Lantern Pharma Inc.

Good afternoon and welcome to our fourth quarter and year end 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. order and year, ended December 31st, 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 we'll 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, 2024, which is on file with the SEC and available on our website. Forward-looking statements made on this conference call are as of today, March 27, 2025, 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, Pauna Sharma, and CFO, David Margrave. Pauna will start things off with introductions and an overview of Lantern's strategy and business model and highlight recent achievements in our operations, after which David will discuss our financial results. This will be followed by some concluding comments from Pauna, and then we'll open the call for Q&A. I'd now like to turn the call over to Ponna Sharma, President and CEO of Lantern Pharma. Ponna, please go ahead.

Matti, thank you. Hello, everyone, and thank you for joining us this afternoon to hear about our fourth quarter and fiscal year 2024 results and corporate progress. 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 and development. Our leadership and the innovative use of AI and machine learning to transform the process of developing 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. 2024 was a transformational year for Lantern Pharma across many measures, portfolio, the platform, and patient impact. I would like to highlight Lantern Pharma and our team's extraordinary progress across our clinical pipeline and our AI platform. These developments aren't merely incremental advancements. They actually represent transformative approaches that are reshaping how we develop precision oncology therapies for patients that usually have very limited treatment options and hopefully enable a much more efficient future for drug developers. Our team today is about 23 people focused and comprised of leaders and high value contributors. And they have made significant strides over the past quarter and actually throughout all of 2024 across all of our clinical programs. and with our AI platform, Radar, and also in our ongoing efforts in developing an entirely new company, Starlight Therapeutics, which was largely possible due to our AI and data-driven model, which is used to understand how and where a molecule can work best against a particular cancer and actually identify the cancers that are going to be most sensitive to a molecule. In fact, this is one of the core features of our AI. Radar, our precision oncology AI platform, has guided the rapid and efficient development of three AI-driven drugs into clinical trials at a pace and cost that has traditionally been unheard of in our industry. Some of our peers, many of whom already reported, their burn rate in one quarter is more than our burn rate has been over the past three years. So just, and their pipeline is not all that as advanced. So we're talking 12 to 14 quarters of our burn versus one quarter of theirs. Well, our team has been very focused on executing of our mission, which is first and foremost, which is transform oncology drug discovery and development. All of our clinical stage drug candidates are now in phase two and phase one trials. They've all dosed multiple cohorts of patients. And we actually have some very exciting preclinical assets like our antibody drug conjugates that are in early development for the next generation of our portfolio. All of our clinical trials I'll be talking a little bit about today, and we will have multiple clinical readouts over the next several quarters as we get insightful data on how patients and cancers are responding to our precision drug candidates. Last year, we shared with you information from our first lead-in cohort of patients in the Phase II harmonic trial, and I'll provide an update on that as well today. Good news is that we're continuing to see some of the remarkable results from patients as we've expanded the trial. Now, our team and many clinicians are particularly excited about and interested also in the programs for our first in human drug candidates, LP184 and LP284. And also, of course, LP300, which is aimed at a very unique population of never smokers that have been impacted by non-small cell lung cancer adenocarcinoma, but have failed other treatment options. This is a growing problem, not only in the US, but globally. And we are actively screening and dosing patients, not only in the US, but in Japan and Taiwan, where the incidence of non-small cell lung cancer among never smokers is nearly two and a half to three times than here in the US. Now, our phase two asset, LP300, which is aimed at a $4 to $5 billion opportunity annually, but also one that's growing, has seen acceleration in enrollment. Our harmonic trial for LP300 has delivered remarkable preliminary results that demand attention. The lead-in cohort achieved an 86% clinical benefit rate and a 43% objective response rate in never-smoker, non-small-cell lung cancer patients. These aren't just numbers. They represent a potential change in survival and hope for patients who have historically been underserved by conventional treatments. What makes these findings particularly significant from a clinical perspective is that never-smoker, non-small-cell lung cancer patients typically have showed very limited response to existing therapies. Their genomic profiles are fundamentally different from smokers, with higher frequencies of actionable driver mutations, but poor response to immunotherapies. They also generally have a very different genome, quieter genome, with much lower tumor mutation burden than smokers. Now, LP300's mechanism, which enhances the efficacy of chemotherapy while potentially protecting normal cells, addresses this major need for never smokers directly. Our strategic expansion to Japan and Taiwan, regions where 33% to 40% of non-small cell lung cancer cases occur, in never smokers compared to just 15% in the US positions us to accelerate enrollment this year and generate robust data sets with great power, statistical power. The geographic strategy strengthens our potential for compelling 2025 readouts. That could transform treatment protocols for this distinct and growing patient population. Additional patient data from the expansion cohort, which has randomized two patients to one in favor of our LP300 arm, continues to support, at the current time, a similar patient response and clinical benefit trend. Lantern plans on sharing additional results, which will include data from patients enrolled in Taiwan and Japan from the expansion cohort later this year, most likely during middle to late of Q2 of 2025. Now, the two FDA fast-track designations that we received for LP184 in glioblastoma and triple negative breast cancer, coupled with three additional rare pediatric disease designations, represent extraordinary regulatory validation of our approach. We're going after very precise cancers, precise data, and these designations aren't really administrative milestones. They're actually indications that we can expedite our clinical development timeline through enhanced FDA interactions and potential for priority review. From a technical standpoint, these designations were underpinned by the mechanistic elegance of LP184's synthetic lethality approach. its ability to exploit specific genomic vulnerabilities in cancer cells while sparing normal cells, particularly through its PTGR1-mediated bioactivation. This offers a precision that conventional therapies cannot match. The market potential across these indications exceeds $10 billion annually, addressing over 150,000-plus patients with limited therapeutic options across solid tumors. Our Phase Ia clinical trial for both LP184 and 284 has successfully progressed through multiple patient cohorts, systematically establishing safety profiles while advancing toward pharmacologically active dose levels. The methodological dose escalation strategy has been executed with efficiency, with no serious adverse events related to the drug candidates observed across multiple cohorts that have been executed. What distinguishes our synthetically full approach is its mechanistic precision. Unlike conventional chemotherapies that can indiscriminately target dividing cells or other alkylating agents, LP184 and 284 exploit specific genomic vulnerabilities in cancer cells, particularly those with deficiencies in DNA damage repair, or DNA damage repair pathways. The pharmacokinetic data from these trials suggest we're approaching concentration levels of the drug that correlate with the nanomolar potency observed in preclinical models. This is a critical inflection point that could demonstrate definitive proof of mechanism in patients and pave the way for future trials and partnerships. LP184 continued advancement through a phase 1A trial in multiple solid tumors, which is targeted to finish enrollment during this coming quarter. And we believe we're very close to the final set of cohorts. But now let us talk about the current phase one status. The phase one results so far for safety, tolerability, and pharmacokinetics, including the MTD determination. We're now on cohort 11 and have early indications of clinical activity that have been observed at these higher dose levels, consistent with the preliminary PK data that we have. Now, during Q4 of 2024, dose levels 7, 8, and 9 were cleared without safety concerns, and preliminary PK data suggests dose proportionality with exposure. Enrollment in dose level 9 and above, we made a concentrated effort to focus that on including patients with advanced solid tumor patients that actually have identified DNA damage repair mutations. A broader clinical data update is slated for Q2 2025 when recruitment for this phase is expected to be completed and we will have a safety and dose response data available to be shared. In terms of future planned phase 1b2 trials, we're already getting to planning the future because we see that we've already submitted a clinical trial protocol to the FDA for a phase 1b2 study in triple negative breast cancer, where we evaluate a combination regimen with the PARP inhibitor olaparib. In our preclinical work, we saw tremendous synergy between olaparib and our drug LP-184. What's again unique about the combination of PARP inhibitors and LP-184 is actually also very elegant. Now PARP inhibitors work by stopping the repair mechanism. So when there is DNA damage caused as a result of killing off cancer cells, PARP inhibitors stop the ability of the cancer cell to repair that. Our drug starts at a different point. It actually breaks apart the DNAs of the cancer cell. So they actually work in a wonderful mechanistic synergy, LP184 breaking apart the DNA, and then PARP inhibitors stopping it from any attempts at repair. So we believe the synergy that we saw in preclinical models that was driven by our AI platform and also validated in a number of studies done with our partners across a number of institutions has a very solid biological basis. So far, the FDA has raised no objections to the protocol and Lantern expects to initiate this trial in both the US and a leading academic center in Nigeria, subject to further funding and clinical priorities. Now in Nigeria, a lot of you may ask, why Nigeria? Nigeria actually has been a hotbed of triple negative breast cancer research and studies. In fact, Roche actually did a trial in TNBC there. But in Nigeria, TNBC occurs at a much higher rate than in many other parts of the world. And there is an active community that has done some wonderful research and epidemiological reviews of TNBC in Nigeria and Sub-Saharan Africa. We'll be working with one of the leading academic centers there. And also, bear in mind, the Nigerian Breast Cancer Study, which is published with the University of Chicago and with Harvard, has published that nearly 46% of breast cancer cases are triple negative breast cancer in Nigeria. And they present with mutations that many of the DNA repair genes, LP184 seems to be particularly attuned to. So this is very exciting. We believe that we'll be able to do our trial with a group of clinicians and experts who are really zeroed in on this disease. And we'll be able to get more rapid enrollment, which is critical. And again, it's critical for our highly efficient model. So we'll have sites in the U.S., but also sites in Nigeria. And we'll talk more about that in the coming weeks. Additionally, an investigator-led study of LP184, which I know many of you are excited to hear about, for recurrent bladder cancer. It's planned to start in Denmark. The clinical trial will test LP184 as a monotherapy, specifically in advanced bladder cancer with patients that have DNA damage repair mutations. Dr. Hele Papat at the Copenhagen University Hospitals, who focuses on prostate, bladder, and some renal cancers, will be the PI on this study. And she's very focused on DNA damage drugs and actually molecular profiling of bladder and prostate cancers. Now, based on work that we have done, but also on published research, about 25% to 30% of bladder cancers at presentation have DNA damage repair mutations, and about 40% at recurrence So again, we think this is a great population to study, great population to validate further the mechanism of this drug, and most importantly, patients that we think we can actually prolong and help their long-term survival. Another great opportunity for MD Anderson, came about with MD Anderson, is our collaboration with them revealed that LP184's remarkable ability to transform immunologically cold tumors into hot tumors. It's a breakthrough with profound implications for expanding immunotherapy benefits to previously unresponsive patients. This isn't merely additive efficacy. It represents a mechanistic synergy that addresses one of immunotherapy's most significant limitations. The technical details here have been fascinating. In fact, LP184 induces replication stress in tumor cells. This then triggers cytosolic DNA accumulation. This accumulation stimulates the immunogenic pathway. This leads to favorable remodeling of the tumor microenvironment, which we've shown in our publications. It reduces the immunosuppressive M2 macrophages and enhances the right kind of T cell functionality. In fact, it's a combination of those two factors, because we have seen T cell functionality change with other immunogenic or immunostimulant type environments, but also the M2 macrophage is fairly unique. So really in preclinical TNBC models, this combination enhanced the tumor growth inhibition from about 51% for our drug alone to over 72% when combined with anti-PD-1 therapy. And this is a therapeutic enhancement that was, again, in cold tumors. And we believe this could translate into meaningful survival benefit for patients with currently very limited options or patients that basically stop responding to PD-1 and PD-L1 therapies. This was publicly shared at a recent poster at the AACR Immuno-Oncology Conference in February and also at the IO Conference last year. IO Summit. This opens up significant opportunities for code development and new indication expansion where PD-1 and PD-L1 have stopped working. And again, this is a massive multi-billion dollar opportunity in a combination setting. Moving on to some of our very exciting new space is Starlight. Starlight is a company that wouldn't exist if it weren't for data and AI. And we unveiled a very unique, innovative trial design for STAR-001 at the Society for Neuro-Oncology 2024 meeting. It featured a unique combination of spironolactone. Now, this exemplifies the power of computational approaches and biomarker-driven approaches in identifying non-obvious therapeutic synergies. Spironolactone is not used in cancer. In fact, this approach exploits synthetic lethality in GBM through a mechanistically elegant interaction. Spironolactone degrades the protein ERCC3, a critical DNA repair protein. It creates a transient vulnerability that the drug STAR-001 then exploits. And so this transient ERCC3 degradation stops the cancer cell from being able to repair itself. And the way that these double-stranded breaks work is that ERCC and some other proteins are needed. And so it actually demonstrates that what we've seen preclinically, a three to six X increase in GBM cell sensitivity. That's pretty massive, three X to six X when you combine these agents. And actually, many of the tumor preclinical models in GBM and other brain cancers actually have shown complete tumor eradication with minimal recurrence. Now, this can be especially critical in very sensitive patients, such as children, the elderly, or those who have undergone multiple lines of prior therapy. Even more interesting is that STAR-001 has shown anti-tumor activity in GBM regardless of MGMT status. And some of you have seen some of that data that we've published in the past. So not only does Star001 have what we believe can be a great anchor molecule, but now through the use of data and biomarker-driven medicine, we've actually been able to now exploit the ability to look at and modulate ERCC3. So we actually increase the potential of this therapy. We make the therapeutic window much more attractive. Now, during Q4, we also started the inaugural scientific advisory board, which I'm very excited about. Dr. Mark Chamberlain and Dr. Kishore Bhatia both worked closely with myself to provide strategic guidance And we were very excited to establish a scientific advisory board that is joined by experts such as Drs. Mitch Berger at UCSF, Dr. Lisa DeAngelis at Memorial Sloan Kettering, and Dr. Stuart Grossman and John Letera at Johns Hopkins, all four of which have deep subject matter expertise, accomplished scientific experts, and leaders in neuro-oncology. In fact, two of them are actually lifetime achievement award winners at Society of Neuro-Oncology. And they're able to now help us shape the development and path for Star001. Remind you, Starlight is 100% owned by Lantern. We'll have the potential to this be a very positive impact on our investors as we monetize this unique asset, the patents, the insights, and its ability to work in certain brain cancers. The dosage and safety data in Phase 1 trial will be used to advance the indications for the 1B Phase 2 trial, which Lantern's wholly-owned subsidiary will sponsor. And we think the market potential for both this drug as STAR-001 and as LP184 will exceed $14 billion, consisting of about 4 plus billion in CNS cancers, both pediatric and adult, and about 9 to 10 billion for other solid tumors. So we believe this has the potential to be a blockbuster drug across a number of indications. And to support a lot of this, we actually were working quite a bit on trying to understand how do we predict the blood-brain barrier permeability And our team did a fantastic job at our patent-pending blood-brain barrier permeability predictive algorithm. It represents what we believe is a computational breakthrough of exceptional significance. With five of the top 11 rankings in the Therapeutic Data Commons leaderboard and the ability now to be a very high-performing algorithm, we can do maybe 100,000 molecules an hour. That translated can mean a million molecules or more in a workday. So we've developed an AI system that outperforms industry standards in terms of accuracy and throughput for a CNS drug therapeutic development. This will also be, in fact, one of the first agentic AIs that we make publicly available for drug developers. So we're going to open this up and partner this with precision medicine groups to help guide their development and also potentially for therapy selection in patients. So we're in fairly advanced discussions now with a number of institutions and organizations a brain tumor group to actually use this algorithm as part of their work. Now, this technological advantage has profound implications for accelerating CNS drug discovery, a notoriously challenging domain where over 98% of small molecules fail to effectively penetrate the blood-brain barrier. And where some of the traditional algorithms have been kind of in the two-thirds to mid-70s, maybe, percent accuracy, now we're seeing a whole new generation of algorithms, including ours, which have taken that up into the low to high 90s. And so this unprecedented accuracy allows us to identify promising CNS penetrant compounds with extraordinary efficiency. Now, again, I also mentioned ours is also high performing. So we've taken some very unique engineering steps to actually decrease the amount of time required. And the computational capability doesn't merely enhance our existing programs. It actually opens up entirely new therapeutic possibilities across multiple neurological indications for not only us, but also for other drug development teams. Now, our AI-powered antibody drug conjugate development module also represents a fundamental reinvention of traditionally resource-intensive high-risk development process. Our AI module for ADC development identified 82 very promising targets and over 290 target indication combinations. And many of these are actually validated because some of them are already in preclinical and clinical trials. So this is one of oncology's most rapidly growing therapeutic modalities. And the technical implications for this ADC module for using AI is pretty substantial. Traditional ADC development requires a lot of iterative testing of antibodies, nanobodies, any kind of, maybe by specific, and then the linkers and various payloads, and a process that can take years and millions or maybe even tens of millions of dollars, just in early stage work. Our computational approach reduces these timelines, we believe, by a third to half and preclinical costs by even more than half, while simultaneously enhancing the target selection process. So this efficiency advantage positions us to rapidly advance multiple ADC candidates with exceptional selectivity profiles and potential for superior therapeutic windows and enables us to allow others to take advantage of this AI. Now, this will be one of the many AI modules we place into what we call an agentic framework, which is really the the kind of the vanguard of AI work today. And once we put into an agentic framework, we can allow it to be used by collaborators and partners. And I'll talk more about this later in today's call. The RADAR platform expansion beyond 100 billion oncology specific data points represents a computational resource of unprecedented scale and specificity in precision oncology. The vast repository of molecular, clinical, pharmacological data enables increasingly sophisticated analysis that traditional approaches simply cannot match, but very importantly, don't have the underlying data and curation already that we've done. Now, the technical sophistication of radar enables multidimensional analysis that identify non-obvious relationships between genomic features, drug responses, and potential combination strategies. This capability has directly enabled our biomarker discovery initiatives, including PTGR1 signature, mechanisms underlying synergistic combinations, such as checkpoint inhibitors or spironolactone with 184, or even rituximab with 284, And as we continue to refine the methodologies and feed data from studies back into the platform, radar evolves from just an analytical platform to a predictive engine capable of identifying promising therapeutic approaches with unprecedented efficiency and precision, and ultimately in the next generation with its own level of automation. So through the integration of advanced AI, computational biology, and precision medicine approaches, we're systematically addressing some of oncology's most challenging domains with an unprecedented level of efficiency and scientific rigor. Our burn rate is a fraction of that of other companies, yet our advancements across multiple molecules, putting them into patients and advancing the platform is something I'm quite excited about. Financially, we closed the year with 24 million in cash, cash equivalents and marketable securities, which I believe will give us runway to execute in our business this year and take our programs to inflection points with data and outcomes. David Margrave, our CFO, will discuss this in more detail in a moment. Our continued execution across these clinical trials and with our precision oncology programs positions us for multiple value trading milestones throughout this year and with the potential to deliver transformative therapies for patients with limited treatment options. Now, I'll turn the call over to David Margrave. We'll talk about our financials and other key metrics. David?

Thank you, Pana. And good afternoon, everyone. I'll now share some financial highlights from our fourth quarter and full year ended December 31, 2024. I'll start with a review of the fourth quarter. Our general and administrative expenses were approximately $1.6 million for the fourth quarter of 2024, up from approximately $1.3 million in the prior year period. R&D expenses were approximately $4.3 million for the fourth quarter of 2024, up from approximately $3.6 million in the fourth quarter of 2023. We recorded a net loss of approximately $5.9 million for the fourth quarter of 2024, or 54 cents per share, compared to a net loss of approximately $4.2 million, or 39 cents per share, for the fourth quarter of 2023. For the full year 2024, our R&D expenses were approximately $16.1 million, up from approximately $11.9 million for 2023. This increase was primarily attributable to increases in research studies of approximately $2.95 million relating to the conduct and support of our clinical trials. as well as increases in research and development payroll expenses of approximately $897,000 and increases in consulting expenses of approximately $376,000. Our general and administrative expenses for 2024 were approximately $6.1 million, up slightly from approximately $6 million for 2023. The increase was primarily attributable to increases in other professional fees. 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. Net loss for the full year 2024 was approximately $20.8 million, or $1.93 per share, compared to approximately $16 million, or $1.47 per share, for 2023. Our loss from operations in the 2024 calendar year was partially offset by interest income and other income net, totaling approximately $1.4 million. Our cash position, which includes cash equivalents and marketable securities, was approximately $24 million as of December 31, 2024. Based on our currently anticipated expenditures and capital commitments, We believe that our existing cash, cash equivalents and marketable securities as of December 31, 2024 will enable us to fund our operating expenses and capital expenditure requirements for at least 12 months from today's date. We expect that we will need substantial additional funding in the near future. And one of our key objectives for the remainder of 2025 will be to pursue additional funding opportunities. As of December 31, 2024, we had 10,784,725 shares of common stock outstanding, outstanding warrants to purchase 70,000 shares, and outstanding options to purchase 1,245,694 shares. These warrants and options combined with our outstanding shares of common stock Give us a total fully diluted shares outstanding of approximately 12.1 million shares as of December 31, 2024. Our team continues to be very productive under a hybrid operating model. We currently have 24 employees focused primarily on leading and advancing our research and drug development efforts. And I'll now turn the call back over to Pana for an update on some of our development programs. Pana?