INKT - NASDAQ

Good morning, and welcome to MiNK Therapeutics' Third Quarter 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. Today's call is being webcasted 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 time lines 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 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 and speak to our outlook for the remainder of the year.

Thank you very much. Good morning, and thanks for joining our third quarter earnings call. Today, I'm going to keep my corporate update short and invite you to join us for two very exciting events next week. The first, MiNK was selected to present five abstracts for presentation at the Society of Immunotherapy for Cancer Conference or otherwise known as SITC conference. The conference will be held in our home city of Boston next week. And following our presentations, we will host our inaugural R&D Day event, which will include presentations from leaders of immune therapies for diseases of the immune system, including cancer, infections and autoimmunity. The event will be invite only for in-person participation, but we will also be publicly webcasting the conference as well. These activities are a combination of significant progress at MiNK. We've continued to advance our invariant natural killer T cell, or iNKT cell platform through multiple clinical trials with our lead product candidate, Agent-797. 797 is an allogeneic or off-the-shelf product in clinical trials designed to administer the product alone or in combination with KEYTRUDA or OPDIVO in solid tumor cancers. We also have advanced our clinical trials in multiple myeloma and severe viral acute respiratory distress syndrome. We've brought these trials to important milestones, which include enrollment completion and data readouts, both of which you'll be hearing more about at the upcoming conference. Our next-generation pipeline is advancing very rapidly. We recently announced 2 exciting CAR-iNKT programs. These include a novel stromal targeting FAP CAR-iNKT for solid tumor cancers and a soon-to-be disclosed armored BCMA CAR-T program, the latter of which is designed as a next-generation scalable approach to deliver durable benefit without lymphodepletion in patients with multiple myeloma. These CAR-iNKT programs are advancing in IND-enabling studies and we announced that our FAP CAR-iNKT will be filed to an IND in 2023 next year. Both programs are advancing into IND studies at this time. Our engineered CAR-iNKT programs are built from our proprietary CARDIS platform. This is designed for the selection of therapeutic candidates that have an optimal safety program profile and key biologic advantages over available products. We'll tell you more about our CARDIS platform at the upcoming R&D Day. Our presentations at SITC will include updates on three clinical programs of Agent-797 in heavily pretreated solid tumor cancers in combination with backbone IO therapy as well as data from our trials in viral acute respiratory distressed syndrome and multiple myeloma. Additionally, our team will present data on our novel CAR-iNKT pipeline candidates demonstrating potential first-in-class features with an allogeneic CAR-iNKT approach. Finally, we will be reporting on novel mechanisms that have not yet been observed on iNKT biology as we advance the science of these cells and continue to believe that these features support the optimal therapeutic platform for delivering a scalable cell therapy product. Before we head into the conference, I want to take a moment just to provide a refresher on iNKTs. These cells are a subset of T cells. They modulate both innate and adaptive immunity. And in cancer, iNKTs can directly kill tumor cells. They also modulate myeloid biology specifically suppressing myeloid-derived suppressor cells. They also recruit additional immune support by driving T cells and natural killer or NK cells to the location of need. These mechanisms support earlier independent data showing that autologous iNKT cells are clinically beneficial in solid tumor cancers, an area in which other cell therapy approaches have not yet shown benefit. We'll discuss these mechanisms at a much deeper level at the upcoming SITC conference. Beyond cancer, our team has explored the application of these cells as a variant agnostic approach for severe infections. Viral ARDS takes the lives of approximately 40% of patients in the intensive care unit, and there are no approved products to address this indication. We previously reported an over 75% survival rate in severely sick patients suffering from ARDS, a marked improvement over the expected 22% survival. New findings from our Phase I clinical trial will be presented at the SITC conference by Dr. Terese Hammond. Terese is the Medical Director of the Cardiac Care unit and ICU at St. John's Health Center, and she's a pulmonary critical care expert specializing in critical care medicine, acute respiratory failure and ECMO and has pioneered the COVID-19 efforts. As a matter of fact, Dr. Hammond was courageously on the front lines at the start of the pandemic and one of the first to take patient samples and help identify the SARS-CoV-2 virus. Our work in iNKTs and severe infections has been selected as fundable by DARPA, and contract negotiations are underway to fund the advancement of Agent-797 in diseases of immune dysregulation. We look forward to additional announcements on this program. Finally, our presentations at SITC will also outline our key pipeline programs, namely MiNK-215, an allogeneic FAP CAR-iNKT, which we believe has the potential to be a differentiated therapeutic agent for solid tumor cancers. We'll also disclose details regarding MiNK-413, an armored BCMA CAR-iNKT, which is an off-the-shelf product designed as a next-generation scalable approach to deliver benefit without lymphodepletion in patients with multiple myeloma. This is a program that we continue to consider to advance through strategic collaborations. Again, these programs are the culmination of our strong advancements at MiNK, spanning key pillars across research, clinical data and manufacturing. Earlier this year, we announced our internalization of our GMP manufacturer to enable independence in delivering these cells at scale. You'll be hearing more about our manufacturing capabilities from Dr. Joy

Thank you, Jen. We ended the third quarter 2022 with a cash balance of $24.2 million as compared to $38.9 million at December 31, 2021. Cash used in operations for the 9 months and third quarter ended September 30, 2022, was $14.4 million and $5.6 million, respectively. This compares to $11.1 million and $3.5 million for the same period in 2021. This expanded funding was primarily related to the internalization of our manufacturing of Agent- 797 that Jen just mentioned. Net loss for the quarter ended September 30, 2022 at $6.3 million or $0.19 per share compared to a net loss for the same period of 2021 of $14.3 million or $0.59 per share. Net loss for the 9 months ended September 30, 2022, was $20.2 million or $0.60 per share compared to $24.4 million or $1.01 per share for the nine months ended September 30, 2021. I will now turn the call over to our operator.

[Operator Instructions] Emily Bodnar with H.C. Wainwright. Your line is open.

Hi, good morning and thanks for taking the questions. I just have two on Agent-797. First, when do you think you'll evaluate other combination agents like the CTLA-4 inhibitors? And do you have plans to maybe evaluate other combinations, beside checkpoint inhibitors? And then on the Phase I study in your combination arm, I believe you're evaluating patients who are checkpoint inhibitor experienced. So do you think you would evaluate patients who are checkpoint naive at any point? Do you have any plans to do that?

Emily, thank you so much for your remarks and you've given me an opportunity to just remind the participants about a couple of things. We've presented data previously at the American Association of Cancer Research, the AACR conference, showing that when you take these cells – a model of lung – a metastatic lung disease preclinical model when you look at therapeutic approaches to eliminate the metastatic lung lesions. And what we presented was when you take available molecules, such as a PD-1 or even a next-generation CTLA-4, you see some reduction in liver met in those populations. When you add the iNKTs, you actually see a marked improvement in the elimination of these cancer lesions in that model and when you conduct either a doublet of the iNKT cells with a CTLA-4 agent, predominantly a next-generation CTLA-4. Botensilimab, which is advancing in a genesis pipeline or a triplet combination with that CTLA-4 and PD-1, you see near complete tumor eradication. Those data have supported our clinical development concepts to advance. Now, we started as with the allowance of the regulators who mandate that early clinical new agents be tested in later disease settings after patients are refractory to prior therapies. We know that that's not an optimal setting to test, but we certainly have been able to leverage those trials not only to provide data showing that these cells can be administered at multiple doses tolerably but also in combination with backbone IO therapy, such as PD-1, KEYTRUDA and OPDIVO in the case of our trials. So we've met our regulatory obligation of demonstrating tolerability and now we have the flexibility to start developing in areas where we believe that these cells will bring even greater impact to patients, such as the earlier disease setting or in combination with important agents. Botensilimab is an Fc-engineered CTLA-4, which is showing benefit beyond what any prior CTLA-4 has demonstrated clinically in the past. We have the opportunity through our collaboration agreement with Agenus to actually advance combinations of iNKTs with this particular product and we'll be announcing our plans to do so relatively soon. So to answer your question, yes, we will be exploring other combinations. We do believe that a CTLA-4 plus these cells can bring optimal benefit, and we've demonstrated such through preclinical models, and we'll be looking forward to doing so in the clinic. Additionally, there are other – so these molecules, as a reminder, iNKTs have an invariant TCR that binds to a specific ligand and that particular ligand, CD1d, is upregulated, following some standard of care chemotherapies such as gemcitabine and others. So well-known, widely used molecules and these – the upregulation may actually enable tumor escape. And we believe that these cells in combination with standard of care chemotherapy may actually help mitigate that. And the mechanisms by which these cells can do so, we will be disclosing at the upcoming SITC conference. So from the conference, we will be able to showcase and support our upcoming clinical development plans with this molecule beyond PD-1 and also in an earlier disease setting where we believe the cells can bring a greater benefit to patients now that we've demonstrated tolerability and early signals of clinical benefit. And we'll also disclose areas where we believe these cells can be added to widely used therapies and expand the benefit. This will enable us to have a path in which dropping the cells on top of standard of care agents will enable a much faster path for development of the cells on their own. I hope that answers your question.

It does. Thanks so much.

Matt Phipps with William Blair. Your line is open.

Hi, this is Hunter on for Matt. A couple of questions from us. First off, could you update us on the status of your plans for starting the GvHD trial? I know previously you had guided to, I think, before the end of this year, but it seems like maybe the language had changed in your Q filing. And then looking towards the solid tumor presentation next week, one, noticed that it's sharing, it will also have data from the multiple myeloma trial. So is it safe to assume that one of those will be the primary focus of the presentation? And then maybe lastly, will there be data sort of on cell persistence and localization in those studies as well?

Thank you very much for your question. Let me address the first, which is your inquiry about GvHD, and we will be announcing our intentions with GvHD cells actually naturally work in that setting. And that setting has become – from a regulatory perspective, there are some considerations that will require us to make some revisions so that we can accelerate our development plans. We'll be discussing that at our upcoming R&D day, how we plan to take advantage of the natural capability of these cells for a development opportunity in patients with GvHD that includes not only engraftment success but also mitigation of GvHD. So stay tuned for that, and it will be a topic of the discussion at our upcoming R&D Day, where we will be making some announcements related to GvHD. Next will be the emphasis of the data. So we have advanced the cells, of course, in multiple myeloma because multiple myeloma is a tumor type that not only allows us translational information and insights because it's an accessible tumor. It's also very rich in CD1d ligand, and that's a natural homing. We've previously discussed our earliest case in the study where we showed that a patient treated with the cells, not only were the cells well tolerated, no neurotoxicity, no CRS. But also we saw signals of clinical improvement, including long-term disease stabilization, exceeding 10 months in a patient who had failed six prior therapies. We also saw a suppression of biomarkers. We will be expanding that data set and reporting on it at the upcoming conference. The showcase of the conference, though, to your earlier point, is on solid tumors. Given that we launched the trial just recently, just in May, and we have seen unprecedented interest and activity. We've enrolled over 40 patients into the trial, and we'll be releasing data on a cohort of patients who have at least achieved some early disease assessments. Now, as you can imagine, these data are still immature, but they allowed us the opportunity not only to see some early signals of safety, clinical activity, but also disease-modulating translational markers. So we will be looking and sharing information with respect to the translational biomarkers that we're evaluating in the trial at the upcoming conference.

Jack Allen with Baird. Your line is open.

Great. Thank you so much. And congratulations to the team on the progress made over the course of the quarter. I think everyone is excited about the SITC presentation. So maybe I'll start by asking a little bit about that. You mentioned these transitional biomarkers in the response to the last question. I was hoping you could dive a little bit more deeply into exactly what measures we'll be looking towards? And then as it relates to the idea of this study being a combination trial, can you provide some context around what you're looking at as far as the bars for success of the study?

So to your first question, I think what is known about these cells is they actually are incredibly active at secreting tumor killing cytokines like interferon gamma and immune regulatory cytokines on the tumor side of things. We will be showcasing data in which we've evaluated both peripheral as well as local information on the biology of these cells that will give us signals of persistence, some of the underlying mechanisms that we believe are supporting the clinical efficacy that was observed in the autologous setting, but also being observed in our allogeneic setting. So I would say there are some known mechanisms of these cells in which they can directly block and kill. They can [ lace ] tumors. They can recruit T cells and NK cells for direct attack as well as for durable memory responses. And they do so through a series of mechanisms, some of which can be elucidated looking at cytokine profile, other immune markers and we'll be sharing that data. I think you'll be enthusiastic about some of the mechanisms that we've been elucidating here and some data in which we can show how these cells help other immune cells like CD8 T cells actually traffic and function. This is a very important part, and I'm hesitant to say much more because of our restrictions with the data presentation at SITC, but our data will reveal some very important interactions between iNKT cells and other very important cells and their function that will help us better understand how these cells are working and eliminating disease. I think that you had another question which escapes me right now.

Yes. I was wondering if you could help contextualize what the thought for success is in the study, given that it's going to be a combination regimen with an immune checkpoint [indiscernible] as well.

So we actually – in negotiation with the agency, we were able to go into a setting in which patients have been treated as standard of care with KEYTRUDA or OPDIVO. Those patients progress on those agents. And in some cases, there is nothing more for those patients so they remain on the approved checkpoint. In the case of non-small cell lung cancer, patients progress on KEYTRUDA and then the only option for them really now is docetaxel, which has about a 9% response rate. And so those patients, many of whom will actually – if they can tolerate it – they remain on KEYTRUDA. We were able to see, based on the mechanism of these cells, if we can add these on to that regimen and actually reverse the progression and expand the benefit of the approved agents. So the bar here is really any signal. These patients are progressing on standard of care, commercially available standard of care, and we're adding ourselves to actually change the disease trajectory in those patients and that means, first, certainly, we want to look at tolerability. But next, we're looking at very, very low response rates in patients with thymomas, cholangiocarcinoma, non-small cell lung cancer, hepatocellular carcinoma, once they're refractory to checkpoint modulating antibodies. So the bar is low. We will be showcasing what these cells can do both clinically and translationally as well as are they tolerable. And that's an important marker for what we then can take these cells into based on these features.

Great. Thanks, so much.

[Operator Instructions] Kalpit Patel with B. Riley Securities. Your line is open.

Good morning. This is Andy on for Kalpit. Thank you for taking questions and congratulations on the progress. Looking forward to the upcoming SITC posters and R&D Day. We've seen other emerging cell types such as gamma delta T cells, garner more partnership interest surrounding engineered cell products as opposed to unedited cells. Are you seeing a similar trend with your pipeline candidates? And any more general commentary regarding your approach to partnerships would be helpful. Thank you.

Thank you for the question, Andy. I'll tell you, we are the most advanced company bringing an allogeneic iNKT that's not engineered into the clinic. So this is really first of its kind data and observations compared to what we see with some other cell types. We also have, of course, the capabilities and the engineering construct, which is, I believe, best-in-class here. And I'll tell you, just as a reminder, MiNK was born out of a long-standing immune-oncology company, Agenus, which boasts really one of the most productive R&D pipeline. Mark Van Dijk, who's our Chief Scientific Officer, had joined through an acquisition. Was a part of the leadership team at Agenus and he's Chief Scientific Officer of MiNK. Mark had designed the antibody discovery platforms at Genmab, Medarex, Agenus. And he's been able to actually engineer some extraordinary platforms for MiNK. And that includes our ability through the CARDIS platform to engineer cells, which you're going to hear much more about at the SITC conference. Also to apply the technology to create iNKT engager technology, which you're also going to hear more about. And we've previously disclosed the platform's capability to reproducibly generate high-quality TCRs. The productivity of our research engine sets us up for an opportunity to actually leverage that research productivity for partnerships. We have already engaged a number of strategic discussions on leveraging partners who could help us accelerate the advancement of some of these technologies as well as continue to support and expand our financial capability. So that will allow us to take advantage of molecules and engineering capabilities and our research productivity, not only to finance the business, but also to accelerate the development of our innovations. So you'll hear more about these conversations as we continue to advance them. What we have disclosed on the infectious disease side, we do have an opportunity, and we are in contract negotiations with DARPA. We were selected as fundable to advance these cells in their native form as a variant agnostic approach to emerging viral and infectious threats. That is an important partnership for us, not only to support our clinical – our preclinical progress, but also to expand the clinical benefit of these advancements. So the cells in their native form, there is no comparator because we're class leading here. And the cells in their engineered form certainly have quite a bit of interest. There's a lot of interest in both directions, the native as well as the engineered, both of which we will take advantage of through less dilutive financing opportunities.

There are no further questions at this time. I would now like to turn the call back over to the presenters for closing comments.

Thank you very much. I appreciate your time on the call today and look forward to speaking with you again next week. Talk with you soon.