Hi, everybody. Thank you so much for joining us today for Lantern Pharma's World Pancreatic Cancer Day Key Opinion Leader Webinar. My name is Nicole Leber with Lantern Pharma, but our speakers today include Dr. Kishor Bhatia, who is the Chief Scientific Officer at Lantern Pharma. We also have Dr. Igor Astsaturov, who is the Co-director of the Marvin and Concetta Greenberg Pancreatic Cancer Institute at Fox Chase Cancer Center. We also have Dr. Ira Sharp joining us today, who is a physician, pancreatic cancer survivor, and patient advocate. With that, I will turn things over to Dr. Astsaturov. Thank you, Nicole. Yes, November the 18th, Thursday, is the World Pancreatic Cancer Day, and we use this opportunity to raise awareness on every possible stage of the urgency to develop new treatment options for patients who suffer from pancreatic cancer. It's a disease that is very difficult to treat, and it is rising in its incidence. We still understand poorly what causes this rise in the incidence of pancreatic cancer, and this is projected to be the third leading cause of cancer death by 2030. With this in mind, I think the plight of the patients and their families should be the focus and center of every scientist, every politician, every physician, every caregiver or family member, even if you are not personally affected by this disease that affects us all collectively as a society. I'm very privileged to be part of this webinar. I think you guys are doing a great job. I can't wait to hear from Kishor about the plans of Lantern to develop a new drug for the treatment of this disease. Thank you, Igor, and thank you, Dr. Sharp, for taking the time to have a discussion on World Pancreatic Cancer Day. Perhaps this might be a good time to get a sense of a patient's journey through diagnosis and treatment of pancreatic cancer. Maybe I'd ask Dr. Sharp to give us some background on his journey. Thank you, Dr. Bhatia. Thank you for asking me to participate today. This month marks exactly 8 years since my diagnosis of pancreatic adenocarcinoma, and in November 2013, I was a 57-year-old practicing internist and absolutely had no thoughts of pancreatic cancer on my personal horizon. About that time, I developed new onset of diabetes, abdominal gastrointestinal bloating and bowel changes and fatigue. After some prodding from my wife, I actually ended up in the hospital. They found a 5.5-centimeter complex mass in my body and tail of pancreas. After endoscopic ultrasound and biopsy, I was diagnosed with that. Needless to say, that kind of diagnosis threw me completely for a loop and my family. I actually began on chemotherapy with FOLFIRINOX, which at the time was considered the best, followed by radiation therapy, followed by surgery for what was then locally invasive stage three. My journey continued six months later, although my resection was an R0 resection with negative lymph nodes, I had a recurrence of a lymph node in my neck and in my adrenal gland, I had enlargement and again, I had metastatic disease. At that time, that's when I began on a clinical trial with ipafricept, which is, as you mentioned, a Wnt inhibitor and it was quite remarkable, at least for me. We were in a phase I clinical trial. Didn't expect to see tremendous results, but I was extremely lucky and within a few months the lymph node resolved, the CA 19-9 tumor marker drops considerably, and I remained on that drug for five years along with gemcitabine and Abraxane, paclitaxel. The course was relatively uneventful, although I did develop mild hemolytic uremic syndrome, presumably from the combination of gemcitabine and the drug, and that when the gemcitabine was discontinued, that resolved. In addition, I developed peripheral neuropathy as a result of the Abraxane, perhaps together with diabetes and that continues, but I stopped the Abraxane and it's been stable. To this date, I am now one and a half, almost two years off all chemotherapy with stable lab results and stable MRIs. That's my general experience and, you know, I'd be happy to answer any questions if you have any and thank you. Dr. Sharp, thank you so much for, you know, being a part of today's webinar. We really appreciate your insight. Turning gears a little bit, Dr. Bhatia, can you provide some background on Lantern Pharma and our development of irofulven and LP-184 for our viewers? Sure. I think key aspect from Dr. Sharp's journey is the importance of new drugs and clinical trials. Our focus in Lantern Pharma drug discovery is fueled by two things. One is the critical need in several areas of cancer for new drugs. At the same time, paralleled with a continuous increase in the amount of genomic and other data. Therefore, it provides the potential to use the data and define how to de-risk the development of drugs. I think the ability for Lantern Pharma to shorten clinical development allows drugs to reach a maturity stage faster and with greater potential of success. LP-184 is a very good example of this development paradigm that Lantern Pharma uses. LP-184 is a drug from a class of molecules called acylfulvenes. These class of molecules are similar to another molecule that is found naturally in Jack-o'-lantern mushrooms. This molecule is called Illudin, and Illudin was discovered in Jack-o'-lantern mushrooms early in the 1920s. It has very high toxicity and therefore very little tumor selectivity. Over a period of time, using structure-activity relationships and derivatization, several groups, including ours, have worked for modifying Illudins to make them more tumor selective, and LP-184 is one such molecule. It has a much broader therapeutic index, and it has high, higher tumor specificity. LP-184 is a completely synthetic molecule. Although its structure is similar to Illudin, the way Lantern Pharma makes this molecule, it makes it completely synthetically without using any Illudin or pre-Illudin compounds from the jack-o'-lantern mushrooms. Okay, great. Again, Kishore, can you explain just a bit more how LP-184 works and why it's so unique? Yeah. LP-184 has the ability to track the tumor alone on this. It requires the presence of the sort of enzyme, or PTGR1, and much of this evidence was provided with the company by a support that any construct for suffices to say that PTGR1 is critical driver of the efficacyof LP-184. That itself provides a sort advantage in terms of efficacy. PTGR1 is expressed high in cell tumors, therefore one can select the higher tumor in LP-184. The damage it causes to the DNA in the tumor cells is the kind of damage that can only be repaired by a certain group of enzymes or certain pathway, or the damage repair mechanism. It turns out that there are several tumors that are deficient in this pathway, and one can imagine therefore that few have tumors that are high in special frequency of one that have the inability to repair the damage to their DNA caused by LP-184 because of the absence of the protein. And now you have LP-184 selectively killing cells and that is really a place that LP-184 works, and works in a manner that we used in selectively to tumors with certain genomic features. Dr. Astsaturov. What challenges are currently associated with pancreatic cancer treatment, would you say, and how might they be overcome? Thank you, Nicole. What is needed in the world of pancreatic cancer and what families and patients are looking for, we need new options. Currently, we have only three lines of chemotherapy for patients who unfortunately have metastatic disease, like in Ira's case. These chemotherapy options are very limited in time and efficacy. Any new drug that comes to the clinical stage is a huge step forward. As Kishor pointed out, instead of treating every cancer with a blanket chemotherapy like we do nowadays, it is really important to come up with something that is more intelligent and more specifically tailored to the genetic makeup of patients' tumor. Here on this slide you show maybe 10%-15% of pancreatic cancers carry mutations in DNA repair pathway, which is called homologous recombination or HR. There is a new class of drugs that is specifically active in this group of patients, in this class of tumors. There is also another even smaller subset of tumors that are carrying mutations in these family of ERCC genes, and this is a pathway that Kishor had mentioned. It's called transcription-coupled nucleotide excision repair pathway. Because everybody who comes through our clinics will have their tumors and their germline DNA tested. Nowadays it is pretty routine for us to understand and detect individual cancer mutations, and therefore we are prepared to deploy targeted specific therapies that are unique for each individual's cancer genetic makeup. I think that is what really bears the promise, and I think that is what is actually needed for the patients and for what we clinicians are looking for. Can you elaborate a bit on the results from the preclinical studies performed to date and their implications on patient outcomes and trial design? Thank you, Nicole. I'm quite privileged that we established this collaboration with the Lantern in order to develop a concept for patients. I came in contact with Lantern when they had this really amazing informatics tool that predicted this derivative of irinotecan, LP-184. The unique feature of this compound is actually it's a fully synthetic derivative, so you can control the stereoisomerism of the molecule. Previous compounds had a racemic mixture of positive and negative stereoisomers. What is amazing in that graph on the left, you can see that the cytotoxicity, which is expressed as IC50, cytotoxic concentration of killing 50% of cancer cells in a Petri dish. That concentration is directly proportional to a single gene of all the 25,000 genes that are expressed in mammalian cells, and that gene was PTGR1. I haven't heard of PTGR1 before, but apparently it is an enzyme called prostaglandin reductase. It's an NADP-dependent reductase that converts certain type of prostaglandins and reduces their oxidation. What was left for us to document experimentally that indeed this association is functional. That means we hypothesized that PTGR1 is the enzyme that converts LP-184 or its precursor irofulven to a fully active alkylating agent. These associations have been previously proposed in the literature, and the experiments were done. PTGR1 was overexpressed or expressed at high level in certain cell lines in vitro, but we went in a slightly different and more genetically precise manner. Here on the graph that you see on the right-hand side, we took two cancer cell lines that are propagated in vitro, and using CRISPR technology, we deleted PTGR1 completely. You see the two lines, green and blue on the top of the graph, which are horizontal. These are the cells that have lost PTGR1. You can push the concentration of LP-184 to micromolar range, and you will not see any cytotoxicity. Whereas the parental cell lines that carry PTGR1 and are depleted with control and non-targeted guide RNA. These cells are very sensitive in a nanomolar range, which is really this very strict, very specific genetic documentation that indeed there is a unique enzyme. What is also interesting in terms of PTGR1 itself, it is induced by another very potent oncogenic transcription factor called NRF2, spelled as N-R-F-two. This transcription factor is a central player in pancreatic cancer progression. It is also induced by oxidative stress, by chemotherapy, by radiation, and in many respects a basis for resistance of pancreatic tumors to cytotoxic genotoxic therapies that we use to treat pancreatic cancer like radiation and chemotherapy. I think to answer your question directly, yes, we have two ideas that we can tailor LP-184 for the patients. One is the genetic vulnerability that is deficiency in DNA repair pathway genes that are mutated oftentimes in pancreatic tumors. Also, which is a very interesting biomarker that we haven't really proven yet in the clinical setting, that is the level of expression of PTGR1, the prostaglandin reductase. 'Cause the more of this protein is expressed, the likely that LP-184 will be converted to fully activated alkylator, which will immediately attack the DNA of the tumor cells. Igor, one of the things that you mentioned was that a higher expression of PTGR1 often is also marker or a correlation with resistance to other chemotherapy drugs. Given that, it makes sense to think that LP-184 can use that vulnerability when tumors are resistant to other chemotherapy drugs because of an increased PTGR1, therefore, has a certain advantage in tumors that are resistant to other chemotherapeutic agents. Yeah, I think that is something that needs to be explored. In fact, one of the ideas that we are discussing internally in my laboratory and with you is to really find ways to combine LP-184 with other chemotherapy agents. When the tumors start developing resistance and up-regulate PTGR1, there you can come in with this compound and you know, exploit the resistance mechanism as a you know mechanism of vulnerability of the tumor cells. One of the potential agents to be combined with is radiation. NRF2 is a very well-established radio resistance marker and is induced by radiation. We also showed in a limited number of experiments that if you irradiated the tumors in vitro or in vivo with a single dose of radiation. It actually drives a multiple fold in that expression of PTGR1 protein and mRNA, suggesting that this linear transcriptional mechanism from radiation to oxidative stress to induction of NRF2 activity to expression of PTGR1 is a very generalizable vulnerability mechanism through which LP-184 can be deployed as a potential partner with radiation therapy. We use radiation quite extensively in pancreatic cancer in patients who have localized tumors, candidates for surgical resection, but also a significant or close to 20% of patients who have localized tumors that cannot be resected because they just so much infiltrate to the major blood vessels that surgeons cannot remove them. Those patients are difficult to manage. They have quite significant local symptoms, and their course is inevitably detrimental. Eventually, they succumb to the tumor. Having a new mechanism that will allow us to exploit the resistance as a point of vulnerability, I think that will be totally amazing. I'm really enthusiastic and looking forward with optimism that we can come up with something new. Yeah. Here on the slide, we see another very elegant study that was done in Astsaturov's lab, which provides more confirmatory evidence about the synthetic lethality of LP-184 in tumors that are deficient in the nucleotide excision repair pathway. Yeah. Here, Kishor, somehow we dropped the error bars, but I assure you that we repeated this multiple times and actually now confirmed that the same phenotype is retained in vitro in vivo in xenograft experiment. If you just drop down the expression of ERCC4, in this case using CRISPR technology to deplete the protein in the cancer cells without introducing the mutations. Many cell lines do not tolerate these de novo mutations if you try to introduce them in the genes of DNA repair pathway. If you just depress the level of expression of ERCC4 by roughly from 100% to 20%, this is sufficient to sensitize tumors to LP-184. Again, suggesting that a subset of cancers where nucleotide excision repair pathway or other DNA repair pathway deficiency may be either genetic or epigenetic. When these genes are underexpressed or expressed at the lower level, these tumors may be vulnerable to certain toxins like LP-184. This is what I was referring to earlier, that indeed PTGR1 is a major dependency for LP-184 activity. If you pay attention to these colored lines. The one in purple color in a kind of this second from the bottom is tumor grafts that we artificially depleted of PTGR1. You can see that these tumors are quite similar to vehicle. They grow with some delay, but eventually they grow out and acquire absolute resistance. There is no effect whatsoever. The green line is the parental cell control cell line, control xenograft, where PTGR1 is actually expressed at a reasonably high level. These tumors are shrinking progressively. We stopped the experiment at two months, but even when we open the animals, Nicole, if you could switch to the next slide, that actually illustrates what we found at the end of the experiment, which you know, lasted for a long two months, which is very similar to sometimes we do in patients. We do two months of chemotherapy and then get a CT scan to see if the tumor is gone or not, as opposed to some traditional xenograft experiments where you treat mice for, like, three weeks and see and report the results right away. We've been as close as possible to the reality of clinical care of the patients. You can see here at the bottom slide, these tumors that were reflected in their size on the green line in the previous slide, in the green color. This is, you know, the minuscule tumors. Sometimes we've found just a residual foci of carcinoma. In one mouse, we had not found nothing, no tumor, no scar tissue, everything is gone. This really tells me that this is a very potent compound. And as long as we balance the toxicity versus benefit, the therapeutic effect, this has a very strong promise in pancreatic cancer field. On the top line, on the top panel are the tumors that are PTGR1 negative, and as expected, from our prior experiments in vitro, in vivo, it reproduces exactly the same situation that tumors had grown, and were insensitive to PTGR1, in the absence of PTGR1, insensitive to LP-184. Although it's not shown here, but LP-184-treated tumors that are PTGR1 deficient looked almost exactly the same. Obviously PTGR1 is a very critical component of providing tumor selectivity, and therefore is also likely to be a critical biomarker in selection of clinical trials. Yeah, I think it's a sort of very unique circumstance. I'm not aware of any other chemotherapy drug would have been that much dependent on a single enzyme or if there was any analogous mechanism of enzymatic conversion of a prodrug to a fully functional alkylator agent that would be cytotoxic to cancer cells. You know, it's really should capitalize on this unique dependency and use PTGR1 in our future studies as a biomarker of potential candidates for this chemotherapy drug. These are ex vivo patient-derived pancreatic cancer models. Yeah, You can say that these are patient-derived xenografts- Right. That were treated ex vivo and then subsequently confirmed in a true xenograft in vivo experiment. What, you know, you found and your collaborators at Champions Oncology found that there is an incredibly high potency of LP-184 in a subset of cancers, of pancreatic adenocarcinomas grown in mice that are carrying deficiencies in DNA repair pathway, including homologous recombination deficiency, ATM. This is I think one of these tumors. I think 643 was carrying a ATM mutation. That is something we should be looking in our patients' tumors. If there is a mutation in DNA repair pathway, and we do it routinely nowadays in our clinical practice. These are the patients who are more likely to benefit. In comparison to olaparib, which is FDA-approved for the treatment of tumors with homologous recombination deficiency. You can see how significantly lower the concentration that you need to expose these tumors to LP-184. It's low nanometer range, and it really provides an enormous killing effect. That essentially tells you that when you put these tumors in humans or when you find these tumors in humans, like you put them in mice, and you administer this drug, you will have reasonable tolerable toxicity, whereas you would deliver a very potent blow to the cancer. May I ask a question? Sure. Of course. PTGR1 expression in normal cells, is there a variability in expression, and is it related to the toxicity of LP-184? It's a very good question, Ira. I appreciate you as a doctor, you know firsthand the side effects of chemotherapy. Yes, indeed, PTGR1 is expressed in normal tissues. Like for instance, we found totally serendipitously that it is expressed in hepatocytes. Obviously, if you expose hepatocytes to LP-184, it induces hepatic toxicity. What was interesting, and we haven't really pursued it rigorously, but an interesting observation is that if you fast mice, if you don't give mice food for overnight, if you check their PTGR1 expression, it's actually several-fold lower as opposed to the mice that are eating ad libitum. If I were a patient, I would have wanted to get this chemotherapy on my empty stomach. Yeah. Wait for a couple of hours and then eat. Yeah, it is a concern, and I think we need to learn more about the drug biodistribution toxicities. That's something that we need to keep bear in mind as we bring these compounds to clinical testing. The good news is that the half-life of LP-184 in human body is gonna be very short. The half-life is about 15 minutes for sure. Correct me if I'm wrong. That's correct. Yeah. It's in and out, and it will rapidly convert almost instantaneously. It's very membrane permeable compound, so it will almost instantaneously convert to a cytotoxin in cells that express high level of PTGR1. If you find somebody who is willing to delay their breakfast and you know, have the drug, chemotherapy with this drug and then go on to you know, with normal life, in 15 minutes, the drug will leave the body, but it will induce damage on the cancer. In follow-up to that, other than fasting, is there any other way to regulate in vivo PTGR1 levels and also NRF2 levels, which Yeah. That's an excellent point. Thinking outside of a box, like how would you do that then so you can locally induce PTGR1 expression? There were published experiments where people used various oxidative agents like resveratrol or some other benign chemicals, but when you treat, you know, an organism, a human or a mouse with these compounds, you induce systemic up-regulation of PTGR1 expression. The idea was to really do it in a localized fashion, and this is where we turned to radiation as a strategy. You can irradiate with very high precision in a very specific area of the human body where cancer is localized. You induce PTGR1 expression, and you can come in with the drug and hit that part of the body very strongly with, you know, double hit. You know, you irradiate it, which uses DNA damage, and the cells will try to repair it, but then you come in with another toxin, which is activated to fully, you know, activate a cytotoxin, alkylating agent, thanks to PTGR1. We still in the preparing to do this experiment. I can't wait to see the result. If our prediction is correct, then yes, we will be able to activate the local expression through radiation therapy. Thank you. Also I think, you know, the thought process based upon some of the data that we see is that given a normal and a tumor cell, both of which might have the same level of PTGR1, the presence of deficiencies in the tumor cell that disable them to repair the damage caused by LP-184 is another window of the driver of selectivity. The normal cell virtually repair the damage and do fine, but it's the tumor that will really selectively die. I think you see that also in the comparison of the IC50s in epithelial cells derived from, you know, from a controlled cell line and non-tumor cell lines compared to those that you have from tumors. The other advantage of LP-184 because of PTGR1 dependency is that it's likely going to have much lesser hematotoxicity because PTGR1 is expressed at much lower levels in many of the hematopoietic cells. This is something that we have to learn. It's, you know, you can't really predict. You know, obviously, in a drug development pipeline, you will have to do toxicology studies in large mammals. Eventually- Good point. Good point. ...when it hits the clinical grounds. Yeah. ...in phase I clinical trial will be what, where we learn a true toxicity and drug doses that patients can tolerate. Yeah. That will also establish potential signal of activity. This is something that is hopefully gonna happen in the near term. Absolutely. We're very much looking forward to launching a phase I clinical trial that will be instrumental in bringing this compound to the clinical stage and explore all these amazing avenues that we outline for ourselves. Since Igor mentioned about the phase I clinical trial, just to get an idea of what, his thoughts and his team, there at Fox Chase thinks in terms of the design of the clinical trial and, you know, how we plan to go about it. Thank you, sure, for asking this question. Nicole, I think it is really an exciting opportunity to bring a scientific idea to the clinical stage. I can't wait to really get this idea to the clinic, to the patients. We have multiple discussions with Lantern, and I think the plan is quite clear. As soon as the FDA gives you permission to conduct a phase I clinical trial, Fox Chase Cancer Center and my collaborators here at our institution will be ready to design, review or launch a clinical trial, offer these opportunities for patients who carry specific genetic biomarkers that we believe will be providing them certain benefit because of the known mechanism of how this drug works. My ambition is nothing but to create more miracles like Dr. Sharp who came eight years ago with a devastating malignancy, metastatic stage. Thanks to innovation and his personal perseverance and our work as a team here at Fox Chase Cancer Center, he is. You stayed on the drug, and I proudly used the last drop of ipafricept on you. We had this dedicated fridge in the pharmacy just to carry your vials. You know, thankfully, when we exhausted the drug and unfortunately this program collapsed for totally unrelated economic reasons. Nonetheless, you're here, well, and I think you're a walking miracle. I anytime I see a new patient, I mention your example of volunteerism, participation in clinical research and clinical trials, being brave, not giving up, you know, how this can create miracles. It has to be coupled with good science and good scientific rationale. I think with this in this, the tools in hand, and with this motivation in our hearts, we can definitely make a difference. Thank you. Thank you, Dr. Sharp and Dr. Astsaturov. Thank you, Nicole. I think, you know, this has been a very interesting discussion. I think we all are quite enthusiastic about moving forward with LP-184 and seeing how we can best serve the right patients, and therefore the clinical study that we are planning to do with Fox Chase Cancer Center become a key aspect of our path forward. Okay. With that, we'd like to open it up for some Q&A. A couple questions coming in here. LP-184, is it administered systemically? And what about intratumoral injection? I can take this question, Nicole. Thank you for the question. It's a really good question. I think intratumoral administration is a good idea because that will obviate the need for selectivity. You can deliver it directly to the tumors. The only caveat to this is that in the case of pancreatic cancer the tumor is localized in a rather inaccessible location. The pancreas is difficult to biopsy. Even the metastases, which are most commonly occurring to the liver or to the peritoneum or lymph nodes, these are also difficult to reach with a needle if you plan to do intratumoral injection. It may be true for some other more superficial tumors. Like for instance, one of the ideas that we discussed is bladder cancer that is locally invasive and oftentimes about 10% of them carry mutations in nucleotide excision repair pathway. Melanoma, that's another potential candidate for local therapy. We do quite actively pursue these approaches in melanoma. Viral vectors and viral therapies are therapeutics I actively pursue in the melanoma field. There is a certain room for a local therapy, but for pancreas cancer my kind of gut feeling is it's gonna be probably challenging just because of the sort of anatomy. Thank you, Igor. I know you answered this one a little bit, but will LP-184 work in previously treated cancers? I think it's also an important issue which we really haven't explored to the greatest level of detail. I think if you were to rephrase this question, ask if tumors acquire chemoresistance, would that chemoresistance be total to all chemotherapy drugs? That may be true because the mechanism of resistance to chemotherapy are variable and multiple. There is a sort of reversion mutations in homologous recombination deficient tumors, for example. There is lots of other genes that would confer cytotoxicity, like 53BP1, p53 binding protein loss is a common loss of sensitivity to platinum and PARP inhibitors in HR deficient tumors. There's epithelial to mesenchymal transition, dormancy, sort of slowing down the cell cycle. That is the way that cancer cells oftentimes avoid cytotoxic chemotherapies. These are all relevant to probably multiple drugs including LP-184. But we also believe that the key vulnerabilities, and we think of two biomarkers that may not be competitive, but oftentimes coincident. Like you have a NER pathway deficiency or any other DNA repair pathway deficiency and high level of PTGR1. These are the two key biomarkers that will probably define a vulnerability of cancers to LP-184. Okay, great. Another couple questions coming in. Are there other methods to promote the specificity of LP-184, such as ADCs, antibody-drug conjugates? Yeah, definitely. Those are some areas that we are pursuing independently as well. We have been working to define the best linker combinations and the best antibody targets. Some of this is in late preclinical testing. I think it's a good point, Kishor. As you create an antibody-drug conjugate, you can deliver LP-184 or any similar compound very precisely to the site of the tumor. Yeah. Another one coming in here. Is endogenous PTGR1 expression pan-cellular? If not, would induction of PTGR1 via local radiation or other means require ectopic expression in order for LP-184 to work in cells that do not normally express PTGR1? I think by and large, PTGR1 expression is pan-cellular. It is really the amount of PTGR1 that varies greatly between different cell types. As Igor has mentioned before, right, provided data from some of his studies. Radiation will upregulate PTGR1 expression. Okay. Last question that came in here. Does radiation potentiate LP-184, and is it time sensitive or dependent? That's a burning question for me and Kishor. We don't know the answer yet, but the experiments are underway. We believe that the transcriptionally related response of induction of PTGR1 is relatively rapid. We approximated that the peak of expression occurs within 2-4 hours post radiation, and it kind of goes away in 24 hours. Anywhere between 2-24 hours time window following a single dose of radiation, we noticed that PTGR1 is induced both transcriptionally and at the level of the protein. Those are the kind of initial pilot data we generated in the lab using in vivo and in vitro models. A true test to the principle will be a combination chemo-radiotherapy experiment, which we're about to start within the next couple of weeks. Stay tuned. We'll let you know once those data are available. Okay. Thank you both so much. Those are all the questions we have gotten so far. I'd like to open it up for a couple closing remarks. Sort of my personal sad side of the story is that my wife, as I told you, passed away from metastatic pancreatic cancer, and she was a faculty at Jefferson. She died on March 31, 2013. Her cancer carried MYC amplification. We found that those cancers that carry MYC amplification were particularly vulnerable. Just a few weeks after she passed away, we found that that drug, Triptolide, is putting her tumor into remission for many months in xenografted animals. So she missed, you know, the chance to be in that trial just by a few months. But that really illustrates the point that we made earlier. Patients are in desperate need for new options. Each drug that comes to the stage in pancreatic cancer may bear a potential to save somebody's life, like it did for you. We didn't have chance for Elena. You know, that inspired me to work on this. You know, we'll keep pushing, and I think eventually we'll succeed and defeat this disease, one patient at a time. On this World Pancreatic Cancer Day, I think we should stay optimistic, maintain our tenacity, maintain our commitment to defeat and fight this disease, 'cause it threatens all of us, whether you get it or you have neighbors, family members who are in desperate need for answers. I want this to be a voice as loudly as possible on that day of November 18th. Yep. Totally agree. Thank you to Igor and Dr. Sharp for joining us, providing both of your insight. We really appreciate it. We just wanna reiterate that we at Lantern Pharma, we're gonna continue to work and find a cure for this awful disease and so that we can find, you know, more success stories like Dr. Sharp's. Very inspiring. If anyone has any additional questions, aside from the ones that were posed today, please feel free to either visit our website, where you can find some more contact information, or you can send an email to ir@lanternpharma.com. That's I-R@lanternpharma.com. Thank you to everyone that joined us today. We really appreciate it.