Longeveron Inc. Price & Performance (LGVN)

Following the company's prepared remarks, we will open the call to questions from With that, let me hand the call over to Wael Hashad, Chief Executive Officer. Thank you, Derek. Good afternoon, everyone, and thank you very much for joining us today.

We are very pleased to update you on highly productive year in 2024 and provide an overview of what to expect in potentially transformational 2025 for Longevron. As a reminder, for those of you newer to our story, Londervarone is a regenerative medicine company developing cutting edge cellular therapies. Our stem cell therapy, LAMA cell B or Laramastro cell, represents a pipeline and a product opportunity. That has delivered several positive initial results across five clinical trials and three indications. Phase one and two in Alzheimer's disease, Phase one and two in aging related frailty, and Phase one in HLHS or hypoplastic left heart syndrome a rare pediatric disease [indiscernible] The company development program for these three initial indications address U. S. Market opportunity of approximately $5 plus billion approximately 4,000,000,000 and up to $1,000,000,000 respectively. Longevron continued to make progress in 2024 with both the LAMA cell B and HLHS and Alzheimer disease programs. Hypoplastic left heart syndrome or HLHS is a key strategic priority for us. We believe the HLHS program has high probability of success and the shortest path to potential regulatory approval and commercialization across our pipeline. In 2024, we continue to advance enrollment in our ongoing Phase 2b study [indiscernible] Which is evaluating glomerulb as a potential adjunct treatment for HLHS.

APIS2 has now achieved more than 90% enrollment and we expect to complete enrollment in the second quarter of this year. Also importantly, ALPHUS-two is a pivotal and if positive acceptable for biological license application or BLA submission for full traditional approval. This significantly accelerates the potential regulatory and is supported by clinical data from ALPS II would allow us to initiate a rolling submission of a BLA with the FDA in 2020 We also continue to advance the Alzheimer disease program. Results from our CLEAR MIND Phase IIa clinical trial was presented in a featured research oral presentation at the twenty twenty four Alzheimer Association International Conference, AAIC. Based on the ClearMIND Phase IIa clinical data and prior Phase one data, the FDA granted Lumacel B Both Regenerative Medicine Advanced Therapy Designation, also known as RMAT, and Fast Track designation for the treatment of mild Alzheimer disease. LAMAISL B appeared to be the first cellular therapy candidate to receive our MAD designation for Alzheimer disease. With this data in hand, we anticipate meeting with the FDA later this quarter to review future clinical and regulatory strategy for continuing this important program. 2025 has the potential to be a transformative year for Longerbron with achieving clarity on Alzheimer's development pathway completing enrollment for the HLHS Phase two trial, which would establish a potential timeline for our first BLA submission.

Starting the year off well, in February, the international nonproprietary name INN Expert Committee of the World Health Organization approved lateromastrocell for the nonproprietary name of the company's cellular This naming approval is an important step in the development and the potential commercialization of Lomacell B. I am thoroughly excited by the opportunity for Loma B, Lonza B, Lonza B patients and our stockholders. With that, I will turn the call to Doctor. Agafinova to provide a updates on our clinical development program Nataya, Thank you, Rael, and good afternoon, everyone. Our stem cell therapy Lonicell B has multiple models of action that include provascular, pro regenerative, and anti inflammatory mechanism promoting tissue repair and healing broad potential applications across across a spectrum of disease areas. Based on positive initial data, Lonisil B programs have received five FDA designations. For the HLHS program, orphan drug designation, Fast Drug Designation, and rare pediatric disease designation. And for the Eizhanger disease program, our Generative Medicine Advanced Therapy RMAT designation, and Fast Track designation, each of which offers benefit for the program's development and regulatory process. As Wael mentioned, our HLHS program is a primary focus for us.

With the near term pathway to potential approval in a rare area of unclear unclear unmet medical needs. We are currently conducting a Phase IIb clinical trial [indiscernible] evaluating the potential of LUNISLB to improve right ventricular function and long term outcomes in pediatric patients with HLHS. LPS II is being conducted in collaboration with the National Lung and Blood Institute through grants from the National Institute of Health. We are very pleased to share that LPS II has now achieved over ninety percent enrollment. We expect to complete enrollment of this trial before the end of the second quarter and then we'll follow the patient's twelve months If results from LPS II are positive, we would be positioned to initiate a rolling BLA submission with the FDA 2026. Turning now to our ovarian disease program, This is also an area of significant unmet need. Nearly seven million Americans are living with Alzheimer's disease. It kills more than more people than breast cancer and prostate cancer combined. And there has not been great progress in this area. Between 02/2021, death from heart disease decreased two point one percent, while death from Alzheimer's disease increased one hundred and forty one percent Potentially helping provide a new option for this patient and their families is our mission.

And we are optimistic given the long history of the data to date. In 2024, data from ClearMIND Phase 2a clinical trial evaluating Lonicell B in Arzheimer disease were selected for a future research oral presentation at the twenty twenty four IZANIA Association International Conference. Held at the July. We are very excited about the trial positive results which we have reviewed previously. The trial achieved the primary safety and secondary efficacy endpoint and the clinical trial LumiCell B treated patients showed an overall slowing prevention of disease worsening compared to placebo. We believe the results from ClearMind's supports the therapeutic potential of Glomicel B in the treatment of mild Alzheimer disease and provided evidence based support of HERDA clinical development. Based on the data generated in our Phase one and Phase two AZZYNA clinical trials, in July the FDA has granted Lonicell B. Bor Regenerative Medicine Advanced Therapy, ARMAT, designation and Fast Track designation for the treatment of mild We plan to meet with the FDA in March to review the future clinical and regulatory to continue advancing this potentially important therapeutic option for patients living with Alzheimer disease. I will hand the call over to Lisa Leclair, our Chief Financial Officer to discuss our financial results for the year. [indiscernible] Thank you, Natalia, and good afternoon, everyone.

This afternoon, we issued a press release and filed our annual report on Form 10 ks, both of which present our financial results in detail.

So I will touch on some highlights. Revenues for 2024 were $2,400,000 up $1,700,000 or 237% when compared to 2023. Mainly as a result of increased participant demand for our frailty and cognitive impairment registry trial in The Bahamas and new contract manufacturing revenue. Contract manufacturing revenue for 2024 one million dollars consisting of $500,000 from our manufacturing lease services and another $500,000 from our manufacturing services contract. This year, we have focused on prioritizing investments in our clinical programs and expense management, and we have successfully Total operating expenses for the year declined 13% year over year with G and A expenses decreasing to approximately $10,300,000 from $12,200,000 in 2023. This G and A expense decrease of approximately $1,900,000 or 16% was primarily due to lower personnel expenses, as a result of reduced severance in 2024 and lower legal and other administrative expenses.

R and D expenses for 2024 also decreased approximately $1,000,000 or 10%. To approximately $8,100,000 The decrease was primarily due to a reduction of $2,300,000 in expenses related to the completed ClearMIND Alzheimer's disease clinical trial reduced costs, for the aging related frailty clinical trial, following our decision earlier this year to discontinue trial activities in Japan, and a $900,000 decrease in supply costs.

These reductions were partially offset by $1,700,000 in higher compensation and benefit costs in R and D and another $300,000 increase in equity based compensation for that Net loss decreased 25% to approximately $16,000,000 for 2024 from a net loss of $21,400,000 for 2023. Cash and cash equivalents as of December 31, 2024 were $19,200,000 The company believes its existing cash and cash equivalents will enable it to fund its operating 2025 based on our current operating budget and cash flow forecast.

It is important to note, however, that as a result of our type C meeting with the U. S. FDA in August 2024, with respect to the HLHS regulatory pathway we have started to ramp up biologics license application, BLA, enabling in 2026 if the current LPUS-two trial is successful. Our operating expenses and capital expenditure requirements are expected to accelerate in calendar 2025 as a result of these activities including CMC, chemistry manufacturing controls, and manufacturing readiness spent as we prepare for the BLA. And there will be a need to increase our current proposed spend and further increase our capital investments as a result.

We intend to seek additional financing and non dilutive funding these ramped up activities and any financing transactions entered into. I will now hand the call back to Wael. Thank you, Lisa.

Over the past decade, stem cell therapy has made tremendous progress transforming from promising field into one delivering tangible clinical outcome. We have seen the solidification of cell therapy's role in regenerative medicine and its potential to treat wide range of conditions. Signaling an exciting future for both scientific innovation and patient care. We believe LAMASA B has the potential to be important cellular therapy option for multiple chronic and life threatening conditions. The data generated to date in HLHS, Alzheimer's disease support that belief. The strength of our clinical data, our experience and committed team and unwavering focus on patients give me confidence in the future of LAMISSA B and LAGIBERONE. Operator, now we would like to open the call for questions from covering analysts.

Thank you. Thank you. Our first question is from Bhubhulan Pachayapan with ROTH Capital Partners. Please proceed with your question.

Good afternoon, Tim. Can you hear me okay? Yes. Vobalan, hi. Hi. Thank you so much. Thanks for taking our questions. So we have couple of them. So firstly, with respect to L3C2 enrollment delay, I was wondering maybe if you could provide some additional color what's causing the enrollment delay because I mean, I'm following up your story for quite some time. So initially, we were planning, I mean, I wanted to see the enrollment wrap up sometime in fourth quarter of last year. And then after that, he said it will be first quarter.

So I'm curious what's causing the delay? I understand you have no control in terms of setting the surgery date.

Which I feel is a key factor. But other than this surgery date, are there any other factors that are causing the enrollment delays?

Yes. Bob Allen, I'll take that question Natayak can add color. Of course, as you know, echolitas is is a rare disease and actually goes into the border of ultra rare And it is very hard sometimes to predict it with a green details of accuracy. The team is pushing to finish enrollment as fast as we as possible. But sometimes delays of the surgery itself can happen, things like that. The great news is we continue to make progress as you can see from one quarter to another or from one call to another. And right now, we're spending above 90% in gold. Actually, that means that we have 35 patients enrolled. So we are talking about honestly the last couple of patients left in the trial And we now with absolute full confidence, we believe that we can finish that enrollment in the next couple of months.

Great. And then moving on, so I have a question. Sorry, go ahead.

I was going to say it's Natalia, I want to add to any comments. Feel free as well if you have any last ones.

Thank you, Bivol. And it's a great question.

And as Rael said, we are definitely making a very, very good progress And the nature of disease sometimes have surprises. And as you mentioned, the Glenn surgery, sometimes the patient goes to the surgery, it seems promising and during the surgery, unfortunately, some patients are not eligible based on intraoperate decision. So again, it's a very complicated indication and we are so far been very successful. So because of that, sometimes we have [indiscernible] but they are not eligible at the end of this. So it's definitely decision, but we keep track of every single patient who are potentially eligible. We approach them and they are we are making great progress on that. So hopefully within one to we will be able to complete enrollment.

That's very helpful. Thanks for that. And then staying on LP Stool Lane, so I was wondering, I mean, I understand the primary endpoint is RVEF and you're tracking that for twelve months. So I was wondering if the FDA would be open to the possibility of considering a composite endpoint because I'm not very sure whether a clinically meaningful difference could be recognized in that twelve months timeframe. So assuming I mean, in addition to RVEF, is it possible you can get some data about the other factors such as prolonged hospitalization and MACI's such as reoperation and aneous interventions and all other events that could potentially all these HLHS patients would normally go through. But that would be embedded in your composite endpoint. That was my question. Rael, would you like me to Yes, you can respond and I can add to it.

Yes.

Okay.

Thank you. Thank you so much. So it's a great question. And you're reading our mind.

So we definitely thinking in line that Just to have with FDA and currently as we mentioned, FDA accepted LPS II clinical trial as pivotal, And also they were willing to see More thoughts around primary endpoint and we currently working this our data. We are working to prepare response to FDA.

To compile convincing evidence that composite endpoint would be the way to go. So we are thinking exactly what you mentioned. We are thinking about composite endpoints. We are thinking about different type of endpoints and hospitalization maybe something else. So [indiscernible] get an alignment with every this year. That we are analyzing the data based on this composite endpoint.

Yes. So thank you, Natalia. Bobanna now I will add just one thing is, it's not just our thoughts. We have actually had that discussion with the FDA as you said. So the agreement is yes, they will accept the composite endpoints. And we want to make sure that these composite endpoints happen in frequency that allow us to detect the difference and success of the trial And the FDA was open to several suggestions from our side. And including hospitalization, survival, and other endpoints. And we are in the process of preparing an SAP and sharing it back and they said they will be happy to discuss that further once they receive the SAP from us.

Great. Switching gears and talking about the Alzheimer's program. So you mentioned that you'll be speaking with the agency sometime this quarter. So I'm curious what are some of the key items that you want to clarify RMED designation and this is it's a very long program. Alzheimer's is not It's not for the faint of heart, just to tell you that. So do you plan to sort of propose a plan for that you will have to do a Phase 2b prior to Phase three? Or is there a way you could sort of bypass 2b and directly go to Phase three. Is there a possibility to do that for that?

So that's a great question. I will tell you that's the reason why we're meeting. We are proposing and we'll get into the details after the meeting, but we are proposing a very accelerated path to commercialization and and regulatory approval. Of course, But at the same time, providing the agency an opportunity to ensure that the safety and the efficacy of the product is fully demonstrated as well. And that path for approval, if the FDA agree with our proposal, will definitely presents a great differential opportunity over existing path and that would be one of the values that we can. And by the way, this is part of the RMAT because the RMAT gives you an opportunity for an accelerated path for approval. So that's what we're asking for. And that's what we're hoping the FDA will agree with our plans for that as well. But we have to wait and see what happened at the meeting.

Great. Maybe one last question. I'm sorry, this is the last question from me. So after 09/30/2026, so the agency may not award any pediatric disease priority review voucher. This news has been around for quite some time. So I'm curious what are the prospects for in your case for the Lomitel B in terms of receiving a PRV should this agent be approved, say, either late twenty six or first half of twenty seven for HLHS. It's a great question, Bob Allen.

First, as you know, the PRB is going for renewal next month. There is on the ballot, there is a give kids a chance Act five, to extend the whole PRV. We believe if we are an going to be part of the pre BLA because we have been acting in a very fast and judicious way. We believe that we will have an extension on this one, but we have to get agreement with the agency at the pre BLA meeting for this as well.

All right. Thank you, team. Congrats on the progress. Thank you. Thank you, Bhushan.

Our next question is from Ram Selvaraju with H. Wainwright, [indiscernible] I was just wondering if you could confirm specifically how many patients remain to be enrolled in ALPS II at this juncture? So that trial as you know, it's a thirty eight patients. We have enrolled thirty five. So we're waiting on three more patients. But if there is one or two more patients are in the hot hour and things like that, we may them and we're not declining them. But the goal is to enroll three, but we could end up enrolling a couple of more if they happen to be in the hopper and consented. So Okay. So just to clarify, it's possible that you could over enroll the study by one or two patients, if during the process of screening to finish enrollment wind up having a couple extra. Is that correct? Correct. Sometimes you have to be I don't want to take chance, Ram, losing a patient as Natalia had mentioned in her answer to Bobalin is sometimes you get surprises at that time of randomization and so on. So we keep the hopper or the feed and pools full because I'm interested in finishing the trial and get done with it once and for all.

In that process, we may end up finishing one or two more patients and that would be a good thing, not a bad thing to have. But we're not delaying it beyond 38 being enrolled, I mean, not in presumably. If we happen to enroll a few more patients, we'll enroll them.

You can confirm, right, that at this juncture you don't see any issue with reaching full enrollment in the trial. Based on the current complement of sites that you have up and running. In other words, you would not need to open any new sites in order to complete enrollment. Is that correct?

Absolutely correct. Okay. Can you just remind us, let us assume that complete the study in the second quarter you complete enrollment in the second quarter. When approximately would you expect to report top line results? So let's say, I'm just hypothetical here, so we can get. If I finish enrollment in May, I will we need twelve months for a study to lock the database and last patient out. And then within three, four weeks after that, we'll have the data announced and everything moving on. So within three weeks after the data, base lock, which would happen twelve months from the last patient in. So just to confirm, that's basically sort of like the summer of twenty twenty six timeframe. Is that correct? Correct. Okay. Switching with respect to the potential future commercial scenario for Lomacell B, in the HLHS context. Maybe you can give us some sort of frame of reference regarding how the drug might be commercialized in that indication And what kind of commercial infrastructure would need to be put in place. Because I would expect given the nature of the epidemiology and how these patients are triaged, you would not really need significant sales and marketing infrastructure.

This is potentially an area in which RelaunchEveron could handle commercialization independently. Is that correct? You're absolutely correct, Ram.

I can tell you right now, the number of treating physicians is about 50 in The United States.

It's a surgeons would do doing this surgery. As you know, we are our treatment is adjunct to the surgery. So surgeons are our target. And actually more than seventy percent of these surgeries happen in the centers that we have conducted our clinical trial. So number one, we have a great opportunity that we know all the treatment position in the future because they have participated in the trial. And then the second thing is the fixed the number 50 of physician treating does not require a significant infrastructure from a sales organization. I mean, it's actually at most, you don't need more than two or three sales individuals with a manager. The whole commercial organization can be less than 15 people, including payer, patient services, all of these type of things. So very minimal infrastructure on the commercial organization side, which is one of the beauty of operating in an orphan disease It's you don't have to make a massive investment. So you're absolutely correct in your assumption.

Okay. With respect to Alzheimer's disease, I was wondering if you had had any recent interaction with non U. S. Regulatory authorities And if there appears to be any differentiated picture with respect to how regulators outside of The U. S. Are thinking about potential approvability criteria for a drug like Lomacel B And if you are exploring the possibility of conducting any clinical exploration of Lomacell MSLB in Alzheimer's disease outside The U. S. At this time. And if so, what the format and scope of that might take? Yes.

Thank you so much for this great question. So I'll answer the first part the next explain what is our intention outside The U. S. So we have not had any interaction with any of [indiscernible] agencies outside The United States specifically regarding the development path for Alzheimer disease. So that's the answer to your first question.

We are in the process of hiring a full time regulatory person now that we are heading into the BLA submission for this one and we have the lead candidates And actually one of the most important tasks that this individual will do as soon as the full time join the company is to have a discussion with both the EMEA, the U. K. MHRA as well as Health Canada, Australia and Japan. Those are the priority international markets that we're going to go after. And that is and our plan is to engage and start discussion regarding the filing of the biological license application in this respective health authorities, but for Lonza B and HLHS, that is our top priority. And then once we do that, we'll get into the Alzheimer's disease. Our Alzheimer disease focus moving on is going to be around partnership.

We We definitely don't want to dilute our efforts, but we want to focus 100% on partnership globally, U. S. And outside The U. S. Okay, great. And one more from me with Thrifty the manufacturing revenue that you historically booked in 2024 Can you give us some sense of what the perspectives are to potentially either emulate that level of business or grow it in 2025 As an example, I believe that you previously had client called Secretome, privately held company, which successfully raised capital. Not sure whether that is going to be source of repeat business for you, but just wanted to get a sense of what you expect the level of manufacturing revenue to be in 2025? If you think it could be the same or higher than what you saw in 2024? Thank you.

Yes. So Ron, that's a great question. We continue to have a very good relationship with Secrotome, actually [indiscernible] in 2025 for them. But and I don't know, I mean, we're happy if they have any additional needs that come throughout the year. We'll definitely think, establish a good relationship and expertise between the two companies. So we continue to develop depending on what their needs are. So they are better to speak up about their needs than me speaking it up. Regarding other opportunity, we remain open to other opportunities. I cannot guarantee the same things because honestly the other thing that is going on parallel here is our CMC readiness process and that is going to require an work on our side. As you know, shifting from a clinical development to a fully commercial EMC requirement is a major step upward.

We have recently hired Devenblas, which we are extremely excited about having him on board He has been a tremendous addition to our team. Making great progress in establishing what I would say is the CMC master plan that ensure that our preapproval and inspection for the facility as well as the whole product characterization will need all the regulatory requirement at the time of the BLA filing. So we're our fourth team ahead on the CMC. That will keep us busy but definitely will stay opportunistic on the CMC sorry, on the CBMO business. And if there is an opportunity, we'll definitely use it and and deliver revenue for the company.

Thank you very much. Congrats once again on all the progress. Thank you.

Our next question is from Michael Okunovich with Maxim Group.

Please proceed with your question.

Hey, guys. Thank you so much for taking my questions today. Congrats on a lot of really good progress here. Thank you, Michael. I guess to start off, I wanted to Follow-up on one of the previous questions. Specifically in regards to you mentioned potential outcomes from that upcoming meeting or really focused on designing the pathway forward and potentially getting something more accelerated and streamlined to approval So do you consider the results of that upcoming meeting to be somewhat of a gating item for these potential partnering discussions and then especially if you have an accelerated pathway you think that could really open up these discussions?

Yes. So you're reading my strategy, my friend. So as you know, Michael, there is over 140 clinical development program currently in the marketplace in various phases of development from Phase one to Phase three. Many of them are developed by small companies. And many of these programs are all hoping to get a partnership from one of the major players because the development cost when as you move toward the finish line Phase three it becomes extensive both on the clinical development and the CMC front. In the hundreds of millions of dollars. So everybody is looking for the same partnership. I really believe we have our strategy is very simple. We have good clinical data and clinical outcome that we have demonstrated so far.

Which we have shared We also are meeting with the FDA and hopefully if the FDA agree with our approach and accelerate it. That also provides an economic opportunity for any partner to see a faster and more economical way to bring that product And hopefully, those two things, the clinical data combined with the accelerated path give us some competitive advantage over the other programs being developed. In improving our chance of landing this partnership. [indiscernible] increase in support from the FDA for cell therapy programs in particular around granting these more streamlined pass through approval. Do you think that could potentially de risk this outcome for these upcoming meetings?

I believe, yes, definitely. Cautiously optimistic with your position, but I don't like to make a statement I'm not in ownership of it. I would like to go through the meeting and hear the confirmation from the FDA. But that with that principle. So That's certainly fair. And then just one last one for me and I'll hop back into the queue. I'd like to see if you could just touch a little bit on your current manufacturing capabilities and then what else is needed on that front to become BLA ready, just given the relatively small size of this market, I wouldn't imagine you would need to scale all that much Yes, that's a great thing, Michael. We definitely as I said, I'm very, very happy and think the next call we can bring Devin to join our earning call and also we'll be in a position where we can answer a lot of more specific around CMC and have him answer those But speaking on his behalf, I will tell you that moving from a clinical development to a fully commercial it is a very major step up from a ramp up And that includes many steps, both at the facility level as well as the product level as well.

Including the stability studies and all of the final formulation [indiscernible] And we have a plan, we have alignment from the FDA, but definitely that's a major work that has to take place. Also, in addition, as you know, CMC, a big portion of that is our quality system. They need to all be 100% into the commercialization level. Our supply chain need to be upgraded to the same level and many other areas within the CMC that all need to do this. It is a major focus for us this year We believe we have a good plan to ramp up these activities. It is going to be the largest portion of our investment this year is in the CMC. As I said, we have an agreement and alignment from the agency, but it's going to be a lot, a lot of work this year and I'm happy in the future to bring Devin's to answer any more specific questions related to CMC. All right. Thank you so much for taking my questions, Wyle.

Lots of work ahead, but lots of exciting progress as well. Thank you, Michael. Thank you. Are no further questions at this time. I would like to hand the floor back over to Wael Hashat, for any closing comments. Thank you, Paul.

And thank you all for attending today's call. We greatly appreciate your interest and support and look forward to updating you on our progress soon. Thank you. Operator, you may end the call now. This concludes today's conference. May disconnect your lines at this time.

Thank you.