Welcome to the Lisata Therapeutics' Third Quarter 2024 Financial Results and Business Update Conference Call. 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 email distribution list, please subscribe to our email alerts on the company website or email me at [email protected] 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 past September when certepetide was granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of cholangiocarcinoma. As mentioned, our regulatory and clinical development strategy for certepetide prioritizes rapid registration. We are actively evaluating certepetide's potential as a selective tumor targeting and penetrating enhancer and tumor microenvironment modifier in combination with a variety of standard of care therapies in advanced solid tumors. Now for an update on our individual development programs. The ASCEND trial is a 158-patient, double-blind, randomized, placebo-controlled clinical trial evaluating certepetide in combination with standard of care gemcitabine and nab-paclitaxel chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma, or mPDAC. The trial is being conducted at 25 sites in Australia and New Zealand, led by the Australasian Gastro-Intestinal Clinical Trials Group, or AGITG, in collaboration with the NHMRC Clinical Trial Center at the University of Sydney. As mentioned on prior calls, the ASCEND trial is an investigator-initiated trial that Lisata inherited upon our acquisition of Cend Therapeutics. After the acquisition, Lisata collaborated with the sponsor of the trial, AGITG, to modify the trial to ensure it provided clinical outcomes that would best support the next steps in development of certepetide from a regulatory perspective. As such, the ASCEND protocol was amended to include another cohort of patients, Cohort B. Cohort B is designed to evaluate a second dose of intravenous certepetide given 4 hours after the first, thereby enabling further certepetide dose exploration and optimization. The ASCEND protocol was also amended to capture overall survival outcomes for both Cohort A and Cohort B. Given that the ASCEND protocol was amended following trial initiation, the outcome data from Cohort B will be delivered months after Cohort A data. Cohort A data reached a predetermined number of events in September of this year, which prompted a preliminary analysis of the data. The results of that analysis were submitted as an abstract for ASCO GI, which takes place in January 2025. We just recently learned the abstract was accepted and the preliminary results of Cohort A will be presented by the study sponsor at the conference. As a reminder, the sponsor has sole ownership and control of the data dissemination. That said, we are in discussions with them to see if we could communicate any information from the preliminary analysis prior to the conference without diminishing the integrity of the abstract and presentation. As it stands right now, however, we will most likely need to wait until the time of the conference before communicating any preliminary results publicly. As noted, we anticipate Cohort B is trailing Cohort A in time, and those data are expected to be mature and available mid-2025 with a final analysis, including both cohorts A and B available thereafter. The BOLSTER trial is our Phase IIa double-blind, placebo-controlled, multi-center, randomized trial in the United States, evaluating certepetide in combination with standard of care in first-line and second-line cholangiocarcinoma. Enrollment was completed in first-line cholangiocarcinoma nearly 6 months ahead of time, accelerating the anticipated top line data readout to mid-2025. A second cohort has been added to the BOLSTER trial, evaluating certepetide in subjects in second-line cholangiocarcinoma on top of standard of care. We have now treated several patients in the second-line cholangiocarcinoma cohort, and enrollment completion is expected in the first half of 2025. CENDIFOX is a Phase Ib/IIa open-label trial in the United States, evaluating certepetide in combination with neoadjuvant FOLFIRINOX-based therapies in pancreatic, colon, and appendiceal cancers. The trial has completed enrollment in the pancreatic cohort and remains on track to complete enrollment in the remaining 2 cohorts by the end of this quarter. Qilu Pharmaceutical, the licensee of certepetide in the Greater China territory, is also currently evaluating certepetide in combination with gemcitabine and nab-paclitaxel as a treatment for metastatic pancreatic cancer. Qilu is currently treating patients in their Phase II placebo-controlled trial in pancreatic cancer. The study is planned to take approximately 18 months to complete enrollment accrual and another 13 months for patient follow-up and data analysis and reporting. In collaboration with AstraZeneca Australia and the funding sponsor of the iLSTA Trial, WARPNINE, we are evaluating certepetide in a Phase Ib/IIa randomized, placebo-controlled, 3-arm, single-blind, single-center safety, early efficacy, and pharmacodynamic trial. The trial is being conducted in Australia, evaluating certepetide in combination with the checkpoint inhibitor, durvalumab, plus standard of care gemcitabine and nab-paclitaxel chemotherapy, versus certepetide in combination with standard of care alone, no durvalumab, versus standard of care alone in patients with locally-advanced, non-resectable pancreatic cancer. Enrollment completion is expected in the first half of 2025 and preliminary results are expected to be announced at ASCO GI in January 2025. A study of certepetide in combination with temozolomide in glioblastoma multiforme, or GBM, has been initiated with several patients already enrolled and treated. This study is designed as a Phase IIa double-blind, placebo-controlled, randomized, proof-of-concept study evaluating certepetide when added to standard of care temozolomide versus temozolomide alone and matching certepetide placebo in subjects with newly diagnosed GBM. This actively enrolling study is being conducted across multiple sites in Estonia and Latvia and is targeted to enroll 30 patients with a randomization of 2:1 certepetide plus standard of care versus placebo plus standard of care. Enrollment completion is expected in the second half of 2025. FORTIFIDE is a Phase Ib/IIa double-blind, placebo-controlled, 3-arm, randomized study in the United States, evaluating the safety, tolerability, and efficacy of a 4-hour continuous intravenous infusion of certepetide in combination with standard of care in patients with second-line metastatic pancreatic cancer who have previously progressed on FOLFIRINOX. As part of the study, we have engaged Haystack Oncology to use their MRD technology to measure circulating tumor DNA levels at multiple time points in patients throughout the study as an exploratory endpoint for analyzing the early therapeutic effect of certepetide. We expect to enroll the first patient in the study in the first quarter of 2025. Additionally, Lisata has recently entered into multiple preclinical research collaborations to broaden our understanding of certepetide's therapeutic potential and identify new non-oncologic opportunities for this development. These collaborations include a sponsored research agreement with the University of Cincinnati to assess certepetide in combination with bevacizumab, a VEGF inhibitor in a preclinical murine model for the treatment of endometriosis. This trial is the first exploration of certepetide in a non-oncologic or cancer-related indication. Our partnership with Valo Therapeutics to investigate the benefits of combining certepetide with Valo's PeptiCRAd, a customizable, oncolytic adenovirus platform technology and a checkpoint inhibitor in a preclinical murine model for the treatment of melanoma. Beyond the studies I've outlined, we are actively exploring additional opportunities to advance our development strategy. However, we remain focused on only initiating trials that can be funded through data and that can be executed within a reasonable period of time. As a reminder, several of the clinical studies I mentioned earlier are investigator-initiated trials. And although we have great confidence in the investigators running these studies, Lisata has limited control and thus timelines and expectations may be subject to change. That said, we are extremely grateful to the investigators and especially to the patients participating in certepetide clinical trials around the world. For those who are interested, a more comprehensive description of each trial is available in the Appendix section of the corporate presentation on our website. Additionally, in the body of the presentation, there are 2 slides that depict the anticipated timing and execution of key milestones and data readouts from our trials. As you will see, there are numerous execution and data milestones projected from our portfolio of clinical trials over the next year and beyond. With that, I will now turn the call back to Dave.

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.

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.

I have a follow-up on that. Based on your description, what is the current standard of care used to manage endometriosis? I have one more follow-up planned 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. Going back to the trials, I understand that the specifics of what is released are determined by the clinicians and lead investigators. However, can you discuss what you have observed regarding patient enrollment? In my experience, patient enrollment can sometimes be problematic, while at other times, it meets expectations. How does the patient enrollment in your major trials compare to typical enrollment rates? I'll return to 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.

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?

We are currently conducting trials in pancreatic cancer, appendiceal cancer, colon cancer, glioblastoma, and cholangiocarcinoma, among others. We aim to explore additional cancers as well. Our evidence suggests that combining certepetide with immunotherapies significantly enhances their effectiveness compared to using the immunotherapies on their own in these solid tumors. There are numerous opportunities in this area. Additionally, as Kristen mentioned, we are also exploring non-oncology areas where diseases exhibit tumor-like behavior or have the required receptors for certepetide's mechanism of action to be effective. This includes potential applications in osteosarcoma, some veterinary uses, and melanoma, among others. Currently, our ability to pursue these opportunities is mainly constrained by our available 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 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 have a question. I understand you can't share much about the Cohort A data for the ASCEND trial. However, could you provide us with an idea of the level of detail we should expect in the readout? I'm assuming we'll receive some PFS data. What would you like to see to continue development?

Thanks, Will, for the question. I can't share much about the data since it's not ours to disclose. However, the protocol is publicly accessible on clinicaltrials.gov, where you can find the major endpoints. You can expect to see progression-free survival at 6 months comparing treatment to placebo, median progression-free survival, and median overall survival as key metrics. Additionally, there will likely be counts of complete responses in each group, along with partial responses and overall response rates. I anticipate these aspects being reported at a minimum, as they are significant. Each of these data points can offer valuable insights, but it's likely that the regulatory standards for eventual approval will stay consistent, with overall survival remaining a key focus. We will closely monitor overall survival and the number of complete responses in the treatment group versus the placebo group to determine our next steps in developing certepetide for metastatic pancreatic ductal adenocarcinoma.

And that does conclude today's Q&A session. And I would like to turn the call back 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.