Working to Address Unmet Needs in Alzheimer Disease With Lomecel-B Cell Therapy

This is the second part of an interview with Joshua M. Hare, MD, FACC, FAHA. For the first part, click here.

Joshua M. Hare, MD, FACC, FAHA

Longeveron recently presented data from the phase 2a CLEAR MIND trial (NCT05233774), which evaluated Lomecel-B for the treatment of Alzheimer disease (AD), at the 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 2nd in Philadelphia, Pennsylvania. During the conference, CGTLive® spoke to Joshua M. Hare, MD, FACC, FAHA, the cofounder, chief science officer, and chairman of Longeveron, and a professor of medicine at Miller School of Medicine, University of Miami, about unmet needs in AD and how lomecel-B may help to address these unmet needs.

In the interview, Hare emphasized the promising safety profile of lomecel-B. He additionally touched on some early signs of efficacy, but pointed out the need for a larger study to gather more data.

CGTLive: Can you discuss the unmet needs in AD and how lomecel-B may help to address these needs?

Joshua M. Hare, MD, FACC, FAHA: AD affects many millions of Americans and up until recently, there have been no disease-modifying treatments whatsoever. It's only recently, in the last year or so that we've seen the approval of a class of medicines that modify the disease by removing amyloid plaques from the brain. They're monoclonal antibodies. These drugs have been a long time coming and are very exciting to have on the market, but their effect is not curative. They slow the progression of the disease, but they affect only 1 component of the disease, which is the deposition of the amyloid fibrils. There remains a very large unmet need for drugs that perhaps improve outcomes, perhaps have a safety profile that's different or better and address different mechanisms of action, and that's where lomecel-B comes in.

We entered the area because of the immunomodulatory effects that lomecel-B has. Lomecel-B is a living human stem cell that's derived from adult bone marrow. It's a cultured cell and it can be used as an allograft, so it's immunoprivileged, and that makes it very versatile because it's essentially an off-the-shelf drug. You don't have to prepare a new batch each time you want to treat a patient. You can make large batches and use them without concern of immunorejection. One of the key things that lomecel-B and other drugs of its class do is a very powerful yet balanced and safe immunomodulatory effect.

Now, because we know another big target in AD is neuroinflammation, we thought several years ago that this would be a very good hypothesis to test, where the lomecel-B is administered just intravenously—not even directly into the central nervous system, but rather a systemic infusion of lomecel-B—could have favorable effects on neuroinflammation and clinical outcomes of patients.

Is there anything else you want to share about the data from CLEAR MIND presented at AAIC?

The one thing I do want to emphasize is the safety profile. Other classes of drugs produce a condition called Alzheimer's related imaging abnormality (ARIA). It was first detected on MRI and it corresponds to either brain edema or hemorrhage in the brain, and it can be clinically significant. This is a concern. We're developing classes of drugs that are effective but also have a high risk factor profile. So we were very pleased with with lomecel-B, there's no evidence of ARIA. The risk profile is excellent because the risk is so low of the lomecel-B infusions. One of the key things that we did in the study, just to emphasize, is repeat dosing. Recurrent dosing with lomecel-B is just as safe as a single administration.

What about the efficacy data? Were the changes representative of what you think might be clinical benefit?

It's a bit early to say that. Of course, this is a small study with 49 patients and not really powered for this, but we are intrigued by the fact that there is directional, actual improvement in some of the cognitive scores... not just a slowing of decline, but actually an increase towards the positive direction in the MMSE and the MoCA scores. So, these are very early days, and we don't want to [read too into] it too much, but we're very excited about that. Of course, we'll be looking at that very carefully in the next larger study that we do, which will be powered around the efficacy end point... If we have an agent here that can actually improve cognitive function in the mild AD patients, that would be a very exciting outcome, one very clinically meaningful for affected patients and their families.

This transcript has been edited for clarity.

REFERENCES
1. Rash BG, Ramdas KN, Agafanova N, et al. The CLEAR MIND Study: Results from a Phase 2a Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Lomecel-BTM in Mild Alzheimer’s Disease Dementia. Presented at: 2024 AAIC, July 28-August 2; Philadelphia, Pennsylvania.