Welcome to the Lisata Therapeutics' Third Quarter 2024 Financial Results and Business Update Conference Call. [Operator Instructions] As a reminder, this call is being recorded today, Tuesday, November 12, 2024. I would now like to turn the call over to John Menditto, Vice President of Investor Relations and Corporate Communications at Lisata. Please go ahead, sir.

Thank you, operator, and good afternoon, everyone. Welcome to Lisata's Third Quarter 2024 conference call to discuss our financial results and to provide a business update. Joining me today from our management team are Dr. David Mazzo, President and Chief Executive Officer; Dr. Kristen Buck, Executive Vice President of Research and Development and Chief Medical Officer; and James Nisco, Senior Vice President of Finance and Treasury and Chief Accounting Officer. Shortly before this call, we issued a press release announcing our third quarter 2024 financial results, which is available under the Investors and News section of the company website, along with a webcast replay of this call. If you have not received this news release or you'd like to be added to the company's e-mail distribution list, please subscribe to our e-mail alerts on the company website or e-mail me at jmenditto@lisata.com to be added. Before we begin, I remind you that comments made by management during this conference call will contain forward-looking statements that involve risks and uncertainties regarding the operations and future results of Lisata. I encourage you to review the company's filings with the Securities and Exchange Commission, including, without limitation, its Forms 10-Q, 8-K, and 10-K, which identify specific risk factors that may cause actual results or events to differ materially from those described in the forward-looking statements. Furthermore, the content of this conference call contains time-sensitive information that is accurate as of the date of this live broadcast, Tuesday, November 12, 2024. Lisata Therapeutics undertakes no obligation to revise or update any statements to reflect events or circumstances after the date of this conference call. With that, I'll now turn the call over to Dr. Mazzo. Dave?

Thank you, John, and good afternoon, everyone. It is my pleasure to be here today to provide an overview of recent business highlights, discuss our third quarter 2024 financial results, and give an update on the progress of our development programs. Through the first 9 months of 2024, we continued our progress in advancing development of certepetide in combination with a variety of anticancer agents of differing modalities for the treatment of advanced solid tumors. The ongoing accumulation of both preclinical data and early clinical data support our belief that certepetide has the potential to become an integral part of a revised standard of care treatment regimen for advanced solid tumors, including pancreatic, cholangiocarcinoma, glioblastoma, colon, appendiceal, and melanoma. Additionally, we have initiated the preclinical investigation of certepetide as a potential therapeutic agent outside of oncology in the treatment of endometriosis, a disease which affects hundreds of millions of women worldwide and for which there remains a pronounced unmet medical need. Dr. Kristen Buck, our Chief Medical Officer and Head of R&D, will provide a detailed update of our ongoing and planned clinical and preclinical programs following the review of our financial results. With that, I will now turn the call over to James Nisco, our Senior Vice President of Finance and Treasury and Chief Accounting Officer. James?

Thanks, Dave. Good afternoon, all. I'm pleased to join you today to present a summary of our third quarter 2024 financial results. Starting with operating expenses. For the 3 months ended September 30, 2024, operating expenses totaled $5.3 million compared to $6 million for the 3 months ended September 30, 2023, representing a decrease of $0.6 million, or 10.5%. Research and development expenses were approximately $2.5 million for the 3 months ended September 30, 2024, compared to $3.4 million for the 3 months ended September 30, 2023, representing a decrease of $0.8 million, or 24.8%. This was primarily due to a reduction in clinical research organization expenses associated with our Phase IIa BOLSTER trial as a result of trial protocol modifications and lower equity expense. Also impacting this decrease were start-up expenses in the prior year related to our glioblastoma multiforme study. General and administrative expenses were approximately $2.8 million for the 3 months ended September 30, 2024, compared to $2.6 million for the 3 months ended September 30, 2023, representing an increase of $0.2 million, or 8.1%. This was primarily due to higher consulting expenses. Overall, net losses were $4.9 million for the 3 months ended September 30, 2024, compared to $5.3 million for the 3 months ended September 30, 2023. It is noteworthy that we continue to make progress according to our plans for our R&D and business activities while still continuing our legacy of prudent capital management and expense minimization. Turning now to our balance sheet and cash flow. As of September 30, 2024, Lisata had cash, cash equivalents, and marketable securities of approximately $35.9 million. Based on its current expected capital needs, the company believes that its projected capital will fund its current proposed operations into early 2026, encompassing anticipated data milestones from all its ongoing and planned clinical trials. With that, I will now turn the call over to Dr. Kristen Buck to provide an overview of the company's development programs. Kristen?

Thank you, James, and good afternoon, everyone. Before I review our development portfolio, allow me to summarize some important background information, especially for those who are listening for the first time. Despite advances in cancer therapy, many solid tumors are still associated with poor patient outcomes. Advanced solid tumors such as pancreatic cancer, gastric cancer, and glioblastoma multiforme are surrounded by a dense fibrotic tissue known as the stroma, which limits access of most pharmacotherapies into the tumor. In addition, many solid tumors also harbor a hostile tumor microenvironment, or TME, which suppresses the patient's immune system and makes it less effective in fighting the cancer. The combination of a dense stroma and a hostile tumor microenvironment prevents many chemotherapies and immunotherapies from being optimally effective in treating these cancers. This, coupled with the fact that most anticancer therapies are not efficient in targeting only cancerous tissue, defines the major challenges in the treatment of solid tumors. To overcome these obstacles, our investigational product, certepetide, leverages the naturally occurring CendR active transport system to selectively deliver anticancer drugs through the stroma into the tumor. Simultaneously, certepetide has been shown to modify the tumor microenvironment, making it less immunosuppressive, and therefore, increasing the tumor's susceptibility to immunotherapy and our body's own immune system while also inhibiting the metastatic cascade. For more specifics regarding certepetide's mechanism of action, I invite you to visit our website and view the animated video pertaining thereto as well as the relevant slides in the corporate presentation. Beyond our strategic clinical development plan, we have focused on optimizing our regulatory strategy. To date, our approach has yielded significant results for certepetide with multiple special regulatory designations across health authorities. These include orphan drug designation, Fast Track designation, and rare pediatric disease designations. One such achievement occurred this…

Thanks, Kristen. As you have heard, we have a lot going on and are looking forward to our data-rich period starting in the very near future. We remain optimistic about the potential of certepetide to transform the lives of patients with cancer and have demonstrated our ability to design and execute a very capital-efficient development plan. However, as I have mentioned before, we continue to be frustrated, as I am sure all of you are, with our share price and our market valuation. Considering our robust advancing clinical development portfolio, focused and rational development and regulatory strategy, continually growing library of supportive evidence, and impeccable capital stewardship, trading at a negative enterprise value is irrational and misleading. We look forward to seeing a market reaction to our upcoming data that reflects what we see as the true value of our development candidate and company. We remain committed to advancing the certepetide program across multiple tumor types and exploring strategic partnerships to maximize its value. We look forward to sharing further updates on our progress throughout the year. And with that, operator, we're ready to take questions.

[Operator Instructions] And our first question today will be coming from Joseph Pantginis of H.C. Wainwright.

This is Sarah on for Joe. I had a question regarding enrollment in the GBM study. And in your last update, I believe you had mentioned you had enrolled 3 patients, and I know more clinical sites have opened since. I was wondering if you can give any insight into maybe how many patients are currently enrolled in the study and how exactly it's progressing.

Thanks, Sarah. Appreciate you joining, and thank you for the question. Our GBM trial has gotten off to a little bit slower start than we expected, mostly because the sites in Latvia, which were intended to provide the lion's share of the patients, ended up taking a bit longer, several months longer to initiate than was previously expected. The Estonian site, though, is now up to 5 patients. And the Latvian sites should be coming online soon, and we certainly hope to have enrollment meet our expectations for completion as indicated on our milestone slide. So thank you very much.

And our next question will be coming from the line of Steve Brozak of WBB Securities.

You've alluded to an endometriosis potential here that I'm kind of curious to. And if you don't mind, just going over the commonality with what you're looking at as far as certepetide and what the common characteristics are and why this is not just something that people should think about, but how it might extend to other things as well. So if you can provide as much detail in what the mechanisms are, what you're looking at, that would be greatly appreciated. And I've got a follow-up after that, please.

Steve, this is Kristen. I will take that. Endometriosis is a tumor-like disease. It's a disease of angiogenesis whereby menstrual material escapes the uterus and goes into the peritoneal cavity. We're targeting endometriosis, one, because it's a significant unmet medical need with over 190 million women suffering from it worldwide for things like pain, discomfort, and even infertility, but two, because endometriosis has upregulated receptors required for certepetide's selective targeting and penetration. And that's the integrins and the neuropilin-1. And so we're trying to assess whether we can stop the angiogenesis of endometriosis by co-administering certepetide with an anti-vascular endothelial growth factor, anti-VEGF. In doing so, we hope that we can have a viable treatment option for these 190 million people worldwide.

Okay. I have a follow-up on that, and I'd like to -- as long how you've described it, what is the current standard of care that is used in dealing with endometriosis? And I've got one follow-up I was planning on after that, please.

Sure, Steve. A lot of it starts with nonsteroidal anti-inflammatories, analgesics, hormonal modulators, and at worst case, surgery to debulk the endometriotic lesions. There's really no cure for this disease. And as I said, it's a very, very big unmet medical need.

Okay. Okay. Going back to -- on the trialing, I know that, obviously, the trials, what is released is specifically dictated by the clinicians, the lead investigators. But in terms of what you've seen as far as patient enrollment, because this is one thing that having done this for a long, long time, patient enrollment sometimes is a problem and other times, it's -- you usually meet it. How would you explain the patient enrollment that you've seen on your -- on the major trials that you've got right now by comparison to the normal enrollment? And I'll hop back in the queue after that.

Well, thank you, Steve. I'll speak a little bit to ASCEND, and then Kristen could speak to BOLSTER and any others that she wishes to mention. But the ASCEND trial enrolled 158 patients over the course of about 1.5 years, which was actually a pretty good enrollment rate considering that it was all done amongst about 20 sites in Australia and New Zealand. The investigators there, the AGITG consortium, are enthusiastic. And obviously, the patients were convinced to not only join the trial, but to stay on treatment. So we take that as a positive sign that there's a great deal of both patient and investigator enthusiasm about the potential for the product. And I think it also speaks to certepetide's benign safety profile that while we hope it has significant impact on augmenting efficacy of the co-administered drugs, it actually does not potentiate further adverse events. And I think that's very, very important for patients who are taking cytotoxics. Kristen, how about you speak to BOLSTER, please?

Sure. As I earlier spoke, BOLSTER, our first-line cholangiocarcinoma cohort, had 40 subjects, and we recruited those within about 6 months of time, which is extremely fast, 6 months ahead of our projected recruitment timeline. The investigators were very eager and so much so that they requested that we continue to open that trial, make it larger, and/or add a second-line cohort, which we have. The second-line cohort for cholangiocarcinoma is recruiting as expected. It's slower than first-line cholangiocarcinoma because it's a subset of patients who have progressed after first line and yet still have performance status capable of going on a new treatment regimen. So unfortunately, these patients who reach second line often have very bad performance status and succumb to the disease very quickly. But just to answer your question succinctly, our first-line recruited 6 months ahead of time. Our second-line in BOLSTER is recruiting as expected.

[Operator Instructions] Our next question will be coming from Pete Enderlin of MAZ Partners.

I'd like to talk about the collaboration with ValoTx. You mentioned you have multiple kind of collaborations and partnerships and joint efforts. So the first question is, how do you prioritize all those opportunities? And conceptually, you could say, take any kind of cancer and each of the different drugs that are in development for that, and then each one of those is potentially an opportunity for enhancement with certepetide. So that's the first question. How do you prioritize pursuing those opportunities? And can you give us some sense of how many you see as realistic opportunities at this point?

I'll start and then maybe Kristen can add some color commentary. But Pete, the way we look at this is it's sort of through a matrix. So first, as you said, in principle, we could combine certepetide with any modality of anticancer agent, a chemotherapeutic, an immunotherapeutic, even a radiopharmaceutical, an siRNA, or antisense pharmaceutical, et cetera. And so what we look for, first of all, as Kristen mentioned early on, we only want to start trials, whether they are preclinical or clinical that will yield data in our current funding window. So there's no point in starting something that won't yield data until 2026, if we have cash until 2026. So we need to prioritize things that are likely to be completed in the 2025 time frame so that we can use that data to further increase the enthusiasm around certepetide and convert that into funding opportunities. We also look at what the unmet medical need would be in the indication of choice, whether the competition is too strong for us or not, whether the length or the duration of a clinical trial might take many, many years or be short. So we look for those places where the disease causes patients to progress and/or succumb more quickly so that we can show an improvement in a shorter period of time. And we also look at the likelihood of the various mechanisms of action with certepetide and the co-administered drugs are being complementary and yielding a much better approach. And so when we put things through that matrix or that funnel, many things fall out before they get to the end and the things that get to the end are the ones that we agree that are a priority. We also obviously look for those things where the partner is either paying for most or all of the collaboration. And all we have to do is provide certepetide, yet we still have access to the data. Kristen, would you like to add anything to that?

I think you said it well, Dave.

Well, let me just ask a little bit of a follow-up. And that is looking at that matrix, you said some of them obviously drop out for obvious reasons. Can you give us any sense of how many are kind of live prospects at this point going forward?

Well, I mean, you can see that we're working -- we have ongoing trials in pancreatic cancer and appendiceal cancer, colon cancer, glioblastoma, cholangiocarcinoma, et cetera. There are a number of other cancers that we would like to do work in. And certainly, we have a growing body of evidence that indicates that the combination of certepetide with immunotherapies really will give those immunotherapies a much increased efficacy profile in comparison to those immunotherapies alone in these solid tumors. And so there are quite a few opportunities along those lines. And then as Kristen pointed out, we're looking at areas outside of oncology where the disease behaves like a tumor and/or has the requisite receptors to allow for the certepetide mechanism of action to be effective. And so there are a bunch of things to be looking at there, including opportunities in osteosarcoma, even some veterinary applications, melanoma. There are quite a few possibilities. Right now, our ability to pursue all those is limited only by capital.

Did you just sort of imply that in oncology, the opportunities in immunotherapy might be more promising than in chemotherapy as a broad statement?

I think that's what I implied it exactly the way I would. They might be. It's early days yet, but we're seeing some really very, very compelling preclinical and early clinical data that might lead us to that final conclusion.

And then just in the format with ValoTx, the collaboration, they do the test, you provide the drug, certepetide. And so is that the preferred way to go about this? And is that primarily for cash reasons or because it's just easier to have somebody else and has the bandwidth to do the clinical trials themselves?

In the case of Valo, it's not a question of bandwidth as much as a question of both in-house expertise and actually availability. So all of our preclinical work that's done, for example, in models with animals, are done outside of Lisata. We do not have laboratories, we do not do animal testing in-house, and we don't have a preclinical group per se. So they're done with academic collaborations, universities, or in some cases, CROs. Valo actually has those capabilities in-house. And so they're able to do the experiment straight away because they have everything they need. They don't have to order it. We don't have to set up contracts with CROs. We don't have to write a protocol. This is a model they have running all the time. They have the availability of the animals and the expertise. And so it was just simpler for them to do it. And that's also why it's less expensive because they're going to do it in-house with existing resources, so we really don't have to pay them for that.

And our next question for today will be coming from Will Hidell of Brookline Capital Markets.

I had one question. I know you don't have -- I know you can't say much about the Cohort A data for the ASCEND trial. But can you give us any idea what level of detail we should expect in the readout? Should we -- I'm assuming we're going to get some PFS data. And what would you like to see to continue development?

Thanks, Will. Appreciate the question. So you're right. I'm not at liberty to say very much about the data because the data is not hours to divulge. But that said, you can look to the protocol, which is available publicly on clinicaltrials.gov. And from that protocol, you can see what were identified as the major endpoints. And so those are the endpoints or the data that you should expect to see or hear about. So that would be progression-free survival at 6 months versus treatment versus placebo, median progression-free survival and median overall survival are at least 3 things that you should see. You should also expect to see a number -- the number -- numerical count of complete responses in each group and maybe partial responses and overall response rates as well. So I would expect those things at a minimum. And those are really important. I mean, for us, we all know that any one of those pieces of data can be quite interesting, but there's a pretty, I would say, reasonable probability that the regulatory standards for ultimate approval will remain consistent going forward. And that regulatory standard is overall survival. So we'll be paying very close attention to overall survival and also the number of complete responses in the treatment group versus the placebo group as we determine what would be the next steps. And hopefully, there will be next steps in the development of certepetide in metastatic pancreatic ductal adenocarcinoma.

And that does conclude today's Q&A session. And I would like to turn the call back over to Dr. Mazzo for closing remarks. Please go ahead.

Again, thank you all for participating in today's call. We look forward to speaking with you again during our next quarterly conference call and to continuing to provide updates on our achievements and progress. We remain grateful for your continued interest and support. Please stay well, and have a good evening.

That concludes today's conference call. You may now disconnect.