Lantern Pharma Inc.

NASDAQ:LTRN

Earnings Call Analysis

Lantern Pharma Reports Progress in Drug Development and Financials for Q3 2024

In Q3 2024, Lantern Pharma demonstrated significant advancement in its AI-driven oncology programs, highlighted by FDA Fast Track designation for LP-184 for glioblastoma. The company reported a net loss of $4.5 million, increasing from $3.2 million year-over-year, with R&D expenses rising to $3.7 million. Cash reserves stand at $28.1 million, expected to last into late 2025. Importantly, initial data from the HARMONIC trial showed an 86% clinical benefit rate in early testing. The company also plans to initiate Phase Ib/II trials for LP-184 in 2025, reflecting a commitment to enhancing treatment options in oncology.

AI Innovation in Oncology

Lantern Pharma is making strides in the transformative realm of oncology through its RADR AI platform, which has enabled the development of 14 drug programs since its IPO in 2020. The company's emphasis is on using AI not just as an ancillary tool but as a core driver of innovation. The RADR platform has successfully progressed candidates into clinical trials, which is a significant achievement in the competitive biotech landscape.

Financial Health

As of September 30, 2024, Lantern reported a cash position of approximately $28.1 million, with a burn rate of $4.5 million for the quarter. This financial backing is expected to sustain operations into late 2025, providing necessary runway to advance clinical programs. The company finished the third quarter with a net loss of $4.5 million or $0.42 per share, which was higher than the net loss of $3.2 million or $0.29 per share reported for the same quarter in the previous year.

Exciting Clinical Advances

Lantern's commitment to advancing its product pipeline is evident in its clinical trials. The ongoing Phase 2 HARMONIC trial for LP-300 has shown an impressive 86% clinical benefit rate among its first seven patients, primarily targeting non-small cell lung cancer in never smokers. The expansion of this trial into Asia, particularly Japan and Taiwan, is underway, as these regions show high prevalence for the targeted cancer type.

Key Regulatory Recognition

A milestone was achieved with the FDA granting Fast Track designation for LP-184 aimed at glioblastoma patients. This designation not only signifies the critical need for new therapies in such dire cases but also opens doors for expedited development processes, potentially leading to accelerated approval. Lantern's focus on pediatric applications has also paid off with three new FDA rare disease designations for LP-184, which enhances its attractiveness for partnerships and further funding.

Pipeline Growth and Future Directions

Looking ahead, Lantern anticipates further clinical trials for both LP-184 and LP-284, both currently in Phase 1 studies. They are expected to advance to Phase Ib or II trials by early to mid-2025. In addition, LP-284 targets hematologic cancers, revealing strong potency, particularly for aggressive non-Hodgkin lymphoma types. The drug industry potential is substantial, estimated at $2.8 to $3 billion annually in the U.S. and Europe.

Strategic Collaborations and Future Partnerships

Lantern also recognizes the importance of partnerships in the success of its drug candidates. While discussions concerning partnership interests for the never smoker trial are at an early stage, the company has begun engaging larger pharmaceutical companies in East Asia. Its focus on collaboration rounds out a strategy that aims not only for clinical success but also for market viability.

Advancements in Biomarker Programs

Lantern has made headway in its biomarker programs, particularly with the PTGR1 biomarker linked to LP-184's effectiveness. This biomarker has been analyzed in patient samples for potential predictive capabilities in treatment response. Such advancements could provide a significant advantage in precisely targeting therapies to the right patient populations and enhance overall treatment outcomes.

Focus on Cost Efficiency

By integrating more operational aspects in-house, Lantern aims to reduce dependency on external providers, thereby decreasing costs. This operational shift is expected not only to streamline development but also to enhance control over clinical trials ensuring tighter data integration and real-time patient insights.

Conclusion: A Promising Future

Lantern Pharma stands at the confluence of innovation and necessity in the oncology space, leveraging its AI-driven platform and robust pipeline to address substantial unmet needs in cancer treatment. With a solid financial foundation and strategic plans for growth and collaboration, Lantern is well-positioned to make impactful strides in drug development and patient care.

Earnings Call Transcript 2024-Q3

[Operator]

Good afternoon, and welcome to our third quarter 2024 earnings call. As a reminder, this call is being recorded [Operator Instructions] 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 third quarter ended September 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, November 7, 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's 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 our R&D efforts.

I'd now like to turn the call over to Panna Sharma, President and CEO of Lantern Pharma. Panna, please go ahead.

[Panna Sharma, executive]

Good afternoon, and thank you for joining Lantern Pharma's Third Quarter 2024 Earnings Call. Today, I'll share our continued progress in advancing our AI-guided clinical programs and discuss our financial results. The pharmaceutical industry is experiencing a fundamental transformation. AI and computational approaches are no longer optional tools, they have become essential drivers of innovation across the entire drug development spectrum. For molecular design to patient selection, for manufacturing to clinical trial execution, AI is revolutionizing how we develop life-changing therapies.

Lantern has been at the forefront of this transformation. Since our IPO in 2020, our RADR AI platform has enabled us to generate and advance 14 drug programs at a fraction of the cost of traditional drug development. More importantly, we've demonstrated the ability to consistently progress these AI-guided candidates into actual patient trials, something very few other AI companies have done, including our ongoing Phase 2 HARMONIC trial and our Phase 1 programs for both LP-184 and LP-284. This quarter validates our AI-driven approach with significant clinical progress across multiple programs, including encouraging early data from our HARMONIC trial and the recent FDA Fast Track designation for LP-184 in glioblastoma. These achievements underscore how our technology-first approach is accelerating the development of precision cancer therapies while maintaining capital efficiency.

Our dedicated teams remain laser-focused on our mission to transform cancer patients' lives while dramatically reducing the time and cost of oncology drug development, a commitment that drives every aspect of our work and is reflected in the momentum we're building across our pipeline. Our company's leadership and the innovative use of AI and machine learning to transform costs and time lines in the development of precision oncology therapies should yield significant returns for investors and patients as our industry matures and adopts an AI-centric and data-first approach to drug development.

Let me start with a high-level view of our clinical progress. We currently have three precision oncology drug candidates advancing through clinical trials, all guided by our RADR AI platform. These include both Phase 1 and Phase 2 programs and alongside these clinical programs, we're evaluating several promising ADC candidates in preclinical development, many of which have come from our AI-driven ADC module. I'm particularly excited to share updates on our HARMONIC trial, which is testing LP-300. The initial data has been very encouraging, and we detailed that in our last earnings call. In our first 7 patients, we saw an 86% clinical benefit rate. To put this in perspective, these are never smoker patients with non-small cell lung cancer who have limited treatment options. So these early signals are particularly meaningful, especially since they cover a wide range of prior kinase mutations.

We continue to enroll additional patients across our U.S. sites but also we've made significant strides in expanding our HARMONIC trial into Asia, specifically Japan and Taiwan. This expansion is strategically important because in these countries, [ never smoker ] lung cancer represents a much larger portion of all lung cancer cases, about 1/3 of new cases compared to what we see in Western countries, which is about 15% to 20%. We're establishing a total of 10 sites across Japan and Taiwan, 5 in each country, we've actually already begun onboarding the sites, and we expect patients to enroll this quarter. This expansion not only accelerates our enrollment in the trial overall but also positions LP-300 in regions where the medical need is particularly high.

Now let me turn to our synthetic lethal drug candidates, LP-184 and LP-284. Both are first-in-human, Phase IA trials, and they continue to show strong progress and are enrolling across centers in the U.S. We've now dosed over 50 patients across both programs. And importantly, we haven't observed any dose limiting toxicities in any of our patient cohorts. This safety profile is particularly encouraging as we advance these programs clinically and sharpen the indications and clinical positioning of these highly potent drug candidates.

We also received exciting news this quarter regarding LP-184, which many of you know, will be developed at STAR-001 in CNS and brain cancer indications through our wholly owned subsidiary, Starlight Therapeutics. The FDA granted us fast track designation for glioblastoma or GBM. This designation not only demonstrates the significant unmet need in GBM, but also provides potential opportunities to expedite development and drive greater commercial value for our molecule. Speaking of GBM, we've been successfully enrolling recurrent GBM patients in our existing Phase Ia trial for LP-184 across three sites, two prestigious academic centers, including Johns Hopkins Medicine and Indiana University and one community site. The data we're gathering from these GBM patients is particularly valuable as they will inform our development for future clinical trials, including Phase Ib/II trials which Starlight Therapeutics expects to initiate in 2025 or any investigator-led initiatives that we undertake. This represents a significant step forward in our CNS cancer program, where effective treatment options are severely limited. At the same time, investors in Lantern will potentially benefit as we look to further develop and finance Starlight Therapeutics.

I'd like to highlight now some particularly exciting opportunities, developments in our biomarker program. As many of you know, PTGR1 was initially identified through our RADR AI platform as a key biomarker for LP-184 response. This discovery represents one of our platform's most significant predictive insights, demonstrating how AI can identify precise biological mechanisms that drive drug response. We've now begun analyzing PTGR1 expression using qPCR in patient samples from our first 7 cohorts in the LP-184 Phase Ia trial. This analysis is crucial because it will help validate our AI-driven hypothesis that has been validated in vitro and in vivo and also through CRISPR experimentation. But now we can also validate it in human clinical trials. This data will allow us to better predict which patients are most likely to respond to treatment and perhaps even look at monitoring progress and sensitivity to our drug.

We also received very important regulatory recognition this quarter with three new FDA rare pediatric designations for LP-184. This is in addition to the existing one for [ ATRT ]. The three new designations were all in ultra-rare childhood cancers. These designations are particularly significant because each one carries the potential to receive a priority review voucher or PRV upon FDA approval. For those who may not be familiar with PRVs, they are transferable assets that can be sold to other pharmaceutical companies and have historically been valued in excess of $100 million. We have four of these, each PRV allows its holder to accelerate FDA review of a future drug candidate making them highly valuable assets in the biopharma industry. The fact that LP-184 has received these designations not only underscores its potential impact in areas of high unmet need amongst children, but particularly where these treatment options are often limited or have no options. This is valuable for patients, but also potentially valuable as future value for our shareholders and our future programs.

Our scientific team has been particularly productive this quarter with three significant publications and presentations and numerous insights about how to guide our drug into future combination trials. Our Chief Scientific Officer, Dr. Kishor Bhatia, will provide additional details around these and other areas that will be important for our future work. This past quarter, we published a peer-reviewed paper highlighting our novel AI-powered approach to ADC development using the RADR platform an area of growing interest in the oncology community. We also presented new findings about our synthetic lethal drug candidate at two major conferences: The immuno-oncology summit, where we shared exciting data about the role of LP-184 in synergy with anti-PD-1 drugs and at the Society of Hematologic Oncology, where we presented insights regarding LP-284. These presentations generated significant interest from collaborators, pharma companies and also help strengthen our AI-driven approach to drug development by giving us insights, models and new data.

We'll also get more details today from my colleague, David Margrave, our CFO today, on our financial position and operations. At a top level, Lantern closed the quarter with approximately $28.1 million in cash, cash equivalents and marketable securities, and we used approximately $4.5 million in operations this past third quarter.

So I'm going to hand this over now to David to talk in more detail about our finance and operations. David?

[David Margrave, executive]

Thank you, Panna, and good afternoon, everyone. I will now share some financial highlights from our third quarter ended September 30, 2024. We recorded a net loss of approximately $4.5 million for the third quarter of 2024 or $0.42 per share compared to a net loss of approximately $3.2 million or $0.29 per share for the third quarter of 2023. For the third quarter of 2024, our R&D expenses were approximately $3.7 million, up from approximately $2.2 million for the third quarter of 2023. This increase was largely driven by an increase in clinical trial activity.

Our general and administrative expenses for the third quarter of 2024 were approximately $1.5 million up slightly from approximately $1.3 million for the third quarter of 2023. The increase was primarily attributable to increases in professional fees and increased patent and legal 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. Our loss from operations in the third quarter of 2024 was partially offset by interest income and other income net totaling approximately $674,000 as compared to a loss offset from interest income and other income net of approximately $362,000 for the third quarter of 2023. Our cash position, which includes cash equivalents and marketable securities was approximately $28.1 million as of September 30, 2024. We anticipate this balance will provide us with a cash runway into at least late 2025. Importantly, we believe our solid financial position will fuel continued growth and evolution of our [ RADR AI ] platform, continue the development of our portfolio of targeted oncology drug candidates and allow us to introduce additional targeted programs and collaboration opportunities efficiently and effectively.

As of September 30, 2024, we had 10,784,725 shares of common stock outstanding, outstanding warrants to purchase 70,000 shares and outstanding options to purchase 1,274,546 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 September 30, 2024.

Our team at Lantern continues to be very productive under a hybrid operating model. We currently have approximately 24 employees and 4 FTE consultants focused primarily on leading and advancing our research and drug development efforts. Many of the initial observations made with the help of RADR are now being brought forth into the clinic, as you can see in our portfolio slide that's being presented. As many of you know, RADR has guided the rapid and efficient development of three AI-guided drug candidates into ongoing clinical trials. As these clinical trials mature and continue to enroll patients, we expect to leverage our internal clinical operations capabilities across these trials and functions, making efficient use of our capital, while lowering dependency on external higher-cost providers. Additionally, we believe having more direct internal ownership, not only reduces our overall financial expenditures, but also gives our team greater ownership, control and access to current information, sites and day-to-day activity in the hospitals and cancer centers relating to our trials. This, we believe, will strengthen our company and allow us to capitalize on observations and decrease our external costs. We are fortunate to have developed a dedicated, highly motivated clinical operations team with alignment around our core values to help us in the efficient management and maturation of these clinical trials across LP-300, both in the U.S. and Asia and our first in-human drug candidates, LP-184 and LP-284.

I'll now turn the call back to Panna for an update on Starlight and its focus on CNS and brain cancers. Panna?

[Panna Sharma, executive]

Thanks, David. We also continue to make significant progress on 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 and AI. The methods and computational approaches to uncover the indications and optimize the use of LP-184 for brain and CNS cancers. Notably, we have started initiating site selection for the upcoming Phase Ib and Phase II trials, especially in recurrent [ IDH ] wild type [ hydrate gliomas ] like GBM and are also in discussions for the use of the drug in potentially -- settings. If you have not reviewed our webinar in webinar Wednesdays regarding Starlight, I would definitely urge you all to listen to the webinars. They provide details on the timing and focus of the trials and also provide insights from Dr. Mark Chamberlain about how we expect to advance this both in adult and pediatric brain cancers.

I'd like to take a moment to emphasize two significant recent developments that further validate our CNS cancer program. First, the FDA's Fast Track designation for LP-184 in glioblastoma represents a crucial milestone. This designation is particularly meaningful because it recognizes both the serious nature of GBM and the significant unmet medical need. We have a new effective single-agent therapy approved for GBM in nearly 20 years. Fast Track status provides us several important advantages, including more frequent interactions with the FDA, the potential for rolling review of our future NDA and if criteria are met, could lead to accelerated approval and priority review. These benefits could potentially shave years off our development time line in GBM and make the asset significantly more valuable in the hands of a larger biopharma partner.

Equally exciting is the formation of Starlight Therapeutics Scientific Advisory Board, which brings together some of the most respected minds in neuro-oncology. Let me share with you the distinguished members who have joined us. Dr. Mitchel Berger from UCSF, who chairs their Department of Neurosurgery and directs both their brain tumor center and center for neurological injury and repair. Dr. Berger is internationally recognized for his expertise in brain mapping during tumor surgery; Dr. Lisa DeAngelis, who serves as Chief Physician Executive at [ Memorial Sloan Kettering ] Cancer Center, where she oversees all clinical operations across their network of sites, She's an internationally recognized expert in brain cancer and help establish Memorial Sloan Kettering's Brain tumor Center; Dr. Stuart Grossman from Johns Hopkins and [ Sydney Kimmel ] Cancer Center, who co-leads their brand cancer program and brings over 22 years of experience directing NCI-funded brain tumor consortia; and lastly, but definitely not least -- in the least, Dr. John Laterra, also from Johns Hopkins, who co-directs their brain cancer program and is internationally recognized for his work on mechanisms of brain tumor malignancy. Dr. Laterra has been an early supporter and has encouraged us to pursue this indication and has helped our research efforts and continues to help guide combination regimen ideas that we think will be significant in the clinical setting. My colleague, Dr. Kishor Bhatia will discuss those later today in our webinar.

The Starlight Advisory Board, which includes two recipients of the Society for Neuro-Oncology's Lifetime Achievement Award brings unprecedented expertise to guide our CNS cancer programs. Their willingness to join our advisory board speaks volumes about the potential they see in our approach to treating these devastating cancers.

Let me walk you through some of our progress now with the synthetic lethal drug candidates, LP-184 and LP-284. The Phase Ia basket trial for LP-184 we've now completed 9 cohorts with escalating doses. We haven't seen any dose-limiting toxicities. We're actively enrolling patients across multiple solid tumor types including those that have high PTGR1 like triple-negative, GBM and pancreatic cancer, and now we're zeroed in on tumors that have DNA damage response deficiency. Based on our pharmacokinetic analysis, we're approaching an exciting milestone. Our upcoming cohort should reach dosage levels where we expect to see therapeutic concentrations of our drug candidate LP-184, and hopefully, impact on the cancers. We anticipate completing enrollment by year-end or in January with initial safety and molecular correlation data expected either late this year or during early 2025.

I'm particularly excited about our progress in developing a companion diagnostic for LP-184, we're advancing a quantitative PCR-based test that could help us identify the patients most likely to respond to treatment, ones that have PTGR1 above a certain threshold, which is a key aspect of our precision medicine approach. We're currently validating this assay using patient samples, but also now using them in the first 7 cohorts in the Phase I trial. These molecular correlations that will be invaluable in designing our future trials and helping us select patients. The combination of clinical progress and diagnostic development exemplifies our comprehensive approach to drug development. We're not just advancing a therapeutic candidate, but also developing the tools to identify the right patients for treatment.

Turning to our LP-284 program, which targets hematologic cancers, we're making equally exciting progress. We're currently dosing our fourth cohort, again, in escalating doses in the Phase Ia trial. And like LP-184, we're seeing favorable safety profile with no dose-limiting toxicities. Let me highlight why we're excited about LP-284, remarkable potency in the [ nanomolar ] range for multiple blood cancer types, but specifically in mantle cell and double-hit lymphomas both very aggressive NHL subtypes, particularly those that have ATM mutations. To put this opportunity in perspective, we're targeting an area of significant -- nearly all [ mantle cell in double lymphoma ] patients and in general hybrid B-cell lymphomas. Again, we received two orphan designations for this drug eventually relapse after current standard treatments. The market opportunity is substantial in the U.S. and Europe alone, about 16,000 to 20,000 new patients annually about a market exceeding somewhere in the range of $2.8 billion to $3 billion just in U.S. and Europe alone.

We're now in the process of expanding our trial to additional hematology focused sites, which we expect will accelerate our enrollment through the end of this year. Based on our current trajectory, we believe we could advance to Phase Ib or future phases like Phase II by early to mid-2025. When we look at both LP-184 and LP-284 together, these are sister molecules. We're seeing consistent patterns that validate our synthetic lethal approach, strong safety profiles, encouraging signs of biological activity and the potential to address significant unmet cancers where oftentimes, there is no here in the later-stage setting. So these are very exciting. This kind of excitement has helped us do one very important thing which is secure 11 FDA designations, fast track designations, orphan drug designations and rare pediatric disease designations. This is a strong testament to our data-driven rapid and focused drug development initiatives. We believe this will aid in more frequent guidance and interaction with the FDA and also strengthen our commercial value in talks with partners and clinicians during adoption. With our HARMONIC trial, LP-300, the data has been very encouraging. And more importantly, this is for patients where there is no real treatment options today. After they fail [ kinase ] therapy, there are very limited treatment options. So these early signals, though in a small group, are particularly meaningful. We also see a diverse set of patients in the U.S. with a varying range of [ kinase ] mutations and also with low to intermediate tumor mutation burden, we should have some interesting implications for biomarker-based selection or monitoring as we mature the drug candidate.

We continue to enroll patients across our U.S. sites and are also expanding into Asia and Japan and Taiwan, as I've stated earlier. In East Asia, including Taiwan, Japan and South Korea, nearly 40% of new cases now in non-small cell lung cancer or amongst ever smokers. This is a remarkable percentage and underscores our commitment to expand the HARMONIC trial to where it's needed in these countries. We're opening up 10 sites in Asia, 5 in Japan, 5 in Taiwan, and very importantly, working close to the top KOLs in each country. Dr. [ Goa ], the National Cancer Center Japan and Tokyo and Dr. [ Lee ] at the National [ Cheng Kong ] University Hospital located in Tainan City in Taiwan.

In the majority of East Asia EGFR mutations comprise a significant an overwhelming percentage of the targetable kinase mutations among ever smokers. We've already seen some early signs of efficacy in our initial cohort. Now this is important because we think this represents an important opportunity in Asia, where we've now begun discussions regarding partnering, licensing or co-development of this asset in that geography.

Now I'll turn the call over to our Chief Scientific Officer, Kishor Bhatia, who will provide an overview of our R&D updates and speak specifically to a number of highly promising combination regimens for LP-184. Ones that have been shaped and informed and guided by RADR, but now ill help shape future clinical trials that will be very meaningful. Kishor?

[Kishor Bhatia, executive]

Thank you, Panna. As we accrue clinical data and define the [ MTD ] in our Phase I clinical trial, we are actively pursuing additional areas of R&D that contribute to further successes of LP-184. A general consensus that has emerged from collective experiences in oncology has been that successful treatments are most likely to be based about combination therapeutics rather than monotherapy. With this in mind, we are studying the optimal selection of potential agents to combine with LP-184, which enhance the efficacy of treatment have little, if any, overlapping toxicity as well as expand indications.

For the past year, our RADR translation and clinical teams have addressed these immediate needs. Towards fulfilling these rapidly, we have also engaged with several expert collaborators that are shown in this slide that is being displayed. And these include scientists from MD Anderson, UNICEF Massachusetts, Boston, Johns Hopkins and the industry of Texas and [indiscernible]. Today, I'm going to talk about three distinct LP-184 combinations. Two of which are in accelerated protocol development by the clinical team. I won't have time to show data, but I can mention here that new unique combinations for LP-184 are emerging from both RADR and [ bench ] studies, the latter including [ ISPA ] analysis studies.

So a significant aspect of [indiscernible] that results from tumor-specific PTGR1 in expression for which now we have a [ biosite ], which causes a [ bioactivation ] of LP-184 in tumor cells is that it ends up in the formation of double-strand breaks. When threatened with LP-184, cancer cells, therefore, need to engage multiple repair factors and pathways beyond transcription coupled [ necrotide ] exceeding repair. [indiscernible] Clearly requires the attention of homologous recombination repair pathways. It was, therefore, expected that LP-184 demonstrated synthetic lethality in tumors deficient in such pathways including mutations affecting BRCA1 and BRCA2. Such synthetic lethality of LP-184 extends beyond the classical BRCA-mutated tumors and also includes tumors with [ BRCA-ness ] such as those with mutations in additional genes involved in the homologous combination pathway. What has been surprising has been the evidence that LP-184 synergizes with PARP inhibitors both in HRD, but also in those HRD tumors that have become PARP inhibitor resistant. This slide shows that [indiscernible] lower doses of LP-184 are sufficient to achieve 3 to 14 fold greater regulation compared to Olaparib alone in tumors mutated either in BRCA1 or BRCA2.

I would particularly like to draw your attention to the synergies seen in both tumors with low doses of LP-184, but if you look at the tumor on the right which, as you can see, is resistant to all our [indiscernible], it is wiped out by LP-184 at 2 milligrams per kg. And when you combine Olaparib with less than 1/4 of this LP-184 grows, this tumor now loses its refractoriness to PARP inhibitors. The likely success of this potential is further supported by similar data generated by our independent collaborators at [ UNICEF ] Massachusetts Boston, who also have suggested additional mechanisms involving depletion of RPA as one of the drivers of this synergy. A combination with PARP inhibitors that can make [indiscernible] resistant tumors sensitive is, therefore, a significant advantage for LP-184. We are particularly only excited by the potential of such a combination and have developed a protocol to actively test this in our Phase Ib clinical trial arm.

There are several reasons why LP-184 might be an exceptional combinatorial agent for power inhibitors, which comes from understanding the PARP inhibitor resistant factors. This next slide identifies factors that have been dispersed to be associated with the resistance to power inhibitors. If you specifically look at [ road 3 ], much of our data suggests that LP-184 effectively combats these factors even in the presence of gene conversion, LP-184 has been effective. loss of [indiscernible] complex that allows tumors to become resistant to PARP inhibitors actually makes tumor sensitive to LP-184. Additional insights have been the agnostic feature of LP-184 to [indiscernible] loss of [indiscernible] impairs prolonged [indiscernible] arrest upon PARP perimeter exposure, thereby using resistance. But [indiscernible] level loss does not affect sensitivity to LP-184, what this means in practical terms is that when using combination with PARP inhibitors, LP-184 is highly indicative, not only for synergy but also for reducing the resistance to PARP inhibitors.

The other molecule that we are proposing to the clinic as a combinatorial partner of LP-184 is a drug that has extensive clinical experience, albeit from non-oncology indications. This drug, spironolactone, is an FDA-approved drug used for various indications, including hypertension and acne. What [indiscernible] specifically to this drug were multiple observations of which the most important was the serendipitous discovery the spiral electron targets ERCC3 to degrade it. The scientific rationale and reasoning of combining LP-184 with spironolactone, was fully justified by a battery of preclinical studies [indiscernible] collaborators conducted. In this slide, in the box A, you can see that spironolactone increases sensitivity of GBM cell lines to LP-184 3 to 6 fold. What this specifically means is that even in settings where there is lower bioavailability of LP-184, the combination can result in sustained DNA damage, as you can see in [ Panel D ] and that these effects correlate with a significant reduction in the repair protein ERCC3 shown in Panel C. Not surprising, therefore, the combination resulted in excellent responses in in vivo glioblastoma models with most cures, only 1 of 5 tumors show recurrence to the combination.

In order to use this combination clinically, we need to better understand the time window where LP-184 should be administered, following spironolactone treatment. So we carried out several [ time code ] studies. In this slide, we demonstrate that ERCC3 is at its lowest level in both orthotopic and subcutaneous glioblastoma xenograft at 8 hours after spironolactone administration dosed as human equivalent of 200 milligrams per [ KD ]. In addition to glioblastoma, the combination of spironolactone enhances the activity of LP-184 in other select tumor types, including ATRT, pancreatic cancer and renal cancers. Even the rare pediatric orphan disease designation and the lack of any approved therapy for ATRT, we are particularly enthusiastic of the clinical studies in ATRT and are in active discussions with several pediatric neuro-oncology groups, including poetic and children's oncology Group.

I will now shift to the third combination we are exploring, which is combining LP-184 with immune checkpoint inhibitors. We have previously observed during our [ steady up ] DNA strand breaks the accumulation of cytogenic DNA in tumor cells following LP-184 treatment. This feature would suggest LP-184 as an immune activating molecule as well to test the potential of LP-184 combined with checkpoint inhibitors. We've developed a collaboration with [ Dr. Lin ] at MD Anderson, who has previously shown that the involvement of replication stress detect correlates with immune responsing tumors. [indiscernible] could be pharmacologically induced this replication stress response defect and, therefore, extend the benefits of immune checkpoint inhibitors for a wider patient population. We have [indiscernible], therefore, that LP-184 treatment might escalate replication stress levels, particularly in [ TNBC ] and induce replication stress response [indiscernible]. As you can see in the slide, when LP-184 cells were assessed for induction of replication stress defend compared to a similar effect induced by what would be expected from a [ cell cycle ] checkpoint inhibitor, the results show a 60% of relative [ defect ] increase by LP-184 compared to 75% with [indiscernible] at equimolar doses. We then tested the effects of a combination of anti-PD-1 antibody in combination with LP-184 in a murine synthetic TNBC model. The results shown in this slide evidence enhancement of tumor growth inhibition from 51% in LP-184 alone detect tumors to 72% in the combination. Additional steady indicate that LP-184 might actually modulate both the pure microenvironment as well as T cell function. Uniquely, it appeared that LP-184 reduces [indiscernible].

Based upon these results, we are now in discussion with various clinical investigators towards development of a clinical study in TNBC cold tumors. Many other rationally designed combinatorial partners are emerging from our RADR and CRISPR based analysis such as inhibitors of [indiscernible] but also include molecules that are outside the [indiscernible] and repair pathways, once that pathway and [indiscernible] particularly like to mention, which is demand is important, is the [indiscernible] pathway, and we hope to share with you in the near future some exciting data business combinations.

And now I'll turn it back to Panna.

[Panna Sharma, executive]

Sure. Thank you very much. As you can see, we're already turning our attention now to the next phases of clinical development and pathway for our exciting drug LP-184. We know that many of these combinations are with drugs that are a part of the meaningful arsenal in cancer, especially PD-1, anti-PD-1 and [ part ] and we expect there to be a lot of excitement in the clinical community as there has been so far in the research community, but also very importantly, in the biopharma community, given the number of [ PARPS ] and their limited range of extended use in some of these tumors and also the same with PD-1. When you have a drug like LP-184 that can widen the therapeutic window and potentially open up new avenues there should be a lot of excitement and potential for partnering opportunity.

Let's now talk a little bit about Webinar Wednesday. We've had a lot of exciting webinars about one a month. For those that have not listened in on the backdrop of these webinars are the details. Our last webinar Wednesday for the year will be held on December 11, not the last Wednesday of November and not the last Wednesday of December, but we know it's a challenging time. So we try to pick right at the middle of the month. That webinar will focus on the power of AI in drug development, specifically around the use of molecular features to predict blood-brain barrier permeability, with RADR. The webinar will discuss also future development plans we have and the potential commercialization and commercial availability of this radar platform module, which leverages extensive molecular feature analysis enrich the proprietary models and proprietary data.

According to the therapeutic data comments, a coordinated initiative to access and evaluate artificial intelligence capability across therapeutic modalities and across stages of discovery, Lantern's BBB algorithms are 5 of the top 10 performing algorithms on the leaderboard. So that's very exciting. And that was some of our early algorithms. In fact, they continue to mature and get refined and have actually matured significantly in some of their future discrimination. So we're pretty excited to talk about that on December 11 with one of our data scientists who's been working on those models.

As you know, 2024 has been a year of progress, accelerated progress where our insights are impacting patients in their journey to fight cancer and also influencing the development decisions and progress -- actually of other cancer companies. Our collective efforts and dedication have fostered a transformational shift for our company, setting us on an exciting trajectory towards the future, where we are improving the lives of cancer patients with affected and affordable treatment options. As you can see, the work being done by Kishor and his team and also our clinical operations team is focused on meticulous execution, but constantly with one hand on the wheel of innovation. During the fourth quarter and into next year, we will have several clinical readouts and milestones to share with our investors as we advance our pipeline and company.

As I've said before, the golden age of AI in medicine is just beginning and it is being powered by large-scale, highly available computing power, massive data storage, massive data collaborations and it is being said by health care patients and cancer data, which is more widely available and at increasing levels of quality much more so than ever before. Companies that harness these capabilities in the biotech and biopharma arena, will be long-term leaders in this biotech are really now becoming more tech bio industry. And we think these are companies that are well poised to create massive value for patients long term and ultimately for investors in our industry.

I'd like to take a moment right now to personally thank our team for helping to prepare us for these calls, to prepare the materials, gather the data, provide insight and to their amazing dedication. If it wasn't for them, we probably would have a very handicap call.

So 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 one of two ways. You can type your question using the Q&A tool or you can click on the raise hand tool to speak directly and we will unmute your line.Yes. I'll go ahead and answer the first question. The first question asked is, one, do we expect additional data regarding our HARMONIC and LP-300 trial?

As we just opened up the sites in Asia, our goal is to gather another 14 to 28 patients actively. And for HARMONIC, we'll know a lot more once we see the impact of the trial expansion in Asia and also the data from the planned interim analysis, which will take place at 31 patients. So those two events will really guide us in terms of the next big clinical readout regarding the HARMONIC trial. And we expect that around mid of next year, if not earlier, but middle of next year is when we're expecting it.

Next question. Any updates on how RADR is growing and collaboration efforts?

As you know, we announced last quarter our collaboration with Oregon Therapeutics, which is going very well. We expect the first phase of that collaboration to finalize some time during the next month probably before the end of the year where we will be able to answer several questions and set the framework for some good joint IP in regards to indications and perhaps biomarker signatures that correlate to response for their drug -- for their PDI inhibitor. We are looking at additional collaborations. As you know, we've had three very important ones with emerging biopharma companies. We're now focused on larger biotech companies. I would say, more mid-market and more -- ones with much more diverse portfolio. So our attention now is increasing to larger companies given that the platform has matured quite a bit over the last 1.5 years.

I'll take the next question coming in the Q&A panel. Can we speak to any partnership interest?

Although it's probably too early to speak to partnership interest for the never smoker trial. We have gotten some conversation started. Obviously, this is, as I mentioned, from a epidemiological basis, never smokers account for 33% to 40-plus percent of non-small cell lung cancer cases in East Asia, again, primarily Japan, Taiwan and South Korea, many of the major regions in China are similar. But so you can expect that we're in discussions with larger pharma companies in Japan now. So that's very early, but we are receiving interest given the focus and given the prevalence of the disease there.

The other thing that I'd like to add is, obviously, we did hint at a biomarker signature correlating to lower intermediate tumor mutation burden. Now we're obviously chasing that down clinically. We've had very good initial data. We're looking to support this data as more patients get enrolled and we understand the tumor mutation burden status of those patients. And that also could mark a very important turning point in terms of interest with all the companies that are going after high tumor mutation burden, whereas this is for lower human mutation burden.

Next question is on Starlight Therapeutics and the scientific advisory board members.

We're quite thrilled about the decisions for Dr. DeAngelis, Berger, Laterra and Grossman to join the Scientific and Clinical Advisory Board, and these guys are among the most preeminent in their field. and for them to be interested in the drug and the indications, again, speaks volumes. [ If we ] think of the potential for this very novel site-activated alkylating agent to potentially transform the lives of both pediatric and adult brain cancer patients.

In my personal feeling, and this is very important, is that we're making progress each quarter. We're opening up sites, we're enrolling patients, we think the biotech market is fundamentally getting stronger. I think there'll be a lot of interest we've had in both private and public financing, and we'll find the best route to capitalize Starlight independently, so it can grow and develop its own trials. We believe that the trials for IB and II or for some other unique trials should be launched sometime in early 2025 for Starlight. But in the meantime, we try to maintain a lot of fiscal discipline. And again, those are planned trials. We'll see how the financing events go, and we try to use a lot of the existing lantern infrastructure and people to advance Starlight in parallel. So there's a lot of work for our team. And again, this work creates a lot of value for our investors long term. But we think this could be one of several planned spinouts from Lantern where the portfolio is more focused. The portfolio is in a certain modality and is aimed at a certain group of cancers or in a certain population.

Well with that, we're coming up against about an hour, 50 minutes into the call, long call today, but I want to thank everyone. We got a good overview of what's next in the combination trials. Again, we're very far into the Phase Ia for LP-184, where we expect to get to an MTD in the next two cohorts, and that should correlate with what we believe is going to be something we can go into future plan to Phase Ib and Phase II planned trials with as well. And we continue to make very solid progress with our AI platform, both with our collaborators and internally with new functionality. And we now will be expanding rapidly into Asia with our LP-300 trial.

Very importantly, as David pointed out, we continue to be very meticulous about execution and cost conscious. We do think that our existing capital and balance sheet allows us to take us through significant events, but we're watching the markets carefully if there's opportunities to partner our assets out or to access the capital markets will do so if it makes sense, but we're also very prepared to continue executing. And at the same time, we do think the markets will probably improve. But more importantly, we'll have opportunities to partner our assets and leverage our capabilities.

Internally, operationally, which is very important, we've begun to slowly bring in but vary step-by-step, aspects of clinical operations to try to build really a world-class [ Ninja ] team in clinical operations that we can use across our trials and [ across ] the various functions. And we think that gives us a lot of synergy, reduces our external spend. But as David pointed out, brings us closer in contact with our patients, our clinical sites and our data. So again, I think we're doing the right things operationally and are very focused on maintaining kind of the burn rate in the same range that we have historically.

So with that, I'd like to thank everyone for their time today. And I want to express my deep gratitude to our team, for our partners and our stakeholders for their support. And also to realize that together, we are really trying to light the way for a brighter, more scalable future in oncology care and oncology drug development. So thank you very much for joining us at the forefront of a new era for drug discovery and joining our -- listening to our team that we believe is bringing us to that [ new ] era.

[David Margrave, executive]

Thank you.