finish line. So hopefully, that addresses both your your question about the PRB and the regulatory support from the FDA.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

Yes. It's pretty confidential, and thanks for that. And then in in the prepared remarks, so Natalia was mentioning about the five year survival, hundred percent five year survival I'm talking about in HLSS one participant. So that five year data is now at least one year old now. So just curious, is there a six year survival data available, or do you stop tracking the patient?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

I'll have the entire Yeah.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

Thank you so much for this question. The study was set up at the beginning to do the five year survival after Glenn procedure, and that's all we have at this point. We don't have to Correct. Fix that here. Yeah. Mhmm.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

Okay. No worries. That's very helpful.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

And then one more on SLHS before I move to my last question. So, Devin, so can you sort of discuss the pros and cons of self manufacturing and commercialization for Lattimore as service of seeking partnerships?

Devin Blass
Devin Blass
SVP & CTO at Longeveron

Sure. Just to clarify, you're talking about the CDMO contract manufacturing part. Yeah.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Yes.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Alright. So so for us, you know, there's, you know, three key factors. The first one was the the timeline to our claim BLA commission. That was a critical driver. One of the options that we were previously looking at was to renovate our existing facility in order for it to pass the preapproval inspection.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

That would have potentially caused delays in our overall timeline versus leveraging an existing facility from a CDMO. The the second, you know, critical driver here was overall cost. So the facility renovations, when you look at that plus additional capital expenditures that you need for new processing and analytical equipment, validation, headcount expansion, ongoing operational overhead. When you total that up, the CMO adoption was one that was, you know, potentially more cost effective. And then the the the last little key driver to this was overall risk. So when, you know, when you're able to leverage CMO's current, you know, proven regulatory track record and experience by outsourcing it to, you a partner, that that potentially, you know, mitigates any potential setback to facility readiness or POI readiness. And so in summary, you know, those those really three things were that we were considering when moving to a a CDMO.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

Right. This will be my last question. So I wanted to follow-up on Ron's question about pediatric DCM. Obviously, this is an interesting area of exploration because there's no FDA approved therapy yet. So the FDA has given you a green signal to move directly into pivotal phase two.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

So can you speak to us what gave the FDA the confidence in this program? Is there some preclinical data that you shared with them that they were very excited about? Maybe if you can tell us or maybe summarize this. And also, during your FDA discussion, can you clarify the focus both on managing the congestive or failure symptoms, or is it more towards mitigating the progression of the structural heart disease?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Yeah. Natalia or Josh can take that question.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

I can start. Maybe, Josh, you can pick up. So there's so what I think what gave confidence to the FDA that we can move forward immediately to the approval with this study is that we design endpoints based on clinically meaningful result clinically meaningful clinical feature for the patient. So, definitely, heart failure is one of the biggest impact for the the weighted cardiomyopathy. So we look at the old cause mortality on hospitalization, heart failure, etcetera.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

So I think the reverse primary endpoint definitely can make difference whether or not loramestrocel affect this patient's life, improvements of heart failure, improvements on everyday activity, which is really meaningful for this for this patient. And, of course, overall survival and transplant free survival. We are going with the field looking at this patient in a complex using the composite endpoint. So I we we can ask a lot of multiple questions on clinical, biostatistic biostatistics, etcetera. So I think all this really gave confidence to the FDA.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

We are on the right direction. Josh, did I miss anything?

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

The the one thing that I would I mentioned that I think may have played into the FDA's decision was that we have you know, there there is an experience with this type of administration And particularly, we at Longevron have treated adults with aging frailty, but there are also published studies in which patients with congestive adults with congestive heart failure due to dilated cardiomyopathy has been treated with very favorable response in very preliminary studies. And I think that may have played a role in allowing us to go directly to a phase two. And with the rigorous study design and endpoints that you mentioned, Natalia, you know, led them it's made it influence them to allow this to be a pivotal study.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

Alright. Thanks for taking that.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Okay?

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

Sorry. Go ahead.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

I was one more thing, Bhupanan. It it's it's always hard to know or predict what exactly the FDA are thought are. But we have been as I mentioned, we have been very transparent with the FDA. We shared with them all the data. I I I think that there is one thing that I don't think we get enough credit for, and hopefully, the FDA has seen that, is that we have a very robust safety data set that was on on this product.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Have over 550 patients in our data set. And, of course, many of them are not pediatrics, and most of them actually are in the agent group. But I think that safety, especially around immunogenicity and the infusion related reactions and all of those type of things. I'm sure this is also have been taken in consideration by the agency in weighing in this decision. I cannot really sit in their mind, but I can tell you, it wasn't it wasn't, like, that they ask a lot of questions, and they requested face to face meetings.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

And we have been able to answer all their questions to their satisfaction, and we're glad that we are in in the position that we are because I really believe that indicates the confidence of the agency in the work that we're doing as well as it's also great for the patients that are really that they don't have to go through multiple years of waiting until potential therapy like this can make it to the market.

Boobalan Pachaiyappan
Managing Director & Senior Research Analyst at Roth Capital Partners, LLC

Alright. Thank you everyone for taking our questions and congratulations on your progress.

Operator

Thank you. The next question we have is from Michael Okonich of Maxim Group. Please go ahead.

Michael Okunewitch
Michael Okunewitch
Senior Research Analyst - Biotechnology at Maxim Group

Hey. Thank you guys for taking my question, and congrats on the great progress.

Michael Okunewitch
Michael Okunewitch
Senior Research Analyst - Biotechnology at Maxim Group

So actually, I'd like to follow-up on that previous question from Google on. So what sort of improvement in survival or time to transplant would be considered clinically meaningful in the DCL? Are there any established thresholds for benefit here?

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Again, Natalia or Josh can take that question.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

So, basically, the standard of care is, you probably know, is a very symptomatic treatment with main cardiovascular medication, base inhibitor, beta blockers, etcetera, to maintain patient heart failure stable. So with this therapy, we are really looking forward to see patients prolong the death period of time when the patient needs heart transplant. Because, eventually, what what is happening from the time of diagnosis to the heart failure, sometimes it takes only two years for this for this kidney with the weighted cardiomyopathy. So and, of course, you know, the heart transplant as a last stage of the treatment is not desirable. So what we are looking forward is to prolong transplant free survival and improve overall well-being of the patient from the point of view of reducing the symptoms of cardiac failure and reducing the possibility the for these patients to develop cardiac failure.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

So we are looking for all cause mortality, transplant. We are looking for based in hospital. We are looking for this different scale to evaluate patient symptoms, development of heart failure, timing from the beginning of the treatment to develop developing of heart failure. So all these are really important for the patient. Are you looking for complete resolution of heart failure?

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

We don't know. We don't know. But uh-huh. Hello? But, definitely, we are looking for a prolongation of time for the patient eventually developing heart failure, improvement of symptoms, and prolongation of transplant free survival.

Nataliya Agafonova
Nataliya Agafonova
Chief Medical Officer at Longeveron

And those are very important important qualitative measure for this patient population.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

Yeah. Let me just add to that. I and if you if you take from the adult experience of therapeutic development, any any measurable reduction in all cause mortality or heart failure hospitalization is considered meaningful, particularly when you have a scenario of pediatric cardiomyopathy presents of such a high burden of of morbidity and mortality. So any any measurable reduction would be, I think, considered meaningful. The the other thing to keep to bear in mind is the underlying biology of the disease and the the possibility that there is a chance here for the therapy to increase the likelihood of a full remission.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

That has been seen in adults in published studies. However, you know, it has to be reinforced, as Natalia said, that we we don't know that for certain. But it is possible that there might be a subset of individuals who have a full remission or at least an increased likelihood of remission. So we will we'll be and by remission, mean, a meaningful recovery in cardiac function. So as part of the study in addition to the clinical endpoints, we will definitely be measuring cardiac function as well.

Michael Okunewitch
Michael Okunewitch
Senior Research Analyst - Biotechnology at Maxim Group

All right. Thank you. I really appreciate that additional color. And then just one more I'd like to ask ask a little about something you talked about earlier in the call. And see if you can expand on the technology underpinning the iPSC platform. And in particular, how does this differentiate you from other cell transplant therapy companies like Lineage or Vertex is doing? Could you just expand on that a little bit?

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

Yeah. That's the I'd I'd be very happy to speak to that.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

So current current approaches for iPS cell transplant into the heart have used what you could call garden variety. I mean, that's not the appropriate term, but a a standard induced pluripotent stem cell that can be differentiated all the way to an immature cardiac myocytes. In studies in which those immature cardiac myocytes have been injected largely in preclinical models, like nonhuman primates, they've been observed to cause malignant ventricular arrhythmias, particularly over the past first two weeks of transplantation. And this observation has very much limited the translation into phase one clinical studies. Regulatory authorities, I think, appropriately exercised the concern that this is, you know, an unacceptable side effect or or or potentially too dangerous.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

So I think one of the most important targets in advances is to develop a protocol where you can develop the cell, making them less likely to cause the arrhythmias and more likely to just form heart muscle cells that can engraft and and beat. So the idea here, we want to increase the recovery in the repopulation of cells and reduce the chance of introducing cells that have electrical activity. And that is the discovery in the in the new technology we're going to start to develop in that we we studied the biology of the cells as they go through the differentiation process from the iPS cell into the immature myocyte. And we discovered that we could identify a subpopulation that eliminated the fraction that caused the electrical instability. So we've we've been able to do that in the dish and biochemically at a molecular level.

Joshua Hare
Joshua Hare
Co-Founder, Chief Science Officer & Chairman at Longeveron

And so now with this patented technology, The US patent was issued about six months ago. So it is a it is a patented discovery, a composition of matter discovery. And as I said in my prepared remarks, we are now about to engage on the necessary preclinical work to lead us to an IND.

Michael Okunewitch
Michael Okunewitch
Senior Research Analyst - Biotechnology at Maxim Group

Right. Thank you.

Michael Okunewitch
Michael Okunewitch
Senior Research Analyst - Biotechnology at Maxim Group

It seems like a really interesting program. Looking forward to updates.

Operator

Ladies and gentlemen, that concludes the question and answer session. And at this time, I would like to turn the call back over to Yael Hachad for any closing remarks.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

Thank you, operator, and thank you all for attending our today's call.

Wa'el Hashad
Wa'el Hashad
CEO & Director at Longeveron

We greatly appreciate your interest and support and look forward to updating you on our continued progress in the future. Thank you. You may end the call now.

Operator

Ladies and gentlemen, that concludes this conference. Thank you for joining us. You may now disconnect your lines.

Executives
    • Wa'el Hashad
      Wa'el Hashad
      CEO & Director
    • Nataliya Agafonova
      Nataliya Agafonova
      Chief Medical Officer
    • Devin Blass
      Devin Blass
      SVP & CTO
    • Joshua Hare
      Joshua Hare
      Co-Founder, Chief Science Officer & Chairman
    • Lisa Locklear
      Lisa Locklear
      CFO
Analysts
    • Derek Cole
      Investor Relations at Investor Relations Advisory Solutions
    • Raghuram Selvaraju
      MD - Healthcare Equity Research at H.C. Wainwright & Co., LLC
    • Boobalan Pachaiyappan
      Managing Director & Senior Research Analyst at Roth Capital Partners, LLC
    • Michael Okunewitch
      Senior Research Analyst - Biotechnology at Maxim Group
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