Longeveron Inc. (LGVN) Q2 2025 Earnings Report, Transcript and Summary

Greetings, and welcome to the Longeveron 2025 Q2 Financial Results and Business Update Call. [Operator Instructions] 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.

Thank you, operator. Good afternoon, everyone, and thank you for joining us today to review Longeveron's 2025 Second Quarter Financial Results and Business Update. After the U.S. markets closed today, we issued a press release with financial results for Q2 2025, which can be found under the Investors section of the Longeveron website. On the call today are Wa’el Hashad, Chief Executive Officer; Dr. Joshua Hare, Co-Founder, Chief Science Officer and Chairman of the Board; Nataliya Agafonova, 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. 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 Wa’el Hashad, Chief Executive Officer. Wa’el?

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 stem cell research in multiple important indications. First and foremost, I am heartened by the team's ability to identify the most expedient, cost-effective pathway 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. As a reminder, for those of you newer to our story, Longeveron is a regenerative medicine company developing cutting-edge cellular therapies. Our stem cell therapy, laromestrocel, has delivered several positive initial results across 5 clinical trials in 3 indications, Phase 1 and 2 in Alzheimer's disease, Phase 1 and 2 in aging-related frailty and Phase 1 in hypoplastic left heart syndrome, or HLHS, a rare pediatric and orphan disease. The company's development program for these 3 initial indications address U.S. market opportunities of approximately $5-plus billion, $4-plus billion and up to $1 billion, respectively. As we have indicated previously, for 2025, we are focused on 3 primary operational goals, number one, advancing ELPIS II, our pivotal Phase 2b study for HLHS; two, HLHS BLA preparedness and commercialization readiness; three, pursuing strategic collaboration for Alzheimer's disease program. HLHS is a key strategic priority for us. We believe the HLHS program has a high probability of success and the shortest path to potential regulatory approval and future commercialization across our pipeline. We were very excited to share in June that we have completed enrollment for pivotal ELPIS II Phase 2b study, evaluating laromestrocel as a potential adjunct treatment to the standard of care for HLHS patients. The determination by the U.S. Food and Drug Administration at our meeting in August of last year that ELPIS II is pivotal significantly accelerates the potential regulatory path for laromestrocel. And if supported by data from the clinical trial, this would allow us to initiate rolling submission of a biological license application with the Food and Drug Administration in late 2026. This would be our first BLA submission, and it would be for an important indication with large unmet need and a significant market opportunity. Now I want to take a moment to acknowledge and give credit to the Food and Drug Administration and its staff for their diligence, preparation and professionalism. We have had 3 important interactions with the agency over the past 12 months. While appropriately challenging and demanding, the agency has sought to understand our development programs and provide input and feedback that has substantially clarified the regulatory pathway for laromestrocel in HLHS, 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 HLHS and Alzheimer's programs both reinforces our confidence in our science and highlights our strategic plans, risk mitigation through a diversified pipeline. This approach supported by expanding our pipeline to include pediatric dilated cardiomyopathy and license additional novo stem cell technology. 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 12 to 18 months are potentially transformational period for l Longeverone with multiple critical milestones, and I am thoroughly excited by the opportunity for laromestrocel with patients, longer and our shareholders. With that, I will turn the call to Dr. Agafonova to provide an update on our clinical development program. Nataliya?

Thank you, Wa'el, and good afternoon, everyone. Our lead investigational product is laromestrocel, a stem cell therapy derived from culture expanded mesenchymal stem cells or MSCs that are sourced from the bone marrow of young healthy adult donors. As Wa'el mentioned, our HLHS 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 3-stage heart reconstruction surgery over the course of the first 5 years of patient's life. Despite this surgical reconstruction, only 50% of the affected children survived to age 15 without heart transplantation. Our laromestrocel program in HLHS is designed to boost improve the heart function in these children with the goal of potentially enhancing their survival. In ELPIS I, our Phase 1 clinical study evaluating laromestrocel in 4 months old infants with HLHS, we observed 100% transplant-free survival for 5 years in all patients following treatment. This contrasts with an approximately 20% death in heart transplant observed in historical control data. This translates to a potential number needed to treat of 5, which is highly favorable, especially for the rare pediatric disease. We can prevent 1 death when treat 5 kids with HLHS. We are currently conducting the Phase 2 clinical trial, ELPIS II, evaluating the potential of laromestrocel to improve right ventricular function and long-term clinical outcomes in infants with HLHS. 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 2 additional patients beyond target enrollment reflects both the unmet need in this area and our commitment to support patients suffering from this devastating condition. We are grateful for the participation of the patients, their families and our investigative sites. With a 12-month follow-up period, we currently anticipate top line results from the trial in the third quarter of 2026. If results from ELPIS II are positive, we would be positioned to initiate a rolling BLA submission with the FDA in late 2026. Switching over to Alzheimer's disease briefly. With the positive results from the Phase 2a CLEAR MIND 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 2/3 clinical trial 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 laromestrocel in addressing Alzheimer's disease. Moving on to our pipeline expansion to pediatric dilated cardiomyopathy. Dilated cardiomyopathy is a disease that affects 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 over congestive heart failure. 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 called idiopathic cardiomyopathy. Pediatric cardiomyopathies affect at least 100,000 children worldwide. DCM is the most common form of cardiomyopathy in children. About 50% to 60% 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 groups are affected, studies show that DCM is more common in infants before age 1 than in older children. Effective treatment options are limited and near 40% of children with DCM requiring a heart transplant or dying within 2 years of diagnosis. Current treatment for DCM focuses on managing symptoms, improving heart function and preventing complications rather than addressing the underlying cause or causes. Many therapeutic agents with known efficacy in adults lack the same evidence in children. Our development program in pediatric dilated cardiomyopathy reinforces Longeveron’s commitment to developing innovative stem cell therapies for rare diseases, particularly for cardiovascular conditions where we believe laromestrocel may have significant potential to improve patient lives. As we reported in July, the FDA had approved our IND application for evaluating laromestrocel as a treatment for pediatric dilated cardiomyopathy. We greatly appreciate the positive interactions 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 2 pivotal registration clinical trial. Moving directly to a pivotal Phase 2 trial is significantly beneficial to the development program and the company. We currently anticipate initiation of pediatric dilated cardiomyopathy Phase 2 clinical trial in the first half of 2026, subject to obtaining necessary financing and look forward to providing additional updates as the development program takes shape. I will hand the call over to Devin Blass, our Chief Technology Officer. Devin?

Thank you, Nataliya, 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 chemistry manufacturing and controls, or CMC. We are executing against a strategic plan to ensure that our manufacturing infrastructure and operations are positioned to support both regulatory expectations and future commercial demand. While our GMP manufacturing facility in Miami remains and continue 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. Our goal is to substantially advance BLA readiness this year ahead of the ELPIS II data readout so that we can move efficiently towards a BLA submission should the data support it. This includes 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 Hare, our Founder and Chief Scientific Officer. Josh?

Thank you, Devin. Good afternoon, everyone. I'm absolutely delighted with the progress we are able to share with you. As Wa'el mentioned, our stem cell therapy laromestrocel has now delivered positive results across 5 clinical trials in 3 indications. These include Alzheimer's disease, aging-related frailty and most importantly, HLHS. 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 Nataliya 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 investment, speed to market, lower regulatory hurdles, all addressing important unmet medical needs. The composition of matter patent we license protects 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 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. 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 transplanted into the heart, a serious side effect has been observed. This 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. I will now hand the call over to Lisa to review our financial results. Lisa?

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 6 months ended June 30, 2025, and 2024 were $0.7 million and $1 million, respectively. This represents a decrease of $0.3 million or 31% 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 clients. Clinical trial revenue for the 6 months ended June 30, 2025, was $0.6 million, which is a decrease of $0.2 million or 31% when compared to $0.8 million for the 6 months ended June 30, 2024. This decline was primarily a result of decreased participant demand. Contract manufacturing revenue for the 6 months ended June 30, 2025, was $0.1 million from our manufacturing services contract, which is a decrease of approximately $0.1 million or 35% when compared to the $0.2 million in contract manufacturing revenue for the 6 months ended June 30, 2024. General and administrative expenses for the 6 months ended June 30, 2025, increased to approximately $5.5 million compared to $4.3 million for the same period in 2024. The increase of approximately $1.2 million 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 6 months ended June 30, 2025, increased to approximately $5.5 million compared to $3.9 million for the same period in 2024. The increase of approximately $1.6 million or 39% was primarily related to a $1.3 million 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 a $0.2 million increase in amortization expense related to patent costs. Partially offset by $0.3 million 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 2024. Our net loss increased to approximately $10 million for the 6 months ended June 30, 2025, from a net loss of $7.5 million for the same period in 2024 for the reasons outlined previously. Our cash and cash equivalents as of June 30, 2025, were $10.3 million. In August, the company completed a public offering, raising approximately $5 million in gross proceeds with up to an additional $12.5 million 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 first quarter of 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've begun ramping up our BLA-enabling activities. We currently anticipate a potential BLA filing with the FDA in late 2026 if the current ELPIS II trial in HLHS is successful. With the significant opportunity presented with the potential BLA filing, our operating expenses and capital expenditure requirements are currently expected to increase throughout the remainder of calendar 2025 and in 2026 in a large part to address CMC and manufacturing readiness. We intend to seek additional 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 nondilutive funding for the Alzheimer's disease program, supporting a proposed single pivotal seamless adaptive Phase 2/3 clinical trial. There can be no assurance we will be able to attain future financing at terms favorable to us or at all. In the event we are unable to attain 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 Longeveron. I will now hand the call back to Wa'el.

Thank you, Lisa. Longeveron has made tremendous progress advancing stem cell research for important development programs, including HLHS and Alzheimer's disease. With the addition of pediatric dilated cardiomyopathy and new stem cell technology licensed from 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 2b clinical trial in HLHS, our first potential BLA submission for HLHS and based on the strength of the Phase 2a 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 Longeveron 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. Operator, we would now like to open the call for questions from covering analysts.

[Operator Instructions] The first question we have is from Ram Selvaraju of H.C. Wainwright.

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 2 just in terms of the total addressable size in terms of number of individuals likely to be afflicted with these conditions.

Thank you, Ram, for this question. I'll take the answer to that. So, 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 both are orphan disease, both are rare disease. And I believe from a pricing strategy standpoint, there should be comparable, though they may not be identical because they are not going to be administered in the same fashion. So, one, HLHS, as you know, these injections are given during the Glenn procedure, and they are injected directly into the right ventricle. For pediatric dilated cardiomyopathy, that would be an infusion, intravenous infusion. So, the method of administration is going to be slightly different, not slightly different. But -- and therefore -- and also the big other difference is that on HLHS, it's a onetime use versus the pediatric dilated cardiomyopathy, the intention is to have a continuous use of the product. 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 HLHS. 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 HLHS. So, the prevalence is in the range of about 2,000 to 3,000 patients in the United States. As you know, the HLHS is about 1,000. The incidence is slightly lower. So, these are the new born children with the condition for pediatric dilated cardiomyopathy, it is lower than 1,000. It's about 600 patients. So hopefully, that addresses. 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.

But it would not be inaccurate to state that because in PBC, you are looking at a different administration paradigm and as you mentioned, longer-term administration that, in effect, whatever pricing you ultimately establish for HLHS will, in effect, if transferred to PBC, 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 correct?

Correct.

And then secondly, just with respect to HLHS regulatory outlook and implications for PBC. If we look at the approval criteria for HLHS, the fact that positive results from ELPIS II are expected to buttress the case for approval of laromestrocel 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, laromestrocel is adjudicated approvable based upon the results of the ELPIS II trial. And as you mentioned in your prepared remarks, you are currently contemplating a Phase 2 study in PBC as well. Then if there are positive results in PBC and we use the laromestrocel approval precedent in HLHS, as illustrative or indicative of the regulatory outlook, then positive results from that Phase 2 trial in PBC should ultimately represent an approvable package. Apologies for the long-winded way of saying it. But what I'm trying to say is, is there direct implications of the regulatory outlook for laromestrocel in HLHS in the PBC indication as well?

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

And just one question... Sorry, go ahead.

Yes. Nataliya, do you want to add anything?

I just would like to add one more point, and we communicated this today as well. We already reached the agreement with the FDA that, that Phase 2 study, which we just designed and submitted an approved IND based on would be sufficient for approval upon the positive results for the pediatric dilated cardiomyopathy.

Okay. Great. That's very helpful clarity. Just one quick question for Lisa. If you look at the Phase 2 study, the proposed Phase 2 study that's envisaged in pediatric dilated cardiomyopathy, can you give us a sense of relativeativeistically speaking, how much more expensive or whether it is likely to be comparable in expense to the HLHS ELPIS II trial? Or is there any point of comparability between those 2 just in terms of overall budget?

So Ram, I think the overall budget we anticipate, and that's why we prefer to focus on rare diseases because we believe that the budget is definitely more manageable. The preliminary budget numbers that we have, and I'm saying preliminary numbers is probably in the range of $15 million to $20 million for the entire cost of the trial from A to Z. And that is not per year cost. That's the total cost. And because this trial is going to span at least 4 or 5 years, the whole time period for measuring the efficacy of the drug is 13 months. So we're looking at start-up time, enrollment time and readout time. we believe that the cost per year could be in the range of about maybe $3 million. And as Nataliya said, we're also looking for similar to what we did with ELPIS II is we're looking for nondilutive funding to support that. And there is a lot of both private and government supported entity that are interested in supporting that type of research.

The next question... Apologies, go ahead.

Sorry. I was just going to say -- I would just say that is a preliminary estimate as we're working through the feasibility right now.

The next question we have is from Boobalan Pachaiyappan of ROTH.

Can you hear me okay?

Yes, Boobalan.

Great. So a few questions from us. So firstly, with respect to HLH. So you stated in your press release that BLA filing could occur by year-end '26 [indiscernible] data. So -- but if you look at from a logistics standpoint, at that time, the FDA's PRV program would have been suspended, assuming there is no new developments in that area. So my question to you is, do you still get to keep the RA pediatric designation and enjoy the associated benefits such as rolling submission and more frequent FDA interactions? And also speaking of FDA interactions, can you comment on whether there is any leadership changes because there's a lot of flux at the FDA level. And I wanted to make sure the offices that you're dealing with are still going to be the same? Or do you expect anyone to be different? The reason I'm asking this question because I wanted to make sure the chances that the Phase 2b can still be registration enabling and not a separate Phase 3 study out of the blue.

That -- those are great questions, Boobalan, as well. So thank you for those. Let me address the PRB first. As we have previously disclosed in all of our communications, we realized that the current PRB will sunset in September of 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, Republicans and Democrats. And there is a significant support for renewal of that, especially it doesn't cost the budget anything because that is a nonbudgetary item. Unfortunately, sometimes these type of things get left out by focusing on other important things that is happening and trade-offs. But there is a lot of support at least from both sides to do it. I also -- we are, as you know, a member of the bio organization, and there is a lot of effort is 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. We have a lot of things that allow us for rolling submission. One of them is the rare pediatric disease designation, but also the Fast Track designation for HLHS is another way of also supporting the rolling submission, and that's why we're going to move ahead and start to do the rolling 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 impacts. So you're correct, the fact that we had our HLHS meeting with the FDA last year in the same time at this time, August of last year. And the agreement is miniated. And I do believe that we have very unique things to support our case. 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 trials. We're not doing similar to Mesoblast or Capricorn 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 prevalence of the disease or the incidence of the disease is fairly sufficient. I mean, we cannot make any larger trial than that. So for all those reasons, we feel confident. So that is part 1 of answering your question. Part 2 is actually we have met with the FDA 2 times over Zoom during the new administration. One in March of this year 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. And because we were asking for to move directly to a pivotal Phase 2 -- pivotal trial with pediatric dilator cardiomyopathy, the FDA requested that we meet in person via Zoom. So we had those 2 interactions. 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. The last thing that I will 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 going to be communicating with them around our final SAP. There are a few updates that we need to give them on the CMC and potency assay. So, we are planning on several interactions. And I can tell you, if you have been following the company since we came, I don't want to leave anything for assumptions. We want to validate everything, so there is no surprises when it comes to the finish line. So hopefully, that addresses both your question about the PRB and the regulatory support from the FDA.

Yes. It's pretty comprehensive and thanks for that. And then in the prepared remarks, so Nataliya was mentioning about the 5-year survival, 100% 5-year survival I'm talking about in participants. So that 5-year data is now at least 1 year old now. So just curious, is there a 6-year survival data available? Or do you stop tracking the patients?

I'll have Nataliya answer that.

Yes. Thank you so much for this question. The study was set up at the beginning to do the 5-year survival after Glenn procedure, and that's all we have at this point. We don't have 6 years data.

Okay. That's very helpful. And then one more on HLHS 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 laromestrocel versus seeking partnership?

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

Yes.

So for us, there's 3 key factors. The first one was the time line to our planned BLA submission. 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 a pre-approval inspection. That would have potentially caused delays in our overall time line versus leveraging an existing facility from a CDMO. The second critical driver here was overall costs. 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 CDMO option was one that was potentially more cost effective. And then the last real key driver to this was overall risk. So when you're able to leverage CDMO's current proven regulatory track record and experience by outsourcing this to a partner, that potentially mitigates any potential setbacks to facility readiness or POI readiness. And so in summary, those really 3 things were some of the things that we were considering when moving to a CDMO.

Great. This will be my last question. So I wanted to follow up on Ram'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 2. 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 if the focus was on managing the congestive heart failure symptoms? Or is it more towards mitigating the progression of the structural heart disease?

Yes. Nataliya or Josh can take that question.

I can start, maybe, Josh, you can pick up. So the -- so 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 clinical features for the patient. So definitely, heart failure is one of the biggest impact for the dilated cardiomyopathy. So we look at the all-cause mortality on hospitalization, heart failure, et cetera. So, I think the rigorous primary endpoint definitely can make difference whether or not laramestrocel affect this patient's life. improvement on heart failure, improvement on everyday activity, which is really meaningful for these patients. 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 endpoints. So we can ask a lot of multiple questions on clinical biostatistics, et cetera. So I think all this really gave confidence to the FDA, we are on the right direction. Josh, did I miss anything?

The one thing that I would I mentioned that I think may have played into the FDA's decision was that we have -- there is an experience with this type of administration in adults. And particularly, we at Longeveron have treated adults with aging frailty, but there are also published studies in which patients with -- adults with congestive heart failure due to dilated cardiomyopathy have 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 2. And with the rigorous study design and endpoints that you mentioned, Nataliya, led them -- it may have influenced them to allow this to be a pivotal study.

One more thing, Boobalan. It's always hard to know or predict what exactly the FDA our thoughts are. But we have been -- as I mentioned, we have been very transparent with the FDA. We shared with them all the data. I think there is one thing that I don't think we get enough credit for, and hopefully, the FDA have seen that is that we have a very robust safety data set as well on this product. We have over 550 patients in our data set. And of course, many of them are not pediatrics, so 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 like -- they ask a lot of questions and they requested face-to-face meetings, and we have been able to answer all their questions to their satisfaction, and we're glad that we are 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 a potential therapy like this can make it to the market.

Congratulations on your progress.

Thank you.

The next question we have is from Michael Okunewitch of Maxim Group.

Congrats on the great progress. I actually like to follow up on the previous question from Boobalan. So, what sort of improvement in survival or time to transplant would be considered clinically meaningful in DCM? Are there any established thresholds for benefit here?

Again Nataliya or Josh can take that question.

So definitely, the standard of care is, as you probably know, is a very symptomatic treatment with main cardiovascular medication, BACE inhibitor, beta blockers, et cetera, to maintain patient heart failure stable. So, with this therapy, we really looking forward to see patients prolong that period of time when the patient needs heart transplant because eventually, what is happening from the time of diagnosis to the heart failure, sometimes it takes only 2 years for the kids with dilated cardiomyopathy. So -- and of course, the heart transplant at the 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 for these patients to develop cardiac failure. So, we are looking for all-cause mortality transplant. We are looking for days in hospital. We are looking for different scales to evaluate patient symptoms, development of heart failure, timing from the beginning of the treatment to developing of heart failure. So, all these are really important for the patients. Are we looking for complete resolution of heart failure? We don't know, 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. And those are very important qualitative measure for this patient population.

Josh, you want to add anything?

Yes. Let me just add to that. If you take from the adult experience of therapeutic development, any measurable reduction in all-cause mortality or heart failure hospitalization is considered meaningful, particularly when you have a scenario as pediatric cardiomyopathy presents of such a high burden of morbidity and mortality. So, any measurable reduction would be, I think, considered meaningful. The other thing to keep -- to bear in mind is the underlying biology of the disease and the possibility that there is a chance here for the therapy to increase the likelihood of a full remission. That has been seen in adults in published studies. However, it has to be reinforced, as Nataliya said, that 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'll be -- and by remission, I 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.

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

Yes, that would be -- I'd be very happy to speak to that. So 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 standard induced pluripotent stem cell that can be differentiated all the way to an immature cardiac myocyte. 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 first 2 weeks of transplantation. And this observation has very much limited the translation into Phase 1 clinical studies. Regulatory authorities, I think, have appropriately exercised the concern that this is an unacceptable side effect or potentially too dangerous. So, I think one of the most important targets and advances is to develop a protocol where you can develop the cells making them less likely to cause the arrhythmias and more likely to just form heart muscle cells that can engraft and beat. So, the idea is 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 new technology we're going to start to develop in that 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 been able to do that in the dish and biochemically at a molecular level. And so now with this patented technology, the U.S. patent was issued about 6 months ago. So it is a patented discovery, 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.

It seems like a really interesting program.

Ladies and gentlemen, that concludes the question-and-answer session. And at this time, I would like to turn the floor back over to Wa'el Hashad for any closing remarks.

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

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