Longeveron Announces Additional Positive Clinical Data and Imaging Biomarker Results from the CLEAR MIND Phase 2a Trial of Lomecel-B™ in the Treatment of Mild Alzheimer’s Disease

• New clinical data showed that Lomecel-B™ improved cognitive function in multiple measures in a dose-response fashion
• Caregiver ratings documented improved quality of life in Lomecel-B™ treated patients
• MRI Biomarker study data showed that Lomecel-B™ countered loss of brain volume in multiple areas associated with Alzheimer’s disease, reduced brain neuroinflammation and improved cerebral blood flow
• Overall results confirmed the drug product’s therapeutic potential in the treatment of mild Alzheimer’s disease and support further development

MIAMI, Dec. 20, 2023 (GLOBE NEWSWIRE) — Longeveron Inc. (NASDAQ: LGVN) (“Longeveron” or “Company”), a clinical stage biotechnology company developing cellular therapies for life-threatening and chronic aging-related conditions such as hypoplastic left heart syndrome (HLHS), Alzheimer’s disease and Aging-related Frailty, today announces additional new clinical and biomarker results from its Phase 2a CLEAR MIND trial of its investigational product Lomecel-B™ for the treatment of mild Alzheimer’s disease.

The expanded data set reinforced the earlier top-line findings showing that the primary safety endpoint was met and provided further support for Lomecel-B’s positive benefit/risk profile. Additional analysis of cognitive function and daily living data consistently showed favorable results with Lomecel-B™ over placebo in a dose-response fashion, with administration of Lomecel-B™ associated with slowing and in some cases improving certain measurements of cognitive function (MoCA, MMSE). New analyses of imaging data measured using MRI showed that administration of Lomecel-B™ was associated with reduced neuroinflammation assessed by Diffusion Tensor Imaging (DTI), and also appeared to counter loss in brain volume in areas associated with Alzheimer’s disease (TBV, hippocampus, ventricles, thalamus).

Wa’el Hashad, CEO of Longeveron, commented: “These new data support our initial results for CLEAR MIND that we announced in October and provide further validation of both the safety and therapeutic potential of Lomecel-B™ in the treatment of mild Alzheimer’s disease. We believe these new data may provide evidence for Lomecel-B’s mechanism of action and add to the robust foundation we are building for its further investigation in Alzheimer’s disease as well as other indications. We anticipate presenting the CLEAR MIND results in a major medical meeting in 2024.”

Summary of new findings:

The latest data further supports the prior findings regarding Lomecel-B’s potential prevention of cognitive decline and improvement in quality of life. In addition to these clinical findings, brain imaging showed improvement in brain architecture measured by volumetric MRI and DTI, respectively.

• Lomecel-B™ (25M x 1 dose, p=0.009) and the pooled treatment group (25M x 1 dose, 25M x 4 doses, 100M x 4 doses, p=0.015) demonstrated statistically significant improvements in the Montreal Cognitive Assessment (MOCA), relative to placebo
• Lomecel-B™ demonstrated a dose-response improvement in Mini-Mental State Examination (MMSE) relative to baseline (mean + SD increase: 3.0+3.6 at highest dose, 39 weeks, p=0.028)
  Lomecel-B™ (100M x 4 doses) demonstrated a higher level of improvement in quality of life observed by caregiver and measured by Alzheimer’s Disease Related Quality of Life scale (ADRQOL).

Neuronal loss in Alzheimer’s disease leads to a common feature of disease such as progressive atrophy resulting in reduction in brain volume and cortical thickness that can be measured with volumetric MRI. Brain tissue loss begins with reduction in temporal lobes structures such as hippocampus followed by atrophy in other parts of the brain (parietal, frontal).

• Lomecel-B™ (100M x 4 doses) reduced the whole brain volume loss by 49% (p=0.034)
  Lomecel-B™ (25M x 1 dose, p=0.015) and the pooled treatment group (25M x 1 dose, 25M x 4 doses, 100M x 4 doses, p=0.038) demonstrated statistically significant reductions in left hippocampal volume loss at Week 39 relative to placebo (Degree of reduction was 84% for 25M x 1 dose).
• Brain volume preservation in the Lomecel-B™ (100M x 4 dose) dose group was accompanied by 20% and 33% reduction in left and right ventricular enlargement at Week 39 compared to placebo, respectively.
• The level of neuroinflammation measured by DTI was lower in all Lomecel-B™ doses at Week 39 compared to placebo.

Taken together, the Company believes the results of the CLEAR MIND study build a strong foundation for further development in mild Alzheimer’s disease patients.

CLEAR MIND Results:

Overall, Lomecel-B™ appeared to demonstrate a positive benefit/risk profile. The primary endpoint of safety was met based on statistical and medical assessment.

The study safety data were consistent with an established safety profile with no incidence of hypersensitivity, infusion-related reactions, no cases of Alzheimer Related Imagine Abnormalities of Edema (ARIA-E) or microhemorrhages and superficial siderosis (ARIA-H) on Magnetic Resonance Imaging (MRI), and no notable changes in laboratory evaluations and electrocardiogram (EKG).

The secondary endpoint of change from baseline to Week 39 in CADS, demonstrated positive results, at the prespecified statistical level of p<0.1, 2-tailed:

• Statistically significant improvement at Week 39 in CADS was observed for the Lomecel-B™ 25 x 10⁶ cells (25M) x 1 dose (p=0.091) versus placebo and for the pooled Lomecel-B™ Groups (25M x 1 dose, 25M x 4 doses, 100 x 10⁶ cells (100M) x 4 doses) (p=0.099).

In terms of the specific components of the CADS score, evaluated at p<0.05, 2-tailed:

• Lomecel-B™ (25M x 1 dose) demonstrated statistically significant slowing of disease progression in left hippocampal volume (p=0.015) relative to placebo

• ADCS-ADL and left hippocampal volume at Week 39 were statistically significant for the pooled Lomecel-B™ treatment groups (25M x 1 dose, 25M x 4 doses, 100M x 4 doses) relative to placebo (p=0.047) and (p=0.038), respectively

• Other doses demonstrated numerical slowing and prevention of disease worsening relative to placebo in CADS, ADAS-cog-13, CDR-SB, ADCS-ADL and left hippocampal volume at Week 39

About The CLEAR MIND Study

The trial was designed to study Lomecel-B™ Effects on mild Alzheimer’s disease: A Randomized, Double-Blinded, Placebo-Controlled Phase 2 Trial (NCT05233774), named the CLEAR MIND trial. The trial included a total of 50 patients 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, 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 trial was designed to test three different dosing regimens of Lomecel-B™ vs. placebo, and patients were randomized in a 1:1:1:1 ratio. The following doses were studied: Lomecel-B™ at a dose of 25 x 10⁶ cells (25M) on Day 0, followed by placebo infusions at Week 4, Week 8 and Week 12; Lomecel-B™ at a dose of 25M administered on Day 0, Week 4, Week 8, and Week 12 for a total of 4 doses; and at a dose of 100 x 10⁶ cells (100M) administered on Day 0, Week 4, Week 8, and Week 12, for a total of 4 doses.

The trial randomized 50 patients (49 were treated) and was conducted at 10 centers in the U.S. The primary endpoint of the trial is safety as measured by the occurrence of serious adverse events (SAEs) within the first 30 days after each administration of Lomecel-B™.

In consideration of the study sample size (N=49 patients), the study employed a novel global statistical test approach known as a Composite Alzheimer’s Disease Score (CADS, which is accepted and increasingly used by the scientific community for AD clinical trials). The CADS served as the secondary outcome measure of the trial and combined information across cognitive, functional capacity and brain MRI domains.

The Secondary Endpoint definition is the change from baseline to Week 39 in the CADS. This score comprised of ADAS-cog-13, ADCS-ADL, CDR-SB, and left hippocampal volume (normalized for intercranial volume).

For efficacy analysis, testing of the secondary endpoint proceeded using a pre-specified, two-sided alpha of 0.1. If statistical significance was achieved at this level for any dose comparison, the study was considered positive and supportive of further study of Lomecel-B™ in a larger, higher-powered study. The individual components of the CADS were evaluated at two-sided alpha of 0.05.

Exploratory endpoints included cognitive evaluation (MMSE, MOCA), quality of life (ADRQOL), brain volumetry (vMRI), other imaging modalities, and biomarkers relevant to inflammation and vascular function.

Assessment Scales

ADAS-cog-13 — Alzheimer’s Disease Assessment Scale-Cognitive 13
CDR-SB ― Clinical Dementia Rating Scale Sum of Boxes
ADCS-ADL — Alzheimer’s Disease Cooperative Study Activity of Daily Living
ADRQOL — Alzheimer’s Disease Related Quality of Life
DTI — Diffusion Tensor Imaging
MMSE — Mini-Mental State Examination
MOCA — Montreal Cognitive Assessment

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 advancing Lomecel-B™ through clinical trials in three indications: hypoplastic left heart syndrome (HLHS), Alzheimer’s disease, and Aging-related Frailty. Additional information about the Company is available at www.longeveron.com.

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. 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, statements about the ability of Longeveron’s clinical trials to demonstrate safety and efficacy of the Company’s product candidates, and other positive results; the timing and focus of the Company’s 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 the Company’s product candidates, including its estimates of the number of patients who suffer from the diseases being targeted; the success of competing therapies that are or may become available; the beneficial characteristics, safety, efficacy and therapeutic effects of the Company’s product candidates; the Company’s ability to obtain and maintain regulatory approval of its product candidates in the U.S., Japan and other jurisdictions; the Company’s plans relating to the further development of its product candidates, including additional disease states or indications it may pursue; the Company’s plans and ability to obtain or protect intellectual property rights, including extensions of existing patent terms where available and its ability to avoid infringing the intellectual property rights of others; the need to hire additional personnel and the Company’s ability to attract and retain such personnel; the Company’s estimates regarding expenses, future revenue, capital requirements and needs for additional financing; the Company’s need to raise additional capital, and the difficulties it may face in obtaining access to capital, and the dilutive impact it may have on its investors; market and other conditions; the Company’s financial performance and ability to continue as a going concern, and the period over which it estimates its existing cash and cash equivalents will be sufficient to fund its future operating expenses and capital expenditure requirements. 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, 2022, filed with the Securities and Exchange Commission on March 14, 2023 and its Quarterly Reports on Form 10-Q filed with the SEC. 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
Mike Moyer
LifeSci Advisors
Tel: 617-308-4306
Email: mmoyer@lifesciadvisors.com