Lantern Pharma - Q2 2024

Transcript

Operator (participant)

Good afternoon, and welcome to our Second Quarter 2024 Earnings Call. As a reminder, this call is being recorded and all attendees are in a listen-only mode. We will open the call for questions and answers after our management's presentation. A webcast replay of today's conference call will be available on our website at lanternpharma.com shortly after the call. We issued a press release after market close today, summarizing our financial results and progress across the company for the second quarter ended June 30, 2024. A copy of this release is available through our website at lanternpharma.com, where you will also find a link to the slides management will be referencing on today's call. We would like to remind everyone that remarks about future expectations, performance, estimates, and prospects constitute forward-looking statements for purposes of safe harbor provisions under the Private Securities Litigation Reform Act of 1995.

Lantern Pharma cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated. A number of factors could cause actual results to differ materially from those indicated by forward-looking statements, including results of clinical trials and the impact of competition. Additional information concerning factors that could cause actual results to differ materially from those in the forward-looking statements can be found in our annual report on Form 10-K for the year ended December 31, 2023, which is on file with the SEC and available on our website. Forward-looking statements made on this conference call are as of today, August 8, 2024, and Lantern Pharma does not intend to update any of these forward-looking statements to reflect events from circumstances that occur after today, unless required by law.

The webcast replay of the conference call and webinar will be available on Lantern's website. On today's webcast, we have Lantern Pharma CEO, Panna Sharma, and members of management. Panna will start things off with introductions and an overview of Lantern's strategy and business model, and highlight recent achievements in our operations, followed by discussions of our financial results and a discussion of the HARMONIC clinical trial results. I'd now like to turn the call over to Panna Sharma, President and CEO of Lantern Pharma. Panna, please go ahead.

Panna Sharma (CEO)

Good afternoon, and thank you, everyone, for joining us to hear about our incredibly productive second quarter of 2024. Today, on the call, I have our CFO, David Margrave, and also our Head VP of Clinical Development, Dr. Reggie Ewesuedo. I'll begin the call by discussing generally the quarter and then hand it over to David to talk about the financials, and then Reggie and I will discuss the progress with our LP-300 clinical trial. As many of you have heard me say in the past, computational and AI-driven approaches are increasing their presence and usage at both large and emerging pharma companies for all facets of drug discovery, chemistry, biology, and even now, manufacturing and patient selection.

At no time has this been more evident than today, where every facet of pharma development, from molecular design to disease modeling, is being rethought as a result of the widespread availability of computational capabilities, high-quality data, and improved automation. Our company's leadership in the innovative use of AI and machine learning to transform costs and timelines in the development of precision oncology therapies should yield significant returns for investors and patients as our industry matures and adopts an AI-centric, data-first approach to drug development. Today, we have three active clinical trials with an additional ADC-based preclinical program and a very active approach in identifying and validating combination approaches with our drugs. With our RADR AI platform, which is at the forefront of cancer drug development, we expect more activity and opportunities where we can continue to use our AI as currency for collaborations, partnerships, and co-development opportunities.

We also plan to continue driving the ongoing innovation in our portfolio of drug candidates and drug programs. This past quarter was a particularly busy one for Lantern, and especially with our clinical operations team, as we had a notable initial readout in our phase 2 HARMONIC clinical trial, where we saw a preliminary but interesting 86% clinical benefit rate in the lead-in patient cohort. Our intellectual property also continues to grow globally, and we were awarded a very important patent in Japan, directed at our LP-284 drug candidate, which is focused on the treatment of B-cell cancers. Going back to our clinical trials, we have also dosed over 40 patients now in our LP-184 and LP-284 clinical trials.

These are trials that are in Phase 1a, and they have not yet seen any dose-limiting toxicities or events, which we will discuss more in depth later in the call. Our team has also achieved significant advancement towards a key milestone in the development of a molecular diagnostic for use with our drug candidate, LP-184.

We expect to potentially use this diagnostic to improve patient selection and stratification, and the novel biomarker is PTGR1, one that we validated extensively, both in the lab but also in silico, and was identified through a number of in silico AI-driven screens. We also launched a very important strategic drug development collaboration using our AI platform, Oregon Therapeutics, to optimize the development of a first-in-class drug candidate, XCE853, a potent inhibitor of cancer metabolism, which we believe can have impact across multiple cancers and has a unique mechanism of action involving proteotoxicity. With Starlight Therapeutics, our wholly-owned subsidiary, focused on CNS and brain cancers, we advanced towards initiating site selection and feasibility for a phase 1b/phase 2 trial in recurrent GBM with drug candidate STR-001.

Our team also successfully launched Webinar Wednesdays, a webinar series focusing on the areas of artificial intelligence, oncology drug development, and leveraging our relationships with leading physician scientists and our collaborators. We also closed the quarter with approximately $33.3 million in cash, cash equivalents, and marketable securities, which our CFO will talk about later in today's call. Many of the initial observations made with the help of RADR are now being witnessed in the clinic, as many of you know. RADR has guided the rapid and efficient development of three AI-guided drugs into clinical trials over the past several years at a pace and cost that has traditionally been unheard of in our industry. Let me walk you through some of the highlights from our AI-powered pipeline, which is, again, currently in the clinic, before I talk about other aspects of our business.

Specifically, with LP-184, our team and many clinicians are particularly excited about and interested in these programs for first-in-human, synthetically lethal drug candidates that are acylfulvenes, LP-184 and LP-284. So far, 7 cohorts of patients, comprised of dose levels 1 through 7, have been enrolled in escalating doses in the ongoing Phase 1a clinical trial for LP-184. This is a first-in-human Phase 1 trial across multiple solid tumor indications that are advanced and refractory to the existing standard of care. Very exciting for us, as there have been no observed dose-limiting toxicities to date. Now, we're at the point in the trial where we expect to reach a dosage level in the coming cohorts, where therapeutic concentrations of the drug should be attainable based on our pharmacokinetic and pharmacodynamic analysis.

It's a mouthful, but all that means is we should start potentially seeing benefit in patients at these cohorts going forward. The trial is actively enrolling patients across multiple U.S. centers. These patients are relapsed, they're refractory to all existing standard of care, typically, and they have advanced solid tumors such as pancreatic cancer, glioblastoma, triple-negative breast cancer, and also now increasingly with solid tumor types, focused on DNA damage response deficiencies. The company believes that enrollment should be complete this year and on track for an initial readout of safety and molecular correlation data by the close of the year.

The dosage and safety data obtained in the phase 1a trial for LP-184 are expected to be used to advance the central nervous system indications for the phase 1b and phase 2 trial, to be sponsored by Lantern's wholly-owned subsidiary, Starlight, as well as other later-phase trials in select tumors that have shown superior responsiveness to LP-184, and also meet our genomically-guided criteria. AI and preclinical studies are also ongoing to further refine drug combination studies. Many of you saw the press release from yesterday, and this press release supports, at least tend to support, the improvement to durability and response with other FDA-approved drugs. Specifically, we published on PARP inhibitors earlier this quarter, and yesterday in immune checkpoint inhibitors.

These are two very exciting areas where the combination of our drug with these, some of the existing approved agents, many of which are multi-billion dollar drugs, actually, we feel, can benefit patients in certain solid tumors, like triple-negative breast cancer or others that have DNA repair deficiency. Globally, the aggregate annual market potential for LP-184's target indications, we believe, is in excess of $10-$12 billion, consisting of about $4-$5 billion in CNS cancers and $7-$8 billion for other solid tumors. For LP-284, the third cohort of patients are being dosed, and no dose-limiting toxicities have been observed in this Phase 1a trial, and we expect to open additional sites throughout the quarter, with the potential to advance to Phase 1b and Phase 2 by the close of this year or early 2025.

LP-284 has shown nanomolar potency across multiple published in vitro and in vivo studies, including mantle cell, double-hit, and other non-Hodgkin's lymphomas, and especially those with DNA damage response deficiency. We published in cancers that had compromised functioning of ATM due to mutations or deletions. Now, nearly all MCL double-hits, high-grade B-cell lymphoma patients, relapse from the current standard of care agents, and there's this urgent and unmet need for novel improved therapeutics for these patients. We believe the annual market potential in this group is in excess of $3 billion. We've also begun a review of some notable mechanism of action that we've observed in LP-284, and we think we can actually leverage those in other diseases and conditions. Lantern expects to review those preclinical studies and findings later this quarter. Our current enrollment efforts are focused-...

On cancer patients with tumors that have what's called DNA damage repair deficiency. They've been observed to have higher sensitivity to 184, and even in some cases, 284. So DDR genomic alterations are of interest for these trials, and we may consider other genomic alterations based on other emerging data. We also continue to make significant progress in the launch of our clinical-stage, CNS, and brain cancer-focused subsidiary, Starlight Therapeutics. This is a company that has been largely developed as a result of big data.

Because the billions of data points that we had in our system, we used AI methods to look at specific indications, validated those computationally, optimized our understanding, and then took them into studies, wet lab studies with animals and mice and PDX models, and now we're actually at a point where we can start taking these indications into the clinic. Notably, we've also actually started site selection for the upcoming phase 1b and phase 2 trials, especially in recurrent IDH wild type high-grade gliomas like GBM. This is very different than the most recent approval, which was an IDH mutant. So if you've not reviewed our webinar Wednesday on Starlight with Dr. Marc Chamberlain, I would definitely urge you all to listen to the webinars, where we provide in detail the timing and focus of the trials that we anticipate launching with Starlight.

Now, the golden age of AI in medicine is just beginning, as witnessed even today by a discussion of today's merger among two big, AI companies, Recursion, in the U.S., and Exscientia in the U.K. And there's a need to really use large-scale, highly available computing power, massive data storage, and the tremendous high-def biology that's available today, and that is what we're at the forefront of. But we're also, at Lantern's way, we're harnessing those capabilities in a way we believe is much more efficient. We want to harness these capabilities in this emerging tech bio industry and be a long-term leader, not only where we create massive value for patients and also continue to drive innovation, but we're also thoughtful about the economics of cancer drug development. It's one of the first reasons many of us joined these companies.

We wanted to not only make drugs faster, but we also wanted to make them smarter and cheaper. Lantern is at the, among the leaders in this transformation of the pace, the risk, and the cost of oncology drug discovery and development. This transformation has a promise not only to make medicines faster, cheaper, and with increased precision for patients, but also to help change the direction of R&D productivity and output in cancer, in the cancer biopharma industry. Now, let's turn to our focus to our financial updates and highlights with David. I'll now turn the call over to our CFO, David Margrave, who'll provide an overview of our quarter's financial results. David?

David Margrave (CFO)

Thank you, Panna, and good afternoon, everyone. I'll now share some financial highlights from our second quarter ended June 30, 2024. We recorded a net loss of approximately $4.96 million for the second quarter of 2024, or $0.46 per share, compared to a net loss of approximately $4.75 million, or $0.44 per share for the second quarter of 2023. For the second quarter of 2024, our R&D expenses were approximately $3.9 million, up from approximately $3.6 million for the second quarter of 2023. This increase was largely driven by an increase in clinical trial activity. Our general and administrative expenses for the second quarter of 2024 were approximately $1.5 million, down slightly from approximately $1.6 million for the second quarter of 2023.

The decrease was primarily attributable to decreases in payroll and compensation expense and decreases in insurance expenses. Our R&D expenses continue to exceed our G&A expenses by a strong margin, reflecting our focus on advancing our product, candidates, and pipeline. Our loss from operations in the second quarter of 2024 was partially offset by interest income and other income net, totaling approximately $449,000, as compared to interest income and other income net, totaling approximately $444,000 for the second quarter of 2023. Our cash position, which includes cash equivalents and marketable securities, was approximately $33.3 million as of June 30, 2024. We anticipate this balance will provide us with a cash runway into at least Q3 of 2025.

Importantly, we believe our solid financial position will fuel continued growth and evolution of our RADR AI platform and continue the advancement of our portfolio of targeted oncology drug candidates. As of June 30, 2024, we had 10,758,805 shares of common stock outstanding, so about 10.75 million shares of common stock outstanding. We had outstanding warrants to purchase 81,496 shares of common stock and outstanding options to purchase 1,063,548 shares of common stock. These warrants and options, combined with our outstanding shares of common stock, give us a total fully diluted shares outstanding of approximately 11.9 million shares as of June 30, 2024.

...Our team continues to be very productive under a hybrid operating model. We currently have approximately 22 employees and four FTE consultants focused primarily on leading and advancing our research and drug development efforts. We see this number expanding slightly in coming quarters as we add additional experienced and talented individuals to help advance our mission. I'll now turn the call over to Reggie for a review of initial phase 2 patient results and future directions for our HARMONIC trial. Reggie?

Reggie Ewesuedo (VP of Clinical Development)

Thank you, David. I will start off by reviewing the study design for the HARMONIC trial. There are two stages in the HARMONIC trial. Stage one is the safety lead-in and then the randomization and expansion stage of the study. It is worth noting at this point, though, that investigators are completely satisfied and aligned with this strategy because it aligns very well with current dosing intervals for the standard of care regimen, as well as the disease evaluation intervals. I will spend the remaining of my time really going over the data. The safety lead-in is now completed with a total of seven patients enrolled, and the preliminary data is the subject of my presentation in most of the subsequent slides. The study started with geographically dispersed sites in the United States, with Dr. Treat at Fox Chase as the global lead investigator.

The number of sites have now been extended to the Asia-Pacific region and includes renowned investigators like Dr. Goto at the National Cancer Center Hospital in Tokyo, as well as other experienced and reputable investigators, both in Japan and Taiwan. The obvious need for this expansion of sites should be pretty obvious. This is due to the fact that relatively high prevalence of the patient population in that part of the world. So let me now present the clinical data as it relates to safety when LP-300 is combined with the standard of care chemotherapy doublet. To summarize, the safety profile is in keeping with what is expected for the standard of care regimen. Overall, the events observed were primarily grade one or two adverse events. Now, most of these events seen in this presentation were attributable to a single patient who entered the study with multiple comorbidities.

Of note, however, having completed this stage of the program, there were no dose-limiting toxicities, severe adverse events, or more importantly, new unexpected toxicities reported. No patient has discontinued any of the treatment due to toxicity. Now, this is key to a new regimen because it speaks to the tolerability of the triplet regimen. I will now hand over the presentation to Panna, the CEO, to review the key takeaways from the clinical data, and I will join him as part of that presentation.

Panna Sharma (CEO)

Thanks, Reggie. I wanna review for everyone the key patient characteristics and our study's endpoints, and obviously, these will remain the same as we go now from the lead in to the expansion phase. The patients are all never smokers that have histopathological evidence of stage three or four primary lung adenocarcinoma. They have to have TKI molecular alterations such as EGFR, MET Exon 14, ROS1, BRAF, ALK, and TRK fusions. They have to have relapsed after one or more lines of therapy with those TKIs. So obviously, these are identified TKIs, which we believe are a small family of all the potential TKI mutations that can possibly occur. That's of no important note because our drug, we believe, has effects on the TKI receptors.

The study endpoints are progression-free survival and overall survival, and we'll give you a little discussion on what we've seen as benchmarks for those toward the end. The secondary endpoints, which we have some of, some of which today are objective response rate, duration of response, and clinical benefit rate. Again, it's very surprising oftentimes that those who stop responding to those TKIs that are never smokers actually have very poor duration of response and after they go to chemo doublets. In fact, usually well under five and six months. So there's a very urgent need for targeting this population. Reggie, you wanna talk a little bit about some of the patient highlights so far?

Reggie Ewesuedo (VP of Clinical Development)

Yes, absolutely. So maybe if we go on to the next slide. As required, one of what we do in clinical trials, obviously, is to look at the data from different angles. The first thing we did here was to look at the spider plot, which goes over the preliminary data, but with the intent to really understand the attributes of the regimen. What you see on this slide or presentation is the onset of the clinical benefit. This is rapid, and it will appear durable. Now, this is key. So what we're expecting is from the regimen, if a patient is treated within the first three cycles, if they are going to derive clinical benefit, that should be sustainable, and that's what we're beginning to observe.

So we'll go on to the next slide, and we'll look at the data from another perspective, which is the waterfall plot. Now, it gives us the magnitude of the clinical benefit, and as you can see on this presentation, it's quite impressive. The response is just after 3 cycles, and this has been seen virtually for all the patients in this cohort. The emerging durability of the clinical benefit, however, is presented on the next slide, which is the swimmer's plot. So again, you begin to get a sense from this presentation that the 86% disease control rate in this patient population with a 43% objective response rate, which includes one patient maintaining a 50% reduction in tumor size over 14 months. Clearly, we are encouraged by these preliminary results. We've shared the results with investigators.

They all, without exception, are very encouraged with what we are seeing here with this regimen. So I'll now go on to the next slide, which talks about really the demographics of this patient, and I want to pay particular attention to where we think we are seeing this benefit in the patients. We are closely monitoring the patients, but it is very clear from this that there are a couple of encouraging observations while assessing the demographics and specifics. One, the patient population is relatively more heterogeneous. That will be the case with typical studies in this space, which tend to be restricted to one driver mutation populations. Two, the tyrosine kinase receptor genomic alterations at baseline is other than EGFR or EGFR alone.

So the 1 or 2 patients we call mutation at baseline, we know those patients don't tend to do well with EGFR, the targeted therapies. But you will also notice that after 3 cycles, the tumor response is remarkably exaggerated at metabolic lesion sites, leading to complete disappearance or resolution to normalcy in size in the case of lymph nodes. Patients with low or intermediate tumor mutational burden are deriving clinical benefit, which is very exciting to us because we believe this will pave the way for a more acceptable and adaptable biomarker selection strategy, since this assessment is already part of routine clinical practice. My next slide relates to the prior lines of cancer treatment and the response we're observing so far. Looking at this data, the median number of prior lines of therapy is 2, with a range of 1 to 4.

Notwithstanding, the preliminary efficacy data suggests that regardless of the number of prior lines of treatment or type of prior tyrosine kinase inhibitor treatment, LP-300, when used in combination with standard of care regimen, is likely to provide clinical benefit. Now, it's important to point out that one of the patients in this cohort had already been exposed to carboplatin chemo doublet but still derived remarkable and durable response. We strongly believe that based on the mechanism of action of LP-300, what we are seeing here is what we've always come to know about the drug, which is that the drug is known to resensitize tumor cells to the effect of chemotherapy through a mechanism where it resets the redox cycle. So this is very encouraging set of data for us. And again, all the investigators, including Dr.

Treat, that we've shared the data with, are very excited, and we look at this as being very promising. Next slide. So I will just review the top part of this slide, and I will invite the CEO, Dr. Sharma, to review the latter part of this slide. So to summarize, we have 7 patients that have been enrolled in the stage one or the safety leading phase of the study. 6 out of 7 patients have derived clinical benefit. 3 of those are partial responders, which are really significant in magnitude of response, including very remarkable reduction in metastatic lesion sites, with an average tumor size reduction of about 51%. There are 3 noticeable stable diseases which have resulted in an average of about 13% tumor size reduction.

Overall, with a clinical benefit rate of 86% and an overall response rate of 43% from this initial cohort, we believe that this is very promising. Notably, from a safety perspective, there are no DLTs, no serious adverse events in excess of what one would expect from the standard of care chemotherapy regimen, but more importantly, no new added toxicity to the doublet regimen, which tells us very clearly that after 3 cycles, this is a regimen that is very tolerable and most welcome in this space. I will hand over to Panna to review the last part of this slide.

Panna Sharma (CEO)

Yeah, thanks, Reggie. So obviously, the key ongoing consideration is really the measuring for the durability of response for going forward, and that's going to be very important for us. You know, we are considering, we believe, to file for a Breakthrough Therapy Designation if we continue to see the types of trends that we're seeing, which again, isn't just the clinical benefit rate, but also, as Reggie pointed to, that there's no increase in toxicity or adverse events, which is very important, because oftentimes in this patient group, again, you're looking at some serious adverse events. And so far, we've been fortunate not to have that, but more importantly, we're not seeing any that are above the normal standard of care, which is critical.

So we believe the types of clinical benefit, coupled with the safety profile that we've observed to date, make us very excited to look at if these statistics continue to hold over the next few cycles, to apply for breakthrough therapy designation. We've also observed, which is very important to note, this has been hypothesized early on, and we're beginning to see some good data, is that tumor mutation burden, or TMB levels, that are measured as either low or intermediate, are responsive to this therapy triplet. And these are typically patients that are not responsive to immunotherapies or checkpoint inhibitors. Usually, high TMB or high PD-L1 is associated with a improved response to PD-L1 and PD-1.

So all signs point to that we really need to accelerate the enrollment of this trial, and we've begun sharing the observations to date with the sites and with our Asian colleagues, and that we believe we'll be able to get to some significant enrollment over the next several months as the trial now goes into the expansion phase. Let's go on to the next slide, please.

Reggie Ewesuedo (VP of Clinical Development)

So let me conclude here, my part of the presentation, and to put the HARMONIC trial in context. I think there are several studies you see on this slide pertaining to the impact or lack thereof of immunotherapy in the never smoker population, which is the population targeted here. The never smokers with advanced lung adenocarcinoma clearly do not respond well to immunotherapy, either when used alone or in combination with the standard of care carboplatin doublet. However, the preliminary profile and activity we're seeing in this study would seem to suggest that this subgroup of patients, who tend to have low or intermediate tumor mutational burden, will potentially benefit from this HARMONIC trial regimen.

The study is currently enrolling in the randomization and expansion phase, and as Panna pointed out, more data in the near future will further define and/or validate the clinical activity that we've observed so far. Could we go on to the next slide, please? This just summarizes at a very high level the key highlights about LP-300. In a previous study, this laid down the scientific rationale for the current design, where we saw very impressive improvement in clinical benefit in terms of survival when we looked at never smokers versus smokers. Thus, the scientific basis for using LP-300 in combination with the current doublet standard of care. The mechanism of action are reflected on this slide.

But one thing that is very fundamental in terms of the regimen, which we are beginning to observe, is that well over 1,000 patients have been dosed with this drug, either alone, even in healthy volunteers, or in combination with different chemotherapy regimens. So the safety profile is well established. No surprise from this study that we have currently, and it's well welcomed by all the investigators as we have looked at the first cohort of patients from a safety and tolerability, you know, perspective. I just thought I should share with you all the comparative data, the historical benchmark for what we are talking about. The next phase of this study, obviously, is combining LP-300 plus the pemetrexed carboplatin doublet versus carboplatin pemetrexed doublet. Now, this is the benchmark.

When you look at overall response rate in these studies, you're going anywhere from about 26% to probably on the very high end, recently with the Mariposa 2 study, about 36%. Right now, with the data that we have, sharing with... This is the opinion of the investigators, we are clearly above what, you know, the, the historical data is, and I think we can attest to that. But more importantly, as the data matures, we are keen on understanding the median duration of response, as well as the PFS, which obviously is the primary endpoint of this study, co-primary endpoint with survival. But all these studies, either with IO agents or bispecifics, as you look at this particular set up, the standard of care regimen, right now, preliminary data obviously is looking better than what has been known in this space.

So I will conclude by saying that, right, the data that we have, the clinical data, from a safety, safety perspective, is spot on, is on the standard of care regimen as expected and safety profile. And in terms of the preliminary and emerging, you know, clinical efficacy profile, I think we're encouraged by what we're seeing. So thank you.

Panna Sharma (CEO)

Well, Reggie, thank you. And thank you to our clinical colleagues and of course, patients for the first phase. Moving back to the other aspects of our portfolio, I know people are very excited about Starlight. We've seen some really good movement this year in brain cancers. Obviously, initially in pediatric brain cancers with the results from Day One Biopharmaceuticals, and now more recently with the result in IDH mutant gliomas. And so it's an exciting time, and I think as we've stated before, we wanna further monetize Starlight, because Starlight is pointed at some very important and significant indications. We've now started site selection for the upcoming phase 1b and 2 trials. We'll make several announcements in the coming months on the progress on those fronts, and also on additional talent and leadership that we plan on leveraging at Starlight.

For those who have not listened in on the backdrop of Starlight or on the details of the trials, we have some webinars that we invite you to listen to. Additionally, a major part of our business, obviously, is to inform, educate, and share with the general public and investors and the oncology community, the details of our programs and our efforts. So last Wednesday of every month, we'll focus on our trials, our publications, our collaborations, and on our AI developments. Our next webinar will be the end of this month, August 28th, on Wednesday, where Reggie will dive deeper into some of the data and clinical readouts, and that'll be followed up with additional data from our AI platform in September, and some insights about our efforts in immuno-oncology with 184 in September. So all very, very relevant.

We've also had additional publications highlighting the clinical value of our Radar work. We had a great publication that showed the potential for LP-184 to be synergistic with PARP inhibitors in a wide range of solid tumors. This was published at AACR Journals Cancer Research Communications. And again, this is in a wide range of solid tumors that are what's called HRD, homologous repair deficient, and this is a very under-addressed, large category that's generating billions in drug sales annually. The preclinical findings in the paper illustrate the potential of LP-184 to be a pan HRD cancer therapeutic, which could be the first drug of this type in this class. So it's a really great observation, and it'll, we believe, help us establish a combination trial in this group of patients, once we've established the MTD in the Phase 1a for LP-184.

Also, as we communicated yesterday, we have new data and scientific findings conducted in conjunction with Doctors Yong Du and Phoebus Lin at MD Anderson, and these were presented at the Immuno-Oncology Summit just yesterday by our colleague. These findings showcase what Lantern believes to be the role of LP-184 to be combined with checkpoint inhibitors to provide greater response in triple-negative breast cancer due to the synergy, but also, we believe, because of a mechanism where LP-184 can transform triple-negative breast cancer tumors that are unresponsive, or what's called cold, to responsive or hot to checkpoint inhibitors. We believe that it reshapes the tumor microenvironment, both through heightened T-cell aggregation and also by decreasing M2 macrophages. Both are really, really critical in heightening the potential for IO therapies to work.

The poster can be found on our website under our Posters section. Now, 2024 has emerged to be a year of progress for us, where we've accelerated ideas and AI-driven insights now to the clinic, and these insights are now not just good publications and great theory, but they're impacting patients in their journey to fight cancer, and also influencing on the development decisions of other people in the cancer category. I think our collective efforts and dedication have fostered a transformational shift, not only for our company, but actually for groups of our industry, and that's setting us on a very exciting trajectory, where we can not only improve the lives of cancer patients, but also do it in ways that is more effective and more scalable. We believe that our business model will drive affordable, more personalized treatment options in cancer.

Now with that, I'd like to now open the call to any questions or clarifications. If you'd like to ask a question, you can do so in two ways. One, you can raise your hand under the participant category. I think there's a hand raised already. Or you can also type it in, and we can look at questions that way. So before we get into questions, I'd like to take a moment to personally thank our team for helping to prepare us for these calls and to gather all this. Takes a lot of work, so thank you for our team for taking time out of their normal day-to-day to help make this happen. So let's take some questions from our audience. I think our first question is from Keith at Chardan. Keith, please go ahead. I think you're muted, Keith.

Okay, let's go on. Let's take a question from John.

Speaker 4

Hello, am I coming through?

Panna Sharma (CEO)

Yep.

Speaker 4

Great. I thought I'd start out with a question on just what kind of threshold you're looking for that shows LP-300 it merits a breakthrough candidacy status.

Panna Sharma (CEO)

I think if we see the current trajectory, in the next, let's say, 12-20 patients, plus we get some durability data, I think that would give us comfort level. But we'd have to see the totality of the data. Seven patients is a good start, but it's preliminary. We'd love to see 21 patients. You know, if we had 14 patients out of 21, that would give us a lot, you know, get us pretty excited. 16 patients, I mean... But the overall clinical benefit rate of 86% is largely unheard of in this group. So, we wanna make sure that's durable. And so more patients drive the N number, and then some durability of response, which I'm sure the FDA will wanna look at for the, for breakthrough.

Speaker 4

... Okay, so about a two-thirds clinical benefit rate is kind of what you'd be looking for?

Panna Sharma (CEO)

That's probably, yeah, that's kind of the guiding. We'd have to take a look at the totality of the data, but yes, I mean, metastatic lesion improvement, no safety issues, those all skew us towards some positive as well, right?

Speaker 4

Mm-hmm. And then looking at the safety profile that you've seen, you know, from the first seven HARMONIC patients and comparing it to some of the other NSCLC populations that were using EGFR TKIs and checkpoint inhibitors, kind of how does that safety profile compare to some of those other molecules out there or biologics out there?

Panna Sharma (CEO)

Well, I'll let our safety expert, Reggie, take that question on.

Speaker 4

Hi, Reggie.

Reggie Ewesuedo (VP of Clinical Development)

Hi. Hi, John. No, that's a very great question. I will just tell you off the bat, what is unheard of in this space is for patients to go on to about 9 weeks or 9-10 weeks of treatment with any kind of dosing interruption or discontinuation of the regimen. I mean, that is very common, you know, with the TKIs in combination. You can look at the current, the Mariposa 2 trial, for example, which is the most recent with the bispecific combination, with the TKI, by the way, for patients in the same population versus the same standard of care.

It shouldn't surprise anybody in this field to know that certainly up to 80% of the patients discontinue treatment for one reason or the other because of toxicities, and they had to interrupt treatment, and a third or more of those patients literally discontinued treatment. So this, again, presenting this preliminary safety data with no new toxicity to these investigators, was really exciting because for this length of time, none of the patients have re- you know, required those discontinuation for any of the... Certainly not LP-300.

Speaker 4

Okay, great. And just one more question on your collaborations. When you look at the Oregon Therapeutics and also Actuate and TTC, how will you determine if this is a success? I mean, what kind of milestones are you looking for kind of internally to show that these are kind of working and they're valuable?

Panna Sharma (CEO)

Yeah, each one is a little bit different. I'll take that question. Unique. I mean, Actuate has filed an S-1 on, and I think that the work our team did was definitely helpful, for them in terms of understanding their patient population and developing, some specific insights related to, people who are refractory to PD-1 therapy that would have potential to benefit, from their drug or elraglusib. Yeah. Elraglusib. It's a little hard to say.

Yeah, hard to say. But, so we think it's, you know, we think that's on track to be successful because we've helped the company. And if they do go public and are able to raise additional capital, we definitely think it's because of the focus around understanding the patient profile. With regards to TTC, that's, they came a little after, so that one, we're still working. We do have some very good ideas. TTC is out raising capital or looking for grant money for the next phase. And, but I... You know, that one is not as well capitalized as Actuate has been, so they're slower. Oregon is the newest one, and I already am pretty excited about what we're doing for Oregon.

You know, it's not, you know, it's barely two months old, so it's very early, but we have some very clear milestones in terms of developing some collaborative IP together that we can monetize, specifically helping them define combinations and define indications that they haven't thought of. So... I think we'll be able to accomplish that. Eventually, the IP has to be monetized for it to be a success for everyone, but you got to have, you know, good, strong, valid ideas and do them inexpensively, which is part of the magic of AI.

Reggie Ewesuedo (VP of Clinical Development)

Yeah, and just adding very quickly to that, John. In simple terms, I think it's the question of: Are we able to allow them to see things and do things that they wouldn't be able to do otherwise? And this goes beyond our collaborations in terms of RADR and AI, and we're seeing just more and more evidence in these collaborations in other ways that's showing insights that wouldn't have arisen without that additional insight. Great. Thank you, guys. Appreciate it.

Panna Sharma (CEO)

Thank you. Then we'll try, Keith again. I don't know if he's back on the line. It's Keith?

Speaker 5

Can you hear me now?

Panna Sharma (CEO)

Yeah, we can hear you, Keith.

Speaker 5

Great. Yeah, it's Keith. Appreciate all the detailed patient data. I guess the first question is, again, with the huge caveat, this is small numbers, but the patient with the RET mutations, you know, had a nice response. Not sure if they were rechallenged with selpercatinib or not, but was that a surprise to you based on your preclinical data?

Reggie Ewesuedo (VP of Clinical Development)

Maybe I'll take that one. It wasn't-

Panna Sharma (CEO)

Yeah. Next slide.

Reggie Ewesuedo (VP of Clinical Development)

Yeah, it wasn't really a surprise, because, again, maybe one of the highlights for LP-300 and what we understand of the mechanism of action, one of the, you know, set of data we've been able to generate pre-clinically is understanding that the drug really binds to cysteine residues and, you know, of different tyrosine kinase receptors, including RET. So seeing this kind of clinical data is very exciting to us, and that's why, in the presentation, I made sure to emphasize that it's not just, you know, a driver mutation of interest, as you've seen other clinical trials in this space, but rather, the protocol is designed to really capture any driver mutations for those patients to come in as far as they are never smokers. So this is very encouraging for us. It didn't come as a surprise.

Speaker 5

...And then with respect to patient 107002, who had progressive disease.

Panna Sharma (CEO)

Yes.

Speaker 5

Anything about their baseline that maybe might have predicted a, you know, less than favorable response there?

Panna Sharma (CEO)

You know, this was the first patient enrolled in the trial. A lot of things going on with the protocol at that time, but this patient really accounted for most of the toxicities you've seen because of comorbidities. So the patient, one would say, wasn't an ideal patient for a clinical trial.

Speaker 5

Okay, great. Thanks.

Panna Sharma (CEO)

We have a question in the chat window that I'm going to go ahead and answer. I'll read it out for everyone. Can you please go deeper into checkpoint inhibitors and the market they currently garner, specifically Keytruda, and why LP-184 may be a great and synergistic partner? Good question. Now, I'm not a Keytruda rep, or I'm not a Merck rep, but having done a lot of work for Merck in my prior career, I can tell you that, the 57-patient trial that they had that got them on the map had remarkable results. The market today for checkpoint inhibitors, including Keytruda, is somewhere close to $42 billion-$48 billion. So it's a significant market.

Now, we all know that Keytruda's, you know, cut some of these early-stage PD-L1s are coming off market, and there's some new PD-L1s already out, or PD-1s. You know, Coherus has one of those already out, I believe. That's a biosimilar. Pricing isn't great, but I've heard that the efficacy is very, very good, and it's a clean biosimilar. So the market, you know, I think, will remain fairly robust. Analysts project it'll grow about 15%-17% because there's a whole new wave of new checkpoint inhibitors. So it's a good market. Now, we're not going after that whole market.

What we're going after is, we believe that there's even a larger group of patients that don't respond to checkpoint inhibitors that could benefit from them, and there's a whole group of people whose lives have been wonderfully prolonged, but their cancer is not cured, so they stop responding to checkpoint inhibitors, and the tumor microenvironment reshapes itself. So that's where LP-184, we believe, can be a great and synergistic partner. The first one, of course, where we have some data on, that we're excited about, is in triple-negative breast cancer. And triple-negative breast cancer can be rapidly evolving in terms of its clonal evolution, so it's also part of the reason why it'd be good to go after.

We think that TNBC would be a great initial target to get early, an early win, and then potentially go after other places where checkpoint inhibitors can be improved, which will be many of those tumors where you have complex tumor microenvironments, and you have rapid clonal evolution. That, to me, can be multiple, multiple $ billions of potential over time. But the key is to pick one where we know that we could have a good, good effect and potential win, and TNBC looks like one where we've seen synergy, we've demonstrated clinical evidence. We see two of the most important hallmarks. One is we're bringing and recruiting the right kind of T-cell environment, and we're also decreasing the number of M2 macrophages, both which have been very, very correlated with reducing response to immunotherapies.

Thank you for that question, John. Take another question in the chat, one that just popped up. Michael, is that right? Yeah. Michael's question I'll read is: Are you open to small pharma partnership opportunities? Well, Michael, being a small pharma ourselves, yeah, absolutely. Yeah. We're a small biopharma that acts like a big pharma, but we are a small pharma. I mean, we're very... So we're always looking for partnership opportunities and welcome you to send myself or members that you know in the company an email, and we'll get back to you quickly. I've time for one more question. I don't know if there's any more questions. Let's see. There's one more question. So I'll go ahead and take this one.

The question is: Given the market cap of the company, do you think Lantern is still relevant to be a major player in the industry? That's a great... It's a good fundamental question as an investor, I think. So thank you for being involved. I think there's room for big companies and small, and I always like to urge everyone that with the exception of a few handful of companies, every big company started small. Except LabCorp, which started because of Roche and US Labs, but very... I mean, even Regeneron and Biogen. Now, is that what we're going to be in the future? Who knows? But I do think that very likely that our approach and our drugs will be partnered, licensed, and sold. That's what we're doing, or we'll spin out the assets.

So I think that we are very relevant to the industry, and I've seen a lot of companies try to copycat our approach. A lot of companies are very interested, so I think we will be very relevant, and I think you will see ups and downs in this industry, just like every other industry. I like to remind people that even Amazon, before it became the huge behemoth, not that we're going to become Amazon, saw 80% and 90% reductions in stock price about four or five times during, you know, on their way up. So stock prices and everything, I think it's a huge indicator of how much your cost of capital will be, but I think we're probably the cheapest company with a phase II drug and two phase I drugs that are first in class.

So that does get me, at times, concerned and frustrated, but, you know. And we're not spending $60 million-$80 million a quarter like some other companies who are in the press today for their merger. So you know, it's, you gotta do things differently, but you also really have to think about how to do them differently. You can't say you're gonna use AI and then spend like Eli Lilly or Roche. So, you know, I think we can do things differently with AI, pick the right kind of very select, focused bets and opportunities, and try to develop those with a tremendous amount of operational efficiency. And so I think that'll pay a lot of dividends to to our investors, but also will allow us to be very relevant in the industry.

David Margrave (CFO)

And just adding to that very quickly, we're beginning to see some great momentum on multiple fronts. We talked a lot today about HARMONIC, but there are some very exciting things going on with our other candidates as well, and then RADR in addition to that. So we're building some great momentum that we think will be value-driving in multiple ways.

Panna Sharma (CEO)

Thank you. So in closing, I wanna express my thanks and our gratitude to our team, our partners, our stakeholders, and those who are following the company for their support and interest. Together, I think we are really lighting the way toward a brighter future in oncology and solving real-world problems for patients with proprietary AI solutions and insight. And we think we're gonna radically alter the potential to change the cost, structure, and timelines in drug discovery. So thank you, everyone, for your time this afternoon. With that, I'd like to adjourn the call today.

David Margrave (CFO)

Thanks a lot.

Panna Sharma (CEO)

Thank you.