Earnings Call Transcript - LTRN Q2 2023

Nicole Leber, Investor Relations

Good afternoon, everyone. I’m Nicole Leber with Investor Relations here at Lantern Pharma. Welcome to our Second Quarter 2023 Earnings Call. I will be your host for today’s call. As a reminder, this call is being recorded and all attendees are in a listen-only mode. We will open up the call for all 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 closed today summarizing our financial results and progress across the company for the second quarter ended June 30, 2023. A copy of this release is available through our website at lanternpharma.com, where you will also find a link to the slides that management will be referencing on today’s call. I 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, 2022, 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 9, 2023, 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 CFO, David Margave. Panna will start things off with 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 Panna, and then we’ll open up the call for Q&A. 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

Thank you for joining us to discuss our second quarter results and corporate progress. This is an exciting time for AI in medicine, which is just beginning to take off, fueled by advanced computing power and extensive data storage. We're seeing a wealth of healthcare and cancer data that is more accessible and of higher quality than ever before. Companies in the biotech and tech bio sectors that leverage these advancements will emerge as long-term leaders, creating substantial value for patients, investors, and the industry. Lantern Pharma is at the forefront of transforming oncology drug discovery and development, seeking to make medications faster, less expensive, and with greater precision for patients while improving research and development productivity in the pharmaceutical sector. I will elaborate on this crucial aspect later in the call. Our proprietary AI platform, RADR, continues to expand in size, scope, and capability and is central to the shift toward AI-driven drug development. When we went public three years ago, we had three drug programs targeting markets estimated at $5 billion to $6 billion in potential annual sales. Today, we have over 14 drug programs, many with orphan drug designations and other commercial protections, targeting markets valued at about $14 billion or more in annual sales. We are also exploring additional promising programs and molecular candidates for future development. Our growing pipeline of oncology drug candidates showcases the rapid identification and validation of new cancer insights through AI and machine learning, allowing us to focus on specific molecules for effective oncology medicines. Notably, RADR has allowed us to reduce the timeline of early-stage drug development by an impressive 70% while cutting costs by around 80% compared to traditional methods within the pharma industry. We believe we can continue to enhance this process. With our advanced AI platform and innovative technologies, we are paving the way for the next generation of oncology drug discovery. In the last two years, we've successfully developed and launched 11 new programs, which highlight the efficiency and innovative nature of our approach. On average, these programs are moving from initial AI insights to first-in-human clinical trials within just 2.5 years, at an average cost of about $2 million each, with some falling below this cost. These figures are unprecedented in oncology drug discovery. A recent study indicated that nearly half of the largest pharmaceutical companies had declining R&D productivity over the past 20 years while spending an average of $6.2 billion for each drug approval. This reality reflects the outdated model of big pharma R&D and indicates that a fundamental rethink is necessary, especially concerning cancer drug pricing. We believe larger pharmaceutical companies will increasingly adopt AI and computational methods to address these challenges. Our RADR platform has demonstrated an 88% predictive accuracy in identifying patients most likely to respond positively to our drugs during clinical trials. We highlighted this success in a real-world study presented at ASCO with our collaboration partner Actuate for their Phase 2 trial. This achievement represents a significant advancement in patient stratification, reducing trial costs and ensuring that we enroll patients who will benefit the most from our targeted therapies. By combining our innovative AI with extensive clinical, genomic, and drug response data, we have significantly improved our ability to mitigate risk and enhance success rates. Studies have shown that biomarker signatures can boost the success rates of oncology clinical development by 5 to 12 times, which also reduces risk and cost while shortening timelines, especially in later-stage trials, highlighting the potential of our technology to lead to the development of targeted cancer therapies. Currently, our AI-driven pipeline consists of 14 drug programs, including those developed in collaboration with RADR and our Phase 2 clinical trial called Harmonic for lung cancer in never smokers. Our commitment to leveraging AI for drug discovery has also led to our partnership with Bielefeld University in Germany to create the next generation of antibody drug conjugates, designed with the RADR AI platform. This collaboration promises to result in therapies with higher efficacy, faster development timelines, and reduced costs for early-stage development. ADCs are an exciting and rapidly expanding treatment modality, projected to grow from $4 billion last year to over $14 billion by 2027. We have created significant value, including the formation of Starlight Therapeutics, focused solely on CNS and brain cancers, demonstrating our dedication to advancing oncology drug discovery. As we accelerate the development of actionable insights, we are well-positioned to partner these assets with larger companies. Alongside this, we have maintained a strong cash position, which has been used wisely to facilitate meaningful advancements. We see our strategy as the future of cancer therapy development where data accelerates programs and reduces risks, moving us closer to delivering transformative medicines. Now, let's turn to some specific highlights from our second quarter. We received FDA clearance for our IND application for LP-184 and activated initial clinical sites for the program while also identifying potential patients for this Phase 1 basket trial targeting multiple solid tumor and brain cancer categories. We completed the IND-enabling studies for LP-284 and plan to submit the IND to the FDA by the end of August, paving the way for a first-in-human Phase 1 trial for LP-284 in advanced non-Hodgkin's lymphomas later this year. Data showcasing LP-284’s anti-tumor potency for mantle cell lymphoma and other non-Hodgkin’s lymphomas was published in Oncotarget this quarter, supporting the advancement of this promising therapeutic option. Additionally, we enrolled more patients in the Phase 2 Harmonic trial of LP-300 for non-small cell lung cancer and expanded patient recruitment across several new trial sites. As mentioned earlier, our collaboration with Bielefeld University aims to create innovative antibody drug conjugates, which we believe will lead to a new wave of ADCs with superior efficacy, faster timelines, and lower costs. Our intellectual property was bolstered this quarter with the allowance of a U.S. patent for the composition of matter of the new drug LP-284, extending commercial protection into early 2039, along with five new patent applications for LP-184 and LP-284 covering their use in combination therapies and specific tumor subtypes where we see the highest potential. Importantly, we maintained fiscal discipline, ending the second quarter with $48 million in cash, cash equivalents, and marketable securities, providing us with a strong financial runway into 2025. I will now hand the call over to our CFO, David Margave, for an overview of the second quarter financial results, after which I will return with more updates on our programs.

David Margave, CFO

Thank you, Panna, and good afternoon, everyone. I’ll now share some financial highlights from our second quarter ended June 30, 2023. Our general and administrative expenses were approximately $1.6 million for the second quarter of 2023, up slightly from approximately $1.4 million in the prior year period. R&D expenses were approximately $3.6 million for the second quarter of 2023, up from approximately $3.0 million in the second quarter of 2022. Our increased R&D expenses were in line with expectations and primarily driven by increases in research studies and R&D related payroll and compensation expenses, which were partially offset by a decrease in product candidate manufacturing expenses. We recorded a net loss of approximately $4.7 million for the second quarter of 2023 or $0.44 per share compared to a net loss of approximately $4.5 million or $0.41 per share for the second quarter of 2020. Our loss from operations in the second quarter of 2023 was partially offset by interest income and other income net totaling approximately $444,000. Our interest income and other income net increased by an aggregate of approximately $541,000 for the second quarter of 2023 compared to the second quarter of 2022. This increase was attributable to an increase in interest of approximately $63,000, increases in dividend income of approximately $168,000, an increase in unrealized gains on investments of approximately $150,000, and an increase of approximately $109,000 in research and development tax incentives related to our Australia subsidiary. As of June 30, 2023, we had approximately 10.86 million shares of common stock outstanding and outstanding warrants to purchase approximately 177,998 shares, and outstanding options to purchase approximately 1.1 million 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 June 30, 2023. Our cash position, which includes cash equivalents and marketable securities, was approximately $48.0 million as of June 30, 2023, and we expect this balance to carry us into 2025. Importantly, we believe our solid financial position will fuel continued growth and evolution of our RADR AI platform, accelerate the development of our portfolio of targeted oncology drug candidates, and allow us to introduce additional targeted products and collaboration opportunities in a capital-efficient manner. Our team continues to be very productive under a hybrid operating model. This hybrid model also removes geographic restrictions to our hiring initiatives, which has given us the ability to recruit extremely high-caliber team members that otherwise might not have been available. We currently have 22 employees focused primarily on leading and advancing our research and drug development efforts. We see this number expanding slightly in the coming quarters as we add additional experienced and talented individuals to help advance our mission. I’ll now turn the call back to Panna for an update on some of our development programs.

Panna Sharma, CEO

Thank you, David. As many of you know, we received FDA clearance for our IND application for LP-184 in June, and I’ve already activated the initial clinical trial sites for our Phase 1 basket trial. The clearance for the IND application was a significant milestone for our LP-184 program, validating our approach of leveraging AI and machine learning to advance our pipeline of novel drug candidates. Insights from our AI platform RADR were instrumental in our development of LP-184 and aided in discovering its mechanism of action, identifying and prioritizing the ideal cancer subtypes to pursue, and generating biomarker signatures that we can use within future clinical trials to help us with patient stratification and selection. We developed these signatures literally sometimes in weeks or months, a process that normally would have taken half a year to 18 months. We believe that LP-184 has blockbuster potential for patients with multiple types of advanced solid tumors and CNS cancers, many of which have no or limited effective therapeutic options. We’re more excited today about the opportunity for this drug than even two and three years ago. Globally, the aggregate annual market potential for LP-184 is estimated to be over $10 billion, consisting of about $5 billion in solid tumors and another $5 billion to $6 billion for CNS cancers, both primary and those arising as a result of metastasis. LP-184 is the first of our drug candidates to be developed entirely internally and with significant use of our AI platform to uncover the subtypes where we believe we can meet highly underserved needs in areas where there are no therapeutic options. This molecule has been advanced now to a first-in-human Phase 1 basket trial, and the trial is designed to evaluate 35 patients and will assess the safety and tolerability of escalating doses using a buoyant design. We also believe that we have seen exceptional results in cancers that have DNA damage response deficiencies, and that’ll be also an additional target for later phases of the trial. The initial trial sites have been opened and we are actively screening patients for dosing with LP-184. We anticipate completing the trial sometime in 2024. Another very promising new molecule is one that we developed from whiteboard to a first-in-human clinical trial in under 2.5 years, and with an estimated cost of under $3 million. This drug was not even on our pipeline when we went public. It’s a very exciting molecule. The initial insights around the specific mechanism of synthetic lethality were derived from large-scale comparative data using our RADR AI platform. We then leveraged our GMP manufacturing process for its sister molecule LP-184 to efficiently ramp up and develop LP-284 while continuing to refine the indications and mechanisms. Ultimately, these studies also led to an orphan designation in mantle cell lymphoma. Today, we are preparing for a first human clinical Phase 1 trial, which we expect to launch in the fourth quarter of this year. As I mentioned earlier, with IND-enabling studies now complete, we anticipate submitting the IND to the FDA by the end of this month, and we also already received orphan drug designation in mantle cell lymphoma. The market we believe for mantle cell and double-hit lymphomas, which are very aggressive non-Hodgkin’s lymphoma subtypes, is currently about $1.2 billion in the U.S. and Europe, and we think the number globally is about 2 to 2.5 times that number. LP-184 and LP-284 represent our synthetic lethality franchise, which has shown significant potency in a wide range of cancers, both as monotherapy and also in combination with other agents. LP-184 has selected preference for solid tumors that have high levels of PTGR1 expression or deficiencies in DNA repair pathways. While LP-284 has shown potent efficacy in a wide range of hematologic malignancies, namely non-Hodgkin’s lymphomas, and we have also seen that LP-284 shows the ability to effectively regress mantle cell lymphoma xenografts after they become refractory to both Ibrutinib and Bortezomib. Both drug candidates have also shown promising activity in a range of pediatric tumors, which will be pursued with research centers focusing on children’s cancer such as University of Texas Health and Greehey Children’s, and we believe these will lead into Phase 1 trials once the dosing and safety have been established from LP-184 and LP-284 early trials. We also know that LP-284 has demonstrated a significant impact on a wide range of sarcomas, including Ewing sarcoma and rhabdomyosarcoma, both pediatric cancers largely. Additionally, LP-184 was granted a rare pediatric disease designation in ATRT, atypical teratoid rhabdoid tumor, an ultra-rare cancer, which has no approved standard of care agents and largely reflects children under the age of five. We published with the National Cancer Institute a pretty unique publication where we uncovered the mechanism of pointing this drug toward these chromatin modeling deficient tumors, namely looking at SMARCB1, and we plan on reporting more details from these studies and the potential emerging indications later this year. Now, moving on to our Phase 2 clinical trial of LP-300, initial patients in our Phase 2 Harmonic trial of LP-300 for never smokers and non-small cell lung cancer have been dosed, and we have five additional active trial sites that we've added. We expect to add additional trial sites throughout this quarter and also multiple patients. We’re also screening and increasingly increasing the number of patients we’re screening. This comes as a direct result of increased awareness among patient advocacy groups and greater investigator interactions and briefings. Additionally, Dr. Joseph Treat of Fox Chase Cancer Center has been appointed as the lead principal investigator for the Harmonic study. Dr. Treat brings a stellar focus and background of serving not only the lung cancer community but also a background in clinical trials in the never-smoker population. He was recently leading a 100-plus patient Phase 2 interventional trial focused on never smokers with Stage 4 disease who had never smoked but irrespective of their driver mutation status. So it’s an ideal backdrop and experience and also the clinical network for the Harmonic trial, and we welcome his active leadership in Harmonic and with Lantern. We’re also exploring the potential to expand the Harmonic trial into Asia, specifically countries that have a higher incidence of never smokers with lung cancer. Overall, we anticipate the enrollment of this two-arm open-label randomized trial, which is targeting 90 patients, should last between 14 and 18 months. The Phase 2 trial is designed to investigate LP-300 in combination with standard of care chemotherapy with the key measured endpoints being overall survival and progression-free survival. In a previous multicenter Phase 3 clinical trial, what we saw was that a subset of never smokers with non-small cell lung cancer that received LP-300 with chemotherapy showed a significant increase in overall two-year survival, showing an overall survival of a 91% increase in the never-smoker population that was given LP-300 and a 125% increase in progression-free survival in that same group of never smokers versus the standard of care of the chemotherapy doublet. I also discussed earlier our exciting collaboration with Bielefeld University to develop breakthrough antibody drug conjugates. This partnership signifies an exciting stride forward in the development of next-generation ADCs using our RADR AI platform. The initial focus of the collaboration is to synthesize and evaluate novel ADCs linked to cryptophycins. This is a promising class of anti-tumor molecules due to their potency at ultra-low picomolar concentrations. We believe we can attach several of these molecules to the antibodies of interest using a fairly unique linker strategy. The cryptophycin-based ADCs will undergo rigorous testing across multiple cancer cell lines, both in vitro and in vivo models, and we anticipate sharing the initial results in the coming months. We also plan to leverage our ADC development module that has been fully integrated now into RADR to launch multiple ADC opportunities through Lantern, and also through our partners and our cryptophycin-based collaboration with the University of Bielefeld. We believe ADCs are a very promising treatment modality with significant opportunities for partnership and also to license with larger pharma companies. Our AI-guided strategy holds immense potential to de-risk the ADC development process while simultaneously enhancing the creation of effective and targeted ADCs. Given the rapidly growing global ADC market, currently valued at over $4 billion, it is projected to reach $14 billion in the course of the next several years by 2027. We’re eager to expand our footprint in this important and emerging space. Under the terms of our collaboration, the team at Bielefeld University under the leadership of Dr. Sewald will synthesize, optimize, and provide initial testing of the cryptophycin-linked ADCs, and Lantern has the exclusive worldwide option to license intellectual property from this collaboration with Bielefeld University, which will include IP generally directed from our joint efforts. We anticipate sharing the results of this work probably during the fourth quarter. Leveraging more than 34 billion oncology-focused data points, we are on pace to surpass 50 billion data points by year-end. Our RADR platform excels in automated large-scale biological analysis and response network analysis, yielding correlations that can be leveraged for target identification, drug response prediction, and tumors and patient selection. But it’s not just about the quality of data. Our RADR platform also continues to evolve in terms of its capabilities. During the second quarter, we launched unique groundbreaking predictive models that enable us to assess blood-brain barrier permeability of any compound. We can do this for tens of thousands of compounds a day now. This capability is crucial for developing therapies targeting neurological disorders, where processing the blood-brain barrier is often challenging by accurately predicting the permeability and availability of that compound. We can optimize the design and delivery of potential treatments, and more importantly, save massive amounts of time and money involved in targeting and understanding blood-brain barrier permeability in early-stage development. Furthermore, our platform’s predictive power now extends to patient response and combination use for immune checkpoint inhibitors. We’ll talk about more of that later this quarter, but the immune checkpoint module now harnesses the power of AI and machine learning, and now RADR can analyze vast amounts of data to predict how patients may or may not respond to these inhibitors. This data includes both antigen data, proteomic data, mutation data, and RNA data. This allows us to identify potential combinations for more personalized treatment strategies, but also, very importantly, for larger pharma companies to manage the downstream long-term value of their investments in these immune checkpoint inhibitors. As I already discussed, we also made significant strides for designing templates for next-generation ADCs using our ADC module, and we think this has the potential to revolutionize the way ADCs are created and provide better high potency therapeutic payloads while minimizing damage to healthy tissue and systems. So RADR continues to advance its capabilities in size and scope but also in functionality. We believe that this will continue to secure Lantern’s position at the forefront of leading-edge AI-based drug discovery and personalized cancer therapy development. So 2023 is shaping up to be a pivotal year for Lantern, where our insights are entering patients and have started their journey to becoming meaningful therapies in cancer while increasing the functionality of our AI platform, our collective efforts, and dedication to fostering a transformational shift for our company, setting us on an exciting trajectory towards a future where we’re touching and improving the lives of cancer patients with effective and hopefully more precise therapies. One of our primary focuses during the second half of this year will be to further advance the enrollment in Harmonic. It’ll also be to advance the enrollment for our Phase 1 trial, LP-184. We’ve opened up the initial sites and we’re actively screening patients today. We also expect our Phase 1 trial for LP-284 to launch in the coming months, most likely in Q4 of 2023. These trials represent significant milestones in our pursuit of advancing AI-powered drug discovery into the clinic. Additionally, we plan on progressing LP-184, known as STAR001, towards Phase 1/2 clinical trials and CNS and brain cancers under Starlight Therapeutics. We think this underscores our commitment to addressing unmet needs in a focused manner, and we think this presents substantial upside for our investors and our patients through Starlight. On the portfolio side, we believe our AI platform will reach over 50 billion data points and will further advance the key modules for immune checkpoint inhibitors and ADC development. These milestones will set a new standard for data-driven drug discovery, but also establish new RADR-based collaborations with companies and research partners. We intend to actively explore licensing and partnership opportunities with biopharma companies to accelerate the path to patients for our therapies and to showcase how our AI-driven approach can generate results for investors and drive the future of our franchise. While we ambitiously drive forward our R&D efforts, we’ll continue to uphold disciplined fiscal management to create further value for our shareholders. As we have pointed out, we’re accelerating the pace at which we develop and validate insights, but we’re also at the same time managing our cash and positioning these assets for partnering with larger companies. As we continue to advance our diverse portfolio, we’ll be presenting new data and findings at several prominent scientific conferences over the coming months. We have one on August 10 at the Society of Neuro-Oncology and the American Society of Clinical Oncology, the CNS Cancer Conference in San Francisco, where we will share findings related to LP-184’s ability to inhibit adult and pediatric CNS tumor cell growth, especially in new data related to ATRT. We will also be at the International Conference on Drug Conjugates for Directed Therapy in Darmstadt, Germany on August 24, where our Chief Scientific Officer, Kishor Bhatia, will be presenting new details about our innovative AI-driven approach to identifying ADC targets with improved tumor selectivity. In fact, we’ll be showcasing our whole tumor selectivity and antibody drug modules there. We will also be presenting at the Society of Hematologic Oncology’s Annual Meeting in Houston, Texas on September 6, where we’ll be sharing new research related to LP-284 and its ability to target genetic deficiencies in non-Hodgkin’s lymphoma. We have a lot of exciting scientific and clinical data that will be presented over the coming months, which will set the groundwork for even more improved opportunities for Lantern Pharma. In closing, I want to express my gratitude to our team, our partners, our collaborators, and also our investors and stakeholders for their unwavering support and dedication to helping us transform the oncology development process. Together, we’re lighting the way towards a brighter future in oncology drug development and solving real-world problems with unique proprietary AI solutions that allow us to develop these precision oncology therapies at significantly reduced costs and timelines that have been unheard of. We believe this places Lantern at the forefront of a new era, as I said, a golden age of medicine due to AI. With that, now I’d like to open the call to any questions or clarifications, but also I’d like to take a moment to personally thank our colleague Dr. Drew Sturtevant, who has been focused on our communication efforts for both the press and scientific community, for helping in our last five earnings calls. I know the team will miss his involvement and his upbeat dedication to Lantern, but we wish him well in his new scientific endeavors. So again, let’s take questions from our audience.

Nicole Leber, Investor Relations

Thank you, Panna. We already have a couple of questions coming in here. The first one is, has the first stage of the Harmonic trial been enrolled yet, and will Lantern report on the first stage of the trial before the completion of the full study?

Panna Sharma, CEO

Great question. I think that’s from John, but yes, we’re in the middle of the first stage of the trial. We will report results as they get reviewed, and we’d expect to report out the first stage. Yes. Thank you.

Nicole Leber, Investor Relations

Another one here from an analyst: how will the genomic and transcriptomic data collected in the Harmonic trial help guide the second stage and potentially a registrational trial?

Panna Sharma, CEO

Yes, regarding that question, we can transition from this trial design into a registrational trial. We anticipate gathering both mutational and transcriptomic data from the liquid biopsies we are collecting, which will help us identify differences in response based on the prior treatments these patients received. We will be able to refine our approach based on the data obtained from the liquid biopsy. This could lead to a range of unique opportunities we have already observed in silico. For example, we have found that high levels of PD-L1 may not respond well to these therapies, so we could investigate options that target low PD-L1 levels or certain signatures that indicate a higher likelihood of response, particularly among never smokers when combined with therapies aimed at resetting the redox cycle and chemotherapy. There are several ideas to explore, but once we acquire the patient data from the liquid biopsy, we can develop a signature that might be useful for a registrational event. Large pharmaceutical companies favor signatures, especially if they can obtain machine learning-derived ones without incurring additional costs, as this enhances the appeal of the asset. Thank you. I believe Tony has a question, correct?

Nicole Leber, Investor Relations

Yes. Tony, I see your hand raised. You should now be able to speak. Can you hear us?

Unidentified Analyst, Analyst

Yes. Can you hear me?

Nicole Leber, Investor Relations

Yes.

Panna Sharma, CEO

Yes.

Unidentified Analyst, Analyst

Yes. Thanks very much. Panna, thanks a bunch for the opportunity. A couple of questions. One is related to Harmonic and you alluded to it just a minute ago, but first let me ask in the previous data, the previous Phase 3 trial, at least, I’m not going to put a percentage on it, but certainly a good bit of the data responding to LP-300 was really driven by females. And so the question is what’s novel? And clearly less driven, substantially less driven by males. What do you think biologically is going on between genders in this study? That’s question one. Question two is, this is really related to checkpoints, but in particular pembrolizumab. And do you have any preclinical data that actually tells you regardless of PD-L1 high or low, that the combination might actually work better in these particular types of patients? So that’s really related to Harmonic. I’ll come back and ask my second question in the end because it’s very different than the first. Thanks.

Panna Sharma, CEO

Thank you, Tony. Regarding the ratio, I believe the trial does not accurately reflect the real-world female-to-male ratio. In the never smoker population diagnosed with non-small cell lung cancer, about two-thirds are female, with adenocarcinoma making up around 60% to 66% of cases. There isn't any specific reason why more females are affected; this is simply the disease's epidemiology, which is consistent across different races and regions. It appears that more females develop certain TKI driver mutations, and some research suggests that lung cancer in females may be linked to estrogen metabolism in the lungs. I anticipate our trial will mirror this trend, with more females than males, although we currently lack enough patient data to confirm this. However, the screening data indicates this is likely. I am uncertain about the biological implications of this and whether it requires our attention. Nevertheless, response rates in both genders were comparable, with slightly better outcomes in some females. Overall survival showed nearly a 90% to 91% improvement in the never smoker population and doubling of progression-free survival, irrespective of gender.

Unidentified Analyst, Analyst

Yes. And the pembrolizumab combination thoughts as it relates to regardless of whether it’s PD-L1 high or low, is there any preclinical data that you are aware of that could support that that actually may be a good place to have a cohort of patients?

Panna Sharma, CEO

No. We do not have information. We just know that never smokers tend to have PD-L1 low in almost all instances. So, PD-L1 high tends to correlate with those who have a high tumor mutation burden, which drives the PD-L1 expression. Thus, people with high tumor mutation burden tend to be smokers—90%-plus of them. We know that when tumor mutation burden is high, it’s less likely to respond to LP-300 and the chemo doublets. So, we understand that this never smoker population tends to generally present with low PD-L1. That has been observed in many studies where they’ve looked at never smokers’ characteristics, PD-L1 high or low, and tumor mutation burden. I can share some studies that were completed. The most interesting was a meta-study done out of Taiwan published last year, which I discussed internally. It analyzed multiple cohorts, looking at various proteomic and genomic indicators of PD-L1, TMB, smoking status, and so forth. However, we don’t have fixed results. It’s conjecture that PD-L1 low is prevalent among most never smokers. We also know anecdotally that PD-L1 low often prevents these patients from receiving pembrolizumab plus chemotherapy in the first-line setting. They typically receive chemotherapy first and then get a TKI only if they harbor one.

Unidentified Analyst, Analyst

And so there are no thoughts around perhaps using a cohort of patients to actually test the combination.

Panna Sharma, CEO

Which combination?

Unidentified Analyst, Analyst

Pembrolizumab plus LP-300.

Panna Sharma, CEO

We do not have an arm currently designed for pembrolizumab plus LP-300. I think right now our thinking is the best potential design is for a TKI plus LP-300. We believe it could enhance the long-term effects of TKIs because we are denaturing some of those TKIs. This could provide an added benefit for something like an EGFR or ALK-based TKI, where we have X-ray crystallography data showcasing that we are denaturing the receptors. This could provide an added benefit. We have seen some synergistic effects in preclinical studies of TKIs combined with LP-300. Feedback from KOLs and clinicians has indicated that they weren’t particularly enthusiastic about administering a TKI with LP-300, but would rather see chemotherapy combined with LP-300, as that’s the standard of care after failing on TKIs.

Nicole Leber, Investor Relations

Thank you, Tony. And that’s all the time we have for questions today. Thank you so much for tuning in, and we hope you have a great rest of your day.