Longeveron Inc.

Ladies and gentlemen, thank you for standing by. Welcome to Longevron 2022 Second Quarter Earnings School. My name is Irene and I will be coordinating this event. If you would like to ask a question on today's call, please press star followed by one on your telephone keypad. If you change your mind, please press star followed by two. I would now like to turn the conference over to our host, Elsie Yao from Stern Investor Relations. Elsie, please go ahead.

Thank you, operator. Good morning, everyone, and welcome to Longevron's second quarter 2022 call. Today, we will provide a business update and discuss financial results for the second quarter of 2022. Earlier this morning, we issued a press release with these results, which can be found under the investors section of our website at www.Longevron.com. I am joined today on the call by the following members of Longevron's management team. Dr. Chris Min, Interim Chief Executive Officer and Chief Medical Officer, Dr. Joshua M. Hare, Co-Founder, Chief Science Officer and Chairman, and James Covijo, Chief Financial Officer. Dr. Min will begin with a brief corporate overview followed by a review of updates from the Aging Frailty Program, including Rogevron's updated strategy in Japan and the data from the Phase 1-2 HARA trial. Then Mr. Covijo will review our 2022 second quarter financial results. Last, we will open the call for Q&A. As a reminder, during this call, we will be making forward-looking statements which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any such statements should be considered in conjunction with cautionary statements in our press releases and risk factor discussions in our filings with the SEC. including our annual report on Form 10-K and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information. Now I'd like to turn the call over to Dr. Chrisman, Interim Chief Executive Officer and Chief Medical Officer of Long Job Iran. Chris?

Thank you, Elsie. Good morning, everyone. Welcome to Longevron's second quarter 2022 business update and financial results call. Longevron is a leading clinical stage biotechnology company developing living cell therapies for chronic aging related diseases and other specific life threatening conditions. At Longevron, our mission is to develop safe and effective cell based therapies for some of the most challenging disorders associated with the aging process and other medical disorders. As a reminder, our lead investigational product is called LomaCellB, and it's a living cell product made from specialized cells isolated from the bone marrow of young healthy donors ages 18 to 45. These specialized cells are known in the literature as medicinal signaling cells, or MSCs, and are essential to our endogenous or built-in repair mechanism. MSCs are known to perform a number of complex functions, including the ability to form new tissues. They also home to sites of injury or disease and secrete bioactive factors that are immunomodulatory and regenerative. We believe that Lomacil-B has multiple mechanisms of action that may lead to an anti-inflammatory, provascular, and regenerative responses, and therefore may have broad applications for a range of aging-related and rare diseases. In the second quarter of 2022, we continue to make progress advancing Limba Cell B for our suite of aging and rare disease indications. We have ongoing trials in Alzheimer's disease, hypoplastic left heart syndrome, or HLHS, and acute respiratory distress syndrome, or ARDS. We are also advancing Limba Cell B for aging frailty. First, I'll start with a brief update on our program for Alzheimer's disease. Neuronal cell death caused by early and substantial neuroinflammation is a significant contributor to the pathogenesis of Alzheimer's disease. In preclinical models of Alzheimer's disease, MSCs like LomasLB have been shown to cross the blood-brain barrier, potentially with an anti-inflammatory effect, improving endothelial function and promoting neurogenesis, the process of new neuron formation in the brain. The phase one study demonstrated the preliminary safety of LomasLB in patients with mild to moderate Alzheimer's disease. While it was a small study, the data also appeared to show a slower decline in many mental state exam score, a tool used to assess cognitive function in patients who received a low dose of Lomacil-B compared to placebo. Based on that study and a growing body of preclinical and clinical evidence, we believe Lomacil-B may prevent slow or even reverse the clinical progression of Alzheimer's disease by reducing disease-related brain inflammation. And this morning, we are pleased to announce that we have achieved the 50% enrollment threshold in our ongoing Phase 2A trial of LOMOS-LB for patients with mild Alzheimer's disease, having enrolled 24 of our anticipated 48 patients. The Phase 2A trial is a forearm, parallel-designed, randomized, and placebo-controlled clinical trial of LOMOS-LB in Alzheimer's patients. The primary endpoint of the trial is the safety of single and multiple infusions of LOMO cell B at two different dose levels, 25 million and 100 million cells. Secondary and exploratory endpoints include brain volume by MRI, biomarkers relevant to inflammation and endothelial vascular systems, and measures of cognitive function. And we are on track to complete enrollment by the end of 2022. And next, I'll move to an update of our HLHS program. As a reminder, HLHS is a rare congenital heart defect that affects approximately 1,000 infants per year in the United States. Patients born with HLHS have an underdeveloped or absent left ventricle, impairing the heart's ability to pump blood. Left untreated, this condition is always fatal. Currently, standard of care is comprised of three reconstructive operations before the age of five, an extraordinary treatment burden for these young pediatric patients. Further, even with these surgical interventions, children with HLHS are at elevated risk of short-term mortality, delayed development, and long-term complications, including organ failure. We have heard from physicians the tremendous unmet need for additional interventions beyond the current standard of care and hope that LomaCell B, with its pro-regenerative, pro-vascular, and anti-inflammatory properties, when administered concurrently with surgical intervention, can fill that gap by improving cardiac performance in patients with HLHS. Last year, the FDA recognized the high unmet need in HLHS, as well as the promising preliminary clinical data from our open-label Phase I ELPIS trial, granting orphan drug and rare pediatric designations to LOMOS-LB for this indication. That trial, the ELPIS-1 trial results, showed that intramarital injection of LOMOS-LB was well-tolerated with no major adverse cardiac events one year post-surgery and no treatment-related infections considered to be related to limbless LB. Further, secondary endpoints suggested that limbless LB may improve long-term patient clinical outcomes. There were no deaths and no need for heart transplants for the 12 months of the study. We also saw no statistically significant deterioration in cardiac structure or function at six and 12 months post-surgery. These patients were followed subsequently for up to 3.5 years after surgery, and none of the participants required a heart transplant. Building on the promising results of ELPAS-1, we have advanced LUMOS-LB into ELPAS-2, a phase 2A trial in which we are now actively enrolling patients. ELPAS-2 is a 38-patient, randomized, blinded, and controlled trial designed to evaluate the safety and efficacy of LUMOS-LB for patients with HLHS undergoing stage two reconstructive cardiac surgery. The primary endpoint is a change in right ventricular ejection fraction, a key measure of cardiac function at 12 months post-treatment. We anticipate enrollment will continue into 2023. Finally, I'd like to cover updates on our aging frailty program, including an in-depth review of the data from our HERA trial that was announced this morning. Aging frailty is an age-associated decline and reversal in a function across multiple physiologic systems that leads to an inability to cope with stressors. This is common among the elderly, affecting millions of individuals in the United States and up to 15% of the population over the age of 65, depending on the specific clinical definition used. Aging frailty manifests typically as a combination of several signs and symptoms that may include sarcopenia or involuntary loss of muscle, associated weakness, fatigue, weight loss, slowness, and low activity. Unfortunately, elderly frail individuals are more vulnerable to poor clinical outcomes related to aging frailties such as infection, falls, fractures, hospitalizations, and even death. At Longevron, we have been evaluating the effect of Lomacil-B that it may have on the health and function of elderly frail patients particularly on their physical and immune system function. In early-stage exploratory trials, we have been measuring biomarkers of inflammation and vascular endothelial function. First, I'll start with an overview of our new clinical development strategy in Japan. Japan has one of the oldest populations in the world, and in 2020, there were over 36 million citizens who are aged 65 years or older, or nearly 29% of the population, and as predicted by 2030, one in three citizens will be elderly. The prevalence of frailty in that age group is approximately 8.7%. Further, the Japanese Pharmaceutical and Medical Devices Agency or PMDA has established a supportive regulatory framework through the Act on the Safety of Regenerative Medicine or ASRM that recognizes the tremendous therapeutic potential of cell therapies. A potential ASRM approval could enable us to enter the Japanese market based on demonstrated safety in Japanese patients with an expectation of efficacy, which can be established through the conduct of a small, well-controlled trial combined with our previous data in aging frailty. Such an approval would allow us to administer LomasLB as a treatment for aging frailty at select clinical sites, addressing a crucial unmet need amongst the Japanese population. As a result, we have re-evaluated our regulatory strategy in Japan to capitalize on the near-term value-driving market opportunity In collaboration with our clinical partners at the National Center for Geriatrics and Gerontology in Nagoya and Jintendo University Hospital in Tokyo, we amended our Phase II trial to change the primary objective to one examined of safety in low-missile B in Japanese elderly with aging frailty. The PMDA accepted the amendment on August 8, 2022, and we expect to dose our first patient by the end of 2022. Next, I'll move on to the results from our Phase I-II trial that were announced this morning. As a reminder, the HERA study was an exploratory trial supported by grants from the NIH and Maryland Stem Cell Research Fund to explore the safety of LMSLB when used in combination with high dose influenza vaccine in older frail individuals. A total of 40 patients were enrolled over two flu seasons, over which two different formulations of the vaccine high dose flu zone were administered, one for each season. The trial measured biomarkers designed to assess whether LomaCellB augmented immune responses following influenza vaccination. This biomarker evaluation was performed with descriptive statistics, and the study was not powered to make definitive conclusions. Today, we announced that the study met its primary safety endpoint with no treatment emergent SAEs within 30 days of LomaCellB infusion, as well as an examination of various safety labs. To evaluate the immune response, we used strain-specific hemagglutination inhibition antibody titer measurement assays over the two flu seasons. Because the Colorado variant of flu was the only strain common in the HD flu zone formulations across those two seasons, we chose to focus our results on this strain. And there was no statistically different response in HAI antibody responses in the LOMOS-LB group when compared to placebo. Interestingly, we observed a 91% increase in HA antibody response to KUKET strain that was not a component of high-dose Luzon in the LOMOS-LB group compared to placebo, representing a possible heterotypic response. This indicates that LOMOS-LB may be stimulating the immune system in a nonspecific way. To further complement these findings, we will be conducting additional immunological studies of samples obtained during the study to evaluate the response of B cells and T cells, immune cells that mount the antibody response to vaccination. In addition to the immune response, we also evaluated several measurements of aging frailty and found that participants receiving LOMO cell B had an increase at the one-year time point in the patient-reported outcomes measurement information system, or PROMIS, physical function instrument compared to a decrease in the placebo group. The promised physical function instrument is designed to measure items over a wide range of function, from self-care to strenuous activities. In addition, at six months, the Lomas Hill Bee Treatment participants had an average change in the six-minute walk test that was 18 meters greater than the participants receiving placebo, which was similar in magnitude to our previous studies, although they did not appear to be statistically significant. While not the primary goal of the trial, these findings support previous findings from our Phase I and Phase IIb trials of Lomacil-B and aging frailty. In summary, we are highly encouraged by these exploratory findings. First, the small study supports the safety of Lomacil-B in combination with flu vaccines like high-dose Fluzone in the aging frailty population. Second, though the study was not sufficiently power to evaluate immune response, We did see preliminary evidence that LomaCellB may have a biologically relevant supportive impact on the immune system. And lastly, the data provided additional evidence that LomaCellB's potential effects on improving key measures of aging frailty, like the promised physical function and change in six-minute walk tests, are present. Based on these data, we plan to pursue additional studies of the immune system using a sophisticated B and T cell sorting to explore specific populations of such cells and anticipate publishing the full study results in a peer-reviewed journal in the future. With that, I'd like now to turn the call over to James Clavijo, Chief Financial Officer, to discuss our financial results for the second quarter of 2022. James? Thanks, Chris.