INKT - MiNK Therapeutics: In The Very Early Days Of A Big Hunt

2023-08-23 05:36:55 ET

Summary

• MiNK Therapeutics is developing "off the shelf" allogeneic cell therapies for cancer using iNKT cells.
• Their first iNKT cell therapy, agenT-797, showed a pro-inflammatory cytokine response and some efficacy in patients with solid tumors.
• The company is initiating a phase 2 trial for agenT-797 in second-line metastatic gastric cancer and exploring its potential in treating COVID-19.

Topline Summary

MiNK Therapeutics ( INKT ) is a member of a small crowd of companies attempting to develop "off the shelf" allogeneic cell therapies for cancer and a few other indications. They're hoping to leverage advances in cell engineering to push forward a more tolerable, easier-to-deliver cell therapy, but it's still very early days for the clinical program, and an investor buying in today is in for a very bumpy ride with no certainty of success and a short cash runway. I would hold off on anything but a small, speculative position at this time.

Pipeline Overview

The platform that INKT is attempting to advance is based on invariant natural killer T (iNKT) cells, a subgroup of T cells that share similar cell surface markers to natural killer cells, but that also express an invariant alpha-beta T cell receptor that recognizes glycolipid antigens and respond by producing a wide range of different regulatory cytokines.

If you would like a very deep dive into the biology of these iNKTs, you can find that here .

Overall, the thinking behind iNKT cells is to promote direct tumor cell killing like other NK cells can, but also to indirectly kill tumor cells by boosting the activity of other T cell populations through cytokine secretion.

The first such iNKT project that the INKT is developed is called agenT-797, an iNKT cell therapy that is expanded ex vivo (ie, outside of living creatures) and transplanted into patients. This is an emerging field of potential commercial products, as NK cells in general have been shown to be feasible, while mitigating risks of adverse outcomes like graft failure and graft-versus-host disease that are major concerns for classical allogeneic stem cell transplants.

In a poster presented at AACR 2023 , INKT gave escalating doses of agenT-797 to patients with various solid tumors. Out of 34 patients who received the therapy, 19 had a grade 3 or higher adverse event, although no deaths or discontinuations of therapy resulted from this toxicity.

Consistent with the rationale for using these iNKT cells, agenT-797 led to a pro-inflammatory cytokine response, with increases in gamma-interferon, TNF-alpha, and interleukin-2 levels. The only other efficacy note was a remarkable response in a patient with gastric cancer when agenT-797 was paired with anti-PD1 therapy. Nine other patients had disease stabilization with agenT-797, with or without anti-PD1 therapy.

A word on these efficacy findings: because the patients were heavily pretreated, I would not be particularly worried about the lack of responses observed at this stage. The study was not really set up to necessarily provide benefit to patients. What it did establish was that the iNKT could be successfully transplanted, with no apparent risk of severe adverse events, and with a signal of efficacy.

Another important factor that could be a differentiator against other cell therapies is that iNKT treatment was feasible without any lymphodepleting chemotherapy. Normally, cell transplants require the elimination of the patient's immune system in order to allow the new cells some room to grow without being destroyed. The iNKT cells were able to be transplanted and remained in the blood for around 8 weeks. Lymphodepletion carries risks of its own, most notably the risk of infection and long-term complications of such large doses of chemotherapy, so this is a very encouraging finding.

And indeed, that signal is being explored more in depth now. Most notably, a randomized, phase 2 trial in second-line metastatic gastric cancer is being initiated at the Memorial Sloan Kettering Cancer Center under Yelena Janjigian, an eminent figure in current esophagogastric cancer research. INKT disclosed that the trial will be externally funded , as well, hopefully helping to offset increases in their cash burn.

AgenT-797 was also assessed as a potential intervention in patients with COVID-19 that has led to acute respiratory distress syndrome. This is one of the life-threatening complications of COVID-19, and it's currently managed with high-dose steroids. A total of 20 patients received escalating doses of agenT-797, with, again, no deaths or discontinuations due to toxicity.

In a very preliminary assessment of efficacy, 3 of 4 patients who were on ECMO and received agen-T797 were alive at 90 days, compared with only 11 of 36 patients (30%) in a control set on ECMO alone. The median survival times were 119.5 and 47 days, respectively. Of course, these numbers are very small, and this wasn't a randomized trial, but this survival benefit would be quite remarkable if it is reproducible, as COVID remains very much with us.

INKT also has a number of preclinical engineered iNKT cells that are being explored in IND-enabling studies. Because at this time the company's prospects are going to rest on the findings for agenT-797, I won't focus on this at this time. Needless to say, they have interesting preclinical results that you can peruse on their website .

Financial Overview

At the end of Q2 2023, INKT held $10.6 million in cash and equivalents, with total current assets of $11 million. This was set against a total operating loss of $6.3 million. This leaves them needing to raise cash through some kind of financing vehicle soon, since the entire runway is set to be gone within 2 more quarters.

Strengths and Risks

At this stage, INKT presents a very interesting science project, with clear evidence that their cells can persist for several weeks once transplanted, without needing to take a patient's cells or undergo lymphodepletion to succeed in transplant. These are notable distinguishing features from approved cell therapies like CAR T-cell treatments.

However, what we don't have yet is a clear sign that the technique will actually improve outcomes for patients. This is not a critique of the company, of course; phase 1 studies are not intended to demonstrate clear efficacy. But the phase 2 gastric cancer study will be very much worthy of following once it kicks off in Q3.

Financial stability is also a major concern here. While the gastric cancer study is going to be funded through the Stand Up 2 Cancer initiative, operating costs remain high relative to the company's cash position. At the time of writing, INKT sits at a market cap of $57 million, which leaves them little room to raise significant funds through a single public offering. They would need to generate some kind of significant catalyst to move this needle, then immediately undergo a dilutive cash raise. And really the only news item I can foresee in 2023 is that announcement that the trial has formally begun.

It's an important step. It starts the clock to real, critical efficacy data. But will it move the needle that much? Sometimes, yes. Sometimes this spurs massive momentum for share price, but it's not something I usually want to count on as an investment vehicle.

There's also the potential announcement of further data characterizing agenT-797 in patients with lung cancer, and it's anyone's guess as to whether that will be a strong catalyst, as well.

Other options like a debt financing and partnerships are difficult to count on, as well. The current uncertainty with interest rates could mean that debt won't be attainable at a reasonable cost. And I am never one to count on big pharma partnerships, since they have so many things that can go wrong in the discussion phase. Moreover, the anti-PD-1 therapy being combined with agenT-797, botensilimab, is being developed by Agenus ( AGEN ), who themselves are trying to move into a commercial product for the first time.

It is worth noting that the company guidance is that they'll be pursuing government, pharmaceutical, and other non-dilutive cash infusions; however, we currently don't have the full picture of how they'll make this work. Unfortunately, for me, until it happens I have to remain skeptical that it will happen, because every clinical-stage biotech touts the "discussions" they're having with respect to partnerships, only to have most of them never materialize.

Bottom-Line Summary

INKT is a very interesting company, one well worthy of your attention. At this time, my sentiment is counter to the "buy" thesis. Formally, then, a sell, based on lack of cash and no clear signals of efficacy just yet. This is not a special indictment of INKT in particular, but companies at this stage of progress are more gamble than investment.

Anyone looking to jump in from here for the long term can expect their investment to be diluted considerably. Whether the share price appreciation is great enough to overcome that is the gamble, and not one I would be willing to recommend to most people at this time. But keep an eye on this company!

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