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spk08: off-the-shelf product of native, non-engineered, invariant natural killer T cells. Agent 797 delivered benefits to patients with heavily pretreated solid tumor cancers. Thirty-four patients with metastatic cancer who have exhausted all available treatments, including prior anti-PD-1 treatment, were treated with a single dose of Agent 797 without administration of toxic lymphodepleting agents. and we administered 797 alone or in combination with pembrolizumab or nivolumab. We reported that agent 797 was well tolerated up to a billion cells dose and promoted clinical benefit in a range of heavily pretreated solid tumor cancers. And in particular, we saw encouraging activity in a patient with metastatic gastric cancer who had no prior response to anti-PD-1 therapy, and that includes a single treatment with anti-P1 pembrolizumab, the patient received four cycles of, and after failure on pembrolizumab, the patient received nivolumab in combination with standard of care chemotherapy, again with no response. After being treated with a single dose of agent 797 in combination with nivolumab, the patient achieved a partial response with a 42% reduction and tumor burden, and this continues now beyond nine months. Sorry, that was our reporting period. This response is continuing at nine months. We also saw benefit in other solid tumor cancers, including durable disease stabilization and biomarker responses in patients with non-small cell lung cancer who had failed prior anti-PD-1, testicular cancer, appendiceal cancers, and other solid tumors. The safety profile 797 was found to be tolerable up to a million cells, no evidence of neurotoxicity. No dose-limiting toxicities were observed, and no severe cytokine release syndrome greater than grade three reported in the trial. And really importantly, we gained insights into the persistence and the homing and the immune-modulating activity of INKT cells in patients. We found that while INKT cells rapidly leave the periphery and enter in home-fit tissues, We see that they're also still persistent and detectable in the periphery for about eight weeks. This is really quite important because this demonstration shows that these cells actually can be viable and persistent without having to look with a patient. We also reported important translational findings that highlight IMKT's ability to generate and drive immune cells into the tumor for destruction of cancer cells. And Mark's going to tell you a bit more about these data in just a moment. Overall, our findings showcase the potential of an allogeneic, off-the-shelf INKT cell therapy in combination with anti-PD-1 in cancers resistant to current treatments, including immunotherapy. They support the expansion of our solid tumor program into PD-1 refractory non-spal cell lung cancer, as well as gastric cancer. And our trial in gastric cancer is being led by a world leader, Dr. Yelena Jinjigian. She's the Chief of Gastrointestinal Oncology at Memorial Sloan Kettering Cancer Center. The trial will advance through non-dilutive, grant-funded program targeted to start in just a few weeks and is planned to enroll about 40 patients over nine centers who will be treated under Memorial Sloan Kettering's umbrella and who will be treated with a cell therapy in combination with standard of care chemotherapy, as well as in combination with a very exciting multifunctional anti-CTLA-4 antibody, which is advancing in late-phase trials. Botansilumab is a lead program from our parent company, Agenis. Now, as a refresher, we have previously published preclinical models and data which demonstrate the potent synergy between INKTs, Anti-PD-1, and Botansilumab. We've published those data and presented them previously at AACR. These data reveal that in preclinical models of metastatic lung disease, the combination of INKT cells, PD-1, and botanosilumab resulted in near complete tumor elimination in this model, B16 model. These data and the safety and clinical benefits that we've observed with 797 in solid tumors support our next phase of development with this program. We expect to provide additional data updates, as well as more detail on our clinical programs in the second half of this year. I will now turn the call over to Dr. Mark Van Dijk, our Chief Scientific Officer, who will provide an update on our Next Generation Pipeline, which includes the IND-enabling activities of our novel FAPCAR-INKT cell therapies, as well as more detail about the functional attributes of 797 that we believe underscore the observations of clinical benefits in solid tumor cancers.
spk00: Mark. Thank you, Jen. We're quite excited about the observations of AHDR of clinical benefit in patients with heavily pretreated metastatic cancers. These patients are the ones who inspire our work as we leverage the INKT platform to expand the clinical benefit observed with approved therapies and develop innovations to address areas where current therapies actually fall short. So our technologies, which you'll hear more about at our annual shareholder meeting, includes the ability to generate armored CAR INKTs, develop INKT engagers, cell engagers, and advance novel PCR therapies. In addition to our native clinical stage agent 797 program, our most advanced preclinical programs include armored allogeneic FAPCAR INKT, and the Next Generation Armored BCMA INKT. So our lead program, Agent 797, is designed to expand clinical benefit observed with approved therapies. And our data at AACR is the first glimpse of the possibility of these cells to deliver on these benefits. It's a well-known phenomenon that anti-PD-1 therapies are effective at countering tumor immune suppression. However, chronic use of these therapies leads to immune exhaustion. So we've previously shown that Agent 797 can improve the anti-tumor activity of immune cells that are present in the tumor microenvironment. Specifically, we've shown that IKT cells can activate dendritic cells, preferentially kill M2 macrophages, and restore killing capacity of exhausted T cells. So in data ascertained from our clinical trial of Agent 797, We showed that agent 797 induced pro-inflammatory cytokine responses, including significant increases in interferon gamma, a hallmark of INKT activation and potentially indicative of tumor INKT activation, which is paramount to tumor control and tumor destruction. Importantly, INKT cells are naturally tissue homing. So in preclinical data previously presented, we've demonstrated that INKTs could be administered without lymphodepletion. They rapidly traffic out of the circulation within days of administration and into tissues, including bone marrow, liver, and lung, where they remain in some cases exceeding 35 days. So in our clinical trials, we reported a similar pattern of rapid translocation out of the circulation, while they remain at detectable limits and persist for approximately eight weeks. In our patient with durable response beyond nine months, we also showed that INKTs drive clonal T cell expansion in cancers with a high neoantigen burden. Immunogenicity really triggering the expansion of these cancer-fighting T cells. While we plan to report more detailed information of INKTs in the tumor microenvironment at a later update this year, currently our data demonstrate a mechanism of INKT cells to enable T cells and NK cells trafficking two tumors, reinvigorate partially-exhausted CD8 T cells, and improve effector functions within the tumor microenvironment, which is exemplified in these patients with clinical or biomarker response after a single dose of agent 797. As we continue to expand the potential of INKTs in solid cancer, we have advanced our next-generation INKT programs, including our novel IL-15 armored FATCAR INKT, MINK215. Cancer-associated fibroblasts, which are targeted with this therapy, are key tumor-supportive components of the immune-suppressive tumor microenvironment in several cancers, including non-small cell lung cancer. This adverse tumor microenvironment can be addressed by our fibroblast-targeting, or FAP, CAR-INKT therapy, which naturally homes to tissue such as the lung. In preclinical models, we reported very exciting data showing the potential of MINK215 which demonstrated robust efficacy in non-small cell lung cancer preclinical models, eliminating tumor burden in the lungs and enhancing tumor-specific CD8 T-cell infiltration through stromal remodeling. This is a program we're actually very excited about, and Dr. Shannon Boy, one of our lead scientists at MINK, will be presenting new data at the American Society of Gene and Cell Therapy annual meeting on May 19th. I will now turn the call over to Jen for closing comments.
spk08: Thank you, Mark. Well, I get more and more enthusiastic about the data that we're advancing and the technology and the science behind these very powerful cells. And in conclusion, I'm really happy to share with you the progress that we've made in advancing this platform. And as Mark just mentioned, not only addressing and expanding the benefits from available therapies for patients today, but what they will need tomorrow. This process, of course, is made possible by the incredible advancement of Dr. Joy Zhao and her team in our CMC group. Our current process, our manufacturing process, is designed to generate for 5,000 doses per year, and we are building currently and expect to have a fully donor-independent process over the course of this next year. And this development will come without the kind of capital-intensive efforts associated with most cell therapy Enjoy it with us today to answer any questions. We'll also be showcasing a deep dive into our manufacturing process, technologies, and advancements at our annual meeting this year. Very importantly, and what has been contributing to our high efficiency is our team is small, and we've kept it that way, and we've made tremendous progress. Launching the company as an IPO in October of 2021, advancing three clinical programs highly efficiently and now identifying tumor types that may allow us to develop Agent 797 on a rapid path to development to expand benefit to patients. And a specific set of solid tumor cancer sets us up very well. And we're doing this with a team of under 35 people. And as Christine will share with you, we've been able to manage our team and our expenses very efficiently, and we're looking forward to being able to financially support the initiatives that I shared with you throughout the course of the year and well into next year. Christine?
spk03: Thank you, Jen. We ended the first quarter of 2023 with a cash balance of $14.9 million as compared to $19.6 million at December 31, 2022. Our cash used in operations for the first quarter was $4.4 million, which compares to $4.2 million for the same period in 2022. Net loss for the quarter ended March 31 with $5.7 million, or 17 cents per share, compared to a net loss for the first quarter of 2022 of $7.8 million, or 23 cents per share. Thank you, and we'll now turn the call back to the operator for questions.
spk06: The floor is now open for your questions. To ask a question at this time, please press star 1 on your telephone keypad. At any point you'd like to withdraw from the queue, please press star 1 again. You'll be provided the opportunity to ask one question and one further follow-up question. We'll now take a moment to compile our roster. Our first question comes from the line of Emily Bodner from HC Wainwright. Your line is open.
spk04: Hi, good morning and thanks for taking the questions. Is there anything you can share about details for the non-small to long cancer expansion study? And then also, I believe you previously said that you were going to also do an expansion in testicular cancer. So is that also still the plan? And then at this point, do you think you're just focusing on combination approaches or do you still think there's a role for monotherapy in your view? Maybe just discuss plans for multiple dosing. Thank you.
spk08: Emily, thank you very much. So to your first question on small cell lung cancer and testicular cancer, indications in which we have observed some specific benefits and non-small cell lung cancer, we are advancing our phase one into a phase 1B. And we're able to enrich a little bit more clearly in lung cancer, the more prevalent tumor non-small cell lung cancer in patients who are refractory. There's really nothing for those patients and very low response rates. We believe that when patients fail anti-PB1 therapy, they have a profile where INTPs may benefit, as Mark mentioned just a bit ago. And adding on to what's available, standard of care, is actually allows us to take a monotherapy approach to development. Just taking standard of care, patients who are on standard of care, When it's not active for those patients, adding on to that gives us an opportunity for rapid development. So while we do see a path for INKTs alone, and we've seen benefit, as you can see with the data presented at ANCR, we do see benefit with INKT 797 specifically without other therapies, both long-term disease stabilization and biomarker responses. we see more robust activity and a very clear path to rapid path to registration when we can add on to available therapy and expand the benefits or reinvigorate a patient's immune system and reactivate it to respond to what's currently available. We will be doing multiple doses in our study while the cells are persisting for about eight weeks. We do plan to dose within, and we'll share more about these trials as we launch them But we will be dosing more than one dose, and we'll probably be dosing consistent with some of the most commonly used therapies at week six or eight that will take advantage of the pharmacology that we're seeing, as well as make the treatment burden as light as possible for our patients. With respect to testicular cancer, that is also a study that will also continue to interrogate signals with that. indication. It's a bit rarer, and so we are just currently enrolling some more patients to deepen our understanding of the biology of patients who fail prior therapies with testicular cancer, but that's an area that we do see benefits and want to continue to explore that. I think I covered all of your questions.
spk04: Yes, that was great. Thank you.
spk06: Our next question comes from the line of Jack Allen from Baird. Your line is open.
spk05: Great. Thank you so much for taking the questions and congratulations to the team on the progress made throughout the quarter. I wanted to ask on the updates surrounding COVID, I think in the press release you outlined that there will be some data presented in late May here. I'd love to hear what we should expect ahead of that data set and any comments you have around, I think there were some ongoing negotiations with DARPA around potential funding for some of these viral I guess, response programs. I'd love to hear any updates there. Thank you so much.
spk08: Thank you so much, Jack, for your question. I am incredibly excited about an upcoming data presentation at the Pulmonary Conference. It's an international conference of infectious disease and pulmonary science. The largest of its kind, about 30,000 participants. It's in Washington, D.C. this year, and our presentation is slated to be presented by Dr. Therese Hammond, who was the lead investigator in our Phase 1 trial, a pioneer in delivering cell therapy to patients with infectious disease, and the presentation is on Sunday, the 21st. And we'll share a bit more about that data at the release of it. What we see is the opportunity here. Now, very importantly, we had a number of key observations with these cells. Number one, we could administer these cells. They were at the site in emergency settings when the patients needed them, and they were able to be administered very easily within the standard practice in an emergency room and an ICU setting. So that set us up for addressing and confirming that these cells are logistically feasible. They could be cryopreserved. They could be administered in the hands of non-oncology experts. These are ICU experts and emergency room critical care physicians who don't have as much experience with cell therapy products. And we were able to deliver benefits to some patients. And we reported pronounced benefit in our cohort that showed survival rates in patients who were elderly, mechanically ventilated, And we saw survival benefits of over 70% alive after a single administration of 797. We also showed that these cells can be dosed in that severe, critically ill population. They could be dosed tolerably to a billion cells. And we also showed that these data compared so favorably to an in-hospital control that had a survival rate of less than 22%, and the CDC data which was really comparable with the in-hospital controls at the time of our enrollment. We've also demonstrated that we could administer these cells not only tolerably, we saw no cytokine release in the population, but we also showed that these cells could be administered in patients who were so severely sick that they needed supportive essentially ECMO procedures. This is a procedure that requires heavy intervention. It's very difficult. It's recirculating the patient's blood supply, and we were able to administer the cells in that setting and see benefits as well. You'll see a deep dive into that data set at the upcoming ATS conference. You will also hear about some exceptional cases where we've administered the cells and saw some remarkable benefit in patients who have cleared COVID but had secondary infections that were resistant to all available antibiotic therapy. And the cells actually promoted some really exciting data in that setting. So you'll hear all about the data sets there. In advancing this program, we do believe that the data we're observing is really far too good to turn away from. Yet our focus and our prioritization has really been advancing the cells in solid tumor cancers. What we have, our negotiations are with non-diluted government-sponsored sources and clinical trial platforms that allow us to very rapidly expand the potential benefit of these cells in patients with acute respiratory distress syndrome, secondary to viruses, and this could go beyond COVID-19. Those discussions are very actively underway, and we will certainly be making some public announcements about the collaborations in the upcoming year term.
spk05: Great. Thank you so much for that comprehensive answer. And then just one brief follow-up on the CAR-INKTs. I'm very much looking forward to that presentation as well at the upcoming ASGCT meeting. I'd love to hear a little bit more, though, about your development strategy as it relates to the CAR-INKTs. Are these assets that you'd look to bring forward on your own? Would you look to partner these assets? I'd love to hear how you're thinking about that. Thank you so much.
spk08: Zach, thank you. I want to make one last comment that I didn't make about the cells and ATS, and then I'm going to come to the FEPCA or NKT. We also will report some very important translational data that shows what these cells can do biologically. In cancer, we saw that these cells can home to tumors and generate a pro-inflammatory phenotype, which is what we really need in that setting. What we see in infections, particularly in acute ARDS, is that the cells actually induce an anti-inflammatory phenotype, which is really powerful and showcases how these cells can modulate immunity based on the disease setting that they're in, which makes them a really remarkable candidate and also underscores the next steps in our platform. I'm the Fat Car INKT in partnering. Partnering is absolutely core to our strategy. As you know, we've been an incredibly aggressive team. Mark and I have worked together with the Agenis Group, and we allowed the access to our remarkably fast and innovative discovery research and finance the business in parallel. So through nearly a billion dollars in partnerships, we were able to continue to finance our innovative pipeline at Agenis and at Mink. Mark and his research team have continued that pace of discovery and innovation. And for our ability to get the science into as many hands and out to as many patients as possible, partnering will be necessary for that. That includes local, national, U.S.-based pharma partners who may be seeking, that have the capabilities that will allow us to expand more quickly. quickly, but also regional partners where we don't yet have the infrastructure or bandwidth. You will be hearing more about that also in the near term and our strategy and access to advancing FAPCAR INKT very quickly. Suffice it to say, though, today we are well positioned to advance FAPCAR INKT through the IND enabling and into the clinic, and that's a very high priority for our company.
spk07: Great, thank you so much. Thank you.
spk06: Our next question comes from the line of Matthew Fitz from William Blair. Your line is open.
spk02: Thanks for taking my question. Jen, I'm wondering if you guys think, you know, what could be special about that gastric cancer patient that had such a strong response? You know, they had an MSI high tumor, but obviously didn't respond to two prior rounds of checkpoint inhibitors. Do you think MSI patients in general might be more prone to INKT selectivity? Do they have more CD1D expression or anything like that?
spk08: That's a great question, and I'm going to turn it over to Mark just after a couple of words. There are a few points that I'd like to have Mark also expand on that we observed, which included the tumor microenvironment modulation that I'll have Mark sort of further expand on. But a very important part of that modulation included increased TCR clonality and diversity. And some of the drivers of that are continuing to be under investigation. But I think what I do see is that MSI-high tumors are quite responsive to PD-1 for a period of time and then no longer. And in this case, we saw absolutely no response, not on Pembromana, not on Nevo, Combo, and not until we added the cells. And there are a couple of features that we presented, and Mark will go into, that may help us better understand the disease-modifying benefit in this particular data set. To the extent that it is translatable across MSI tumors, we will explore and are actively doing so. Our clinical trial with Dr. Janjigian will allow us to answer this question as well. Mark, I'll open it to you to say a few words.
spk00: Yeah, thanks, Jan. It's an interesting question, and we've been, of course, scrutinizing this deeply. And it's the case that in tumors that actually have an infiltrate of T cells or, you know, that are high in tumor mutational burden, there is a T cell response. But clearly with this patient having gone through two rounds of PD-1 directed therapy, this isn't enough to actually either, you know, get into the tumors pervasively and actually start doing something. And what happened after INKT infusion is that somehow that got unlocked and these T cells started to do what they were actually generated for, is attack the tumor cells. So what we see in preclinical models is that, you know, INKT cells are more resistant to quite a few of the immune suppressive mechanisms that tumors employ to keep T cells down. And what we see in, for instance, our FAPCAR model, but also in some of our 797 preclinical models is that these tumor suppressive of these immune suppressive mechanisms actually get neutralized or countered by INK T cells. If you could think about the local TGF-beta or actually the cells that secrete TGF-beta, CXCO12 that keeps the T cells out, all of those actually, and specifically the myeloid component, all of those get translated, transformed into pro-inflammatory, non-immune suppressive And that actually brings the T cells in and also reinvigorates the T cells. We've also seen that, for instance, supernatant that we get from activated IKT cells is able to rescue partially exhausted T cells. So all of those mechanisms, I think, contribute as a whole, as a package, it's not a one-trick pony, to activating the T cells that are there in the gastric cancer patient, but obviously you're not able to do anything. And I think that very well fits what we see in our preclinical models as well and is one of the key features that we think is going to build the platform for IKT cells in solar tumors.
spk07: Great. Thanks, Mark.
spk06: Our next question comes from the line of Kalpit Patel from B. Reilly Securities. Your line is open.
spk01: Good morning. This is Andy on for Kalpit. Thank you for taking our question. Starting off, what should we anticipate next from agent 797 and solid tumors? Is there any dose escalation work still remaining?
spk08: Andy, thank you. We will continue to interrogate dose, frequency, and optimization. Though I should say to you that I feel based on the pharmacology data that we've generated and the signals of activity that we've identified and the tolerability profiles, where we feel very close and confident with our dose, but it will be important just to strengthen our data packet for future regulatory interactions to continue to deepen our scientific exploration of dose and dose frequency. The next phase for us will be multiple doses, and that will be happening near immediately.
spk01: Great, and then maybe one additional follow-up With your upcoming presentation on MINK 215, is it fair to say that you're prioritizing this program ahead of 413? And maybe give us a sense of the timelines of when we should anticipate these programs to enter the clinic.
spk08: Sure, sure. So I'll answer the second question, which is on 413. I personally believe, and our key opinion leaders have continued to emphasize this point, that there is a critical need for an accessible, affordable product, the target BCMA, that expands the duration, the durability, and really eliminates the continued antigenic profile, the BCMA target. What we do see today with autologous products is that they work well, high response rates. They're not as durable as they need to be, and when patients progress, about two-thirds of them are still revealing the antigen BCMA. So I do think that there's a major opportunity to advance an allogeneic, off-the-shelf, armored BCMA that shows superior qualities as a next generation therapy for patients. For MIG to do so, given the competitive landscape, it would be an intensive effort and one that we are deprioritizing to FAP, which is novel, engineered, and within our solid tumor strategy. So our BCMA program has continued to advance. We've continued to deliver the manufacturability and scalability, and we're interrogating it and getting it ready for a phase one clinical trial, and it's really quite close. Yet, this would be something that we have advanced some discussion to really expand our footprint and leverage additional external non-dilutive to advance this program in this competitive setting. That's our INTP. It's really, we think, an outstanding product. Our preclinical data continue to get stronger. The profile of the molecule is very compelling. The need is great, and there are a host of solid tumors that are expressing cancers that actually we believe we can bring benefit to. And for all of those reasons, we've accelerated this novel and differentiated product into the forefront of our trial, and we will be filing an IND in 2024. That will bring us into the clinic very, very quickly. We have a very fast path from IND filing to first in humans, so those would be tied together really quite quickly towards the middle to second half of 2024.
spk07: Thank you, ladies and gentlemen.
spk06: This does conclude today's call. Thank you for your participation. You may now disconnect.
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