Lisata Therapeutics, Inc.

Welcome to the Lissetta Therapeutics Third Quarter 2004 Financial Results and Business Update Conference Call. Currently, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ask a question at that time, please press star 11 on your telephone. You will then hear an automated message advising your hand is raised. As a reminder, This call is being recorded today, Tuesday, November 12, 2024. I would now like to turn the call over to John Mendito, Vice President of Investor Relations and Corporate Communications at Lasada. Please go ahead, sir.

Thank you, Operator, and good afternoon, everyone. Welcome to Lasada'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 Nisko, 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 jamendito at lasada.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 LASADA. 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. La Sada 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 nine months of 2024, we continued our progress in advancing development of Sertepatide in combination with a variety of anti-cancer 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 Sertepatide 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. Kristin 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 Nisko, 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 three months ended September 30th, 2024, operating expenses totaled $5.3 million compared to $6 million for the three months ended September 30th, 2023, representing a decrease of $0.6 million or 10.5 percent. Research and development expenses were approximately $2.5 million for the three months ended September 30th, 2024, compared to $3.4 million for the three 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 startup expenses in the prior year related to our glioblastoma multiform study. General and administrative expenses were approximately $2.8 million for the three months ended September 30th, 2024, compared to $2.6 million for the three months ended September 30th, 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 three months ended September 30, 2024, compared to $5.3 million for the three 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 30th, 2024, Lasada 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 a 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 anti-cancer 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, Certepatide, leverages the naturally occurring SendR active transport system to selectively deliver anti-cancer drugs through the stroma into the tumor. Simultaneously, certepatide 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 certepatide'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 certepatide 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 certepatide prioritizes rapid registration. We are actively evaluating certepatide's potential as a selective tumor targeting and penetrating enhancer and tumor microenvironment modifier in combination with a variety of standard of care therapies and 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, excuse me, gemcitabine and nabpaclitaxel chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma or MPDEC. Excuse me. The trial is being conducted at 25 sites in Australia and New Zealand, led by the Australasian Gastrointestinal 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 LASADA inherited upon our acquisition of SEND Therapeutics. After the acquisition, LASADA 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 Sertepatide 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 Sertepatide given four hours after the first thereby enabling further Sertepatide 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, excuse me, cohort A 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 multicenter 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 six 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. Sendafox is a Phase 1b, 2a open-label trial in the United States evaluating certepetide in combination with neoadjuvant fulfurinox-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 two cohorts by the end of this quarter. Chilu Pharmaceutical The licensee of Sertepatide in the Greater China Territory is also currently evaluating Sertepatide in combination with gemcitabine and nabpaclitaxel as a treatment for metastatic pancreatic cancer. CHELA 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 I-Lista trial, Warp 9, we are evaluating certepatide in a Phase 1b, 2a, randomized placebo-controlled, three-arm, single-blind, single-center, safety, early efficacy, and pharmacodynamic trial. The trial is being conducted in Australia, evaluating certepatide in combination with a checkpoint inhibitor, durvalumab, plus standard-of-care gemcitabine, and NAB paclitaxel chemotherapy versus certepatide 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 GBMs. 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 two-to-one certepetide plus standard of care versus placebo plus standard of care. Enrollment completion is expected in the second half of 2025. Fortified is a Phase 1b, 2a double-blind, placebo-controlled, three-arm randomized study in the United States evaluating the safety tolerability, and efficacy of a four-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 fulfirinox. As part of this 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 Sertepatide. We expect to enroll the first patient in the study in the first quarter of 2025. Additionally, Lissata has recently entered into multiple preclinical research collaborations to broaden our understanding of Sertepatide'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. A partnership with Velo Therapeutics to investigate the benefits of combining certepetide with Velo's Pepticrad, a customizable oncolytic adenovirus platform technology, and a checkpoint inhibitor and 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, LASADA 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 Certepatide 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 two 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've 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 Certepatide 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 valuations. 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 Certepitide 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.

Thank you. As a reminder, to ask a question, please press star 11 on your telephone. You will hear an automated message advising your hand is raised. One moment for the first question. And our first question today will be coming from Joseph. Pan Guinness of HC Wainwright. Your line is open.

Hi, good afternoon. This is Sarah on for Joe. Thanks for taking the question. I had a question regarding enrollment in the GBM study and in your last update, I believe you had mentioned you had enrolled three 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. Thank you.

Thanks, Sarah. I 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 five 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.

Thank you. One moment for the next question. And our next question will be coming from the line of Steve Brozak of WBB Securities. Your line is open.

Yes, hi. Thanks for taking the questions. 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 certepatide 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 certepatides selective targeting and penetration, and that's the integrins and the noropillin-1. And so we're trying to assess whether we can stop the angiogenesis of endometriosis by co-administering certepetide with an antivascular 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, how you 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 non-steroidal 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 very, very big unmet medical need.

Okay. Thank you. Okay. Going back to on the trialing, I know that, you know, 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 Now, having done this for a long, long time, patient enrollment sometimes is a problem and other times you usually meet it. How would you explain the patient enrollment that you've seen 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. Thank you.

Well, thank you, Steve. I'll speak a little bit to ASCEND, and then Kristen can speak to Bolster and any others that she wishes to mention. But the ASCEND trial enrolled 158 patients over the course of about a year and a half, 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 Certepatide'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 six months of time, which is extremely fast, six months ahead of our projected recruitment timeline. You know, the investigators were very eager, 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 cholangiocosmoma 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 six months ahead of time. Our second line in bolster is recruiting as expected.

Got it. Thank you. I'll hop back in the queue. Thanks, Steve.

Thank you. One moment for the next question. And as a reminder, if you would like to ask a question, please press star 11 on your telephone. Our next question will be coming from Pete Enderlin of MozPartners. Your line is open.

Thank you. Hello, everybody. Hi, Pete. I'd like to talk about the collaboration with Valotex. Excuse me. You know, you mentioned you have multiple kind of collaborations and partnerships and and joint efforts. So the first question is how do you prioritize all those opportunities? And you know, 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 certepatide. So that's the first question. 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 the way we look at this is it's sort of through a matrix. So, you know, first, as you said, in principle, we could combine Certepatide with any modality of anti-cancer agent, a chemotherapeutic, an immunotherapeutic, even a radiopharmaceutical, an SRNA or antisense pharmaceutical, et cetera. And so what we look for, well, first of all, as Kristen mentioned early on, we only want to start trials, whether they are preclinical or clinical, that will yield the 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 timeframe so that we can use that data to further increase the enthusiasm around Certepatide 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 Certepatide and the co-administered drugs of 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 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 sootepetide, 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, you know, 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 like 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 certepatide 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 sutepatide 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. Okay. Exactly the way I would, you know, 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. Thanks.

And then just in the format with Valitex, the collaboration, they both, do the tests, 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 LASADA. 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, you know, 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. You know, 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.

Okay, great. Thank you very much for the information. Thanks, Pete.

Thank you. And one moment for the next question. And our next question for the day will be coming from Will Hedell. of BookLine Capital Markets. Your line is open.

Hi, thank you for taking questions. I have 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? I'm assuming we're going to get some PFS data data, and what would you all 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 ours to divulge. But that said, you know, 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 the endpoints or the data that you should expect to see or hear about. So that would be progression-free survival at six months versus, you know, treatment versus placebo. Median progression-free survival and median overall survival are at least three things that you should see. You should also expect to see, you know, 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, you know, 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 certepatitis in metastatic pancreatic ductal adenocarcinoma.

Okay, thank you.

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