Lisata Therapeutics, Inc.

Welcome to the DESADA Therapeutics Third Quarter 2023 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 bar 11 on your telephone. You will then hear an automated message advising that your hand is raised. As a reminder, this call is being recorded today, Thursday, November 2nd, 2023. I will now turn the call over to John Mendito, Vice President of Investor Relations and Corporate Communications at Lissata. Please go ahead, sir.

Thank you, operator, and good afternoon, everyone. Welcome to Lissata's third quarter 2023 conference call to discuss our financial results and the opportunity 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, Vice President of Finance and Treasury. Shortly before this call, we issued a press release announcing our third quarter 2023 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 if you'd like to be added to the company's email distribution list, please email me at jmendito at lasada.com. 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 10Q, 8K, and 10K, 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 only as of the date of this live broadcast, Thursday, November 2, 2023. Lasada 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 will now turn the call over to Dr. David Mazzo. Dave?

Thank you, John, and good afternoon, everyone. Thank you for joining us today as we provide an overview of recent business highlights, discuss our third quarter 2023 financial results, and give an update on the progress of our various development programs. The third quarter was another productive quarter for Losada as we added to the momentum of the first half of 2023 with the initiation and advancement of new clinical development programs targeting a variety of advanced solid tumors using Lister 1, our lead product candidate, in combination with multiple anti-cancer agents of differing modalities. As we have previously reported, we have both preclinical data and early clinical data in humans that we believe demonstrates the potential of LISTA-1 to become an integral part of a revised standard of care treatment regimen for many difficult-to-treat cancers. During this call, our Chief Medical Officer, Dr. Kristen Buck, will provide an update on our clinical programs following the review of our financial results. And with that, I now will turn the call over to James Misko, our Vice President of Finance and Treasury. James?

Thanks, Steve. Good afternoon, all. I'm pleased to join you today to present a summary of our third quarter 2023 financial results, starting with operating expenses. For the three months ended September 30th, 2023, operating expenses totaled $6 million compared to $37.7 million to the three months ended September 30, 2022, representing a decrease of 84.2%. Excluding the in-process research and development expense of $30.4 million related to our merger with SEND Therapeutics in September 2022, operating expenses decreased by $1.4 million, or 18.6%, compared to the three months ended September 30, Operating expenses comprise the following. Research and development expenses were approximately $3.4 million for the three months ended September 30, 2023, compared to $3.3 million for the three months ended September 30, 2022, representing an increase of 1.3%. Expenses this quarter were primarily due to study activities associated with the bolster trial here in the United States, enrollment activities for the ASCEND study in Australia, startup activities for the glioblastoma multiforme study in Europe, and general chemistry, manufacturing, and control activities for LISTA-1 to support all development activities. General and administrative expenses were approximately $2.6 million for the three months ended September 30, 2023, compared to $4.0 million for the three months ended September 30, 2022, representing a decrease of $1.4 million, or 35.3 percent. This was primarily due to non-recurring merger-related costs in the prior year. a decrease in equity expense due to prior year performance stock unit vesting, merger option assumption expense, and departing board member restricted stock unit vesting, and timing of our annual stockholder meeting versus the prior year. Overall, net losses were $5.3 million for the three months ended September 30, 2023, compared to $37.4 million for the three months ended September 30th, 2022. Excluding the in-process research and development expense of 30.4 million related to our merger with SEND Therapeutics in September 22, net losses for the three months ended September 30th, 2023 decreased by 1.7 million or 24.7% compared to the three months ended September 30th, 2022. Turning now to our balance sheet and cash flow. As of September 30th, 2023, the company had cash, cash equivalents, and marketable securities of approximately $54.4 million. The company remains confident that its projected capital will fund its current and proposed operations into early 2026 encompassing anticipated data milestones from all its ongoing and planned clinical trials. This completes my financial overview, and I will now turn the call over to our Chief Medical Officer, Dr. Kristen Buck, for the review of our clinical development pipeline. Kristen?

Thank you, James, and good afternoon, everyone. As those who have been following us know, Lasada's pipeline is built on a portfolio of proprietary and patented technology that is grounded in strong scientific rationale and a body of published preclinical and early clinical data. Our platform technology is designed to address major impediments to the successful treatment of advanced solid tumors in an environment of increasing pharmacoeconomic pressures. Generating meaningful clinical data is important in this field, and I can assure you that our entire organization has this goal top of mind in everything we do. With that, I will now provide an overview of LISTA-1 for the treatment of advanced solid tumors in combination with other anti-cancer agents. Despite advances in cancer therapy today, many solid tumors remain difficult to treat effectively. Cancers such as pancreatic cancer, gastric cancers, and other solid tumors are surrounded by a dense fibrotic tissue known as the stroma, which limits access of most pharmacotherapies to the tumor. Many tumors also have a hostile tumor microenvironment, or TME, which suppresses a patient's immune system and makes it less effective in fighting 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 challenge of maximizing effectiveness and safety in the treatment of solid tumors. To combat this, Lissata's approach is to activate the C&R rule or SEND-R system, a naturally occurring active transport system to selectively deliver anti-cancer drugs through the stroma and into the tumor. Lissata's lead product candidate, Lista-1, the recipient of multiple orphan designations, including for pancreatic cancer in both the United States and Europe, as well as for malignant glioma in the United States, is an investigational drug that actuates the Sendar active transport mechanism while also having the potential to modify the tumor microenvironment and make it less immunosuppressive. Lista-1 targets tumor vascular endothelial cells as well as tumor cells themselves based on its affinity for alpha-V, beta-3, and beta-5 integrins that are selectively upregulated on these cells in comparison to healthy tissue. Lista-1 is a 9-amino acid cyclic internalizing RGD peptide that, once bound to these integrins, is cleaved by proteases expressed in the tumor microenvironment to release a linear peptide fragment called a SEND-R fragment. The SEND-R fragment has high affinity for and then binds to an adjacent receptor called neuropillin-1. also upregulated on tumor vascular endothelial cells and tumor cells to activate the CN rule active transport pathway and ferry anti-cancer drugs more efficiently into solid tumors. Additionally, LISTA-1 has been shown in a range of preclinical models to modify the tumor microenvironment, making it less hostile to immune cells, reducing tumor resistance to anti-cancer medications, and impeding and or preventing the metastatic cascade. These results come internally from LASADA and from collaborators and research groups around the world and have been the subject of over 300 related scientific publications. Along with our collaborators, we also have amassed significant non-clinical data demonstrating enhanced delivery of a range of emerging anti-cancer therapies, including immunotherapies and RNA-based therapeutics. To date, ListaOne has demonstrated favorable safety, tolerability, and activity to enhance delivery of standard-of-care chemotherapy for patients with metastatic pancreatic cancer. Our development programs are designed to exploit the potential of ListaOne to enhance a variety of anti-cancer treatment modalities in a range of solid tumors. Currently, Lista-1 is the subject of about a dozen planned or active clinical trials globally for the treatment of various solid tumors. Let me touch on a few of these individually. The ASCEND trial is a 155-patient, double-blind, randomized, placebo-controlled clinical trial evaluating Lista-1 in combination with gemcitabine and nabpaclitaxel in patients with metastatic pancreatic ductal adenocarcinoma. also known as MPDAC. The trial is being conducted at up to 40 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 previously reported in September, a positive outcome from the planned interim futility analysis was announced by the studies Independent Data Safety Monitoring Committee, which recommended continuation of the study without modification. In addition, we are excited to report that full enrollment in Cohort A of ASCEND has been achieved and that overall enrollment in the study is now approximately 95% complete. With that, we now project to have top line data from Cohort A as early as the fourth quarter of next year, a full year earlier than originally anticipated. We plan to use the results of the ASCEND trial to explore possible conditional approvals in several jurisdictions and to design an optimized Phase III program in MPDAC. The BOLSTER trial is a Phase IIa, double-blind, placebo-controlled, multicenter, randomized basket trial with investigational sites planned in the United States, Europe, Canada, and Asia, evaluating Lista1 in combination with standards of care in advanced solid tumors, including head and neck, esophageal, and cholangiocarcinoma. This trial will include both cytotoxic and immunotherapy standards of care. As previously announced, patients have now been treated in the head and neck squamous cell carcinoma and cholangiocarcinoma cohorts, and we expect a first patient in the esophageal cancer cohort by early next year. Dendifox, the Phase 1b-2a open-label trial in the United States evaluating Lista-1 in combination with neoadjuvant full furanox-based therapies in pancreatic, colon, and appendiceal cancers continues to make steady progress with approximately 80% of the overall target number of subjects in the study enrolled. We expect enrollment completion of the pancreatic cohort during the fourth quarter of this year and completion of the remaining two cohorts over the next two quarters with data readout in pancreatic cancer in late 2024. This trial will provide us with pre- and post-treatment biopsy immunoprofiling data as well as long-term outcome data. Lista-1 is also being evaluated in combination with gemcitabine and nabpaclitaxel in a Phase 1b-2a open-label trial in China, led by our licensee in that territory, Qilu Pharmaceutical. During the 2023 ASCO Annual Meeting, Qilu Pharmaceutical presented an abstract sharing preliminary data from the study, which corroborated previously reported findings from the Phase 1b-2a trial of Lista-1 plus gemcitabine and nabpaclitaxel conducted in Australia in patients with metastatic pancreatic ductal adenocarcinoma. Final data are expected by the end of the second quarter of 2024. In collaboration with our funding partner, WARP9, the ILISTA trial is a Phase 1b, 2a, randomized, single-blind, single-center safety and pharmacodynamic study in Australia, evaluating ILISTA1 in combination with the checkpoint inhibitor, Dervalumab, plus standard-of-care chemotherapy, nabpaclitaxel, and gemcitabine, versus standard-of-care alone in patients with locally advanced, non-resectable pancreatic ductal adenocarcinoma. Enrollment completion is expected during 2024. IGOLISTA, a Phase I B2A proof-of-concept safety and early efficacy study evaluating LISTA-1 in combination with nivolumab, and Fulfironox as a first-line treatment in locally advanced non-resectable gastroesophageal adenocarcinoma is still pending initiation as a function of availability of funding by our partner, WARP9. We hope to have further update on timing related to the execution of the study in coming quarters. We are also poised to initiate the study of Lista-1 in combination with temozolomide in glioblastoma multiforme, or GBM. This study is designed as a Phase IIa, double-blind, placebo-controlled randomized proof-of-concept study evaluating Lista-1 when added to standard-of-care temozolomide versus temozolomide and matching Lista-1 placebo in subjects with newly diagnosed glioblastoma multiforme. It will be conducted across multiple sites in Estonia and Latvia and is targeted to enroll 30 patients with a randomization of 2 to 1, Lista 1 plus standard of care versus placebo plus standard of care. We are pleased to report that the EU clinical trial application has been approved, and we expect the first patient treated before the end of this calendar year. Importantly, as recently announced, Lista 1 has been granted orphan designation by the U.S. Food and Drug Administration for malignant gliomas. This action by the FDA not only highlights the unmet medical need, but also recognizes the potential of Lista-1 to benefit patients in this indication. Lastly, we also plan to initiate a study of Lista-1 in combination with hyperthermic intraperitoneal chemotherapy, more commonly referred to as HIPEC, intraoperative intraperitoneal lavage in peritoneal carcinomatosis. a cancer that develops as a result of contiguous spread of primary cancers such as ovarian, colorectal, and appendiceal along the peritoneum. The study will be a phase one, single center, unblinded, randomized, controlled trial to determine the safety and tolerability of Lista-1 administered intrapartineally in patients with peritoneal metastases from colorectal, appendiceal, or ovarian cancer undergoing cytoreductive surgery and HIPEC. Twenty-one total participants will be randomized two to one to receive Lista-1 with HIPEC versus HIPEC alone after cytoreductive surgery. We anticipate the first patient will be treated in the fourth quarter of 2023. For those who are interested, a more complete description of each of our trials is available in the appendix section of the corporate presentation on our website. Additionally, in the body of the presentation, there are two milestone slides that depict the anticipated timing of key execution milestones and data readouts from our trials. With that, I will now turn the call back to Dave.

Thank you, Kristen. In the last three and nine months of 2023, we have made notable progress on several fronts, including the broad application of LISTA-1 in combination with a variety of anti-cancer agents for the treatment of a variety of solid tumor types. To maximize impact and confidence in the results, we have designed our studies to be scientifically and medically rigorous and to provide results expeditiously while also assuring that we are operating in a maximally capital-efficient manner. Now, with more than two years of capital available on our balance sheet, we believe we are well-positioned to focus on the execution of our development plans and to achieve our goal of getting meaningful clinical data readouts as soon as possible. And with that, operator, we're ready to take questions.

presenters. And as a reminder, to ask a question, please press bar 1-1 on your telephone. You will then hear an automated message advising that your hand is raised. Each listener will be permitted to ask one question at a time and will be sent to the queue for any additional questions. Your question comes from the line of Steve Brozek of WBB Securities. Your line is now open.

Thank you for taking the question. I actually have one, but a follow-up as well because they're related. You've gone over a lot of trial descriptions. How would you describe as the meaning, the import of what these designations that you've been describing are to the trialing system? And I've got a follow-up after that, please.

Thanks, Steve. Appreciate the question. So, you know, I think actually it's a very pertinent question because in the industry we toss around the nomenclature of orphan drug designation and fast-track designation pretty freely. And I think most people might have at least a partial understanding, but I think it's worthwhile explaining. So let's start with fast-track designation. Fast-track designation allows the applicant That would be for a given product and a given indication to be eligible for accelerated approval consideration and for a more rapid review cycle with the FDA, both of which are extremely beneficial in terms of getting to market faster. It also allows for more interaction with FDA in a specialized way. And similarly, orphan drug designation, first of all, it points to the fact that the indication will have less than 200,000 patients in a given year diagnosed with that particular indication. And as a result, it's also eligible for more rapid review cycles, more rapid and consistent interaction with the agency. Importantly, you're also eligible to receive grants from the Orphan Drug Division of FDA to develop your products because often they're not as commercially lucrative. And finally, you get an extended period of exclusivity in the market. So that is, in addition to patent protection, you have some market exclusivity. So they're actually quite valuable designations. They're not given out freely. It's not something that you just make an application and you're guaranteed a result, but there's a pretty critical review process. And we were very pleased that the FDA and the EU have granted orphan drug designation for MPDAC to LISTA-1, and also for GBM-GLIO for LISTA-1 here in the United States.

Okay. And that actually highlights the next follow-up, and I'll hop back into Q. Thank you. You've got these, you know, designations which are obviously significant. You've got multiple programs running with quantifiable endpoints. You've been pretty much delivering on everything you said you were looking to do. Yet, obviously, the market isn't really viewing or understands this. What are your thoughts around on your market cap and specifically your stock price given your execution? What do you think it is? And thanks. And I'll hop back in the queue.

Thanks, Steve. I actually appreciate the opportunity to address that somewhat forthrightly because it's something that's on everybody's mind. There's a clear inconsistency with the advanced stage of our clinical programs, the positive data we've generated, our financial position, and the fact that we continue to execute according to plan and that the plan is rather comprehensive and a rather low market cap. In fact, anyone can look and see we're trading roughly somewhere between 35% and 40% of our cash on hand, which is just irrational. I think we have a couple of explanations for that. Part of it is that the entire biotech market has suffered considerably since the beginning of the year with high interest rates, and everybody's stock is down. But in our particular case, there are a few unique characteristics that I think are impeding a stock advance within the short term, but that I think are available to be overcome in the long term. One of those is that we are fortunate to have a large body of our shareholders. By our calculation, in rough terms, about two-thirds of our shareholders are long-only holders. These are people who have bought into the company either when it was in its private stages or at the time of our recent merger or in recent financing, but did so because they believe in the potential of the programs And in order to see the programs reach their maximum value, they are not trading the stock. They're ignoring the fluctuations in stock price and in the market. They're treating us much like they would treat an investment in a private company. And they're sitting back and waiting for the, in inverted commas, pivotal data to come out of these trials. And so with a very little float, that is a very small fraction of our shareholders trading actively on any given day, there's not really an opportunity for a market to be made for our stock. There's not a lot of people who are buying or selling. And those very few who do, we trade on average 20 to 25,000 shares a day out of over 8 million outstanding. It's a very volatile situation. So I think our opinion is that that will change based on two things. As we get to data, which, as those who have looked at our milestone slide will see, is going to be occurring throughout 24 and 25, and also as we then are able to announce additional business development deals and ultimately do another financing, which will allow larger funds to enter the stock because they can't do so on the market because of the low trading volume, I think we'll see that all change. But like most people right now in the biotech world, the real focus is on impeccable execution to data, generating as close to unambiguous data as possible, and then letting the product for themselves. So that's what we believe is the problem. There's certainly no issue with the fundamentals of our company, the execution, or our plan, which has been scrutinized pretty thoroughly by a lot of potential partners who are also just sitting there waiting for us to show data.

Got it. All right. Let me hop back into Q. Thank you for taking the questions. Thanks, Steve.

Thank you so much. And your next question comes from the line of Kent Bolivar from GroupLine Capital Markets. Your line is now open.

Hi. Good afternoon, and thank you for taking the question. First question regards the ASCEND trial, and admittedly, it may be too early to provide any insight on this, but the trial has enrolled very consistently and ahead of your original plan. And other than unmet need and potentially a great drug, which we'll just lay out as givens for now, what are your thoughts with regard to why this has worked so well? Is it a function of the populations in Australia and New Zealand being relatively treatment naive and there's less competition for trials? Or, you know, what have you seen going on that has worked to your benefit here?

Thanks, Kemp. Appreciate that. I think, you know, we see a couple of factors that are helping the trial enroll very, very rapidly. First of all, you know, It is a randomized and blinded trial, but in this particular trial, the people who receive the control arm are still receiving standard of care. So there's no downside to joining this trial. It's not as if you would be put on a true placebo and you would not get any treatment, which would obviously be unethical in an oncology trial. I think you've already touched on one of the situations there. There seems to be a large and growing presence of pancreatic cancer in this part of the world. And there are relatively few treatment centers because the population of Australia is concentrated around the edges of the country. The country is enormous, but as you all know, the interior is referred to as the outback because it's a desert-like area and there's really very little population. People are concentrated in areas and they go to these larger centers pretty regularly. It's not as if there are many, many centers around the country for them to go. And so the people who are at those centers have been actively involved in the development of our trial of our drug from the beginning. It was in Australia that the early phase 1B, phase 2A, very compellingly positive data were generated. And so there's an enthusiasm that I think is moving forward. And the fact that the addition of LISTA1 to standard of care doesn't seem to exacerbate The safety side effects of the standard of care is another reason why people are very eager to take on this particular trial. So as you pointed out, it's enrolling very rapidly. Cohort A has been enrolled since the May-June timeframe, and we're about 95% of the way there. So the official projection is we'll be done by second quarter of next year, but I think anybody can do a quick extrapolation and recognize that it likely to be done very, very much sooner than that.

Right. Thank you. And just looking at your spending guidance, which honestly looks pretty level over the course of the runway period, how sensitive would that be to the ebb and flow of enrollment in your trials? Because you have Ascend wrapping up sooner than expected. It's probably one of your larger trials at this point. So how should we think about the correlation between those two things from here?

Well, like all trials, spending is correlated. Except for startup at the beginning and closeout at the end, the steady state costs are per patient cost. So as you enroll, you incur expense. And then when you stop enrolling, you stop those types of expenses. But we also have to recognize that we have organized these trials, almost all of our trials, but Ascend specifically, to be done, first of all, in Australia, where the costs generally are lower than they might be in the United States, and where we get about 48% of all R&D dollars spent rebated back to us at cash at the end of the year. And also, we are essentially co-funding this trial, if you will. I mean, we're providing the maximum amount of funding, but the number of the standard of cares from the hospitals are being funded by those hospitals. So there will be a reduction in expenditure relative to Ascend once full enrollment is completed, but it may not be of the same magnitude that one might expect for a trial being completely funded by a sponsor here in the United States. But we still see a reduction in costs associated with that.

Got it. And I'm assuming those rebates would show up as a contrary to the expense line as opposed to the top, coming in on the top line. Is that right?

I'll ask our head of finance. James, what's the accounting on the rebate?

Yeah, that's correct. We do have four qualifying research and development activities in Australia. We are eligible to receive a refundable tax incentive between 43 and a half up to 48 and a half. So that does, you know, largely offset, you know, let's say half of the expenses for the Ascend study in Australia.

And is that accounted for as a reduction in expense or as revenue?

That is accounted for as a reduction in expense. So that would be a reduction to the R&D expense. So it's incorporated therein.

Thank you for that. Thanks, Kim.

Thank you so much. And your next question comes from the line of Pete Anderlin of MADS Partners. Your line is now open. Thank you.

My first question is a follow-up of an earlier one about the valuation of the stock, and that is since ListaOne, you know, seems to enhance the efficacy of a wide variety of oncology drugs and a variety of different modalities as well, the question is have you guys experienced any increase in inbound inquiries from bigger pharmas that are interested in collaborating with you?

Hi, Pete, and thanks for the question. It actually gives me a chance to talk a bit about the business development activities. The simple answer to your question is yes. And I mentioned earlier the consummation of a lot of those potential deals is going to be based very, very much so on the delivery of the data that will come out over the course of these years. I think all of these companies have products that do well by a variety of different definitions, but could clearly do better. And there's the implication so far with the data that's been generated to date that LISTA-1 can allow them all to do better. And that should lead us to a number of possibilities for either exclusive or non-exclusive deals, both on the R&D and the commercial side, with a lot of players in the oncology world, or just simply the ability to market LISTA-1 more broadly and have it utilized more broadly in the market when that time comes. But yes, we've had quite a lot of interest shown, and I think an expectation that that interest will continue to increase as data is generated.

And if I can qualify that a little bit in terms of drilling down, do you see different levels of interest depending on the types of cancer or also since there are varying side effects in a lot of these treatments, does it vary somewhat by the type of modality like chemo, RNA, immunotherapy, or whatever? Or is it pretty much across the board?

I would say it's reasonably distributed. The interest is reasonably distributed among people who are either developing new cytotoxics or already marketing chemotherapeutics or immunotherapeutics. We've even had discussions with radiopharmaceutical companies, companies that have antisense products, even companies with cellular therapies and nanoparticles. So I think there's a broad level of interest because the mechanism of action of LISTA-1, in theory, should help all of those better target solid tumors, and infiltrate those tumors.

And also reduce side effects, I guess, is an important part of it as well.

I don't know if it'll reduce side effects. I want to be very careful what we say. That would be wonderful. But what we will say is that the evidence to date shows that Lister 1 will not increase the side effects of those agents. So you should get better efficacy with the same level of side effects. Normally, to get better efficacy, you increase concentration and that leads to greater side effects. So I think we're going to be able, but I wouldn't say that we eliminate side effects. We're not that far along yet.

No, thank you. And then just one quick one for Kristen. Did you mention the number or the percentage of enrollment so far in the bolster trial? I didn't get it if you did.

No, I did not. The bolster trial recently opened and we're early in enrollment.

Okay. Thanks a lot. I'll get back in the queue. Thank you.

Thank you so much, and again, if you would like to ask a question, please press R11 on your telephone. And there are no further questions. This concludes the question and answer session. I will now turn the call back to Dr. Mazzo for closing remarks.

Well, 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. Stay well and have a good evening.