Greetings, and welcome to the Longeveron data call. At this time, all participants are in a listen-only mode. A brief question- and- answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. 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 the phase II-A clinical trial of Lomecel-B in the treatment of Alzheimer's disease, known as the CLEAR MIND trial. Earlier this morning, we issued a press release with the top line results, which can be found on the investor 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 recorded 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 II-A 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 term 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 endpoints 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. With that, I will turn it to Nataliya, and then I will make closing comments and definitely take some questions. Thank you. Nataliya?
Thank you so much. 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 six weeks screening period, 12 weeks of treatment period, and 27 weeks follow-up period. Study population included patients 60 to 85 years old with mild Alzheimer's disease, which was defined by National Institute on Aging-Alzheimer's Association criteria. With Mini-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 four groups, with ratio 1 : 1: 1 : 1, with 12 patients per group. Group 1 included patients who received placebo at day zero, week four, eight, and 12. Group 2 included patients received 25 million cells, which we consider low dose, at day zero, followed by placebo at week four, eight, and 12. Group 3 included patients who received Lomecel-B in dose of 25 million cells at week zero, four, eight, and 12. Group 4 consists of group of patients who receive Lomecel-B in dose of 100 million cells, which we consider high dose, at day zero and week four, eight, and 12.
During the treatment period and after the last infusion of study drugs, all patients were evaluated for safety by measuring MRI to evaluate Alzheimer's related imaging abnormalities, neurological assessments, electrocardiogram, laboratory evaluation, collecting adverse events, 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 words about our secondary endpoint... In consideration of the 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 composite endpoint, which comprised of the measure of the patient's cognitive assessment, ADAS cognitive performance, measure of dementia, dementia, Clinical Dementia Rating Scale, Sum of Boxes, measure of activity of daily living, ADCS-ADL, which is the caregiver observation of patient behavior during the period of four weeks, and measure of left hippocampal volume, which play a key role in forming memories, and the hippocampus is one of the first areas to be affected by the Alzheimer's disease. Here you can see a summary of baseline characteristics. Demographic characteristics were consistent across the treatment groups. Mean age was mid-70s across all groups and overall, with a slightly lower average in group 3 at age 70.
The sample consists of 85% female, 45% male, 96% White, 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 27-30. Primary safety endpoint was defined as a rate of serious adverse events four weeks after each infusion. The study met primary endpoint based on statistical and medical evaluation. Let me walk you through this. One SAE after each infusion for each active treatment group was reported and none for placebo. One serious adverse event onset was after infusion three, and the other two onset after infusion four. Confidence interval of placebo ranges from 0 - 26.5.
Lower confidence limit of each active arm is less than 26.5, so there is an overlap of confidence intervals for placebo and each active group. This overlap indicates a lack of statistical support for concluding a difference in serious adverse event rate within four weeks after infusion between placebo and active treatment groups. However, this trial is not sufficiently 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 three serious adverse events are heterogeneous. There is no cluster of each event in one system organ class, and each serious adverse event was a worsening of preexisting condition. Also, the incidence of serious adverse events is low.
Each of the three patients received full four infusions and had no dosing interruptions or infusion reactions. None of these patients discontinued study earlier. None of these patients had abnormal neural exam results or MRI Alzheimer-related imaging 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 one patient's serious adverse event was reported after infusion 4 in group 2, which occurred after placebo infusion. Most frequent treatment-emergent adverse events were COVID-19 and urinary tract infection, in five and four patients, respectively. Review of the overall safety data showed that they were consistent with an established safety profile, with no incidents of hypersensitivity, no cases 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 endpoint. 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, 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 of those comparisons, the study was considered positive. The individual components of the composite endpoint were evaluated at two-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 left hippocampal volume at week 39. In Lomecel-B 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 statistically significant improvement at week 39 in activity of daily life. In Lomecel-B high dose treatment group relative to placebo, with P-value 0.04. In pooled Lomecel-B treatment group combining two doses relative to placebo, with P-value 0.03. In pooled Lomecel-B treatment group combining three doses relative to placebo, 0.047.
A dose response and 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 in dementia score, CDR-SB. No statistical significant difference was observed between any Lomecel-B dose and placebo for cognitive ADAS-Cog cognitive testing scale. In conclusion, I would like to say primary endpoint met based on statistical and medical evaluation. Lomecel-B is safe, well tolerated, and comparable to placebo. Lomecel-B demonstrated benefit over placebo by preventing deterioration in cognitive and atrophy 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 the series. The results of CLEAR MIND study provide a strong foundation for further development in mild Alzheimer's disease patient population. Thank you very much.
Thank you, Nataliya. I hope everyone has 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 CADS components that have demonstrated value to the patients with Alzheimer's, 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.
Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we pull for questions. Our first question comes from Michael Okunewitch from Maxim Group. Michael, please proceed.
Hey there. Thank you for taking my question. Congrats on the data today.
Thanks, Michael.
Sure.
Thank you.
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 very good question. So first of all, as I mentioned, definitely the changes in hippocampal volume, which is responsible, hippocampus, especially left part, is responsible for forming memory. Patients with Alzheimer's disease, observation, is that the volume of left hippocampus is very sensitive to progression of disease. And, over time, compared to the healthy population, it's extremely diminished. So the significance of our findings is that, first of all, we were not powered even for, for this particular endpoint. And we see the strongest signal in preserving the function of hippocampus versus to placebo.
So if, if we look at the data, you can see there, I cannot drive the slide, but we can appreciate as placebo steadily decline, which is basically reflecting patient populations with with Alzheimer's disease. But you can see clearly that all Lomecel-B arms remain steady and even improving slightly. So this is significant. So definitely there is a vascular component of our product which can help the patients with Alzheimer's disease.
All right. Thank you for that.
Did I answer your question?
Yes, very good answer.
Thank you.
Then, as a follow-up, I'd like to go a bit more and discuss a bit about strategy, to see if you could talk a bit about next steps. Based on these initial results, d o you have any indication as to what kind of size you'd need for a subsequent study? And also, if you do decide to go the partnering route, while giving 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, we have it. So, definitely we need to work on a 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, and 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.
Do I believe the data is compelling enough to go and seek a partnership? I really do believe that. I think that, as Nataliya said, this trial was not powered to show any of these measures. The fact that we have some of these findings coming with, you know, strong signals here, I think that provides enough value to seek partnership. I also would tell you that the product also has demonstrated, in both phase one and phase two now, a very good safety profile, which really makes benefit-risk ratio very favorable. Well, definitely the partnership is on our plan, but we don't have any final things yet.
Of course, there is a lot that need to be done in the next few weeks.
All right. Thank you. And then just one last one from 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?
Yeah, so-
Go first, sorry.
I'll have Nataliya add the medical one. Of course, you know, 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 three program and get the product approved first. I don't see anything, and I see a value of combining it with any therapeutic option that could help the patients be better. Nataliya, you can be more specific from a science, if you'd like to add more comment.
Thank you, Wa'el. So definitely, there are brain changes associated with Alzheimer's disease, you know, besides beta- amyloid and tau protein pathology. So, Lomecel-B may play like, anti-inflammatory and neurovascular regenerative role to decrease inflammation and preserve brain function. So that's mechanistically how we think, at least at this point, but we never know what is going to happen in the future. Great idea. Thank you.
All right. Thank you very much for taking my questions. 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 Hashad 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 II-A CLEAR MIND study. We really believe it reinforces the safety profile of Lomecel-B, and provides a solid foundation to build on for the secondary endpoint. We're also planning to share additional data, both on the exploratory endpoints and the biomarker in a few weeks, so stay tuned for that. We definitely plan to present this data in more detail in scientific conferences in the future. In addition to that, we also plan to publish the outcome of the phase II-A CLEAR MIND study in a scientific journal as well. 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. I look forward to discussing more of this in the future. Thank you, everyone, for attending today, and we'll talk soon.