Longeveron® Presents Study Results from CLEAR MIND Phase 2a Clinical Trial of Lomecel-B™ in Mild Alzheimer’s Disease at the Alzheimer’s Association International Conference® (AAIC)

Rhea-AI Summary

Longeveron (NASDAQ: LGVN) presented positive Phase 2a clinical trial results for Lomecel-B™ in mild Alzheimer's Disease at the Alzheimer's Association International Conference® (AAIC) 2024. The CLEAR MIND trial, involving 48 patients, demonstrated improved cognitive function, quality of life, and brain volume. Key findings include:

- Established safety profile with no hypersensitivity or infusion-related reactions
- Slowing of disease worsening compared to placebo
- Statistically significant improvements in cognitive assessments and daily living activities
- 49% reduction in brain volume loss
- Potential reduction in neuroinflammation

Lomecel-B™ has received both Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the FDA for mild Alzheimer's Disease treatment.

Positive

• Phase 2a CLEAR MIND trial met primary safety and secondary efficacy endpoints
• Lomecel-B™ showed improved cognitive function and quality of life in mild Alzheimer's Disease patients
• 49% reduction in brain volume loss observed in treated patients
• Statistically significant improvement in left hippocampal volume relative to placebo
• 20-30% reduction in left and right ventricular enlargement
• FDA granted Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations for Lomecel-B™

Negative

• None.

Insights

Medical Research Analyst

The Phase 2a CLEAR MIND trial results for Longeveron's Lomecel-B™ in mild Alzheimer's Disease (AD) are promising, but warrant cautious optimism. Here are the key takeaways:

• Safety profile: Lomecel-B™ demonstrated a favorable safety profile with no reported cases of hypersensitivity, infusion-related reactions, or amyloid-related imaging abnormalities (ARIA). This is particularly noteworthy given the safety concerns associated with some other AD therapies.
• Efficacy signals: The trial showed positive trends in several cognitive and functional measures, including statistically significant improvements in the Montreal Cognitive Assessment and the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL). However, it's important to note that this was a small Phase 2a trial with only 48 patients.
• Brain volume preservation: Lomecel-B™ treatment was associated with a 49% reduction in brain volume loss, which is a promising biomarker for disease progression. This effect was statistically significant for left hippocampal volume.
• Potential anti-inflammatory effects: Diffusion tensor imaging MRI results suggest that Lomecel-B™ may reduce neuroinflammation, which aligns with its proposed mechanism of action as a medicinal signaling cell therapy.

While these results are encouraging, larger studies will be necessary to confirm the efficacy and long-term safety of Lomecel-B™. The upcoming FDA meeting will be important in determining the path forward for this potential therapy.

Financial Analyst

The positive Phase 2a results for Lomecel-B™ could have significant implications for Longeveron (NASDAQ: LGVN) and the broader Alzheimer's Disease (AD) market:

• Market potential: With millions affected by AD globally, a safe and effective treatment could generate substantial revenue. However, it's important to note that Lomecel-B™ is still in early-stage development.
• Competitive landscape: The AD market is becoming increasingly competitive with recent approvals of antibody therapies. Lomecel-B™'s differentiated mechanism of action and potentially better safety profile could be advantageous if confirmed in larger trials.
• Regulatory tailwinds: The FDA's granting of Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations for Lomecel-B™ in AD could accelerate development and potentially reduce costs.
• Financial implications: As a clinical-stage biotech, Longeveron will likely need additional funding to advance Lomecel-B™ through larger, more expensive late-stage trials. Positive Phase 2a data may improve the company's ability to raise capital or attract partnerships.
• Risk factors: Despite promising results, investors should be aware that many AD drug candidates have failed in later-stage trials. The small sample size (n=48) of this study also warrants caution in interpreting results.

While the news is positive for Longeveron, the long road to potential approval and commercialization means investors should carefully consider the risks and potential rewards in the context of the company's overall pipeline and financial position.

– Featured Research Session oral presentation highlights findings that show Lomecel-B™ improved cognitive function, quality of life, and brain volume in the treatment of mild Alzheimer’s Disease –

– Study meets its key objectives to advance data supporting favorable benefit/risk profile, support target engagement, and provide additional support for the efficacy profile of Lomecel-B™ –

– Therapeutic potential demonstrated in MRI biomarker results showing 49% reduction in brain volume loss and improvement in inflammation featured in poster presentation –

MIAMI, July 28, 2024 (GLOBE NEWSWIRE) -- Longeveron Inc. (NASDAQ: LGVN), a clinical stage regenerative medicine biotechnology company developing cellular therapies for life-threatening and chronic aging-related conditions, announced that its positive Phase 2a clinical trial data and biomarker results were featured in two presentations, including a Featured Research Session oral presentation, at the Alzheimer’s Association International Conference^® (AAIC), taking place July 28 – August 1, 2024, in Philadelphia and online.

“As a medicinal signaling cell therapy that has multiple potential mechanisms of action to address inflammatory responses in the brain, Lomecel-B™ offers potential to address the underlying pathology of Alzheimer’s Disease without the limitations of previous therapies,” said Wa’el Hashad, Chief Executive Officer at Longeveron. “We are very encouraged by the safety profile and efficacy evidence that support the differentiated therapeutic potential of Lomecel-B™ and lay the foundation for its future clinical development. We’re pleased to connect with the Alzheimer’s community at AAIC 2024 and contribute to the growing body of evidence that fuels the continued development of novel therapeutics for this devastating disease.”

The randomized, placebo-controlled Phase 2a CLEAR MIND trial evaluated a total of 48 patients (36 were treated with Lomecel-B™ and 12 received placebo) who were 60-85 years old and had a diagnosis of mild Alzheimer’s Disease in accordance with National Institutes of Health – Alzheimer’s Association (NIA-AA) criteria, a Mini-Mental State Examination (MMSE) score of 18-24, and a brain MRI and positron emission tomography (PET) scan consistent with Alzheimer’s Disease. The clinical trial achieved its primary safety and secondary efficacy endpoints, and the study results presented at AAIC 2024 support the therapeutic potential of Lomecel-B™. Key findings include:

• The established safety profile of Lomecel-B™ for single and multiple dosing regimens was demonstrated in study data that showed no incidence of hypersensitivity, infusion-related reactions, and no cases of amyloid-related imaging abnormalities (ARIA).
• Patients treated with Lomecel-B™ showed an overall slowing of disease worsening compared to placebo.
• Positive efficacy results were demonstrated via a change from baseline at week 39 of the trial at prespecified levels using the Composite Alzheimer’s Disease Score (CADS) – a secondary outcome measure that combines information across cognitive, functional capacity, and brain MRI domains.
• Administration of Lomecel-B™ was associated with slowing cognitive and functional decline as demonstrated by statistically significant results in the Montreal Cognitive Assessment and statistical trending improvements compared to placebo in CDR-SB and MMSE.
• There was a statistically significant improvement relative to placebo observed in the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL).
• Lomecel-B™ minimized the loss in brain volume in areas associated with Alzheimer’s Disease (TBV, Hippocampus, Ventricles, Thalamus), statistically significant for left hippocampal volume relative to placebo. Along with positive changes in brain volumes, there was 20-30% reduction in left and right ventricular enlargement, respectively.
• Diffusion tensor imaging MRI supports the concept that Lomecel-B™ has the potential to reduce neuroinflammation compared to placebo.
• Lomecel-B™ treated patients demonstrated a numerical improvement relative to placebo in quality of life observed by caregivers and measured by the Alzheimer’s Disease Related Quality of Life (ADRQOL) and Quality of life AD (QOL-AD) scales.

“In recent years, we’ve seen an enhanced industry focus on bringing novel Alzheimer’s Disease therapeutics to market to treat the millions of people who suffer each year,” said Nataliya Agafonova, M.D., Chief Medical Officer at Longeveron. “The emergence of new Alzheimer’s Disease therapies has demonstrated that we are increasingly capable of treating a condition once deemed untreatable, and the next step in this endeavor is to develop a therapeutic that is both safe and effective in treating this disease. The results from the Phase 2a CLEAR MIND trial are highly encouraging and demonstrate the potential of Lomecel-B™ to fulfill this need, and I look forward to its continued development.”

“We believe these results provide important validation of both the safety and therapeutic potential of Lomecel-B™ in the treatment of mild Alzheimer’s Disease and suggest, with further clinical evaluation, that this cellular therapy has the potential to have a positive impact on patients afflicted with this devastating disease,” said Joshua Hare, M.D., Co-founder, Chief Science Officer, and Chairman at Longeveron. “We look forward to meeting the FDA to review this data and discuss the future development path for Lomecel-B™ in Alzheimer’s Disease.”

The FDA has granted 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 the FDA during Lomecel-B^TM’s development for Alzheimer’s Disease.

About Lomecel-B™
Lomecel-B™ is a living cell product made from specialized cells isolated from the bone marrow of young healthy adult donors. These specialized cells, known as medicinal signaling 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 Lomecel-B™ 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 Longeveron Inc.
Longeveron is a clinical stage biotechnology company developing regenerative medicines to address unmet medical needs. The Company’s lead investigational product is Lomecel-B™, an allogeneic medicinal signaling cell (MSC) therapy product isolated from the bone marrow of young, healthy adult donors. 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. Lomecel-B^TM development programs have received five separate and distinct FDA designations: for the HLHS program - Orphan Drug designation, Fast Track designation, and Rare Pediatric Disease designation; and, for the Alzheimer’s Disease 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 Statements

Certain 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 risks and uncertainties that could cause actual results to differ materially from those anticipated by the statements made herein. Forward-looking statements are generally identifiable by the use of forward-looking terminology such as “believe,” “expects,” “may,” “looks to,” “will,” “should,” “plan,” “intend,” “on condition,” “target,” “see,” “potential,” “estimates,” “preliminary,” or “anticipates” 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, the potential for Lomecel-B™ to be an effective treatment for Alzheimer’s Disease or achieve U.S. FDA approval as a Regenerative Medicine Advanced Therapy (RMAT). 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, market and other conditions, our limited operating history and lack of products approved for commercial sale; adverse global conditions, including macroeconomic uncertainty; inability to raise additional capital necessary to continue as a going concern; our history of losses and inability to achieve profitability going forward; the absence of FDA-approved allogeneic, cell-based therapies for Aging-related Frailty, Alzheimer’s Disease, or other aging-related conditions, or for HLHS or other cardiac-related indications; ethical and other concerns surrounding the use of stem cell therapy or human tissue; our exposure to product liability claims arising from the use of our product candidates or future products in individuals, for which we may not be able to obtain adequate product liability insurance; the adequacy of our trade secret and patent position to protect our product candidates and their uses: others could compete against us more directly, which could harm our business and have a material adverse effect on our business, financial condition, and results of operations; if certain license agreements are terminated, our ability to continue clinical trials and commercially market products could be adversely affected; the inability to protect the confidentiality of our proprietary information, trade secrets, and know-how; third-party claims of intellectual property infringement may prevent or delay our product development efforts; intellectual property rights do not necessarily address all potential threats to our competitive advantage; the inability to successfully develop and commercialize our product candidates and obtain the necessary regulatory approvals; we cannot market and sell our product candidates in the U.S. or in other countries if we fail to obtain the necessary regulatory approvals; final marketing approval of our product candidates by the FDA or other regulatory authorities for commercial use may be delayed, limited, or denied, any of which could adversely affect our ability to generate operating revenues; we may not be able to secure and maintain research institutions to conduct our clinical trials; ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations; if we receive regulatory approval of Lomecel-B™ or any of our other product candidates, we will be subject to ongoing regulatory requirements and continued regulatory review, which may result in significant additional expense; being subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our therapeutic candidates; reliance on third parties to conduct certain aspects of our preclinical studies and clinical trials; interim, “topline” and preliminary data from our clinical trials that we announce or publish from time to time may change as more data become available and are subject to audit and verification procedures that could result in material changes in the final data; the volatility of price of our Class A common stock; we could lose our listing on the Nasdaq Capital Market; provisions in our certificate of incorporation and bylaws and Delaware law might discourage, delay or prevent a change in control of our company or changes in our management and, therefore, depress the market price of our Class A common stock; we have never commercialized a product candidate before and may lack the necessary expertise, personnel and resources to successfully commercialize any products on our own or together with suitable collaborators; and in order to successfully implement our plans and strategies, we will need to grow our organization, and we may experience difficulties in managing this growth. 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, 2023, filed with the Securities and Exchange Commission on February 27, 2024, as amended by the Annual Report on Form 10-K/A filed March 11, 2024, its Quarterly Reports on Form 10-Q, and its Current Reports on Form 8-K. The forward-looking statements contained in this press release are made as of the date of this press release, 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 Contact:
Derek Cole
Investor Relations Advisory Solutions
derek.cole@iradvisory.com

Media Contact:
Andrea Cohen
Sam Brown Inc. Healthcare Communications
andreacohen@sambrown.com
(917) 209-7163

Photos accompanying this announcement are available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/e9e96d9c-d6c3-4aec-ba85-36631b520211
https://www.globenewswire.com/NewsRoom/AttachmentNg/f106bde7-972a-4687-a91e-03e924f409fc
https://www.globenewswire.com/NewsRoom/AttachmentNg/cfb4911d-2b0b-4c52-b2fa-b6982947155d

FAQ

What were the key results of Longeveron's CLEAR MIND Phase 2a trial for Lomecel-B™ in Alzheimer's Disease?

The CLEAR MIND Phase 2a trial showed that Lomecel-B™ improved cognitive function, quality of life, and brain volume in mild Alzheimer's Disease patients. It demonstrated a 49% reduction in brain volume loss and potential reduction in neuroinflammation compared to placebo.

How many patients were involved in Longeveron's CLEAR MIND Phase 2a trial for LGVN?

The CLEAR MIND Phase 2a trial involved a total of 48 patients, with 36 treated with Lomecel-B™ and 12 receiving placebo.

What regulatory designations has Lomecel-B™ received from the FDA for Alzheimer's treatment?

The FDA has granted Lomecel-B™ both Regenerative Medicine Advanced Therapy (RMAT) designation and Fast Track designation for the treatment of mild Alzheimer's Disease.

When and where were Longeveron's CLEAR MIND trial results presented for LGVN?

Longeveron presented the CLEAR MIND Phase 2a trial results at the Alzheimer's Association International Conference® (AAIC) held from July 28 to August 1, 2024, in Philadelphia and online.