Q2 2025 Longeveron Inc Earnings Call

Speaker #1: A brief question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star, then zero, on your telephone keypad.

Speaker #1: 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.

Speaker #4: Thank you, operator. Good afternoon, everyone, and thank you for joining us today to review Longeveron's Q2 2025 financial results and business update.

Derek Cole: 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 US markets close today, we issued a press release with financial results for Q2 2025, which can be found under the investor section of the Longeveron website. On the call today are Wael 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.

Speaker #4: After the U.S. markets close today, we issue a depressed release with financial results for Q2 2025, which can be found under the Investor section of the Longeveron website.

Speaker #4: On the call today are Wael 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.

Speaker #4: 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.

Speaker #4: 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.

Derek Cole: 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 Wael Hashad, Chief Executive Officer. Wael.

Speaker #4: 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 Wael Hashad, Chief Executive Officer.

Speaker #4: Wale.

Speaker #2: 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.

Wa'el Hashad: 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, Lateral Mastercell, has delivered several positive initial results across five clinical trials in three indications: Phase I and II in Alzheimer's disease, Phase I and II in aging-related frailty, and Phase I in hypoplastic left heart syndrome, or HLHS, a rare pediatric and orphan disease.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: Our stem cell therapy, Latermastracel, has delivered several positive initial results across five clinical trials in three indications. Phase one and two in Alzheimer's disease, phase one and two in aging-related frailty, and phase one in hypoplastic left heart syndrome or HLHS.

Speaker #2: A rare pediatric and orphan disease. The company's development program for these three initial indications addressed U.S. market opportunities over approximately five plus billion dollars, four plus billion dollars, and up to one billion dollars respectively.

Wa'el Hashad: The company's development program for these three initial indications addresses US market opportunities of approximately $5 plus billion dollars, $4 plus billion dollars, and up to $1 billion dollars, respectively. As we have indicated previously, for 2025, we are focused on three primary operational goals. Number one, advancing ELPAS-2, our pivotal Phase IIb study for HLHS. Two, HLHS DLA preparedness and commercialization readiness. Three, pursuing strategic collaboration for the 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 ELPAS-2 Phase IIb study, evaluating Lateral Mastercell as a potential adjunct treatment to the standard of care for HLHS patients.

Speaker #2: As we have indicated previously, for 2025, we are focused on three primary operational goals. Number one, advancing open to our pivotal phase two B study for HLHS.

Speaker #2: Two: HLHS BLA preparedness and commercialization readiness. Three: pursuing strategic collaboration for the 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.

Speaker #2: And future commercialization across our pipeline. We were very excited to share in June that we have completed enrollment for pivotal open to phase two B study evaluating Latermastracel as a potential adjunct treatment to the standard of care for HLHS patients.

Speaker #2: The determination by the U.S. Food and Drug Administration at our meeting in August of last year that open to is pivotal significantly accelerates the potential regulatory path for Latermastracel.

Wa'el Hashad: The determination by the US Food and Drug Administration at our meeting in August of last year that ELPAS-2 is pivotal significantly accelerates the potential regulatory path for Lateral Mastercell. 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 DLA 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 three important interactions with the agency over the past 12 months.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: We have had three important interactions with the agency over the past 12 months. While appropriately challenging and demanding, the agency has sought to understand our development program and provide input and feedback that has substantially clarified the regulatory pathway for Latermastracel and HLHS, Alzheimer's disease, and now pediatric-related cardiomyopathy.

Wa'el Hashad: 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 Lateral Mastercell and 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 programs both reinforces our confidence in our science and highlights our strategic plan's 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. 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.

Speaker #2: For which we recently received an initial New Drug Application approval and IND approval. We are grateful for their efforts and appreciate their collaborative approach and the opportunity to reach alignment on our development program.

Speaker #2: Our success advancing the HLHS and Alzheimer programs both reinforces our confidence in our science, and highlights our strategic plans risk mitigation through a diversified pipeline.

Speaker #2: This approach is supported by expanding our pipeline to include pediatric-related cardiomyopathy and licensing additional novel 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.

Speaker #2: The next 12 to 18 months are a potentially transformational period for Longeveron, with multiple critical milestones. I am thoroughly excited by the opportunity for Latermastracel with patients, Longeveron, and our shareholders.

Wa'el Hashad: The next 12 to 18 months are a potentially transformational period for Longeveron with multiple critical milestones, and I am thoroughly excited by the opportunity for Lateral Mastercell with patients, Longeveron, and our shareholders. With that, I will turn the call to Dr. Agafonova to provide an update on our clinical development program. Nataliya?

Speaker #2: With that, I will turn the call to Dr. Agafonova to provide an update on our clinical development program. Nataliya?

Speaker #3: Thank you, Wael, and good afternoon, everyone. Our lead investigational product is Latermastracel, a stem cell therapy derived from culture-expanded mesenchymal stem cells, or MSCs.

Nataliya Agafonova: Thank you, Wael and good afternoon, everyone. Our lead investigational product is Lateral Mastercell, a stem cell therapy derived from culture-expanded mesenchymal stem cells, or MFEs, that are sourced from the bone marrow of young, healthy adult donors. As Wael 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 three-stage heart reconstruction surgery over the course of the first five years of patient life. Despite this surgical reconstruction, only 50% of the affected children survive to age 15 without heart transplantation. Our Lateral Mastercell program in HLHS is designed to boost and improve the heart function in these children with the goal of potentially enhancing their survival.

Speaker #3: That are sourced from the bone marrow of young, healthy adult donors. As Wael 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.

Speaker #3: 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.

Speaker #3: Despite this surgical reconstruction, only 50% of the affected children survive to age 15, without heart transplantation. Our Latermastracel program in HLHS is designed to boost improve the heart function in these children with the goal of potentially enhancing their survival.

Speaker #3: In open to one, our phase one clinical study evaluating Latermastracel in four-month-old infants with HLHS, we observed 100% transplant-free survival for five years in all patients following treatment.

Nataliya Agafonova: In ELPAS-1, our Phase I clinical study evaluating Lateral Mastercell in four-month-old infants with HLHS, we observed 100% transplant-free survival for five 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 five, which is highly favorable, especially for the rare pediatric disease. We can prevent one death when treating five kids with HLHS. We are currently conducting the Phase II clinical trial, ELPAS-2, evaluating the potential of Lateral Mastercell 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.

Speaker #3: This contrasts with an approximately 20% death and heart transplant observed in historical control data. This translates to a potential number needed to treat of five, which is highly favorable, especially for the rare pediatric disease.

Speaker #3: We can prevent one death when treat five kids with HLHS. We are currently conducting the phase two clinical trial open to two evaluating the potential of Latermastracel to improve right ventricular function and long-term clinical outcomes in infants with HLHS.

Speaker #3: We completed enrollment of the trial in June, enrolling 40 patients at 12 premier infant and children's treatment institutions across the country. The slide over enrollment of the trial including two additional patients beyond target enrollment reflects both the unmet need in this area and our commitment to support patients suffering from this devastating condition.

Nataliya Agafonova: The slide over enrollment of the trial, including two additional patients beyond target enrollment, reflects both their 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. This 12-month follow-up period, we currently anticipate top-line results from the trial in the third quarter of 2026. If results from ELPAS-2 are positive, we would be positioned to initiate a rolling DLA submission with the FDA in late 2026. Switching over to Alzheimer's disease briefly.

Speaker #3: We are grateful for the participation of the patients, their families, and our investigative sites. This 12-month follow-up period we currently anticipate top-line results from the trial in the third quarter of 2026.

Speaker #3: If results from open to two are positive, we would be positioned to initiate enrollment BLA submission with the FDA in late 2026. Switching over to Alzheimer's disease briefly.

Speaker #3: With the positive results from the phase two A clear mind clinical trial, the publication of that data in Nature Medicine and the positive Thai 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 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 Latermastracel in addressing Alzheimer's disease.

Nataliya Agafonova: With the positive results from the Phase IIa ClearMind clinical trial, the publication of that data in Nature Medicine, and the positive type B meeting with FDA regarding pathway to DLA submission in Alzheimer's disease that yielded alignment on the proposed trial study design, population, and endpoints for the single pivotal Phase II III clinical trial that, if positive, would be acceptable for DLA submission for Alzheimer's disease, we believe we have a strong opportunity to forge collaborations and partnerships for the advancement of Lateral Mastercell 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 causes the size of the heart chamber to enlarge and the pumping strength of the heart to diminish.

Speaker #3: Moving on to our pipeline expansion to pediatric-related cardiomyopathy. Dilated cardiomyopathy is a disease that affects the muscle cells of the heart, known as cardiac myocytes.

Speaker #3: 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 overcongestive heart failure.

Nataliya Agafonova: Together, these adaptations lead to cardiac failure, diminished blood flow to the body, and over-congestive heart failure. The manifestation of congestive heart failure includes 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 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 one than in older children.

Speaker #3: The manifestation of congestive heart failure includes 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.

Speaker #3: That's why it’s 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.

Speaker #3: According to the Pediatric Cardiomyopathy Registry, DCM is reportedly more common in boys than in girls. Although all age groups are affected, studies show that DCM is more common in infants.

Speaker #3: Before age one, more children are affected than in all other children. Effective treatment options are limited, and nearly 40% of children with DCM require a heart transplant or die within two years of diagnosis.

Nataliya Agafonova: Effective treatment options are limited, and near 40% of children with DCM require a heart transplant or die within two years of diagnosis. Current treatment for DCM focuses on managing symptoms, improving heart function, and preventing complications rather than addressing the underlying 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 Lateral Mastercell may have significant potential to improve patient lives. As we reported in July, the FDA had approved our IND application for evaluating Lateral Mastercell as a treatment for pediatric dilated cardiomyopathy. We greatly appreciate the positive interactions with the FDA and the extensive discussion of our development plan and the clarity provided on the regulatory pathway.

Speaker #3: 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.

Speaker #3: Our development program in pediatric-related cardiomyopathy reinforces Longeveron commitment to developing innovative stem cell therapies for rare diseases, particularly for cardiovascular conditions where we believe Latermastracel may have significant potential to improve patient lives.

Speaker #3: As we reported in July, the FDA had approved our IND application for evaluating Latermastracel as a treatment for pediatric-related cardiomyopathy. We greatly appreciate the positive interactions with the FDA.

Speaker #3: 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: The accepted IND application provides for moving directly to a single Phase II pivotal registration clinical trial. Moving directly to a pivotal Phase II trial is significantly beneficial to the development program and the company. We currently anticipate the initiation of pediatric dilated cardiomyopathy Phase II 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.

Speaker #3: Moving directly to a pivotal phase two trial is significantly beneficial to the development program and the company. We currently anticipate initiation of pediatric-related cardiomyopathy phase two clinical trial in the first half of 2026.

Speaker #3: Subject to obtaining the necessary financials, we look forward to providing additional updates as the development program takes shape. I will hand the call over to Devin Blass.

Speaker #3: Our Chief Technology Officer. Devin?

Speaker #4: 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.

Derek Cole: Thank you, Nataliya, and good afternoon, everyone. As we look ahead to the potential DLA 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 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.

Speaker #4: 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 demands.

Speaker #4: 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.

Speaker #4: This approach allows us to leverage the scale of experience and compliance infrastructure of a dedicated commercial manufacturer while preserving our internal capabilities for future pipeline programs.

Speaker #4: Our goal is to substantially advance BLA readiness this year ahead of the open to data readout. So that we can move efficiently towards a BLA submission.

Derek Cole: Our goal is to substantially advance DLA readiness this year ahead of the ELPAS-2 data readout so that we can move efficiently towards a DLA 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.

Speaker #4: Could the data support it? This includes progressive key activities, progressing key activities such as technology transfer and process and analytical method validation planning. We believe this investment in CMC will enable our long-term success.

Speaker #4: I will hand the call over to Josh Hare, our founder and Chief Scientific Officer. Josh?

Speaker #5: Thank you, Devin. Good afternoon, everyone. I'm absolutely delighted with the progress we are able to share with you. As Wael mentioned, our stem cell therapy, Latermastracel, has now delivered positive results across five clinical trials in three indications.

Joshua Hare: Thank you, Devin. Good afternoon, everyone. I'm absolutely delighted with the progress we are able to share with you. As Wael mentioned, our stem cell therapy, Lateral Mastercell, has now delivered positive results across five clinical trials in three 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 DLA 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.

Speaker #5: 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.

Speaker #5: 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-related cardiomyopathy, as Nataliya mentioned.

Speaker #5: 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.

Speaker #5: 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.

Joshua Hare: 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.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: 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.

Joshua Hare: 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.

Speaker #5: 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.

Speaker #5: 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 conform myocytes, heart muscle cells, without causing the arrhythmia.

Speaker #5: 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.

Speaker #5: Lisa?

Speaker #6: 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.

Lisa Locklear: Thank you, Josh, and good afternoon, everyone. This afternoon, we issued a press release and filed our quarterly report on Form 10-2, both of which present our financial results in detail, so I will touch on some highlights. Revenues for the six 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 client. Clinical trial revenue for the six 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 six months ended June 30, 2024. This decline was primarily a result of decreased participant demand.

Speaker #6: So I will touch on some highlights. Revenues for the six months ended June 30th, 2025, and 2024 were $0.7 million and $1 million respectively.

Speaker #6: 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 client.

Speaker #6: Clinical trial revenue for the six 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 six months ended June 30, 2024.

Speaker #6: This decline was primarily a result of decreased participant demand. Contract manufacturing revenue for the six months ended June 30th, 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 six months ended June 30th, 2024.

Lisa Locklear: Contract manufacturing revenue for the six 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 six months ended June 30, 2024. General and administrative expenses for the six 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 six months ended June 30, 2025, increased to approximately $5.5 million compared to $3.9 million for the same period in 2024.

Speaker #6: General and administrative expenses for the six months ended June 30th, 2025, increased to approximately $5.5 million compared to $4.3 million for the same period in 2024.

Speaker #6: 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 six months ended June 30th, 2025, increased to approximately $5.5 million.

Speaker #6: 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.

Lisa Locklear: 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 DLA 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 six 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.

Speaker #6: And also at $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.

Speaker #6: Our net loss increased to approximately $10 million for the six months ended June 30th, 2025, from a net loss of $7.5 million for the same period in 2024 for the reasons outlined previously.

Speaker #6: Our cash and cash equivalents as of June 30th, 2025 were $10.3 million. In August, the company completed a public offering raising approximately $5 million in gross proceeds.

Lisa Locklear: 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 and 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 DLA enabling activities.

Speaker #6: 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.

Speaker #6: 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.

Speaker #6: We believe these programs 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 have begun ramping up our BLA enabling activities.

Speaker #6: We currently anticipate a potential BLA filing with the FDA in late 2026 if the current open two trials in HLHS are successful. With the significant opportunity presented by 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, largely to address CMC and manufacturing readiness.

Lisa Locklear: We currently anticipate a potential DLA filing with the FDA in late 2026 if the current ELPAS-2 trial in HLHS is successful. With the significant opportunity presented with the potential DLA 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 non-dilutive 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/or non-dilutive funding for the Alzheimer's disease program, supporting a proposed single pivotal seamless adaptive Phase II/III clinical trial.

Speaker #6: We intend to seek additional financing opportunities capital raises as well as non-dilutive 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 two three clinical trial.

Speaker #6: 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.

Lisa Locklear: 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 DLA submission late next year makes this an extraordinarily exciting time for Longeveron. I will now hand the call back to Wael.

Speaker #6: A 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.

Speaker #6: I will now hand the call back to Wael.

Speaker #2: 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-related cardiomyopathy and a new stem cell technology licensed from the University of Miami, we are building a robust pipeline with the potential to help patients globally.

Wa'el Hashad: 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 license 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 IIb clinical trial in HLHS, our first potential DLA submission for HLHS, and based on the strengths of the Phase IIa clinical data, potential partnering for the 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, and commitment allow Longeveron to achieve a tremendous amount of progress for a company of our size with a smaller team and fewer resources at the moment.

Speaker #2: We are now approaching multiple potentially transformational milestones, es, including completion of pivotal phase two B clinical trial in HLHS. Our first potential BLA submission.

Speaker #2: For HLHS and based on the strength of the Phase Two A clinical data, potential partnering for the Alzheimer's disease program. I have mentioned before that I’m incredibly proud of our team's effort and accomplishment on behalf of patients and shareholders.

Speaker #2: 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.

Speaker #2: We deeply appreciate the support of all 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.

Wa'el Hashad: 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.

Speaker #1: 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 your telephone keypad.

Lisa Locklear: 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 your telephone keypad. The confirmation tone will indicate your line is in the question queue. You may press star and then two 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 Selvagiu of HC Wainwright. Please go ahead.

Speaker #1: The confirmation time will indicate your line is in the question queue. You may press star and then two if you would like to remove your question from the queue.

Speaker #1: 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 Selvaju of HC Wainwright.

Speaker #1: Please go ahead.

Speaker #7: 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.

Derek Cole: 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 the total addressable size in terms of number of individuals likely to be afflicted with these conditions.

Speaker #7: Can you confirm whether or not the target patient populations and indeed target addressable markets in HLHS and pediatric-related 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?

Speaker #7: 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 the number of individuals likely to be afflicted with these conditions.

Speaker #5: Thank you, Ram, for this question. I’ll take the answer to that. Overall, the answer is that the markets are similar but not identical, from the exact number of population, and I’ll explain it just in a minute here.

Wa'el Hashad: Thank you, Ram, for this question. I'll take the answer to that. So the overall answer is the markets are similar but not identical from the exact number of population, and I will explain it just in a minute here. But both are orphan disease, both are rare disease, and I believe from a pricing strategy standpoint, they 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 therefore, and also the big other difference is that on HLHS, it's a one-time use versus the pediatric dilated cardiomyopathy.

Speaker #5: But both are orphan diseases, both are rare diseases, and I believe from a pricing strategy standpoint, they should be comparable, though they may not be identical, because they are not going to be administered in the same fashion.

Speaker #5: So one HLHS, as you know, these injections are given during the Glenn procedure and they are injected directly into the right ventricle. The for pediatric-related cardiomyopathy, that would be an infusion intravenous infusion.

Speaker #5: 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 one-time use.

Speaker #5: Versus the pediatric-related 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-related cardiomyopathy is slightly lower than the HLHS.

Wa'el Hashad: The intention is to have a continuous use of the product, so it's a chronic utilization. Now, in terms of 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 newborn 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.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: The incidence is slightly lower. These are the newborn children with the condition. For pediatric-related cardiomyopathy, it is lower than 1,000; it's about 600 patients.

Speaker #5: 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.

Speaker #5: But it would not be inaccurate to state that because in PDC, you are looking at different administration paradigm and as you mentioned, you know, longer term administration.

Derek Cole: But it would not be inaccurate to state that because in PDC, 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 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 correct?

Speaker #5: That, in effect, whatever pricing you ultimately establish for HLHS will, if transferred to PDC, ultimately result in higher market penetration because of the ease with which one can conduct an infusion as opposed to direct injection into the heart.

Speaker #5: 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 PDC.

Wa'el Hashad: Correct.

Derek Cole: And then secondly, just with respect to HLHS regulatory outlook and implications for PDC, if we look at the approval criteria for HLHS, the fact that positive results from ELPAS-2 are expected to buttress the case for approval of Lateral Mastercell 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 PDC?

Speaker #5: If we look at the approval criteria for HLHS, the fact that positive results from open to two are expected to buttress the case for approval of Latermastracel in this disease indication.

Speaker #5: 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 PDC?

Speaker #5: For example, if an HLHS Latermastracel is adjudicated approvable based upon the results of the open to two trial, and as you mentioned in your prepared remarks, you are currently contemplating a phase two study in PDC as well.

Derek Cole: For example, if in HLHS, Lateral Mastercell is adjudicated approvable based upon the results of the ELPAS-2 trial, and as you mentioned in your prepared remarks, you are currently contemplating a Phase II study in PDC as well, then if there are positive results in PDC and we use the Lateral Mastercell approval precedent in HLHS as illustrative or indicative of the regulatory outlook, then positive results from that Phase II trial in PDC 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 Lateral Mastercell in HLHS in the PDC indication as well?

Speaker #5: Then, if there are positive results in PDC, and we use the Latermastracel approval precedent in HLHS as illustrative or indicative of the regulatory outlook, then positive results from that phase two trial in PDC should ultimately represent an approvable package.

Speaker #5: Apologies for the long-winded way of saying it, but what I’m trying to say is, are there direct implications of the regulatory outlook for Latermastracel in HLHS in the PDC indication as well?

Speaker #5: Right. So, of course, that's a question ultimately the FDA will have to decide on. But I will give you my thoughts. I do believe if we have positive data coming out of the HLHS trial, that this will definitely help support the case for the pediatric-related cardiomyopathy when we come to the regulatory review process.

Wa'el Hashad: Right. So of course, that's a question ultimately the FDA will have to decide on it, but I will give you my thought. I do believe if we have 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.

Speaker #5: However, I do believe that the FDA will still want to see the study results from the pediatric-related 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.

Speaker #5: 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 side of the risk—that would be a big added support from at least that point.

Speaker #5: And And I'm just wondering for question. Sorry, go ahead. Yeah, Nataliya, do you want to add anything?

Derek Cole: And then just one very quick question. Sorry, go ahead.

Wa'el Hashad: Yeah. Nataliya, do you want to add anything?

Speaker #3: I just would like to add one more point and the communicated this today as well. We already reached the agreement with the FDA that that phase two study which we just designed and submitted and approved IND based on would be sufficient for approval upon the positive results.

Nataliya Agafonova: 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 II study, which we just designed and submitted and approved IND based on, would be sufficient for approval upon the positive result for the pediatric dilated cardiomyopathy.

Speaker #3: For the pediatric-related cardiomyopathy.

Speaker #5: Okay, great. That's very helpful clarity. Just one quick question for Lisa. If you look at the phase two study, the proposed phase two study that's envisaged in pediatric-related 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 open to two trial?

Derek Cole: Okay. Great. That's very helpful clarity. Just one quick question for Lisa. If you look at the Phase II study, the proposed Phase II 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 ELPAS-2 trial? Or is there any point of comparability between those two just in terms of overall budget?

Speaker #5: Or is there any point of comparability between those two 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.

Wa'el Hashad: 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 in numbers, is probably in the range of $15 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 four or five years, the whole time period for measuring the efficacy of the drug is 13 months. So we're looking at startup time, enrollment time, and readout time. We believe that the cost per year could be in the range of about maybe $3 million.

Speaker #5: The preliminary budget numbers that we have, and I'm saying preliminary numbers, is probably in the range of 15 to 20 million dollars for the entire cost of the trial from A to Z.

Speaker #5: And that is not a per year cost; that's the total cost. And because this trial is going to span at least four or five years, the whole time period for measuring the efficacy of the drug is 13 months.

Speaker #5: So we're looking at the startup time enrollment time and readout time. We believe that the cost per year could be in the range of about maybe 3 million dollars.

Speaker #5: And as Nataliya said, we're also looking for similar to what we did with open to two, is we're looking for non-dilutive 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.

Wa'el Hashad: And as Nataliya said, we're also looking for, similar to what we did with ELPAS-2, is we're looking for non-dilutive funding to support that. And there is a lot of both private and government-supported entities that are interested in supporting that type of research.

Speaker #1: The next question we have.

Nataliya Agafonova: The next question was just that that's in.

Speaker #5: I'll just add that.

Speaker #1: Apologies, go ahead.

Lisa Locklear: Well, let's just go ahead.

Speaker #5: Oh, sorry. Ram, I was just going to say, I would just say that is a preliminary estimate as we're working through the feasibility right now.

Nataliya Agafonova: Oh, sorry. Ram, I was just going to say, I would just say that is a preliminary estimate as we're working through the feasibility right now.

Speaker #5: Understood.

Derek Cole: Understood.

Speaker #1: The next question we have is from Bhubalan Pachayapan of ROTH. Please go ahead.

Lisa Locklear: The next question we have is from Bumelan Pattayapan of RTH. Please go ahead.

Speaker #8: Hi, good afternoon everyone. Can you hear me okay?

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

Speaker #5: Yes, Bhubalan.

Wa'el Hashad: Yes, Bumelan.

Speaker #8: Hi, great. So thanks. A few questions from us. So firstly, with respect to HLHS, you stated in your press release that the BLA filing could occur by year-end 2026.

Joshua Hare: Hi. Great. So thanks. A few questions from us. So firstly, with respect to HLHS, so you stated in your press release that DLA filing could occur by year end '26. So if you look at, you know, from a logistic standpoint, at that time, the FDA's PRV program would have been suspended, assuming, you know, there are no new developments in that area. So my question to you is, do you still get to keep the RAAP pediatric designation and enjoy the associated benefits such as rolling submission and more frequent FDA interactions?

Speaker #8: So if you look at, you know, from a logistics standpoint, at that time, the FDA's PRV program would have been suspended assuming, you know, there is no new developments in that area.

Speaker #8: So my question to you is, do you still get to keep the rare pediatric designation and enjoy the associated benefits such as rolling submission and more frequent FDA interactions?

Speaker #8: And also speaking of FDA interactions, can you comment on whether there is any leadership changes or, you know, because there have been a lot of flux of 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 we expect anyone to be different.

Joshua Hare: And also, speaking of FDA interactions, can you comment on whether there are any leadership changes or, you know, because there's been a lot of flux 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 anyone to be different? The reason I'm asking this question is because I wanted to make sure the chances that the Phase IIb can still be registration-enabling and not a separate Phase III study, you know, out of the blue.

Speaker #8: The reason I'm asking this question is that I wanted to make sure the chances that Phase 2B can still be registration-enabling and not a separate Phase 3 study, you know, out of the blue.

Speaker #5: That's those are great questions, Bhubalan as well. So thank you for those. Let me address the PRV first. As we have previously disclosed in all of our communications, we realize that the current PRV will sunset in September of 2026.

Wa'el Hashad: Those are great questions, Bumelan, as well. So thank you for those. Let me address the PRV first. As we have previously disclosed in all of our communications, we realize that the current PRV 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 non-budgetary item. Unfortunately, sometimes these types of things get left out by focusing on other important things that are happening and trade-offs. But there is a lot of support, at least from both sides, to do it.

Speaker #5: Unless it’s reauthorized by Congress and approved by the Senate. I can tell you, as a member of the board sitting on California Life Sciences, that I got the opportunity to meet with a lot of members of Congress from both sides of the aisle, Republicans and Democrats, and there is significant support for renewal, especially since it doesn’t cost the budget anything because that is a non-budgetary item.

Speaker #5: Unfortunately, sometimes these types 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.

Speaker #5: As you know, we are also a member of the bio organization, and there are a lot of efforts going on in the bio space. You can also see it on their website that this is one of their top priorities.

Wa'el Hashad: I also, we are, as you know, a member of the Bio organization, and there are a lot of efforts going also on Bio, and you can see it also on their website that this is one of their top priorities. So I'm cautiously optimistic that this will be renewed, but definitely right now, as we stand, the 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.

Speaker #5: So I'm cautiously optimistic that this will be renewed, but definitely right now as we stand, the likelihood it is going to sunset in 2026.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: 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 as this, August of last year.

Wa'el Hashad: 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 at the same time as this time, August of last year. And the agreement is minuted, 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 trial. We're not doing similar to Mesoblast 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 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.

Speaker #5: And the agreement is mandated 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.

Speaker #5: Number one, we're doing head-to-head trial. We're not doing similar to mesoblast or Capra core at least the data submitted. We are doing head-to-head trial and that is as robust as it gets.

Speaker #5: The number of patients, 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.

Speaker #5: So for all those reasons, we feel confident. So that is part one of answering your question. Part two, is actually we have met with the FDA two times over Zoom during the new administration.

Wa'el Hashad: So for all those reasons, we feel confident. So that is part one of answering your question. Part two is actually we have met with the FDA two times over Zoom during the new administration, one in March of this year when we met with them for the Type B meeting, and the second one in June to review the IND for the pediatric dilated cardiomyopathy. And you know, because we were asking for to move directly to a pivotal Phase II pivotal trial with pediatric dilated cardiomyopathy, the FDA requested that we meet in person via Zoom. So we had those two interactions, and I can tell you, yes, they have asked some 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.

Speaker #5: One in March of this year when we met with them for the type B meeting. And the second one in June to review the IND.

Speaker #5: For the pediatric-related cardiomyopathy, and you know, because we were asking to move directly to a pivotal Phase 2 trial for pediatric-related cardiomyopathy, the FDA requested that we meet in person via Zoom.

Speaker #5: So we had those two 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.

Speaker #5: 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.

Wa'el Hashad: 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 potential say. 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 are no surprises when it comes to the finish line. So hopefully, that addresses both your question about the PRV and the regulatory support from the FDA.

Speaker #5: 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 potential say.

Speaker #5: 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.

Speaker #5: 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 PRV and the regulatory support from the FDA.

Speaker #8: Yes, it's pretty comprehensive and thanks for that. And then in the prepared remarks, so Nataliya was mentioning about the five-year survival 100% five-year survival.

Joshua Hare: Yes. That's pretty comprehensive, and thanks for that. And then in the prepared remarks, so Nataliya was mentioning about the five-year survival, 100% five-year survival I'm talking about in HLHS participants. 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 patients?

Speaker #8: I'm talking about in HLHS, one participants. 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 patients?

Speaker #5: I'll have Nataliya.

Wa'el Hashad: I'll have Nataliya answer.

Speaker #3: Thank you so much. Yeah, 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.

Nataliya Agafonova: 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 six-year data.

Speaker #3: We don't have six years of data.

Speaker #8: Okay, no worries. 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 on commercialization for Latermastracel versus seeking partnership?

Joshua Hare: Okay. All right. 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 Lateral Mastercell versus seeking partnership?

Speaker #5: Sure, just to clarify, you're talking about the CDMO? Contract manufacturing? Yeah.

Derek Cole: Sure. Just to clarify, you're talking about the CDMO contract manufacturing?

Speaker #8: Yes.

Joshua Hare: Yes.

Derek Cole: Yeah.

Speaker #5: So for us, you know, there are three key factors. The first one was the timeline to our planned BLA submission. That was a critical driver.

Joshua Hare: Yes.

Derek Cole: So for us, you know, there's three key factors. The first one was the timeline to our planned DLA 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 timeline versus leveraging an existing facility from a CDMO. The second critical driver here was overall cost. So the facility renovations, when you look at that, plus additional capital expenditures that you would 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.

Speaker #5: 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 timeline.

Speaker #5: Versus leveraging an existing facility from a CDMO, the second critical driver here was overall cost. When you look at the facility renovations, plus additional capital expenditures that you would need for new processing and analytical equipment, validation, headcount expansion, and ongoing operational overhead, the total adds up. The CDMO option was one that was potentially more cost-effective.

Speaker #5: And then the last little 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 PLI readiness, and so in summary, you know, those really three things were some of the things that we were considering when moving to a CDMO.

Derek Cole: 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 PLI readiness. And so in summary, you know, those really three things were some of the things that we were considering when moving to a CDMO.

Speaker #8: Right. 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.

Joshua Hare: Great. And this would 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 II. 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?

Speaker #8: So the FDA has given you a green signal to move directly into pivotal phase two. So can you speak to us what gave the FDA the confidence in this program?

Speaker #8: Is there some preclinical data that you shared with them that they were very excited about? Maybe if you can tell us or summarize this.

Speaker #8: And also during your FDA discussion, can you clarify the focus was on managing the congestive heart failure symptoms or is it more towards mitigating the progression of the structural heart disease?

Speaker #5: Yeah, Nataliya or Josh can take that question.

Wa'el Hashad: Yeah. Nataliya or Josh can take that question.

Speaker #3: I can start maybe Josh, you can pick up. So I think what gave confidence to the FDA that we can move forward immediately to the approval with this study is that we designed endpoints based on clinically meaningful clinical features for the patient.

Nataliya Agafonova: I can start. Maybe Josh, you can pick up. So I think what gave confidence to the FDA that we can move forward immediately to the approval with this study is that we designed an endpoint based on clinically meaningful clinical features for the patient. So definitely, heart failure is one of the biggest impacts for the dilated cardiomyopathy. So we look at the all-cause mortality on hospitalization, heart failure, etc. So I think the rigorous primary endpoint definitely can make a difference whether or not Lateral Mastercell affects 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 endpoint. So we've been asked a lot of multiple questions on clinical, biostatistics, etc.

Speaker #3: So definitely heart failure is one of the biggest impacts for the dilated cardiomyopathy. So we look at the all-cause mortality on hospitalization, heart failure, et cetera.

Speaker #3: So I think the rigorous primary endpoint definitely can make difference whether or not Latermastracel affects this patient's life. Improvement on heart failure, improvement on everyday activity, which is really meaningful for these patients.

Speaker #3: 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.

Speaker #3: So we’ve been asked a lot of multiple questions on clinical, biostatistics, et cetera. I think all this really gave confidence to the FDA that we are on the right direction.

Nataliya Agafonova: So I think all this really gave confidence to the FDA we are on the right direction. Josh, did I miss anything?The

Speaker #3: Josh, did I miss anything?

Speaker #5: The one thing that I would mention that I think may have played into the FDA's decision was that we have experience with this type of administration in adults.

Lisa Locklear: one thing that I would mention that I think may have played into the FDA's decision was that we have, you know, 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 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 two. And with the rigorous study design and endpoints that you mentioned, Nataliya, you know, led them to, it may have influenced them to allow this to be a pivotal study.

Speaker #5: And particularly, we at Longeveron have treated adults with aging frailty. However, there are also published studies in which patients with congestive heart failure due to dilated cardiomyopathy have been treated with a very favorable response.

Operator: All right. Thanks for taking that request. Sorry, go ahead, William.

Wa'el Hashad: I will say one more thing, Bobalan. It's always hard to know or predict what exactly the FDA 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 has 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. Most of them actually are in the aging group. But I think that safety, especially around immunogenicity and infusion-related reactions and all of those types of things, I'm sure this has also been taken into consideration by the agency in weighing in this decision.

Wa'el Hashad: 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 really don't have to go through multiple years of waiting until potential therapy like this can make it to the market.

Operator: All right. Thank you, everyone, for taking your questions, and congratulations on your progress.

Operator: Thank you.

Operator: The next question we have is from Michael Okunic of Maxim Group. Please go ahead.

Derek Cole: Hey, thank you guys for taking my question and congrats on the great progress. So I'd actually like to follow up on that previous question from Bubalon. So what sort of improvement in survival or time to transplant would be considered clinically meaningful in the DCM? Are there any established thresholds for benefit here?

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

Um,

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?

Wa'el Hashad: Again, Nataliya or Josh can take that question.

Again, Nataliya or Josh can take that question.

Operator: So definitely, the standard of care, as you probably know, is a very symptomatic treatment with main cardiovascular medication, ACE inhibitor, beta-blockers, etc., to maintain patient heart failure stable. So with this therapy, we are 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 two years for this kid with dilated 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 for these patients to develop cardiac failure. So we are looking for all cause mortality transplant.

Thank you. Probably known as a very symptomatic treatment with, um, main, um, cardiovascular medications. So you inhibit our beta blockers, etc., to maintain the patient's heart failure stable.

Uh, so did this therapy? We, uh, are really looking forward to seeing patients. Um,

Uh, prolonged that period of time when the patient needs heart transplant. Because eventually I would, um,

What is happening, uh, from the time of diagnosis to the heart failure? Sometimes it takes only 2 years for this, uh, for this kit with dilated cardiomyopathy. So, um, and of course, you know, the heart transplant as a last stage of the treatment is not desirable.

Operator: 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 development of heart failure. So all these are really important for the patient. Are we looking for complete resolution of heart failure? We don't know. We don't know, but 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. And those are very important qualitative measures for this patient population.

So what we are looking forward is to prolong transplant, free survival and improve overall, um, well-being of the patient, uh, from the point of view of reducing the symptoms of cardiac failure and reducing the um uh uh the possibility for this patient, to develop cardiac failure. Um, so we are looking for, uh, all cause mortality transplant. We're looking for dates in hospital. We are looking for that different scales, uh, to evaluate patient symptoms, um, development of heart failure time. And from the beginning of the treatment to develop uh, developing of heart failure. So all these are really important for the patients. Um, are we looking for complete, um, resolution of heart failure? Uh,

They don't know, we don't know. But, um,

Hello.

Uh, but definitely uh uh we are looking for um, a prolongation of time. Uh, for the patient eventually developing heart failure, Improvement of symptoms and uh prolongation of transplant, free survival and those are very important important qualitative measure for this patient population.

Lisa Locklear: Yeah, 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 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, you know 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.

You uh, take from the, um, adult experience of, uh, uh therapeutic development. Any 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, um, of morbidity and mortality. So any, any measurable reduction

Um, I think this would be considered meaningful. The other thing to keep in mind is the underlying biology of the disease.

Lisa Locklear: So we will 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.

And the the possibility that there is, uh, a chance here for the therapy to increase the likelihood of a full remission, uh, that has been, uh, seen in adults in published studies. Uh, however, you know, it has to be reinforced, as Natalya 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 um or at least an increased uh likelihood of remission. So we will we'll be and by remission, I mean a meaningful recovery in cardiac function. So as part of the study in in addition to the clinical end points, we will definitely be measuring uh cardiac function as well.

Derek Cole: All right. Thank you. I really appreciate that additional color. And then just one more, I'd like to ask a little 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?

All right, thank you. I really appreciate that additional color. And then just, um, one more. I'd like to ask a little 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?

Lisa Locklear: Yeah, that'd 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 it's 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 non-human primates, they've been observed to cause malignant ventricular arrhythmias, particularly over the first two weeks of transplantation. And this observation has very much limited the translation into phase one clinical studies. Regulatory authorities, I think, have appropriately exercised the concern that this is an unacceptable side effect or potentially too dangerous.

Yeah, that'd be, uh, I'd be very happy to, uh, speak to that. So, uh, the current approach is for IP cell transplant into the heart. Have you used?

Uh, uh, uh, what you could call garden variety. I mean, that's not the appropriate term, but it's 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 uh, pre-clinical models, like non-human primates. They've been observed to um, cause malignant ventricular, arrhythmias, uh, particularly over the fast. 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 uh, this is a

Lisa Locklear: 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 and 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.

Um, you know, an unacceptable side effect of—or, or potentially too dangerous. So, I think one of the most important, uh, targets and advances is to develop a protocol where you can develop the cells, um, 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 here is we want to...

Increase the recovery and 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 uh, 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 sub-population that uh eliminated the fraction that caused the electrical instability. So we've we've been able to do that in the dish.

Lisa Locklear: And so now with this patented technology, the US patent was issued about six months ago. So 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.

And biochemically, at a molecular level. And so, now with this patented technology, the US Patent was issued about six months ago. So it is a patented, uh, discovery composition of matter, uh, 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.

Derek Cole: Right. Thank you. Seems like a really interesting program. Looking forward to updates.

Right. Thank you. 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 floor back over to Wael Hashad for any closing remarks.

Ladies and gentlemen, that concludes the question and answer session. At this time, I would like to turn the floor back over to Mohamed Hashad for any closing remarks.

Wa'el Hashad: 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.

I 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.

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