Welcome to the Lisata Therapeutics First Quarter 2023 Financial Results and Business Update Conference Call. Currently all participants are in listen-only mode. [Operator Instructions] As a reminder, this call is being recorded today, Tuesday, May 9, 2023. I will now 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 first 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, Chief Executive Officer; Dr. Kristen Buck, Executive Vice President of Research and Development and Chief Medical Officer; and James Nisco, Vice President of Finance and Treasury. Shortly before this call, we issued a press release announcing our first quarter 2023 financial results, which is available under the Investors & News section of the company website, along with the 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 e-mail distribution list, please email me at jmenditto@lisata.com. Before we begin, I remind you that comments made by management during this conference call will contain forward-looking statements and 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 only as of the date of this live broadcast, Tuesday, May 9, 2023. Lisata 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. Mazzo. Dave? Dave, I believe you may be on mute.

There we are. We're having technical difficulties today. My apologies, everyone. And thank you, John, for the introduction. And good afternoon, everyone, and thank you once again for joining us as we provide an overview of recent business highlights, discuss our first quarter 2023 financial results and give an update on progress of our various development programs. During the first quarter, the vast majority of our efforts remain focused on advancement of our clinical development programs for the treatment of advanced solid tumors. As those who follow us now know, Lisata is a clinical-stage therapeutic development company with a novel solid tumor targeting and penetration technology to improve the efficacy of anticancer drugs. Our development portfolio contains programs that are designed to bring significant therapeutic improvement in the treatment of solid tumors in a pharmacoeconomically attractive paradigm. LSTA1, our lead product candidate, is the subject of multiple planned and ongoing clinical trials being conducted globally in a variety of solid tumor types and in combination with multiple anticancer agents of different modalities. Based on substantial preclinical and, most importantly, early human clinical data, we believe that LSTA1 has the potential to become an integral part of a revised standard-of-care treatment regimen for many difficult-to-treat cancers. Our Chief Medical Officer, Dr. Kristen Buck, shortly will provide more specifics on our clinical programs following our review of financial results. However, before we get to those subjects, I will take a moment to elaborate on the organizational change that we announced last week. Operating a sustainable clinical-stage biopharmaceutical business involves constant vigilance of capital utilization and often difficult decisions by management teams and Boards of Directors involving programs and people. The need for scrutiny of resource allocation has become even more acute in the volatile and unpredictable capital markets environment of today and…

Thanks, Dave. Good afternoon all. I'm pleased to join you today to present a summary of our first quarter 2023 financial results. Starting with operating expenses. Research and development expenses were approximately $3.2 million for the three months ended March 31, 2023, compared to $3.3 million for the three months ended March 31, 2022, representing a decrease of $0.1 million or 3.2%. This was primarily due to expenses associated with our XOWNA Phase IIb study, the FREEDOM Trial, in the prior year, partially offset by study start-up activities in the current year associated with the planned Phase II proof-of-concept BOLSTER Trial studying LSTA1 in various solid tumors in combination with the corresponding standards of care. Enrollment activities for the LSTA1 Phase IIb ASCEND study and chemistry and manufacturing and control activities for LSTA1. General and administrative expenses were approximately $3.7 million for the three months ended March 31, 2023, compared to $3.3 million for the three months ended March 31, 2022, representing an increase of $0.3 million or 9.8%. This was primarily due to the addition of one employee acquired through the merger with Cend Therapeutics, an increase in external legal fees and an increase in accounting and tax-related fees. Overall, net losses were $6.2 million for the three months ended March 31, 2023, compared to $4.2 million for the three months ended March 31, 2022. Turning now to our balance sheet and cash flow. As of March 31, 2023, the company had cash, cash equivalents and marketable securities of approximately $61.1 million. These figures do not include the recently announced $2.2 million in non-dilutive funding that we received as an approved participant of the Technology Business Tax Certificate Transfer Program sponsored by the New Jersey Economic Development Authority, which will be recorded in the second quarter of 2023. As we have reported previously, the program enables qualifying New Jersey-based biotechnology companies to sell a percentage of their New Jersey net operating losses and research and development tax credits to unrelated qualifying corporations. With several operational initiatives underway that will help manage external costs and, as Dave mentioned, the elimination of the President and Chief Business Officer position, we now project that our current available capital should take us into the first quarter of 2026, encompassing anticipated data milestones from all of our ongoing and planned clinical studies. 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. I realize that we just reviewed our programs a few weeks ago during our full year 2022 results call, but I believe it's important to keep our stakeholders up to date on the continuous progress being made by the Lisata team. Lisata'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 technologies are designed to address major impediments to successful treatment of solid tumors in the context of increasing pharmacoeconomic pressures on the health care system. We appreciate the critical importance of generating meaningful clinical data to advance our platform technology, 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 a summary and status update for each of Lisata's active clinical development programs. Kicking off with our lead product candidate, LSTA or LSTA1, for the treatment of advanced solid tumors in combination with other anticancer agents. Despite advances in cancer therapy today, many solid tumors remain difficult to treat effectively. Cancers such as pancreatic cancer, gastric cancer and other solid tumors are surrounded by dense fibrotic tissue known as stroma, which limits access of most pharmacotherapies to the tumor. Many tumors also exhibit 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 TME negatively impacts the ability of many cytotoxic agents and immunotherapies to effectively treat these cancers. This, coupled with the fact that most anticancer therapies are not efficient in targeting only cancer tissue, defines the major challenge in maximizing effectiveness and safety in the treatment…

Thanks, Kristen. As Kristen has outlined, the Lisata team is making continual progress advancing our development programs with the goal of maximizing the potential of our development pipeline. 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. We are excited by the promise of our platform technology and are committed to achieving meaningful data readouts as soon as possible with the goal of benefiting patients, the physicians who treat them and our shareholders. And with that, operator, we're now ready to take questions.

[Operator Instructions] Our first question comes from Steve Brozak with WBB Securities. Your line is open.

Yes, hi. Thanks for taking the question. In listening to the list of trial approaches, I'm seeing that everything is really adding to the current standard of care in all of these critical indications. What kind of feedback are you getting from your clinician partners that you're working with on what they're seeing, the importance and how this basically works into what they've done in the past? And I'll hop back in the queue after that. Thank you.

Thanks, Steve. Nice to talk to you. And appreciate your question. So before we started these trials, Kristen spent a good deal of time talking to key opinion leaders, influential practicing oncologists throughout the country and, in fact, throughout the world to get their feedback on where the highest unmet medical needs were, which solid tumors were the ones where we could make the biggest difference and whether or not they felt that the approach that we were espousing actually was sensible to them. And the feedback that we got then which led to the initiation of these trials and the feedback that we continue to get is that the clinicians are extremely enthusiastic about the prospect of taking existing standards of care and actually making them optimized, making them work maximally in terms of efficacy without causing any further detrimental safety issues. They think that this is an approach that will be faster to conclusion, faster eventually to potential market and faster to patients in the long run than brand-new NCEs that have to start developing an efficacy profile from scratch. And they also believe that in this pharmacoeconomically challenging environment where the Inflation Reduction Act and other pressures are putting increased scrutiny into drug prices and looking for ways to introduce innovation in a cost-effective manner, the ability to take something as simple as a small cyclic peptide and use it to significantly augment the efficacy of known drugs, many of which are already generic or will be generic, seems to make a lot of sense to them. And of course, our trials are mostly blinded, so they can't see any specific results per se, but there's a strong sentiment among them that LSTA1 is doing exactly what we reported to do.

Can I tack on one addendum? On the regulatory side, given the fact that obviously it's one of the considerable hurdles in these spaces, what do you see there in terms of the advantage? And again, this time, I will hop back in the queue.

Well, I think the advantage from a regulatory perspective is, to some extent, obvious. When you're just adding something into an already existing regimen, and we -- and by adding, I mean we simply co-administer these products. So there's no -- the only mixing, if you will, that takes place is inside the body. That makes formulation and stability and all of those chemistry and manufacturing control issues simpler to deal with. These are not new chemical entities in the sense that we're not tethering the anticancer agents with LSTA1, so lots of preclinical work doesn't need to be done. Separate toxicology doesn't need to be done on these new entities. And the fact that LSTA1 in and of itself seems to be so benign from a safety perspective makes this very easy to go -- to predict. And so we've had very positive interactions with the FDA, the TGA in Australia, and we've just started our interactions with the EMA in Europe. And so far, we haven't seen any particular hurdles, and the discussions are proceeding as we expected.

Go it. Again, thanks for taking the questions. And let me hop back in the queue.

Thanks, Steve.

Thank you. Our next question comes from Kemp Dolliver with Brookline Capital Markets. Your line is open.

Great. Thank you. Couple of questions regarding the ASCEND trial. First is you amended the protocol in the last few months, and I want to get more details regarding the changes and the rationale for the changes.

Certainly, Kemp. Thanks for dropping on the call and for the question. So we actually will be releasing some information in the next couple of weeks. We will give a much broader discussion of the evolution of ASCEND, but I can give a top line summary right now. When ASCEND was started, it has had sort of a single purpose was to replicate the Phase Ib/IIa data but in a placebo-controlled trial. And the AGITG did something that typically a commercial drug developer wouldn't do, but they actually decided that they wanted to power the trial to determine some efficacy endpoints as well. So that was the trial that we inherited. When we looked at that trial, we saw that, that was great, but there were at least one other thing that we thought should have been done, and that's the basic tenet of the amendment and that we added a second cohort of patients, very creatively called cohort B. And that second cohort actually will receive two doses of LSTA1 separated by about four hours. So they still receive gemcitabine, nab-paclitaxel and LSTA1 essentially co-administered at the start. But four hours later, they'll get a second dose of LSTA1. And the reason for that is, if you look at the pharmacokinetic profile, the Cmax, the Tmax and the half-life of these different compounds, you realize that gemcitabine has a half-life of roughly 2 hours or 90 minutes or something like that. LSTA1 has a half-life of about the same, but nab-paclitaxel has a half-life of about 10 to 12 hours. And so there was at least some thought process that said if you waited two or more half-lives after the first dose of LSTA1, essentially, you're outside the therapeutic range of LSTA1, gemcitabine is all gone, but you're still within the therapeutic range of nab-paclitaxel. And a second dose of LSTA1 might provoke improved penetration of the remaining nab-paclitaxel into the tumor and might have a positive effect on tumor efficacy. So in some ways, this is part of what would be a typical Phase IIb trial in that we're doing a little bit of dose ranging, if you will, as part of the trial as well. But we have now also these 2 cohorts, and so we can compare each cohort against placebo and then the 2 cohorts against each other and then perhaps the combination of the 2 cohorts if there's no difference against placebo as well and get a really strong indication of therapeutic effect size as well as safety profile for the -- what would be likely the Phase III trial that would follow.

Great. That's helpful. So you mentioned powering and, I think, registrational trial, but that would seem to be -- is it fair to say that that's possible but low probability?

Yes, that's our -- our expectation is not that this will be a registration trial but that it will be a solid support for designing a registration trial that will go forward. Now that said, we will pursue every avenue with FDA and especially the TGA in Australia, where the majority of the sites are for this trial, to see if the data are positive and statistically significant, if they would consider an accelerated path or a conditional path to approval.

Super. Thank you.

Our next question comes from Pete Enderlin with MAZ Partners. Your line is open

Thank you. Hi, everybody. Conceptually, I thought that, originally, the idea was that LSTA1 could either be co-administered, which is what you're just talking about, or tethered. And you just said, Dave that that's not really what you're anticipating now. So is it true that you're really not contemplating...

No, let me clarify. Okay. So the two approaches, either co-administration or tethering, remain distinct possibilities. I think in the past I've described the co-administration approach as the rapid -- most rapid approach to a first registration for the reasons that I outlined briefly a moment ago. With tethering, you create a new chemical entity that needs to be fully characterized both biologically and chemically. And those are much -- you're basically starting from 0 with that kind of product. With co-administration, you're basically starting using the knowledge base of the established standard of care and just adding on to it. So it's a simpler, faster, most likely less expensive way to getting to answers and to a registration. And that's what we're pursuing first. But it doesn't mean that tethering is off the table. It just means it's second in line from a priority perspective internally.

Thanks for clarifying that. And then sort of looking several years ahead, but that's what we try to do, when you're talking about combination therapies, which is what these all are, and the agreements that you have or the ones that you contemplate and try to enter into, do you tie the sales and the pricing together? Or is each company sort of on its own and they're separate and independent for each entity that you bring to the party in a particular application or indication? For example, I mean, you can have gemcitabine or paclitaxel and LSTA1, and you could either have a package sale or sell them and price them independently. So which way do you typically anticipate going?

So we would -- right now, the anticipation is that this will be an add-on to existing therapy. And those -- as I said, those therapies could already be generic or could become generic by the time we get to market. But our product will not be generic. It will still be under patent. And it will be priced accordingly as an add-on, which augments efficacy of those less expensive and more tried-and-true, well-characterized standards of care. So I think that it would be unlikely based upon our current thinking that we would bundle these, meaning actually package them together and price them as a bundle, because we wouldn't own the other products. We wouldn't be in a position to manufacture them. We could source them and bundle them, but there's no real benefit necessarily to doing that. And what we're doing is looking to create a large list of nonexclusive opportunities that essentially demonstrates that in combination with certain products, those products get better, and so their sales will benefit. And it only works if they add on with us, and so we will benefit separately. Now as we get further along, it's not completely out of the question that someone would want to make this an exclusive benefit in a class of compounds, and so we would price a deal for exclusivity appropriately in that case.

But -- and the initial agreements that you have with these other players, you don't really spell out exactly what -- any such combination?

The current agreements are essentially development agreements. They just say that we will work together to demonstrate, hopefully, that the addition of LSTA1 improves the products that are already considered standard of care. And if that works, as I said, that will be enough to improve everyone's bottom line in the long run. But at that point, it's possible that those companies may want to enter into exclusive deals to prevent us from being combined with other compounds of the same class in those indications. And in order to get exclusivity like that, the deals would have to be much richer as it relates to us.

Right. Okay, great. Thanks a lot.

Thank you. Our next question comes from Joe Pantginis with H.C. Wainwright. Your line is open.

Hey, everybody, good afternoon. And thanks for taking the question. Two questions, if you don't mind, Dave. So first, it's nice to see you guys continuing with your track record on cash management especially in the continuing environment. So with that said, I guess my two questions really are, obviously, you're expanding your clinical trial, so that will be the lead driver for expenses increasing. But where do you currently stand on your current manufacturing needs for LSTA1 as well as your interim to more long-term needs?

Thanks, Joe. I appreciate the question and thanks for participating. So as I think both James and Kristen have said during their prepared remarks, with the changes that we've made, we now can assure that we will fund all of our programs. And as I've mentioned, I think, in the past, some of these programs are co-funded, and many of them are being operated in areas where we'll get R&D rebates, which contributes to a reduction in costs. And some of them are completely funded by the other partner, but yet we retain rights to our product. With that said, we now can project with a fair degree of confidence that we will be, with our existing capital, able to fund all of our programs, both ongoing and proposed, as outlined in the corporate presentation, through to availability of data. And so that's into the early part of 2026. And all of the things that we talked about starting are already included in that as are all of the drug and manufacturing needs, including clinical supplies as well as the appropriate validations and stability, manufacturing and lots to keep the CMC portion of development essentially in line with the clinical portion.

That's great to hear. And then curious, with all the programs that you discussed today, which one of these indications have the -- I would say, like the rate-limiting step with regard to patient enrollment with regard to competing for patients with other studies?

There are a fair number of pancreatic cancer studies ongoing, and there are studies in all these other solid tumors. So we do have competition, but I think there is quite a bit of enthusiasm about our trial. And you know what, rather than fumbling through this answer, I'm going to put Kristen on the spot and see if she can give some sense about what we think will be the toughest to enroll and how we've constructed our enrollment projections.

Yes, thanks for the question. And I'll start off by saying we do have a lot in pancreatic cancer, but we've been very careful to not have them cannibalize each other such that some -- as you well know probably, pancreatic cancer has 2 main standards of care, FOLFIRINOX and gem/nab-paclitaxel. So we've tried to exploit both of those standards of care such that those who are eligible for FOLFIRINOX will have a separate trial, and those who are eligible for gem/nab are in a separate trial. And then in one of our pancreatic trials, we are doing nonresectable locally advanced such that we could change a tumor that is nonresectable and make it resectable. So that's a different patient population. For the ASCEND trial, there really isn't competition because it is occurring in Australia. So if I were to answer the second question, which is the hardest to recruit, I would say one of the arms of the BOLSTER Trial may be difficult to recruit, which is esophageal -- excuse me, esophageal carcinoma squamous cell type. It's not the most common in the U.S., but it is the most challenging to treat, so we may have to go to Asia and other parts of Europe to recruit this trial. But for the most part, we've been very diligent and strategic in choosing our patient population such that we wouldn't internally cannibalize each of our trials.

Got it. Appreciate all the color.

Our next question is a follow-up from Pete Enderlin with MAZ Partners. Your line is open.

Yes, just a quick one. What do you have in the way of remaining New Jersey tax NOLs? And what would be the timing of their availability and contemplated use of those?

Okay. Well, the contemplated use is easy. We applied that to what generally is characterized as general...

No, no, I mean, how soon you take advantage of them. I know you use it for whatever. But...

Right. So we have approximately $2 million to $3 million left under the current program, which caps every company at $20 million lifetime benefit. That could change. It's already changed once two years ago from $15 million to $20 million. The state could raise it again. But under the current cap, we have a couple of years of availability left in terms of -- and we probably collect roughly half next year and half of what's remaining the following year, and that would probably take us to the cap. So that's roughly somewhere between $1 million to $1.5 million a year over the next two years is what remains in terms of current eligibility.

Okay. Well, every bit helps.

Yes.

Nice one.

Thank you. This concludes the question-and-answer session. I would now like to turn the call back over to Dr. Mazzo for closing remarks.

Thanks, operator. And again, thank you all for participating to today's call. And I really appreciate the questions that gave us the opportunity to provide some additional color. We look forward to speaking with you again during our next quarterly conference call and continuing to provide updates on our achievements and progress. We remain grateful for your continued interest and support in Lisata. And we wish you a very good evening. Thank you, and goodbye.

Thank you for your participation. This does conclude the program. You may now disconnect. Everyone have a great day.