MiNK Therapeutics, Inc. Q4 FY2022 Earnings Call

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 Zack Armen, Head of Investor Relations at MiNK.

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.

Thank you so much, Zack. 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. 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, and 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-PD-1 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 iNKT 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 Immunotherapy for Cancer or SITC 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 administered tolerably alone and in combination with commercially approved anti-PD-1. We demonstrated that we could dose patients tolerably up to 1 billion cells per dose without lymphodepletion and with no observations of cytokine release syndrome (CRS) or neurotoxicity. These data enable development flexibility to deliver the benefit of these cells without the toxicity observed with first-generation cell therapies. Furthermore, we concluded our Phase I study of 797, or allo-iNKTs in patients with viral ARDS. We reported a 70% survival rate, which compares favorably to hospital control and CDC data showing survival rates of 10% to 22%. Even more compelling were the observations of a reduction in secondary infections that are often fatal in ICU patients. We've submitted these data to a top-tier journal and expect 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 achieved. MiNK addresses the limitation of using 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 and 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, which are signaling cells that help the immune system recognize tumors. We've also shown that iNKTs can kill M2 macrophages. M2 macrophages are immunosuppressive cells that constrain the body's ability to fight tumors. We 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. As we reported at SITC 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 MiNK-215. MiNK-215 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 variant natural killer T cells—can benefit patients in several ways. FAP is a protein that's found in high levels on the stroma of many evasive solid tumor cancers, but is 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. Therefore, by targeting FAP with CAR-iNKT, it is possible to overcome these barriers of resistance and activate a potent immune response against cancer. In summary, targeting FAP with CAR-iNKTs can provide a highly specific and effective approach to fighting cancer while minimizing damage to healthy tissues and boosting the body's natural immune defense. The molecule is in IND-enabling studies for 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. At MiNK, we'll focus our internal efforts on deepening our data sets and selecting 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. We 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 curation. I will now turn the call over to Christine to go over our financials.

Thank you, Jenn. We ended the fourth quarter of 2022 with a cash balance of $19.6 million compared to $38.9 million at December 31, 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 period 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 resulted in decreased supply costs prospectively. Net loss for the quarter ended December 31, 2022, was $7.8 million or $0.23 per share compared to a net loss for the same period of 2021 of $5.8 million or $0.18 per share. Net loss for the year was $28.0 million or $0.83 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.

Our first question comes from Emily Bodnar from H.C. Wainright. Please proceed.

Hi, good morning. Maybe without specifically talking about data, can you just comment on what may be the plans for gastric cancer for an expansion cohort? And are gastric along the only indications you're planning to evaluate? Or is this just the first and then you'll look to see if there are any others after that? And are they going to be combination cohorts or monotherapy cohorts? Thanks.

Emily, thanks for your question. We are currently focused on expanding data sets and indications where we are quite enthusiastic about the result. 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. That includes patients with PD-1 refractory lung cancer, where the response rates are just 9% when treated with docetaxel. There’s an enormous opportunity to expand benefit. We also see quite a bit of complementarity by adding ourselves into this setting, either alone or in combination with approved PD-1s. These indications enable a path forward where we may be able to rapidly develop the product as a monotherapy on top of available standard-of-care. So those are the two that we've talked about, and we will deepen the discussion following our data presentation at AACR on other areas where we’ll continue to explore the benefits of iNKTs in different solid tumor cancers.

Okay. Makes sense. And maybe can you just reiterate the timelines for when you might have MiNK-413 enter the clinic?

MiNK-413 is our armored BCMA-CAR. We've brought that through the critical gating items for manufacturing for the master cell bank. This product could be ready for IND enablement in 2024.

Our next question comes from the line of Kalpit Patel from B. Riley. Please proceed.

Good morning, and thanks for taking my question. 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 what proportion of those patients would have lung cancer or gastric cancer?

Thanks for your question, Kalpit. We'll have to hold off responding until you see the data set. Just a reminder, we launched the trial in March and had completed accrual for the Phase I dose escalation and preliminary expansion. It is a Phase II, the 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 in a standard Phase I cohort with some operational enrichment for specific tumor types, where you may see some enhanced representation of specific tumor types in the cohort. Most of these patients are there due to the limited therapeutic options for patients at this stage in development. We completed accrual to it at the beginning of the year, so we’ll present as much data as possible from that cohort by the time of the data presentation at AACR.

Okay. And then in the planned expansion cohorts for lung cancer, are the patients going to be primarily checkpoint-naive? Or are you going to include both checkpoint-naive and checkpoint-refractory patients in that study?

Mostly checkpoint-refractory for a few reasons. We've demonstrated that we can dose monotherapy iNKT in patients who have failed prior IO therapy, and we have been able to dose in combination. We could do so tolerably to 1 billion cells, and we'll be sharing the data from those signals. Importantly, one thing that is commonly observed in patients who are PD-1 refractory is the exhausted CD8+ T cells; those that actually cannot enter the tumor. In the past November, we presented data demonstrating that our iNKTs can actually reverse the CD8 exhaustion signature and also kill M2 immunosuppressive macrophages. Both of those mechanisms set us up for bringing benefits to patients who have in fact failed anti-PD-1 therapy due to the translational data we’ve generated and shared. IO-naive patients with non-small cell lung cancer are a very limited population. So, we're really focused on the refractory patients.

Okay. Makes sense. Thanks very much for taking my question.

Our next question comes from the line of Jack Allen from Baird. Please proceed.

Great. Thank you so much, and congratulations on the progress. 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 you had previously around Genesis' proprietary CTLA-4 inhibitor, Botensilimab, and any potential combination use there?

Jack, I'm glad you asked. We will be making some announcements at AACR about the combinations that we did not elucidate previously regarding different combinations we’ll be advancing, both in our hands as well as in combination with some agents from Genesis' portfolio. Importantly, Genesis' most recent data presentation was at ASCO GI regarding Botensilimab, and for those who may be less aware, the product appears to bring extraordinary benefit to a host of solid tumor cancers that have failed prior therapies. That includes metastatic colorectal cancer as well as PD-1 refractory non-small cell lung cancer. At the most recent earnings call, they shared response rates that exceed 50% in that cohort of patients with non-small cell lung cancer. Previously, we collaborated on preclinical studies that demonstrated the synergy and complementarity of agenT-797 or iNKT cells in combination with both Botensilimab and Beltsville. In that model, the combination of CTLA-4 and PD-1 eliminated about 30% to 40% of the disease. The cells alone achieved a similar level of reduction, and when combined, we saw nearly complete eradication of liver metastases. This sets us up with really important opportunities to expand the benefit of what we see with Botensilimab due to the complementarity of the mechanisms I’ve mentioned before. We have additional preclinical data that we will also release in other indications where this combination may be productive. One area we believe the cells can expand the benefit of Botensilimab is in patients with metastatic liver disease. We had patients in our studies with metastatic liver disease where the cells not only home to the disease but also modulate it and eliminate the disease in some cases. We believe there’s an enormous opportunity to expand the benefit of Botensilimab by adding iNKT cells agenT-797 to this combination, and we will discuss this further at AACR.

Great. Thank you so much. And I have two quick follow-ups. The first one is about development timelines as they relate to graft versus host disease. Should we expect that this will be a partnered indication? And outside of the broader MiNK portfolio, could you comment on a recent clinical hold from one of your competitors on an autologous iNKT program and how you view the safety of allogeneic versus autologous iNKTs?

Thank you for your questions, Jack. Regarding the first one, we believe there is significant potential for GvHD, and we have supportive data that points to a promising pathway for patient benefit in both GvHD and engraftment success. We are exploring options to move this forward into the clinic without incurring additional costs to our balance sheet at this time, which may involve strategic collaborations and investigator-sponsored support. We will provide more details on this soon. Our program has been designed to facilitate a rapid approval process for the cells, and we expect to make announcements about it in the coming weeks. Concerning the connectivity you brought up, there was a patient who experienced a fatality during a clinical trial for neuroblastoma. This patient had metapneumovirus, which is unfortunately prevalent and can be deadly in pediatric patients who are lymphodepleted. In the trial with Fast Connect, they did lymphodeplete their patients, which we believe is not necessary for our method. We have shown that allo-iNKTs can be administered safely without causing neurotoxicity, CRS, or other severe side effects. Therefore, I am confident that the cells can be given and dosed safely without the need for lymphodepletion. We will also provide an update regarding the safety profile of the cells in this context. The issue with the patient appears related to lymphodepletion and subsequent viral infection, leading to a very unfortunate outcome. However, we do not feel this impacts the safety or tolerability of iNKT cells.

Our final question comes from the line of Matt Phipps from William Blair. Please proceed.

I was wondering about the FAP-CAR and the preclinical data presented at SITC, where some of the efficacy data was best combined with NY-ESO-1 T cells. How does that preclinical data influence your thoughts around combination development for this program? Do you plan on looking at any biomarkers for enrollment or an immune-excluded phenotype? How do you decide on patient populations for that program?

That's a great set of questions, Matt. For that program, we actually set it up using the NY-ESO-TCR to exemplify what a chronic antigen-stimulated environment would look like. We examined what happens when immune cells are continuously perturbed, and can these cells overcome that perturbation to reinvigorate CD8+ T cells towards potential cures? At our poster at SITC, we demonstrated that we could do that. The model was to help us better understand the mechanistic review of how these cells reverse exhaustion and carry CD8+ T cells into the stroma to invoke tumor cell killing. The design of that molecule gives us opportunities for potentially selecting patients based on biomarkers. We won't restrict that at the beginning, but we will measure it upfront. If minoring turns out to be another way to enhance clinical benefit, we can decide to restrict the population further based on expressing biomarker profiles. So, we will start broad and then assess whether we need to exclude or enrich for tumors.

Got it. Regarding the BCMA program, do you have evidence yet regarding treating multi-myeloma cell lines that have relapsed or grown out of previous BCMA therapy exposure? Moreover, why not pursue different targets like GPRC5D or maybe a dual targeting construct, considering how entrenched BCMA therapies are becoming?

BCMA therapies are certainly competitive, and we’re seeing remarkable progress with newer BCMA therapies that show high response rates. However, there are still ongoing issues with durability of response, even when patients continue to express the BCMA antigen. Parameters indicate that 2/3 of these patients experience progression on BCMA. We also observe challenges in access for those patients, and both of these issues are where our iNKT product can offer significant advantages. We've demonstrated scalability with our manufacturing capabilities, which could enable broader access to BCMA therapies. Moreover, we’ve armored our BCMA with IL-15 and presented data at SITC showing superior antitumor immunity in our IL-15-BCMA CAR-iNKT compared to what's commercially available now. This program is very exciting for us and we've prioritized it to select opportunities that we believe can create significant value sooner. The BCMA program is one we're committed to advancing due to the reasons I've outlined, and we’re considering strategic collaborations predominantly with groups seeking a generation of BCMA treatments that are more accessible and sustainable compared to what's currently available.

I would now like to turn the call over to Jenn Buell, CEO, for closing remarks.

Thank you very much, Operator. It was a pleasure to be with you all today, and I look forward to speaking with you at AACR. Thank you again. Bye-bye.

Thank you, ladies and gentlemen. This does conclude today's call. Thank you for your participation. You may now disconnect.