Mesenchymal stem cell therapy (Longeveron)

MIAMI, April 22, 2025 (GLOBE NEWSWIRE) -- Longeveron Inc. (NASDAQ: LGVN), a clinical stage regenerative medicine biotechnology company developing cellular therapies for life-threatening and chronic aging-related conditions, today announced that the Company’s CEO, Wa’el Hashad, issued the following letter to Longeveron shareholders. Dear Fellow Shareholders, Twenty twenty-four was a year of execution for Longeveron. We made significant progress advancing Longeveron’s founding mission - developing cutting-edge cellular therapy research to impact patients’ lives for the better by addressing unmet medical needs. We have come a long way pursuing that mission and now have clarity on the pathway to our first potential Biological License Application (BLA) submission. Today, I am excited to update you on our overall strategy, progress, and key priorities and goals for 2025. Strategic Overview and 2024 Progress: Over the past decade, stem cell therapy has seen remarkable strides, transforming from a promising field into one delivering tangible clinical outcomes. We've seen the solidification of cell therapy's role in regenerative medicine and its potential to treat a wide range of conditions, signaling an exciting future for both scientific innovation and patient care. Longeveron has been at the forefront of this evolution in medicine. Our lead investigational product is laromestrocel (Lomecel-B™), a stem cell therapy derived from culture-expanded mesenchymal stem cells (MSCs) that are sourced from bone marrow of young healthy adult donors. The number of functional MSCs in the body declines as we age, which has driven interest in their use for aging-related conditions. Their unique properties — including the ability to reduce inflammation, promote tissue repair and regeneration, modulate immune responses, and improve vascularization — also support their application in some rare cardiovascular diseases/conditions with high unmet medical need. We believe that by using the same cells that promote tissue repair, organ maintenance, and immune system function, we can develop safe and effective therapies for some of the most difficult diseases and conditions. A decade ago, our stem cell therapy vision was an academic idea. Today, laromestrocel represents a pipeline in a product opportunity that has delivered positive results from multiple clinical trials: Phase 1 & 2 in Alzheimer’s disease, Phase 1 & 2 in Aging-related Frailty, Phase 1 in Hypoplastic Left Heart Syndrome (HLHS), a rare pediatric disease. We are currently conducting a pivotal Phase 2b clinical trial for HLHS. Our development programs for these 3 initial indications address market opportunities of what we estimate to be approximately ~$5+ billion, ~$4+ billion and up to ~$1 billion, respectively. Earlier this year, the World Health Organization’s International Nonproprietary Names (INN) Expert Committee approved “laromestrocel” as the non-proprietary name for Lomecel-B™ — a key milestone in the development and future commercialization of our stem cell therapy. As we did this past year, in 2025, we will continue focusing our efforts on two of our most promising programs: HLHS and Alzheimer’s disease. Hypoplastic Left Heart Syndrome (HLHS): HLHS is a rare pediatric disease in which the left ventricle (one of the pumping chambers of the heart) is either severely underdeveloped or missing. Because the left ventricle is the chamber that normally pumps blood to the body, infants born with this condition have a profound reduction in blood flow and thus cannot get the normal supply of oxygen to their organs. In order for the children to survive, they must undergo a complicated, three-stage heart reconstruction surgery over the course of the first 5 years of their lives. Despite this surgical reconstruction, only 50% of the affected children survive to age 15 without heart transplantation. Our program is designed to boost/improve the heart function in these children with the goal of potentially enhancing their survival. In our Phase I clinical trial (ELPIS I) evaluating laromestrocel in 4-month-old infants with HLHS, we observed 100% transplant-free survival up to five years following treatment. This contrasts with an approximately 20% mortality rate observed in historical control data. Five-year post-treatment long-term survival data from the ELPIS I Phase 1 clinical trial was presented at the Congenital Heart Surgeons’ Society (CHSS) 51st Annual Meeting in October 2024. We are currently nearing completion of enrollment for our Phase 2b study, ELPIS II, which is evaluating laromestrocel as a potential adjunct treatment to the standard of care for HLHS. ELPIS II has achieved nearly 95% enrollment, and we expect to complete enrollment in the second quarter of this year. In September 2024, we completed a Type C meeting with the U.S. FDA regarding our HLHS development program and the pathway toward a potential BLA submission. We reached foundational alignment on the primary endpoint and secondary endpoints for the ELPIS II trial. The FDA confirmed that, contingent on positive results, ELPIS II may be considered a pivotal trial and potentially acceptable for BLA submission seeking full traditional approval. With this regulatory clarity, we are now focused on BLA preparedness and enabling activities for the HLHS program. Notably, because this program has received Rare Pediatric Disease Designation, we may be eligible to receive a Priority Review Voucher (PRV) if our BLA is approved. We may use the PRV internally or sell to a third party. Historically, PRVs have commanded values exceeding $100 million. Alzheimer’s Disease: The laromestrocel Alzheimer’s disease (AD) program continues to garner important recognition and support. In 2024, data from the CLEAR MIND Phase 2a clinical trial evaluating laromestrocel in mild Alzheimer’s disease were presented as a featured research oral presentation at the 2024 Alzheimer's Association International Conference held at the end of July and as a late breaking poster presentation at the 17th edition of the Clinical Trials on Alzheimer’s Disease Conference (CTAD24) in October. We are very excited about the trial’s positive results. The trial met its primary objective of demonstrating safety, with laromestrocel being well-tolerated. In addition, we observed encouraging trends suggesting a potential slowing or prevention of disease progression in patients treated with laromestrocel compared to placebo. This program has received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations, providing us with the opportunity for enhanced and frequent communication with the FDA to facilitate the development and review process. In March of this year, results from the trial were published in Nature Medicine. Also in March of this year, we held a Type B meeting with the FDA to discuss the regulatory pathway for a potential BLA for laromestrocel in mild Alzheimer’s disease. We reached foundational alignment on the overall study design for a proposed single, pivotal, seamless adaptive Phase 2/3 clinical trial. To support an accelerated path to potential approval, the FDA agreed to consider a BLA submission based on positive interim results from this planned single study. With this regulatory clarity in hand, we are focused on seeking partnership opportunities and/or non-dilutive funding for the Alzheimer’s disease program. Our Core Business Objectives: Our strategic plan is built on the strength of the science underlying our stem cell therapy laromestrocel. For 2025, we are focused on four key objectives: Pivotal Phase 2 clinical trial (ELPIS II) is nearing enrollment completion. Regulatory pathway clarified with U.S. FDA. Potential to initiate rolling BLA submission in 2026. Potential to receive a Rare Pediatric Disease priority review voucher associated with HLHS upon BLA approval which could have significant monetary value and further enhance our product’s value proposition upon approval. Successful meeting with FDA confirmed ELPIS II could be pivotal. 2025 will see significant focus on organizational readiness for potential BLA filing for HLHS in 2026. Our goal is to accomplish BLA readiness this year ahead of data readout to potentially shorten the timeline to BLA submission. Emphasis on Chemistry, Manufacturing, and Controls (CMC) preparedness. Hired industry veteran Chief Technology Officer to support BLA preparedness. We are committed to helping HLHS patients worldwide. In 2025, we intend to take initial steps connecting with non-U.S. regulatory bodies, including EMA (European Union), MHRA (United Kingdom), PMDA (Japan) and HealthCanada. Recognizing substantial revenue potential from worldwide commercialization, we anticipate capitalizing on recent rare disease pricing trends and the unique aspects of our treatment. We believe our Alzheimer’s disease program holds immense potential. Due to the large size of the affected population, it involves larger-scale studies and commercialization requirements. This scale of development effort necessitates significant investment, prompting our focus on potential strategic partnerships with biotech/pharmaceutical companies and/or non-dilutive funding sources. We believe the clarity on the pathway to potential BLA submission and the need for only a single pivotal clinical trial enhance the attractiveness and economic benefits of the program to potential partners. We strive to be prudent stewards of shareholder capital and focus allocating it to the organization’s top priorities to effectuate optimal resource utilization and alignment with strategic objectives. We prudently manage expenses. In 2024, we reduced total operating expenses 13% while continuing to effectively advance our development programs. Financial Position and Capital Strategy: Longeveron is working diligently to effectively advance our development programs while managing expenses and our capital. We will need additional capital to achieve our business strategy and objectives. We indicated in our recently filed Annual Report on Form 10K that we anticipated our existing cash and cash equivalents would fund our operating expenses and capital expenditure requirements into the fourth quarter of 2025. However, as we also indicated, as a result of our successful Type C meeting with the FDA in August 2024 with respect to the HLHS regulatory pathway, we have started to ramp up BLA enabling activities to prepare for a potential filing with the FDA in 2026 if the current ELPIS II trial is successful. We expect our operating expenses and capital expenditure requirements to accelerate this year as a result of these activities, including CMC (Chemistry, Manufacturing, and Controls) and manufacturing readiness. We intend to seek additional financing and non-dilutive funding options to support these activities, and additional non-dilutive funding and/or strategic partners to support the AD development program. We anticipate that our current cash projections may be impacted by these ramped up activities and any financing transactions we enter into. 2025 Goals and Priorities Our goals for 2025 center on efficient, effective execution of our strategic plan with an emphasis on three primary operational goals: Outlook Longeveron has made tremendous progress in two important stem cell development programs over the past 12 months, successfully delivering on our strategic plan. We are now approaching multiple potentially transformational milestones over the next 12 months including completion of enrollment in our pivotal Phase 2b clinical trial in HLHS which may establish the timeline for a potential BLA submission for HLHS, and potential partnering for the Alzheimer’s disease program. Our team’s expertise and industry experience enable the organization to accomplish so much with a small team and few resources. Generating several positive initial results across five clinical trials in three indications, continues to position Longeveron as a leader in stem cell therapy research and, potentially, commercialization of cellular therapeutics. We believe Longeveron’s demonstrated track record of successful clinical execution, strength of data generated to date and the potential size of addressable markets provide for a compelling investment opportunity. We deeply appreciate the support of our stakeholders and look forward to continued collaboration and progress in the future. Sincerely, Wa’el Hashad CEO, Longeveron Forward-Looking Statements Certain statements in this letter that are not historical facts are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, which reflect management’s current expectations, assumptions, and estimates of future operations, performance and economic conditions, and involve known and unknown risks, uncertainties, and other important factors that could cause actual results, performance, or achievements to differ materially from those anticipated, expressed, or implied by the statements made herein. Forward-looking statements are generally identifiable by the use of forward-looking terminology such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expects,” “intend,” “looks to,” “may,” “on condition,” “plan,” “potential,” “predict,” “preliminary,” “project,” “see,” “should,” “target,” “will,” “would,” or the negative thereof or comparable terminology, or by discussion of strategy or goals or other future events, circumstances, or effects and include, but are not limited to, statements about the various below-listed factors. Factors that could cause actual results to differ materially from those expressed or implied in any forward-looking statements in this release include, but are not limited to, our cash position and need to raise additional capital, the difficulties we may face in obtaining access to capital, and the dilutive impact it may have on our investors; our financial performance, and ability to continue as a going concern; the period over which we estimate our existing cash and cash equivalents will be sufficient to fund our future operating expenses and capital expenditure requirements; the ability of our clinical trials to demonstrate safety and efficacy of our product candidates, and other positive results; the timing and focus of our ongoing and future preclinical studies and clinical trials, and the reporting of data from those studies and trials; the size of the market opportunity for certain of our product candidates, including our estimates of the number of patients who suffer from the diseases we are targeting; our ability to scale production and commercialize the product candidate for certain indications; the success of competing therapies that are or may become available; the beneficial characteristics, safety, efficacy and therapeutic effects of our product candidates; our ability to obtain and maintain regulatory approval of our product candidates in the U.S. and other jurisdictions; our plans relating to the further development of our product candidates, including additional disease states or indications we may pursue; our plans and ability to obtain or protect intellectual property rights, including extensions of existing patent terms where available and our ability to avoid infringing the intellectual property rights of others; the need to hire additional personnel and our ability to attract and retain such personnel; and our estimates regarding expenses, future revenue, capital requirements and needs for additional financing. Further information relating to factors that may impact the Company’s results and forward-looking statements are disclosed in the Company’s filings with the Securities and Exchange Commission, including Longeveron’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission on February 28, 2025, its Quarterly Reports on Form 10-Q, and its Current Reports on Form 8-K. The Company operates in highly competitive and rapidly changing environment; therefore, new factors may arise, and it is not possible for the Company’s management to predict all such factors that may arise nor assess the impact of such factors or the extent to which any individual factor or combination thereof, may cause results to differ materially from those contained in any forward-looking statements. The forward-looking statements contained in this press release are made as of the date of this press release based on information available as of the date of this press release, are inherently uncertain, and the Company disclaims any intention or obligation, other than imposed by law, to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. Investor and Media Contact: Derek Cole Investor Relations Advisory Solutions derek.cole@iradvisory.com A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/cfb4911d-2b0b-4c52-b2fa-b6982947155d

Planned single, pivotal Phase 2/3 clinical trial, if positive, acceptable for Biological License Application (BLA) submission for Alzheimer’s diseaseAlignment with FDA on proposed trial study design, population and endpointsInitiation of planned pivotal Phase 2/3 clinical trial anticipated in 2H 2026, contingent upon obtaining non-dilutive funding and/or partnering supportLaromestrocel (Lomecel-B™) has received FDA Regenerative Medicine Advanced Therapy (RMAT) designation for Alzheimer’s disease which provides frequent interactions with the FDA, intensive guidance on drug development, and eligibility for accelerated approval and priority review MIAMI, March 20, 2025 (GLOBE NEWSWIRE) -- Longeveron Inc. (NASDAQ: LGVN), a clinical stage regenerative medicine biotechnology company developing cellular therapies for life-threatening and chronic aging-related conditions, today announced the positive outcome of a Type B meeting with the U.S. Food and Drug Administration (FDA), supporting the advancement of laromestrocel (Lomecel-BTM), a proprietary, scalable, allogeneic, investigational cellular therapy, as a potential treatment for Alzheimer’s disease (AD). The Company and the FDA reached foundational alignment on the overall study design for a proposed single, pivotal, seamless adaptive Phase 2/3 clinical trial, including proposed AD patient population, proposed placebo control, laromestrocel (Lomecel-BTM) dose selection and frequency, trial duration and trial endpoints. To accelerate the pathway to potential approval, the FDA agreed to consider a BLA based on positive interim trial results from the planned single study. Longeveron has previously completed two positive clinical trials studying patients with mild AD: a Phase 1 study and a multi-center, randomized, double-blind, placebo-controlled Phase 2a clinical trial (CLEAR-MIND), results of which were presented at the 2024 Alzheimer's Association International Conference (AAIC) and published in Nature Medicine in March 2025. The Phase 2a CLEAR-MIND study results showed a favorable safety profile, absence of amyloid-related imaging abnormalities (ARIA) with laromestrocel (Lomecel-BTM) administration, and several domains of potential clinical efficacy, including cognition, function, quality of life, and reduction in brain atrophy. The results of the CLEAR-MIND trial formed the basis for the FDA RMAT designation. “We are pleased to have alignment with the FDA on the development pathway for our laromestrocel development program in Alzheimer’s disease, a debilitating neurodegenerative disorder that leads to progressive memory loss and has a significant burden on patients, families, caregivers and society in general,” said Nataliya Agafonova, Chief Medical Officer of Longeveron. “Laromestrocel’s multiple potential mechanisms of action to address inflammatory responses offer the potential to address the underlying pathology of Alzheimer’s disease without the limitations of previous therapies. We look forward to further advancing this potentially transformative stem cell therapy treatment option for patients suffering from mild Alzheimer’s disease.” Contingent upon obtaining additional non-dilutive funding and/or partnering support, the Company anticipates initiating the pivotal clinical trial in the second half of 2026. The FDA has granted laromestrocel (Lomecel-B™) both Regenerative Medicine Advanced Therapy (RMAT) designation and Fast Track designation for the treatment of mild Alzheimer’s disease, which allow greater access to FDA interaction during laromestrocel’s (Lomecel-B™) development for Alzheimer’s disease. Laromestrocel (Lomecel-B™) is, to Company’s knowledge, the first cellular therapeutic candidate to receive FDA RMAT designation for Alzheimer’s disease. About laromestrocel (Lomecel-B™)Laromestrocel is a living cell product made from specialized cells isolated from the bone marrow of young healthy adult donors. These specialized cells, known as mesenchymal stem cells (MSCs), are essential to our endogenous biological repair mechanism. MSCs have been shown to perform a number of complex functions in the body, including the formation of new tissue. They also have been shown to respond to sites of injury or disease and secrete bioactive factors that are immunomodulatory and regenerative. We believe that laromestrocel may have multiple potential mechanisms of action that may lead to anti-inflammatory, pro-vascular regenerative responses, and therefore may have broad application for a range of rare and aging related diseases. About Alzheimer’s Disease (AD)Alzheimer’s disease is neurodegenerative disorder that leads to progressive memory loss and death and currently has very limited therapeutic options. AD is the leading form of dementia. This disease affects millions of Americans, leads to early mortality, and creates a tremendous burden on families and society that costs the U.S. hundreds of billions of dollars annually in direct costs and lost productivity. One in three older adults dies with Alzheimer’s or another dementia. Inflammation in the brain – a process called neuroinflammation – is a key feature of AD. This pro-inflammatory state appears essential for the clinical manifestation of dementia resulting from AD. In addition to affecting the brain tissue itself, neuroinflammation also impairs the blood vessels in the brain and the exchange barrier between the blood and the brain, called the blood-brain barrier (BBB). Ultimately, these pathological processes lead to the structural changes in the brain and resulting dementia. Longeveron is testing laromestrocel (Lomecel-B) as a potential treatment for mild AD based on the hypothesis that its multiple possible mechanisms of action (MOAs) can simultaneously address multiple features of AD. About Longeveron Inc.Longeveron is a clinical stage biotechnology company developing regenerative medicines to address unmet medical needs. The Company’s lead investigational product is laromestrocel (Lomecel-B™), an allogeneic mesenchymal stem cell (MSC) therapy product isolated from the bone marrow of young, healthy adult donors. Laromestrocel (Lomecel-B™) has multiple potential mechanisms of action encompassing pro-vascular, pro-regenerative, anti-inflammatory, and tissue repair and healing effects with broad potential applications across a spectrum of disease areas. Longeveron is currently pursuing three pipeline indications: hypoplastic left heart syndrome (HLHS), Alzheimer’s disease, and Aging-related Frailty. Laromestrocel (Lomecel-B™) development programs have received five distinct and important FDA designations: for the HLHS program - Orphan Drug designation, Fast Track designation, and Rare Pediatric Disease designation; and, for the AD program - Regenerative Medicine Advanced Therapy (RMAT) designation and Fast Track designation. For more information, visit www.longeveron.com or follow Longeveron on LinkedIn, X, and Instagram. Forward-Looking StatementsCertain statements in this press release that are not historical facts are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, which reflect management’s current expectations, assumptions, and estimates of future operations, performance and economic conditions, and involve known and unknown risks, uncertainties, and other important factors that could cause actual results, performance, or achievements to differ materially from those anticipated, expressed, or implied by the statements made herein. Forward-looking statements are generally identifiable by the use of forward-looking terminology such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expects,” “intend,” “looks to,” “may,” “on condition,” “plan,” “potential,” “predict,” “preliminary,” “project,” “see,” “should,” “target,” “will,” “would,” or the negative thereof or comparable terminology, or by discussion of strategy or goals or other future events, circumstances, or effects and include, but are not limited to, statements about the various below-listed factors. Factors that could cause actual results to differ materially from those expressed or implied in any forward-looking statements in this release include, but are not limited to, our cash position and need to raise additional capital, the difficulties we may face in obtaining access to capital, and the dilutive impact it may have on our investors; our financial performance, and ability to continue as a going concern; the period over which we estimate our existing cash and cash equivalents will be sufficient to fund our future operating expenses and capital expenditure requirements; the ability of our clinical trials to demonstrate safety and efficacy of our product candidates, and other positive results; the timing and focus of our ongoing and future preclinical studies and clinical trials, and the reporting of data from those studies and trials; the size of the market opportunity for certain of our product candidates, including our estimates of the number of patients who suffer from the diseases we are targeting; our ability to scale production and commercialize the product candidate for certain indications; the success of competing therapies that are or may become available; the beneficial characteristics, safety, efficacy and therapeutic effects of our product candidates; our ability to obtain and maintain regulatory approval of our product candidates in the U.S. and other jurisdictions; our plans relating to the further development of our product candidates, including additional disease states or indications we may pursue; our plans and ability to obtain or protect intellectual property rights, including extensions of existing patent terms where available and our ability to avoid infringing the intellectual property rights of others; the need to hire additional personnel and our ability to attract and retain such personnel; and our estimates regarding expenses, future revenue, capital requirements and needs for additional financing. Further information relating to factors that may impact the Company’s results and forward-looking statements are disclosed in the Company’s filings with the Securities and Exchange Commission, including Longeveron’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission on February 28, 2025, its Quarterly Reports on Form 10-Q, and its Current Reports on Form 8-K. The Company operates in highly competitive and rapidly changing environment; therefore, new factors may arise, and it is not possible for the Company’s management to predict all such factors that may arise nor assess the impact of such factors or the extent to which any individual factor or combination thereof, may cause results to differ materially from those contained in any forward-looking statements. The forward-looking statements contained in this press release are made as of the date of this press release based on information available as of the date of this press release, are inherently uncertain, and the Company disclaims any intention or obligation, other than imposed by law, to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. Investor and Media Contact:Derek ColeInvestor Relations Advisory Solutionsderek.cole@iradvisory.com A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/e9e96d9c-d6c3-4aec-ba85-36631b520211