Lantern Pharma Inc. (LTRN) Earnings Call Transcript & Summary

Good day. I'm Dr. Joseph Treat. I'm a Professor of Medical Oncology at Fox Chase Cancer Center in Philadelphia. I've been in clinical trials in lung cancer only for quite a while. I have a special interest and part of a research group, which I co-lead that, specifically looking at patients who are never smokers and trying to develop both new treatment options as well as looking at some of the factors that might be important at a preclinical level with collaboration with one of the more prominent scientists here, Dr. Margie Clapper, who does some preclinical laboratory investigation. And as a companion to that, along with Dr. Nick Bodor, we already have a clinical trial up and running dedicated toward this never-smoking EGFR mutated setting. And so my research interest is very much in this area of never smokers who develop lung cancer. So a basic question is what is a never smoker and there are different definitions, perhaps the strictest and the one that you typically see in clinical trials, is this 100-cigarette definition -- 100 cigarettes over a lifetime, more than that, you're a smoker. Well, I think we can all kind of see how that can be quite an exact in terms of what people remember, how they stated, how it's recorded and how it's transmitted to data sheets. Yes. So it's really is quite different. Almost every aspect of it is different and the differences keep emerging. The first and the most graphic difference is the population of demographics. They tend to be women, and there's geographic differences that are very profound. Western population, such as here in the U.S.A., Europe, only see about 10% to 12% of these tumors in these individuals having something called the EGFR mutation. Whereas in Asia, Japan, Korea, China, abundance of data shows that the rate of EGFR mutations is as high as 35% to 40%. So that's just a staggering difference besides these observable quite apparent demographic differences. The differences in tumor behavior, these tumors tend to be a bit more slow growing. They are also more likely to be sensitive to chemotherapy. But curiously and importantly, they are not likely to be responsive to the really great development over the last several years, which is the immunotherapy type drugs. So they're just different almost any way you look at it, treatment response, what they respond to, what the patient looks like, it's a different -- just a different sort. So this is one of the things that is kind of one of the leading candidates for explaining why checkpoint or PD-L1 inhibitors don't seem to work very well in this patient population. And it's kind of -- you can kind of tell a story in a fairly direct way, meaning when people smoke, over time, the tumors pick up. And over years, these cells pick up multiple, multiple mutations -- tumor mutation burden, and they tend to be the highest in the tumor types that are at the highest association with smoking such as squamous cell, non-small cell lung cancer and small cell. And as we know, small cell is almost 100% associated with smoking, whereas this patient group, these women, never smokers, many times Asian, are the opposite. They are obviously, never smokers. So tumor mutation burden in patients who are never smokers is very small. It's very light. And so what's the implications there. So again, in a general -- I'm not an immunologist, but in a general way of conceptualizing this, the cells that are -- should be responsible for recognizing and attacking aberrant cells, cancer cells, the T lymphocytes, if there's not a lot of mutational presence, a low mutational burden, in essence, they don't have much to recognize and see. And it's been well documented that if you look at tumor specimens, biopsies of individuals who have cancers that arise in never smoking situation, there's very little T cell infiltration. They are called cold tumors because there's not a lot of these inflammatory type cells. So it undoubtedly has some implications, this low TMB burden is a factor in why immunotherapies have not been very successful. There is an interesting data set from prior work with this drug that really needs to be pursued. There were couple of studies done quite a few years ago, looking at chemo plus/minus LP-300. And later, much later after the trials were done, there was retrospective subgroup analysis. Now we always approach this with a grain of salt. We're all -- we all know that retrospective analysis can be misleading. However, I think sometimes we see outcomes that are more compelling and sometimes very compelling than other retrospective analysis. And when you look at the retrospective analysis of these 2 different Phase III trials that were done a few years ago, again, chemo plus/minus LP-300, both trials on retrospective analysis showed very striking survival differences in the group that got LP-300 and were never smoking or females or both. And the differences here are not just 1 or 2 months, they're really almost double the expected survival time or the outcome data in the chemo-only arm. So this is a very dramatic difference again in retrospective data, but I think it really demands further looking. So it isn't just the retrospective data because I think you do need -- you obviously need some very direct preclinical data that gives a mechanistic explanation of why a drug is working in a particular situation and the preclinical data here supports that this drug can be an important component of treatment in EGFR-mutated tumor. It binds to the receptor, binds to other receptors. So there's a mechanistic explanation. It also has some interference with some important biochemical steps in terms of drug -- chemotherapy drug activity. So there's more than one mechanism of action, which directly supports using this drug in this type of population. We are very pleased that we're leading this trial across the country and internationally. Having said that, we do have a known track record of how often we can accrue patients with this type of epidemiologic background or demographic background, meaning never smoking. And these are tough trials to accrue in the United States. We anticipate in a year's time this institution, which is a large urban-based center, that we probably will accrue 6 to 8 patients a year. And so obviously, we'll need the help of other centers in this country and likely more importantly, in Asia where the patient population is much more abundant in terms of the demographic that's appropriate. I should mention some of the -- just the working aspects of this trial, who is eligible, what's the appropriate patient to consider referral to a center that has this trial up and running. So first of all, it is a patient with -- actually can be one of several different type of mutations, but EGFR, ALK and some others are included. And obviously, just based on the numbers, EGFR will be the most common. Regardless of the mutation, they must have received an appropriate tyrosine kinase inhibitor. So in the case of EGFR, that's likely to be the well-known first-line choice drug and for the other mutations, other TKIs as appropriate, they must have received them and had the disease progression on those. So we don't want to supplant recognized excellent first-line therapy. This is a second line approach. And so that is important. The second thing is they have to have a demographic of a nonsmoking background. So if one wants to see if this trial is applicable to any given patient, there are various ways to access. Certainly, one can call the centers that have the trial up and running, such as here at Fox Chase in Philadelphia. Secondly, go to the web, put in the search engine, Harmonic trial. It will pop up and you can pursue it that way.

Hello. Thank you for attending the webinar. By way of introduction, I'm Dr. Reggie Ewesuedo, leading clinical development team here at Lantern Pharma. At this time, we will take any questions that you might have. While we're waiting for questions, I just want to let you know that just recently on Monday, we also made an announcement to the expansion of this trial in the Asia Pacific region, specifically in Japan as well as Taiwan. So we're going to be conducting this study, extending from the United States to several sites in those 2 countries. We're excited about the opportunity to develop LP-300 in this particular patient population. It looks like we have our first question. The first question is about LP-300 drug. Is LP-300 a pan tyrosine kinase inhibitor, if I heard you that correctly? Yes, that's our thinking at this point. Based on all the preclinical experiments that we've done recently, as we learned about the retrospective data that Dr. Treat talked about. I think it's only reasonable to imagine that those patients that benefited from the drug are very likely patients that will have driver mutations. We went back to the drawing board and we did a couple of studies, and we were able to show very clearly the drug binds [indiscernible] to cysteine residues in those receptors and inhibits the activity of kinases. So yes, we think it's a pan tyrosine kinase inhibitor. There's a question talking about have you seen any responses? Interestingly, so far, we just started. We have a safety lead-in stage in this study for which we have enrolled a total of 6 patients. And to the extent that the combination is tolerable with pemetrexed and carboplatin, we want to move on to the Stage II of the study, which would be a randomized trial -- a 2:1 randomization strategy. Now the first 2 patients that enrolled so far have [indiscernible] for response. We have a patient that had a dramatic partial response. So yes, we've seen response. It's too early, just enough to, but we still have additional patients that are enrolled in Stage I, and they will be due for response assessment in the coming weeks. And then there's a question about a patient that is a never smoker but has squamous cell, EGFR Exon 19 deletion will be considered? That's a very good question. And quite frankly, the way the protocol is written, it just depends on a case-by-case basis. And the answer to that is if a patient has been exposed to a tyrosine kinase inhibitor, such patients as never smokers would qualify for the study. So yes. And a question about the sites in Asia. What are 3 sites in Asia, if I heard you that correctly? We have sites in Japan. We have 5 sites in Japan. And there are also 5 sites in Taiwan. And we're also looking at some sites in South Korea, I understand. And then there's a question about the press release. Is the press release you just mentioned a confirmed PR? We released it on Monday. So yes. And there is a question about insurance. Do patients need to have health insurance? Just like in any clinical trial in the United States, if a patient goes to their physician and they qualify for a clinical trial, whatever measures that we usually take in that institution, that's really. There's nothing unusual about this trial. But we're willing to work with any patient and their physician to see how best we can help them participate in this trial. Then there's a question about how many patients get this lung cancer every year in the United States and globally? I will speak specifically to the United States. Well above 0.25 million individuals who have lung cancer in the United States, adenocarcinoma accounts for the majority of it, up to over 60% of those patients. And in that population, the never smokers like Dr. Treat talked about, we are looking upward of about 15% of these patients are never smokers. And then the question about access to this trial in France? At this time, we really don't have any sites that we're considering for a trial in Europe. But again, depending on the results, we are very enthusiastic that this trial will be very, very helpful in this patient population. So there's always the opportunity. But at this time, the answer is no. We're in the United States, as well as moving on to Asia Pac, where the majority of patients that are never smokers, that proportion, that prevalence is much higher in the Asia Pacific region, upward of about 60% or 80% of females in some of these countries. So that's why strategically, we are moving to those regions of the world. Which chemotherapy are you using, any one? Is the standard of care chemotherapy is a platinum doublet? So carboplatin plus pemetrexed will be the standard of care in that second-line setting. We're adding LP-300 to the standard of care. And there is a question about LP-300, a second line. When, for example, osimertinib or Tagrisso will be resistant? That's a very good question. We just talked about the idea that mechanistically, this drug is a pan tyrosine kinase inhibitor. We also know that patients on osimertinib, when they develop resistance, it's either on-target or off-target resistance, including new driver mutations like MAX mutations. This drug, we know from our preclinical experiments, also mitigates the activity of signaling pathway of several tyrosine kinase receptors. So we believe very strongly that even if patients have failed a tyrosine kinase inhibitor, this drug potentially will still lead to some activity, at least [ abrogation ] or signaling in the new mutant tyrosine kinase receptor. And then the question is, can you take this as a pill also or just IV? Just IV. It's a [ 30-minute ] infusion, which obviously, that I think within the realm of chemotherapy, that is well acceptable as it were. And so far, we haven't had any problems either in previous clinical trials and the new trial that we have. So it's well accepted in terms of the future duration. There's a question about partnering of this program with other researchers of big pharma in the U.S. or otherwise. Yes, we are always interested in talking to potential partners that want to collaborate with Lantern Pharma in any development program. So if there's a way you want to contact us, please feel free to do so and we will have further discussions. If someone can tolerate chemo, can they still take this drug? Is this a chemo? That's a very, very good question, too. LP-300 is not your classic cytotoxic chemotherapy to the extent that actually it has been given to healthy volunteers. So that tells you it is not in that league of cytotoxic chemotherapy agents. However, in this study, it will be administered in combination with cytotoxic chemotherapy, pemetrexed and carboplatin, which are the standard of care. So in that sense, what we've seen so far, the previous study and in the current study is that most of the side effects we see in patients are usually typical of those of the cytotoxic chemotherapy and not LP-300. Are side effects manageable? Yes, they are. In fact, like I talked about most of the side effects for LP-300 are usually GI disorders: nausea, vomiting, headache, occasionally fatigue. That's when it was given as a single agent and injection site reaction. And what we do with that, we just increased the infusion time and that resolves the problem most of the times. Other than that, the issue about bone marrow suppression, [indiscernible] are usually seen in combination of the drug, but attributed to the standard of care treatment. What is the goal of PFS, progression-free survival and overall survival? How much percentage in benefit in the long run? Very fascinating. Because when we looked at retrospective data, what we saw in the never-smokers like Dr. Treat alluded to, was an improvement of overall survival of more than double. We had 25.2 months for patients that got LP-300 in combination with the standard of care versus about 13 months for those who got standard of care. So there are improvements shows us very clearly that this drug, there will be a significant improvement if this drug were to be approved. Now in terms of this study, what we've assumed based on retrospective data is that it will be a PFS improvement of 6 months. So from the standard of care 6 months to 12 months with combination and the same with survival, from 12 months to 24 months. So we're expecting that there will be a hazard ratio of about 0.5 in the study. Does it protect brain? What about blood brain barrier? LP-300 does not cross the blood brain barrier. We don't have any data to suggest otherwise. Let's see what else we have. Is your CEO still talking about and excited about this drug? Is he taking any questions? Absolutely. He is excited about this drug. And again, like I said, if you -- maybe you [indiscernible], we just announced that we're expanding the trial to Asia Pacific region, specifically Japan and Taiwan. That's because we believe very strongly in this drug. So he is excited about this drug. And we will be prepared to take any questions, not in this webinar. But in future, if you have any questions, definitely send them my way. He will answer your questions. Can you take this drug with a TKI or EGFR drug? That's, again, is another fabulous question. We believe that there is a scientific rationale for the combination. And I think one of the questions we were asking ourselves and obviously, other subject by the experts is how best to harvest that opportunity. So yes, the drug can be given in combination with the tyrosine kinase. Scientifically the rationale is strong. It is just now a function of trying to figure out the best strategy and when to do that. Will you be looking at other cancers? At this point, no. We are not thinking about doing that. What are the anticipated time lines for completion and publication of trial results? That's a very good question as well. Now this study is in 2 stages. The fourth one is the safety. Currently, we have 2 more patients to go to complete stage 1 and then we have some preliminary activities as well from the set of patients. For the main study, the stage II is designed in such a way that we have an interim analysis where we observed about 31 patients that would have had progressed. Now we are guesstimating that should happen anywhere from about 12 to 24 months from now. The reason I say that it's not that we're extending to the Asia Pac region, where we have more of these patients than in the United States. We expect to see an uptick in enrollment. And with that uptick in enrollment, we expect that in the next 12 to 24 months, we should have some data that we'll be able to share, if not in [ advance ], at least an interim analysis on the study. There's a question here about which sites are near my house? Is there a website to look up locations? Absolutely. There's a website to look up locations, but you could also go to the website that Dr. Treat talked about, and I'll repeat that, harmonictrial.com, that's the website -- harmonictrial.com. Once you get on that website, you will see all the information you need, you can contact us. We direct you to the nearest sites participating in the trial in your area. Secondly, I think that will be very, very helpful and useful to you and any person in your network as well. Any other question? Is LP-300 used by itself or in combination with chemo and which chemo? I think I've addressed that. The answer, it's not used by itself. By way of mechanism, the 2-broad mechanism that the drug possesses. One is literally to make the standard of care cytotoxic chemotherapy better. By better, not only in activity, in overcoming mechanisms that the standard of care cytotoxic chemotherapy will have been exposed to, but it also aggregates the side effects of some of those drugs. The platinum agents like cisplatin and carboplatin were used in this study as well as taxanes, but we are [indiscernible] about pemetrexed as well. So we expect that the drug will be beneficial to these chemotherapies, the tumors that would have been resistant, the drug would make those tumors more sensitive to the standard of care. [indiscernible]. The second is that the drug on its own, the activity that it has around tyrosine kinase receptors. It will inhibit those receptors that are already part of the problem for the patients that have lung cancer, the never smokers. So in that sense, it will have potentially single-agent activity, that is the combination with the standard of care and that single-agent activity that we think will be superior to standard of care treatment and perhaps even to tyrosine kinase imbibes on their own. That's a long comment and the question here. Let me see what this is. According to the American Cancer Society, lung cancer is the second leading cause of cancer in the U.S. with over 200,000 patient diagnosed annually. Historically, never smokers with non-small cell lung cancer make up 15% to 20% of all lung cancer patients, representing an approximate annual market potential of $1.5 billion to $2 billion. Can you please give additional understanding with regard to this? I think the data you've quoted is in the right trajectory in terms of the number of patients diagnosed annually, somewhere -- more than 200,000, slightly more than that, about 0.25 million patients diagnosed. And by the way, almost half of those patients are going to die of the disease, but the majority of these patients have what you call the adenocarcinoma. And out of that group, they are the ones that tend to have what we classify as driver mutations, the EGFR mutations, and that 15% to 20% never-smokers predominantly tend to have this driver mutations. The assumptions around the market potential I assume are correct, but that is not my expertise. But the little I do know, in this field, I've been in drug development for well over 25 years. You're right, I think you are right in the ballpark. Then it's a question about, have you experienced any specific challenges or issues during this safety leading and are you able to give any insight on how these are addressed? That's a very good question. And specifically, we would not experience any challenges in the safety leading that is not typical of the drug from what we know from previous clinical trials. So the way the study is designed, we have a safety leading 6 patients. And so far, we've had no problems with dose-limiting toxicity. So thank you all for your questions, and you know the site for the trial. Please go there. If you have any further questions, want to find any more information about the trial, we are here to answer your questions. We're excited about this drug, and thank you again for attending the webinar.