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spk07: Good morning, and welcome to Mink Therapeutics' fourth quarter and full year 2022 conference call and webcast. All participants will be in a listen-only mode until the question and answer session. Please note, this event is being recorded. If anyone has any objections, you may disconnect at this time. I will now turn the call over to Zach Arman, Head of Investor Relations at Mink.
spk03: Thank you, and thank you all for joining us today. Today's call is being webcast and will be available on our website for replay. I'd like to remind you that this call will contain forward-looking statements, including statements regarding our clinical development, regulatory, and commercial plans, as well as timelines for data release and partnership opportunities. These statements are subject to risks and uncertainties, and we refer you to our SEC filings for more details on these risks. Joining me today on the call are Dr. Jennifer Buell, President and Chief Executive Officer, and Christine Klaskin, Principal Financial and Accounting Officer. Now, I'd like to turn the call over to Dr. Buell to highlight our progress in 2022 and plans for the year ahead.
spk00: Thank you so much, Zach. Good morning, everyone. Thanks for joining our fourth quarter and full year 2022 earnings call. It's a great pleasure to be with you today and to share an update on the progress of our company. And I'm really excited and proud to share that our dedication to advance the field of cell therapy has yielded quite exciting and differentiated results in 2022 and set us up for a very active 2023. We've made important strides in advancing INKT cells, our platform, in generating critical data in research as well as in the clinic, some of which we've already presented publicly and more of which will be coming your way this year. Recall that Agent 797, our lead product advancing in the clinic, is an allogeneic, unmodified, or naked INKT cell. These cells have shown promise as a monotherapy as well as in combination with approved anti-PD1s, Keytruda or Opdivo, in clinical trials. And these are trials in patients that are heavily pretreated with solid tumor cancers. We're excited to present an update on this progress at the upcoming AACR meetings next month, and we'll also be announcing our plans for developing INKPs in solid tumor cancers such as non-small cell lung cancer and relapsed refractory gastric cancer in collaboration with world leaders in these diseases. These data build upon our earlier presentation at the Society of Immune Therapy for Cancer, or CITC, conference in Boston last November. We also detailed our findings in our inaugural R&D day last November, where we reported on our lead program, and we showed that it can be demonstrated tolerably alone and in combination with commercially approved anti-PD1s. We demonstrated that we could dose patients tolerably up to a billion cells per dose without lymphodepletion and with no observations of cytokine release syndrome, CRS, or neurotoxicity. These data enable the development flexibility to deliver the benefit of these cells without toxicity observed with first-generation cell therapies. Furthermore, we concluded our Phase I study of 797, our allo-INKTs, in patients with viral ARDS. We reported 70% survival, which compares favorably to in-hospital control and CDC data of survival rates of 10% to 22%. Even more compelling were the observations of a reduction in secondary infections that are oftentimes fatal in patients in the ICU. We've submitted these data to a top-tier journal and expect a publication this year. Now, these results in patients with viral ARDS have generated great interest from government and public financing and private financing opportunities. We're currently in discussions to externally finance the development of INKT cells in acute infections and associated fatal consequences like respiratory distress, an indication for which there are no approved therapies. We'll be providing more updates on the advancement of these discussions this year. The development of allo-INKTs and indications outside of oncology is only made possible through the manufacturing productivity that our team has made. MINK has addressed the limitations of the use of cell therapy products beyond oncology and in infections in many ways. First, we focused on the development of INKT cells, which have shown promise in treating viral infections and respiratory illnesses by using INKT cells We can avoid some of the limitations associated with traditional cell therapies, such as the need for matching donors and recipients, the use of lymphodepletion, and the limitations of cost and scalability. We've addressed this. We've invested in high-throughput manufacturing technology, which allows for the rapid production of large quantities of INKT cells. generating billions of cells from a single donor and thousands of doses per donor. Our process is now FDA cleared for implementation into our clinical trials without external dependency. Our manufacturing approach is designed to make INKT cell therapy more accessible to patients and to improve the scalability of cell therapies overall. As we continue to make progress in our clinical programs, we're also making important advancements in deepening our understanding of the novel mechanisms of action of INKT cells and their unique advantages over available cell therapies. At the end of last year, we presented data elucidating the long hypothesized mechanism of INKT cells that underscore their potential as a highly effective living medicine for patients with cancer. Specifically, Our scientists demonstrated that INKTs have the killing power of NK cells and the memory of T cells. They activate dendritic cells. These are signalers that help the immune system recognize tumors. We've shown that INKTs also kill M2 macrophages. M2 macrophages are immunosuppressive cells that constrain the body's ability to fight tumors. And we also reported that INKTs can restore the tumor killing capacity of exhausted T cells. This is a very important mechanism in which CD8 T cells become exhausted and lose their tumor fighting capability. And as we reported at CITSE last year, INKTs can overcome this mechanism and reinvigorate exhausted CD8 T cells, restoring their killing capacity. These mechanisms help to explain some of the early signals of benefit that we've observed in solid tumor cancers. Additionally, our research team has made important progress on our pipeline, including the development and advancement of MINK215. MINK215 is an armored IL-15 FAP CAR INKT designed to target the tumor stroma and modulate the tumor microenvironment to increase tumor killing capability. Targeting FAP, which is fibroblast activation protein, with CAR INKTs, these are chimeric antigen receptor invariant natural killer T cells, can benefit patients in several ways. FAP is a protein that's found in high levels in the stroma of many evasive solid tumor cancers, but it's absent in most normal tissues. By targeting FAP CAR INKT, we could specifically seek out and destroy cancer cells that express FAP while leaving healthy cells intact. Moreover, FAP is known to play a key role in promoting tumor growth and metastatic disease, and FAP inhibits the body's immune response against cancer. So by targeting FAP with CAR-INKT, it's possible to overcome these barriers of resistance and activate a potent immune response against cancer. So in summary, targeting FAP with CAR-INKTs can provide a highly specific and effective approach to fighting cancer while minimizing damage to any healthy tissues and boosting the body's natural immune defense. The molecule is an IND-enabling studies for an IND submission planned in 2024. Now, we are in dynamic markets and a unique time where fiscal responsibility and prudence will be critical to delivering the value of our science and the potential of our technology for patients with cancer. Partnering remains core to our strategy to fully leverage the potential of our platforms and products quickly, and these include public and private collaborations. At Mink, we'll focus our internal efforts on deepening our datasets and select solid tumor cancer indications where INKTs can complement available and approved standard of care and we believe expand the benefit of available therapies to patients with specific tumor types and will further elucidate our development plans with the data release at the upcoming AACR conference. We will continue to leverage our research productivity and exciting findings outside of oncology through strategic collaboration. I will now turn the call over to Christine to go over our financials. Thank you, Jen.
spk02: We ended the fourth quarter 2022 with a cash balance of $19.6 million as compared to $38.9 million at December 31st, 2021. Cash used in operations for the year and fourth quarter ended December 31, 2022 was $18.9 million and $4.4 million respectively. This compares to $12.8 million and $1.7 million for the same periods in 2021. This increased funding was related to the internalization of our CGMP manufacturing of Agent 797 for clinical trial supply, which has increased our production and results in decreased supply cost prospectively. Net loss for the quarter ended December 31, 2022, with $7.8 million, or 23 cents per share, compared to a net loss for the same period of 2021 of $5.8 million, or 18 cents per share. Net loss for the year was $28.0 million, or 83 cents per share, compared to $30.2 million, and $1.16 per share for the year ended December 31, 2021. Thank you. We'll now turn the call over for questions. Operator?
spk07: The floor is now open for your questions. To ask a question 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 render our roster. Our first question comes from the line of Emily Bodner from HC Wainwright. Please proceed.
spk01: Hi, good morning. Maybe without specifically talking about data, can you just comment on what made you select gastric cancer for an expansion cohort? And are gastric and lung the only indications you're planning to evaluate, or are these just the first and then you kind of will look to see if there's any others after that? And are these going to be combination cohorts or monotherapy cohorts? Thanks.
spk00: Emily, thanks for your question. So we are currently focused on expanding data sets and indications where we are quite enthusiastic about the results, gastric and lung. are opportunistic for two reasons. One, when patients are refractory to anti-PD-1 therapy, there are very limited treatment options for them, and that includes in patients that are PD-1 refractory with lung cancer, the patients are treated with doxotaxil, 9% response rates, and there's an enormous opportunity to expand benefit. We also see quite a bit of complementarity by adding our cells into this setting, either alone or in combination with approved PD-1s. These indications enable a path forward where we may be able to develop the product quite rapidly as a monotherapy on top of available standard of care. So those are the two that we've spoken about, and we'll deepen the discussion following our data presentation at AACR on some other areas where we'll be continuing to explore the benefits of INKTs. in different solid tumor cancers.
spk01: Okay, makes sense. And maybe can you just reiterate the timelines for when you might have MINK413 enter the clinic? Thanks.
spk00: MINK 413, our armored BCMA car, we've brought that through the critical gating items for manufacturing for MasterCell Bank, and this product could be ready for IND enablement in 2024.
spk07: Our next question comes from the line of Kalpeet Patel from B. Riley. Please proceed.
spk06: Yeah, hey, good morning, and thanks for taking the questions. Maybe starting with expectations for the AACR update, can you give us a sense of how many patients' worth of data we should expect there, and then maybe what proportion of those patients would have lung cancer or gastric cancer?
spk00: Thanks for your question, Talbot. We'll have to hold responding until you see the data set, but just a reminder, what we have spoken about is we launched the trial in March and had completed accrual for the Phase I dose escalation and preliminary expansion. So it is a Phase I solid tumor study. It does have a mix of patients, predominantly those who are refractory to all prior therapy. So these are late line patients. They are a standard phase one cohort with some operational enrichment for certain tumor types, which you may see some enhanced representation of specific tumor types in the cohort, most of which is a measure of the limited therapeutic options for patients at this stage in development. But our cohort, we completed accrual to it at the beginning of the year, so those will be presenting as much data as possible from that cohort by the time of the data presentation in AACR.
spk06: Okay, and then in the planned expansion cohorts for lung cancer, are the patients going to be primarily, you know, checkpoint-naive, or are you going to include, you know, both checkpoint-naive and checkpoint-refractory patients in that study?
spk00: Mostly checkpoint-refractory for a few reasons. We have been able to demonstrate that we can dose monotherapy, INKTs, in patients who have failed prior iotherapy, and we have been able to do in combination, we could do so tolerably to a billion cells, and we'll be sharing the data from those signals. I think importantly, one thing that is commonly observed in patients who are PD-1 refractory is the exhausted CVHT cells, those cells that actually cannot enter the stroma. I said to you this past November, we presented data demonstrating that our INKTs can actually reverse the CD8 exhaustion signature and also kill M2 suppressive, immune suppressive macrophages. Both of those, we believe, set us up for bringing benefits in patients who have actually failed anti-PD-1 therapy because of the translational data that we've been able to generate and present. IO-naive patients with non-small cell lung cancer are very far fewer of the population. So we're really focused on these refractory patients.
spk06: Okay. Makes sense. Thanks very much for taking the questions.
spk07: Our next question comes from the line of Jack Allen from Baird. Please proceed.
spk05: Great, thank you so much, and congratulations on the progress. I guess my first question was around the decision to move forward with the PD-1 inhibitors. I was wondering if you had any comments about the thoughts that you previously had around Agenis' proprietary CTLA-4 inhibitor, boletizumab, and any potential combination use there?
spk00: Jack, I'm so glad you asked. We will be making some announcements at AACR about the combination, which we did not elucidate in our, about different combinations that we'll be advancing both in our hands as well as in combination with some of the agents from Agenis' portfolio. I think really importantly, Agenis' most recent data presentation was at ASCO-GI and Botanzilumab. And for those who may be less aware, the product appears to be bringing extraordinary benefits to a host of solid tumor cancers that have failed prior therapies, and that includes MSS, colorectal cancer, as well as PD-1 refractory non-small cell lung cancer. In their most recent earnings call, they shared the response rates that are really exceeding, I think, 50% in that cohort of patients with non-small cell lung cancer. And what we had previously collaborated on were preclinical studies that actually demonstrated the synergy and complementarity of HF797 or INKT cells in combination with botanfilumab, the urinized version, and valcilumab. So in the model, it was a B15OVA model with metastatic lung disease, and we saw that the combination of CTLA-4PD1 eliminated about 30 to 40% of the disease. The cells alone did about that same reduction in liver mass. When you put the three or two together, so the cells in combination with botancilumab or the cells in combination with botancilumab and belstilumab, we saw near complete tumor eradication. So it sets us up for a few really important opportunities that could be expanding the benefit of what we see with botancillinab because of the complementarity of the mechanisms that I mentioned before. We have some additional preclinical data that we will also be releasing in other indications where the combination may be quite productive. One of the areas that we believe the cells can expand the benefit of botancillinab is in patients with metastatic liver disease. What we see, and we've shared a bit about, is that in a patient, in our study, with metastatic liver disease, we saw that the cells not only home to liver disease, but also modulate the disease and eliminate the disease in some settings in those liver mets. So we do believe that there's an enormous opportunity to expand the benefits of BotanZoMap by adding the INKT cells, 8 and 797, to this combination. And we'll be talking more about that at AACR.
spk05: Great. Great. Thank you so much. And then I just have two quick follow-ups. I guess on the first one, outside of oncology, how are you thinking about the timetable as it relates to development in graft-versus-host disease? And should we expect that that's going to be a partnered indication at this point? And then outside of the broader mink portfolio, I was wondering if you had any comments on a recent clinical hold from one of your competitors on an autologous INKT program and how we're thinking about the safety of allogeneic versus autologous INKTs?
spk00: Okay, great questions, Jack. So on the first, as I mentioned, of course, we're in a really dynamic market where we need to be quite thoughtful. And for GVAC, we see an enormous potential there, and we have some supportive data to indicate a quick path forward to bring benefits to patients, both not only for but also for engraftment success. This is an area where we are looking at ways of advancing this into the clinic in ways that would not result in additional expense from our balance sheet right now, and that's through strategic collaborations and investigator-sponsored support as well. So we'll be talking more about that soon. We've designed the program, and it is designed in a way that we believe can bring the cells forward to a potential very rapid approval, and we'll be making some announcements about that program in the upcoming weeks. The epidemic statement that you're referring to, that was a patient who had had a fatality on a clinical trial. This is a patient with neuroblastoma, and that patient actually had a metanemovirus, which is commonly seen, and it's fatal, in pediatric patients who are lymphodepleted. And as you can see from the trial with Acinex, they actually lymphodepleted their patients, which is not something that we believe we need to do. We have not lymphodepleted. We've demonstrated that we can administer the allo-INKTs very tolerably, no neurotox, no CRS, no related serious toxicities above grade three. So we're in a position where I do believe that the cells can be administered in dose really quite tolerably without lymphodepletion. And we also are seeing and will be sharing an update about the persistence of the cells even in that setting. So I think that the case with Apinex is related to lymphodepletion and subsequent viral infection secondary to the lymphodepletion that led to a very unfortunate circumstance for this patient. I don't think that it reads through to the safety or tolerability of INKP cells.
spk04: Thanks so much.
spk00: Thank you.
spk07: Our final question comes from the line of Matt Phipps from William Blair. Please proceed.
spk04: Morning, Jen. You know, I was wondering on the Fafcar, in the preclinical post you guys had to see some of the efficacy data was actually best combined within NYESA1 T-cells. So how does that kind of preclinical data influence your thoughts around maybe combination development of this program, and then do you plan on trying to look at any biomarker for enrollment or like an immune-excluded phenotype, or just how do you pick patient populations for that program?
spk00: Well, that's a great set of questions, Matt. Thank you. So for that program, we actually set it up using the NYSOTCR and that model to exemplify what a chronic antigen-stimulated environment would look like. So what happens when immune cells are sort of constantly perturbed? And then can these cells actually overcome that perturbation and also reinvigorate CD8 T cells to killing potential? And at our poster at CISI, we actually demonstrated that we could do that. So that model was to help us better understand what these cells can mechanistically view to reverse exhaustion and then carry the CD8 T cells into the stroma and invoke killing. Now the design of that molecule with FAP targeting gives us opportunities for a potential biomarker selected population. We won't restrict for that at the beginning, but we will measure for it upfront. So we will look if it will be necessary to enhance clinical benefit by restricting the population to FAP expressing tumors or if we may have more broad activity independent of the biomarker selection. So we'll start broad and then we will assess and then decide if we need to exclude or enrich for the FAP-expressing tumors.
spk04: Got it. Thanks. And then on the BCMA program, you know, do you guys have evidence yet? I can't remember. I don't think this is a city, but of kind of treating a multiple myeloma cell line that relapsed or grew out of previous BCMA therapy exposure with something maybe that's kind of commercial late stage. And I guess why not go after something different like GPR or C5D or maybe a dual targeting construct just given how entrenched BCMA therapies are becoming?
spk00: You know, Matt, BCMA therapies certainly are competitive. I hear that we're seeing some remarkable progress with some of the more modern BCMA therapies, including very high response rates. But there is a continued problem, and we have Marcella Mauss on our scientific advisory board. And what we see is that patients continuously progress on BCMA, and two-thirds of them still express the BCMA antigen. So there does appear to be a challenge with respect to durability of response in those patients despite the high response rate. And we also still see challenges in access for those patients, and both of which I think that the INKT product can address. We've been able to demonstrate really robust scalability with our manufacturing capabilities, and that would read through certainly to our ability to enable broader access to a BCMA. We've also armored our BCMA with IL-15, and we have conducted, and we presented it to CIPSE, and I'll share that poster with you. We did present data that actually demonstrated superior anti-tumor immunity using our IL-15 BCMA CAR-IMKT compared to what's commercially available right now. That program, due to its competitive nature, we have prioritized that program, and we've announced that previously, in order to be really selective with opportunities that we believe can bring significant value creation even sooner. Now, the VCMA program is very exciting for us and a program that we're committed to advancing because of the reasons that I mentioned previously. It is a program that we would contemplate strategic collaboration for as well, and we've embarked in discussions predominantly with groups who actually need a next-generation VCMA that is more accessible and sustainable compared to what's available right now.
spk04: Great. Okay, thanks, Jen.
spk00: Thank you, Matt.
spk07: I would now like to turn the call over to Jen Buell, CEO for Closing Remarks.
spk00: Thank you very much, Operator. It was a pleasure to be with you all today. Looking forward to speaking with you at AACR. Thank you again. Bye-bye.
spk07: Thank you, ladies and gentlemen. This does conclude today's call. Thank you for your participation. You may now disconnect.
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