Earnings Call Transcript - INKT Q1 2023

Operator, Operator

Ladies and gentlemen, thank you for standing by. Welcome to the MiNK Therapeutics’ First Quarter 2023 Financial Results Call. I would now like to turn the call over to Zack Armen, Head of Investor Relations. Please go ahead.

Zack Armen, Head of Investor Relations

Thank you, operator, 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; Dr. Marc Van Dijk, Chief Scientific Officer; Dr. Joy Zhou, Head of Manufacturing; and Christine Klaskin, Principal Financial and Accounting Officer. Now I’d like to turn the call over to Dr. Buell to highlight our progress from the quarter.

Jennifer Buell, CEO

Thank you very much, Zack. Good morning, and thank you for joining our first quarter 2023 earnings call. We’re very happy to be here with you and to present on an exciting first quarter, which culminated in a significant presentation at the American Association of Cancer Research Conference or the AACR conference just a couple of weeks ago. Dr. Benny Carneiro, a medical oncologist and associate professor at Brown University Oncology presented data on our Phase I study. He reported the first pivotal clinical benefit of an allogeneic or off-the-shelf iNKT therapy in patients with solid tumor cancers. Dr. Carneiro specifically highlighted clinical responses and biomarker responses in patients who have failed all available therapies, including anti-PD-1 therapy. We observed these responses in patients with metastatic gastric cancer, non-small cell lung cancer, testicular cancer, and long-term disease stabilization in a number of other solid tumor cancers. These data underscore what we believe to be the most flexible and impactful cell therapy in development. MiNK remains at the forefront of this technology advancing iNKTs in the clinic as we’re making progress not only in the clinic but also in our manufacturing suites. Furthermore, we’re advancing a very robust pipeline of novel therapies that Dr. Marc Van Dijk will share with you shortly. So first, I’m going to highlight the clinical data in a bit more detail. At AACR, we reported that our lead product, which is agenT-797, an allogeneic off-the-shelf product of native non-engineered invariant natural killer T cells, really benefits 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 1 billion cells dosed and promoted clinical benefit in a range of heavily pretreated solid tumor cancers. In particular, we saw encouraging activity in a patient with metastatic gastric cancer who had no prior response to anti-PD-1 therapy, despite receiving four cycles of pembrolizumab. After failing on pembrolizumab, the patient received nivolumab in combination with standard of care chemotherapy, again with no response. Following treatment with a single dose of agenT-797 in combination with nivolumab, the patient achieved a partial response with a 42% reduction in tumor burden, which continues now beyond nine months. We also observed benefits in other solid tumors, including durable disease stabilization and biomarker responses in patients with non-small cell lung cancer, testicular cancer, appendiceal cancer, and other solid tumors. The safety profile of 797 was found to be tolerable up to 1 million cells, with no evidence of neurotoxicity. No dose-limiting toxicities were observed, and no severe cytokine release syndrome greater than Grade 3 was reported in the trial. Importantly, we gained insights into the persistence, homing, and immune-modulating activity of iNKT cells in patients. We found that while iNKT cells rapidly leave the periphery and home to tissues, they remain persistent and detectable in the periphery for about eight weeks. This demonstration shows that these cells can be viable and persistent without having lymphodepletion. We also reported important translational findings that highlight iNKT’s ability to generate and drive immune cells into the tumor for destruction of cancer cells. Marc is going to tell you more about these data in just a moment. Overall, I would like to 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 immune therapies. They support the expansion of our solid tumor program into PD-1 refractory non-small cell lung cancer, as well as gastric cancer. Our trial on gastric cancer is being led by a world leader, Dr. Yelena Janjigian, Chief of Gastrointestinal Oncology at Memorial Sloan Kettering Cancer Center. The trial will advance through non-dilutive grant-funded programs targeted to start in just a few weeks, enrolling about 40 patients across nine centers who will be treated under Memorial Sloan Kettering’s umbrella with cell therapy in combination with standard of care chemotherapy as well as a very exciting multifunctional anti-CTLA-4 antibody, which is advancing in late-phase trials. Botensilimab is a lead program from our parent company, Agenus. As a refresher, we have previously published preclinical models and data demonstrating the potent synergy between iNKT, anti-PD-1, and now Agenus’ botensilimab. We presented those data previously at AACR, showing that in preclinical models of metastatic lung disease, the combination of iNKT cells, PD-1, and botensilimab resulted in near complete tumor elimination. Our clinical data and observed safety profile with 797 in solid tumors support the next phase of development with this program. We expect to provide additional data updates and more detail on our clinical programs in the second half of this year. I will now turn the call over to Dr. Marc Van Dijk, our Chief Scientific Officer.

Marc Van Dijk, Chief Scientific Officer

Thank you, Jen. We’re quite excited about the observations at the AACR of clinical benefit in patients with heavily pretreated metastatic cancers. These patients inspire our work as we leverage our iNKT platform to expand the clinical benefit observed with the two therapies and develop innovations to address areas where current therapies actually fall short. Our technologies, which you will hear more about at our annual shareholder meeting, include the ability to generate armored-CAR-iNKTs, develop iNKT engagers, cell engagers, and advance novel TCR therapies. In addition to our native clinical-stage agenT-797 program, our most advanced preclinical programs include armored-allogeneic FAP-CAR-iNKT and a next-generation armored-BCMA-iNKT. Our lead program, agenT-797, is designed to expand clinical benefit observed with approved therapies. The data at AACR is the first glimpse of the possibility of these cells to deliver those 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. We’ve previously shown that agenT-797 can improve the anti-tumor activity of immune cells present in the tumor microenvironment. Specifically, we’ve shown that iNKT cells can activate dendritic cells, preferentially kill M2 macrophages, and restore the killing capacity of exhausted T cells. In 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 indicative of tumor iNKT activation, which is paramount to tumor destruction. Importantly, iNKT cells are naturally tissue homing, and in preclinical data previously presented, we’ve demonstrated that iNKTs can be administered without lymphodepletion. They rapidly traffic out of circulation within days of administration into tissues, including bone marrow, liver, and lung, where they remain for some cases exceeding 35 days. In our clinical trials, we reported a similar pattern of rapid translocation out of circulation while remaining detectable and persisting for approximately eight weeks. In patients with durable response beyond nine months, we also showed that iNKTs drive clonal T-cell expansion in cancers with high neoantigen burden, triggering the expansion of these cancer-fighting T cells. While we plan to report more detailed information about iNKT in the tumor microenvironment at a later update this year, currently, our data demonstrate the mechanisms of iNKT cells to enable T cells and NK cells to traffic into tumors, reinvigorate partially exhausted CD8 T cells, and improve their functions within the tumor microenvironment, exemplified by the 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 FAP-CAR-iNKT MiNK-215. Cancer-associated fibroblasts, which are targeted with this therapy, are key 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 tissues such as the lungs. In preclinical models, we reported very exciting data showing the potential of MiNK-215, demonstrating 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 very excited about, and Dr. Shannon Boi, 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.

Jennifer Buell, CEO

Thank you, Marc. I grow more enthusiastic about the data that we’re advancing, the technology, and the science behind these very powerful cells. In conclusion, I’m really happy to share with you the progress we’ve made in advancing this platform. As Marc just mentioned, we are not only addressing and expanding the benefit from available therapies for patients today, but also considering what they will need tomorrow. This process, of course, is made possible by the incredible advancements of Dr. Joy Zhou and her team in our CMC group. Her current manufacturing process is designed to generate over 5,000 doses per year. We are currently building and expect to have a fully donor-independent process over the course of this next year. This development will come without the capital-intensive efforts associated with most cell therapy entities. Joy is with us today to answer any questions, and we will also be showcasing a deep dive into our manufacturing process, technologies, and advancements at our annual meeting this year. Very importantly, what has contributed to our high efficiency is our small team, which we’ve intentionally kept that way. We’ve made tremendous progress since launching the company as an IPO in October of 2021, advancing three clinical programs very efficiently, and now identifying tumor types that may allow us to develop agenT-797 on a rapid path to expand benefits to patients. This specific set of solid tumor cancers positions us very well for future developments. We’re doing this with a team of only 35 people, and as Christine will share with you, we’ve managed our expenses very efficiently, looking forward to supporting the initiatives I shared with you throughout the year and into next year. Christine?

Christine Klaskin, Principal Financial and Accounting Officer

Thank you, Jen. We ended the first quarter of 2023 with a cash balance of $14.9 million 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. The net loss for the quarter ended March 31 was $5.7 million or $0.17 per share compared to a net loss for the first quarter of 2022 of $7.8 million or $0.23 per share. Thank you. We’ll now turn the call back to the operator for questions.

Operator, Operator

The floor is now open for your questions. Our first question comes from Emily Bodnar from H.C. Wainwright. Your line is open.

Emily Bodnar, Analyst

Hi. Good morning and thanks for taking the question. Is there anything you can share about details for the non-small cell lung 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 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.

Jennifer Buell, CEO

Thank you very much. To your first question on small cell lung cancer and testicular cancer indications in which we have observed specific benefits, we are advancing our Phase 1 into Phase 1b, and we’re able to better enrich for the more prevalent tumor, non-small cell lung cancer, in patients who are refractory. There’s really nothing toward those patients, resulting in very low response rates. We believe that when patients fail on anti-PD-1 therapy, they may benefit from iNKTs. Adding iNKTs to the available standard of care allows us to take a monotherapy approach to development. We see a path for iNKTs alone, as we have seen benefit, which is reflected in the data presented at AACR. We see more robust activity and a clear path for rapid registration when we can add to available therapy, reinvigorating a patient’s immune system to respond to what’s currently available. We will be doing multiple doses in our study. While the cells persist for about eight weeks, we plan to dose consistently with some commonly used therapies at weeks six or eight, which will take advantage of the pharmacology seen while making the treatment burden lighter for our patients. Regarding testicular cancer, that study will continue to interrogate signals with that indication, as it is a bit rarer. We currently enrolling more patients to deepen our understanding of the biology of those who fail prior therapies. That is an area we want to continue to explore.

Emily Bodnar, Analyst

Yes. Thank you.

Operator, Operator

Our next question comes from the line of Jack Allen from Baird. Your line is open.

Jack Allen, Analyst

Great. Thank you so much for taking questions and congratulations to the team on the progress made throughout the quarter. I wanted to ask on the updates on 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 diseases, I guess, response programs. I’d love to hear any updates there. Thank you so much.

Jennifer Buell, CEO

Thank you so much, Jack, for your question. I am incredibly excited about the upcoming data presentation at the pulmonary conference, the largest of its kind with about 30,000 participants, which will take place in Washington, D.C. this year. Our presentation, slated for Sunday, the 21st, will be delivered by Dr. Terese Hammond, the lead investigator in our Phase 1 trial, a pioneer in delivering cell therapy to patients with infectious diseases. We’ve made key observations with these cells, being able to administer them in emergency settings when patients needed them, confirming that they are logistically feasible. They can be cryopreserved and easily administered within the standard practice in an emergency room or ICU setting. In our cohort, we saw survival rates of over 70% alive after a single administration of 797 for elderly patients on mechanical ventilation, while in-hospital controls had survival rates of less than 22%. We also showed that we could tolerate the administration of these cells up to 1 billion cells in severely sick populations requiring ECMO procedures. You will see a deep dive into that data set at the ATS conference, along with exceptional case presentations showing remarkable benefits for patients who had cleared COVID but had secondary infections resistant to all available antibiotic therapy with the cells promoting exciting data. Additionally, we are actively negotiating non-dilutive government-sponsored sources for clinical trials to rapidly expand the potential benefit of these cells in patients with acute respiratory distress syndrome secondary to viruses, beyond just COVID-19. Those discussions are ongoing, and we will make public announcements about collaborations in the near term.

Jack Allen, Analyst

Great. Thank you so much for that comprehensive answer. And then just one brief follow-up on the CAR-iNKTs and very much looking forward to that presentation at the upcoming ASGCT meeting. I’d love to hear a little bit more about your development strategy as it relates to the CAR-iNKTs. Are these assets that you look to bring forward on your own? Or would you look to partner these assets? I’d love to hear how you’re thinking about that.

Jennifer Buell, CEO

Jack, thank you. I want to make one final comment about the cells and ATS, and then I’m going to address the CAR-iNKTs. We will report important translational data showing what these cells can do biologically. In cancer, they can help to generate a pro-inflammatory phenotype, while in infections, particularly in acute ARDS, the cells induce an anti-inflammatory phenotype. This showcases how they can modulate immunity based on the disease setting, making them a remarkable candidate and underscoring the next steps in our platform. As for the FAP-CAR-iNKT and partnering, partnering is critical to our strategy. We, Marc and I, have worked together with the Agenus Group and gained access to innovative discovery research, financing the business in parallel. With nearly $1 billion in partnerships, we’ve continued to finance our innovative pipeline at Agenus. At MiNK, Marc and his research team have maintained this pace of discovery and innovation. Our ability to get the science into the hands of as many patients as possible necessitates partnering, which includes local, national U.S.-based pharma partners looking to expand their capabilities but also regional partners where we don’t have adequate infrastructure. You will hear more about that soon and our strategy for accessing and advancing FAP-CAR-iNKT very quickly. For now, we are well positioned to advance FAP-CAR-iNKT through IND enabling and into the clinic as a high priority for our company.

Jack Allen, Analyst

Great. Thank you so much.

Operator, Operator

Our next question comes from the line of Matthew Phipps from William Blair. Your line is open.

Matthew Phipps, Analyst

Thanks for taking my question. Jen, I’m wondering if you guys think – what could be special about that gastric cancer patient that had such a strong response. 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?

Jennifer Buell, CEO

That’s a great question. I’ll turn it over to Marc after a couple of points. There are a few observations we made, including tumor microenvironment modulation that I’ll have Marc further expand on. An important part of that modulation included increased TCR clonality and diversity. Some of the drivers of that are still under investigation. We observed that MSI-high tumors are responsive to PD-1 for a while and then not. In this case, we saw absolutely no response on pembrolizumab, neither on nivo combo, until we added the cells. Several features we presented could help us better understand the disease-modifying benefit in this specific dataset. To the extent that it is translatable across MSI tumors, we are actively exploring that in our clinical trial with Dr. Janjigian.

Marc Van Dijk, Chief Scientific Officer

Yes. Thanks, Jen. It’s an interesting question. We’ve been scrutinizing this deeply. In tumors with T cell infiltrates or high tumor mutational burden, there is a T cell response. However, after two rounds of PD-1-directed therapy, this patient still faced tumor progression without response. Following iNKT infusion, the T cells unlocked and began attacking the tumor cells. In preclinical models, iNKT cells are more resistant to several immune-suppressive mechanisms that tumors employ to inhibit T cells. We have shown in our FAP-CAR model and the 797 preclinical models that these immune-suppressive mechanisms get countered by iNKT cells, creating a pro-inflammatory non-immune suppressive environment, allowing T cells to infiltrate and reinvigorate. Our recent findings suggest multiple pathways contribute to T cell activation in gastric cancer patients, supported by evidence from our preclinical models.

Operator, Operator

Our next question comes from the line of Kalpit Patel from B. Riley Securities. Your line is open.

Unidentified Analyst, Analyst

Good morning. This is Andy on for Kalpit. Thank you for taking our questions. Starting off, what should we anticipate next from agenT-797 in solid tumors? Is there any dose escalation work still remaining?

Jennifer Buell, CEO

Andy, thank you. We will continue to interrogate dose frequency and optimization. I should say that I feel confident about the dose selected, but it will be important to strengthen our data package for future regulatory interactions by further exploring dose and frequency. The next phase will be multiple doses, initiating immediately.

Unidentified Analyst, Analyst

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 for when we should anticipate these programs to enter the clinic?

Jennifer Buell, CEO

Sure. On 413, there is a critical need for an accessible, affordable product targeting BCMA to expand its durability and eliminate the continued antigenic profile. Autologous products are effective, but with low durability. I believe there is a major opportunity to advance an allogeneic off-the-shelf armored-BCMA showing superior qualities as next-generation therapy for patients. However, we prioritize MiNK and FAP due to the competitive landscape. We've continued to advance our BCMA program while leveraging external non-dilutive capabilities to move it forward competitively. The iNKT profile is compelling, the need is great, and we believe we can bring benefit to many solid tumor cancers. We plan to file an IND in 2024, entering the clinic quickly with rapid paths from IND to first-in-human trials in mid to late 2024.

Operator, Operator

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