Longeveron Inc. (LGVN) Earnings Call Transcript & Summary

Greetings, and welcome to the Longeveron Data Call. [Operator Instructions]. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Tom Johnson, Director with LifeSci Advisors. Thank you, Tom. You may begin.

Thank you, operator. Good morning, everyone, and welcome to Longeveron's conference call to discuss top line results from a Phase IIa clinical trial of Lomecel-B in the treatment of Alzheimer's disease, known CLEAR MIND trial. Earlier this morning, we issued a press release with the top line results, which can be found on the Investors section of our website. I'm joined on the call today by the following members of Longeveron's management team. Mr. Wa'el Hashad, Chief Executive Officer; Dr. Nataliya Agafonova, Chief Medical Officer; Dr. Josh Hare, Chief Science Officer and Founder; and Lisa Locklear, Chief Financial Officer. Mr. Hashad will begin with a brief review of the data about the top line results, and Dr. Agafonova will walk through the details. Following the data review, we will open the call up to questions. As a reminder, during this call, we will make forward-looking statements, which are subject to various risks and uncertainties, which could cause our actual results to differ materially from these statements. Any such statements should be considered in conjunction with the cautionary statements in our press release and risk factors discussed in our filings with the SEC, including our quarterly reports on Form 10-Q and annual report on Form 10-K and cautionary statements made during this call. We assume no obligation to update these forward-looking statements or information. Now I'd like to turn the call over to Mr. Wa'el Hashad, Chief Executive Officer of Longeveron. Wa'el?

Thank you, Tom. Hi, everyone. Good morning. Thank you for joining us early in the day. We are very excited about sharing with you the results of Phase IIa CLEAR MIND study from Lomecel-B and Alzheimer's dementia. Today, as you have seen in our press release, we announced the top line results. We met our primary endpoints in terms of safety endpoints, which reinforces the safety profile of Lomecel-B. And in addition to that, we also show a positive and statistically significant in key secondary end points, both at the composite CADS score as well as the components of the CADS scores. And Nataliya -- Dr. Nataliya Agafonova, she will share with you in more details all the results. And with that, I will turn it to Nataliya,and then I will make closing comments and [indiscernible] some questions -- thank you.

Thank you so much, Wa'el, and good morning, everyone. I'm here to present the results of top line result data of our study CLEAR MIND. Here, you can see the study design. This is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of Lomecel-B in patients with mild Alzheimer’'s disease. The study duration was 45 weeks which included 6 weeks screening period, 12 weeks of treatment period and [ 3 to 7 ] weeks follow-up period. Study population included patients of 60 to 85 years old. This mild Alzheimer’'s disease, which was defined by National Institute of Health Alzheimer Association criteria. This Mean-Mental score of 18 to 24, which is the score consistent with mild cognitive impairment excluded all other causes of dementia rather than Alzheimer's disease by brain MRI and confirmed by amyloid PET scan. Patients were randomized to 4 groups with ratio 1:1:1:1 with 12 patients per group. Group I included patients who received placebo at day 0, week 4, 8 and 12; Group II included patients received 25 million cells, which we consider low dose and at day 0, followed by placebo at week 4, 8 and 12; Group III included patients who received Lomecel-B in dose of 25 million calls at week 0, 4, 8 and 12 and Group IV consists of a group of patients who received Lomecel-B in dose of 100 million cells, which we consider high dose at day 0 and week 4, 8 and 12. During the treatment period and after the last infusion of study groups, all patients were evaluated for safety by measuring MRI to evaluate Alzheimer’-related imaging abnormalities, neurological assessment, electrocardiogram, laboratory evaluation, collecting adverse event and for efficacy by measuring clinical scales, quality of life for patients and caregivers and multiple biomarkers, imaging and fluid biomarkers. Primary endpoint was safety and I'd like to say a couple of words about our secondary endpoint. In consideration of this study sample size, which was 49 patients, the study employed the novel global statistical test approach known as the Composite Alzheimer's Disease Score or CADS, which is accepted and increasingly used by the scientific community for Alzheimer’'s disease clinical trials. Secondary endpoint was a cognitive endpoint, which comprised of the measure of the patient's cognitive assessment, adopt cognitive 13, measure of dementia -- Clinical Dementia Rating Scale Sum of Boxes, measure of Activity of Daily Living, ADCS-ADL, which is the [ indiscernible ] of the [ future ] observation of patient's behavior during the period of 4 weeks and measure of left hippocampal volume, which play a key role in forming memory and the hippocampus is 1 of the first areas to be affected by the Alzheimer’s disease. Here, you can see a summary of baseline [indiscernible] demographic [indiscernible] were consistent across the treatment groups, near age was mid-70s across all groups and overall, this is slightly low average in Group III of age 70. The sample consists of 65% female, 45% males, 96% whites and 4% black and 75% Hispanic with each of these trends approximately equivalent across all treatment groups. Mean body mass index was also consistent across the treatment groups, ranging from 27 to 30. Primary safety endpoint was defined as a rate of serious adverse events 4 weeks after each infusion. The study met primary endpoint based on statistical and medical evaluation. Let me walk you through this. 1 SAE after each infusion for each active treatment group was reported -- reported and none for placebo. 1 serious adverse event onset was after infusion 3 and the other 2 onsets after infusion 4. Confidence interval of placebo ranges from 0 to 26.5. Lower confidence limits of each active arm is less than 26.5%. So there is an overlap of confidence intervals for placebo and each active group. This overlapping gives us a lot of statistical support for concluding a difference in serious adverse event III given 4 weeks of the infusion between placebo and active treatment goals. However, this trial is not efficiently powered to detect such an effect. So the results should be used only as a supplement to expert medical and clinical judgment for determination of the endpoint in this trial. Therefore, the quantitative overview of each serious adverse event was done. These 3 serious adverse events are heterogeneous, there is no cluster of each event in 1 system organ class and each serious adverse event was a worsening of preexisting conditions. Also, the incidence of our serious adverse events is low. Each of the 3 patients received full 4 infusions and have no dose interruptions or infusion reactions. None of these patients discontinuee study earlier. None of these patients had abnormal neuro exam results or MRI Alzheimer’-related image and abnormality findings. In addition, each SAE was reviewed by Data Safety Monitoring Committee, with no safety issues raised. And I'd like to also note that 1 patient here is adverse event. was reported after infusion 4 in Group II, which occurred after placebo infusion. Most frequent treatment emergent adverse events were COVID-19 and urinary tract infection in 5 and 4 patients respectively. Review of the overall safety data showed that they were consistent with an established safety profile with no incidence of hypersensitivity, no causes of Alzheimer-related imaging abnormality, no clinically asymptomatic microhemorrhages as revealed by the MRI and no notable changes in laboratory evaluation and electrocardiogram. There were no deaths on the study reported. And now let me walk you through our secondary efficacy endpoints. And just to orient you, you can see on the right upper corner, the arrow, which points to a direction of improvement. The study was not powered for efficacy analysis, taking of the secondary end point preceded using a prespecified 2-sided alpha of 0.1. The statistical significance was achieved at this level for any dose comparison, the study was considered positive. The individual components of the composite endpoint were evaluated as 2-sided alpha of 0.05. You can see that statistically significant improvement at week 39 in composite endpoint was observed for the Lomecel low dose relative to placebo with p-value 0.091 and pooled Lomecel-B group relative to placebo with p-value 0.099. Lomecel-B also demonstrated statistically significant slowing of disease progression in less hippocampal volumes at week 39. In Lomecel low-dose treatment group relative to placebo with p-value 0.015 and pooled Lomecel-B treatment group relative to placebo with p-value 0.039. In addition, at week 39, numerical slowing of disease worsening in left hippocampal volume was observed in all Lomecel-B treatment groups relative to placebo. Lomecel-B demonstrated statistical significant improvement at week 39 in activity of daily lives. In Lomecel-B high-dose treatment group relative to placebo with p-value 0.04, in pooled Lomecel-B treatment group combining 2 doses relative to placebo with p-value of 0.03. In pooled Lomecel-B treatment group combining 3 doses relative to placebo 0.047. If dose responds to an improvement in activity of daily living at week 39 was also observed and all Lomecel-B treatment groups experienced greater improvement relative to placebo. All Lomecel-B treatment groups experienced greater benefit than placebo not statistically significant. And week 39 Dementia Score [ CDR-SB ] not statistical significant difference was observed between Lomecel-B dose and placebo for cognitive ADAS-cog-13 scale. In conclusion, I would like to say primary endpoint [ math ] based on statistical and medical evaluation, Lomecel-B is safe, well tolerated and comparable to placebo. Lomecel-B demonstrated [ benefits ] over placebo by preventing deterioration in cognitive and atrophic signals. We are absolutely encouraged by the findings from CLEAR MIND study on both safety and secondary endpoints. Also, we expect additional exploratory and biomarker data, and they will be available in [indiscernible]. The results of CLEAR MIND study provides a strong foundation for further development in mild Alzheimer’'s disease patient population. Thank you very much.

Thank you, Nataliya. I hope everyone have seen from the information and the data that's shared by Nataliya that the data is very encouraging considering the size of the trial. We're definitely very pleased with the outcome. You can see there is several measures of our cash components that have demonstrated value to the patients with Alzheimer -- mild Alzheimer's dementia. So without any further ado, we're going to open it up for questions, and then I will make some closing remarks at the end. Thank you.

We will now be conducting a question-and-answer session. [Operator Instructions] Our first question comes from Michael Okunewitch from Maxim Group. Michael?

Congrats on the data set. I'd like to first just get at the hippocampal volume endpoint and ask just, I guess, broadly in Alzheimer's disease, how closely correlated is the decline in hippocampal volume to progression of the disease at a functional level? And then do you have any indication of how clinically meaningful the change of decline between the Lomecel-B groups and the placebo was in this study?

Thank you so much, Michael. This is a very good question. And -- so first of all, as I mentioned, definitely, the changes in hippocampal volume, which is responsible hippocampus, especially left part which is responsible for forming memory. And patients with Alzheimer's disease observation is that the volume of left hippocampal is very sensitive to progression of disease and over time compared to the healthy population is extremely diminished. So the significance of our findings is that first of all, we were not powered even for this particular endpoint. And we see the strongest seasonal in preserving the function of hippocampus versus to placebo. So as you look at the data, you can see the -- I cannot guide the slide, but we can appreciate as placebo steadily declined which is basically a reflection in patient populations with Alzheimer’'s disease. But you can see clearly that all Lomecel-B arms remains steady and even improving slightly. So this is -- it's significant. So definitely, there is a vascular component of our products, which controls the patient with Alzheimer’'s disease. Did I answer your question?

Yes, very good answer. Then as a follow-up, I'd like to go a bit more and discuss a bit about strategy, and see if you could talk a bit about next steps -- based on these initial results, do you have any indication as to what kind of size you need for a subsequent study? And also, if you do decide to go the partnering route while, given your prior pharma experience, would you consider this data compelling enough to go and shop that around to big pharma?

That's a very good question. Michael, of course, as you know, we are just got the data within the last couple of days, and we wanted to share it externally as soon as we have it. So definitely, we need to work on more formal plans to approach both partnering and explore what is exactly the next step. I also want to remind you that we plan to share this data also with the FDA and then review it with them as well as part of the -- our plan to move forward. So there is a lot of things that we need to do before I give you a final answer. But definitely, partnering is in our plan. And do I believe that data is compelling enough to go and seek a partnership. I really do believe that. I think as Nataliya said, this trial was not powered to show any of these measures and the fact that we have some of these findings coming with strong signals here. I think that provides enough value to seek partnership. I also would tell you that the product also have demonstrated in both Phase I and Phase II now a very good safety profile, which really makes benefit-risk ratio very favorable. So well, definitely, the partnership is in our plan, but we don't have any final things yet. And of course, there's a lot that needs to be done in the next few weeks.

All right. And then just one last one for me, and I'll hop back into the queue. -- given the great safety profile as you just mentioned and also the novel mechanism of action within Alzheimer's, do you have any indication as to what the likelihood is that this is something that could be combined with the amyloid clearing antibodies? And is there any mechanistic rationale for a synergy there?

I'll have Nataliya add the medical one. Of course, I would tell you that just from being in the industry for a very long time, there is nothing that we should expect that prevent us from being combined with any of the monoclonal antibodies or any other things. As I said, that would be based on the medical judgment of treating physicians, we definitely need to demonstrate the value in our Phase III program and get the product approved first. But I don't see anything, and I see a value of combining it with any therapeutic option that could help the patients be better. And Nataliya, you can be more specific from a sense if you'd like to add more comments.

Thank you, Wa'el. So definitely, there are brain changes associated with Alzheimer disease besides better amyloid and tau protein pathology. So Lomecel-B may play like anti-inflammatory and perivascular regenerative [ pull ] to decrease inflammation and preserve brain functions, so that's mechanistically how we think at least at this point. But you never know what is going to happen in the future. Great idea. Thank you.

Right. Once again, congrats on the data.

Thank you Michael.

Thank you.

This concludes our question-and-answer session. I would like to turn the floor back over to Wa'el [ indiscernible ] for closing comments.

Thank you. Well, thanks, everyone, for coming to our conference today. And at short notice. As I said, we're extremely happy and pleased with the outcome of the Phase IIa CLEAR MIND study. We really believe it reinforces the safety profile of Lomecel-B and provide a solid foundation to build on for the secondary endpoints. We're also planning to share additional data both on the exploratory endpoints and the biomarker in few weeks, so stay tuned for that. And definitely, we plan to present this data in more details in scientific conferences in the future. In addition to that, we also plan to publish the outcome of the Phase IIa CLEAR MIND study in a scientific journal as well. So stay tuned for all of those things to come. Thank you very much to the entire Longeveron team who have really worked tirelessly to get to the outcome of this trial or the conclusion of this trial, and I look forward to discussing more of this in the future. Thank you, everyone, for attending today, and we'll talk soon.

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.