MSU Research Foundation Podcast
The MSU Research Foundation Podcast takes you behind the scenes of research and entrepreneurship within Michigan State University's ecosystem. Discover how ideas create impact, with stories from dedicated researchers, ambitious entrepreneurs, and the innovators shaping Michigan's future. From breakthrough discoveries to startup journeys, explore how the MSU Research Foundation helps fuel innovation and economic growth across the state.
MSU Research Foundation Podcast
Advancing Killer Cell Immunotherapy with Mark Frohlich
Season 1 Episode 7:
In this episode, we talk with Dr. Mark Frohlich, CEO of Indapta Therapeutics, a biotech company working to make cancer treatment safer, more effective, and more accessible. Indapta is developing natural killer (NK) cell therapies—an emerging form of immunotherapy that uses the body’s own immune system to fight disease.
Mark shares his path from clinical oncology to biotech leadership and explains why NK cells are generating excitement as a next-generation alternative to existing treatments like CAR-T. We discuss how Indapta’s work could help more patients benefit from cell therapy, what it takes to move from lab research to human trials, and how strong partnerships—including early support from Michigan State University—are fueling the company’s progress.
Host: David Washburn
Guest: Dr. Mark Frohlich, CEO of Indapta Therapeutics
Producers: Jenna McNamara and Doug Snitgen
Music: "Devil on Your Shoulder" by Will Harrison, licensed via Epidemic Sound
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Today's conversation was with Dr Mark Frohlich.
David Washburn:Mark is the Chief Executive Officer of Indapta Therapeutics. Indapta is a startup company that was launched in 2016. It's a biotech company focused on natural killer cell therapies to help treat cancer and other autoimmune diseases. It has roots in Michigan State University and one of its early founders was a former faculty member. So I think you'll enjoy this conversation with Mark. We'll hear about his background, a little bit more about the startup company and their technology, so I hope you enjoy it. Startup company and their technology so I hope you enjoy it. Hi there.
David Washburn:So today I'm talking with Chief Executive Officer of Indapta Therapeutics. So, Indapta was launched in 2016 and is a biotech company focused on developing natural killer cell therapies to treat cancer and autoimmune diseases. It also has Michigan State University roots. One of its founders, Dr. Sungjin Kim, is a former faculty member here at Michigan State University and, although Dr. Kim has left Michigan State a few years ago, we are connected from his time here. So, and in full disclosure, the MSU Research Foundation, through our captive venture funds, is an investor in Indapta Therapeutics and nothing in this conversation should be taken as investment or legal advice. So, Mark, welcome. Thank you appreciate the opportunity.
David Washburn:So you've been with the company for about three years and I wondered if you could at least start with a little more background on you and your journey and how you ended up at Indapta and what attracted you to the company?
Mark Frohlich:Yeah, absolutely. So I'm a medical oncologist by training and I've been doing cell therapy pretty much my whole career. So I left academia in the early 90s and kind of worked at a number of biotech companies: Excyte Therapies, Dendreon, Juno, Pac Pharma and then consulted for a dozen different companies after kind of leaving Juno, and so the focus of all those companies really been in some kind of form of cell therapy. And the reason I got really interested in cell therapy is that I was trained as an oncologist and the time I trained you know all the standard, you know therapies for cancer really, you know largely chemotherapy, radiation therapy, and you know clinical research at the time really kind of consisted of mixing and matching different chemotherapy agents, you know, with really limited success.
Mark Frohlich:And what really intrigued me when I was working on the lab and then also in, you know, in the clinical trial setting was kind of newer immunotherapy modalities and I was really struck by the promise of you know type of therapy that would really harness the patient's you know own immune system to target the cancer while not and not having that kind of toxicity that I typically saw for the patient. So that's what really got me excited and you know I had always, you know, aspired to, you know, pursuing a career in academic medicine. But then I began to realize that a lot of that kind of translation from scientific discovery, you know, to a therapy for patient really happens in biotech. And so that's when I made the transition there and it's been incredibly gratifying because, you know, the reason I chose oncology is I could see, you know, from my time in the lab, that our scientific understanding was increasing exponentially and I figured that within my career that was going to translate into improvements in patient care and that's really borne out.
Mark Frohlich:I mean, I think nowadays people take for granted that immunotherapy is part of the standard treatment paradigm for most cancers. And you know it wasn't so long ago, a decade ago, where that was not the case. And you know, at Dendron, when we were, you know, had the first, you know, immunotherapy approved by the FDA, you know that whole development process when we would talk to physicians and investors, it really people either fell in the believer, the non-believer camp, and now it's kind of taken for granted. So that's been incredibly gratifying, but, you know, obviously still a lot of work to be done and that's kind of why I'm still at this and passionate about, you know, developing additional cell therapies is that you know there's a lot of patients who still need to benefit more from immunotherapy, and so that's what we're really trying to do.
David Washburn:Well, and it's a great place for you to be if you, you know, you, you have the academic pedigree and, uh, you still get the opportunity to to collaborate with uh, with researchers there, but also, uh, you know, and the clinical side, with patients, and so you're, you're, you're, you're right in the middle to your point and uh, um, uh, it, it. It's really an exciting place to be and I agree a lot of that, a lot of that translational work is happening in these biotech companies. So I introduced Indapta to start off the conversation, but I'm sure I didn't do it the way you do it and I wondered if you could give the Indapta pitch. If you would, it's always great to hear it from the CEO because it's going to be perfect.
Mark Frohlich:So On the platform technology and how we're different?
Mark Frohlich:Yeah, yeah, yeah though, yeah, what really? So I spent most of my career kind of working on t-cells right, which is really always been thought the major workhorse for, you know, the immune system, for, you know, cancer infection etc. And at the time that I, you know, joined Indapta, there was increasing data to suggest that this new, you know, this additional subset of immune cells called natural killer cells really had potent ability to target cancer in a different way. And kind of what's unique about what we call innate immune cells or natural killer cells being one of those types, is that they have multiple different activating and repressive receptors on them that allow them to really distinguish between an abnormal cell and a normal cell. And so they, you know, people have taken natural killer cells grown from healthy donors what we call an allogeneic product or off the shelf product and administered them to patients and unlike the side effects that you'll see with the FDA approved CAR T- cell therapies that have been very effective in a number of cancers is, we don't see any of that cytokine release syndrome or neurologic toxicity. That has been, you know, a significant concern and sometimes life-threatening for patients and requires these therapies really to be administered in specialty centers where they know how to deal with that.
Mark Frohlich:So I really what I really saw was the promise of NK cells as really being to democratize access to these types of cell therapies, so with that kind of a safety profile that they might be able to be administered in a community oncology office as opposed to, you know, a tertiary equitinary care center where these others need to be administered. And the early data was really suggesting that would be done. And the company had generated some very promising preclinical data, you know, in the test tube and in mice, to suggest that this particular subset of cells that were discovered by Sungjin Kim at MSU, as you noted, you know, had the, you know were extremely potent and very differentiated from conventional natural killer cells. And so, you know, I was encouraged that what we were seeing preclinically could translate to benefit for patients, and that's what ultimately led me to joining Adapta.
David Washburn:So there's a sort of a I guess, a dosing question. So potentially it's sort of less dosing if I think I heard a little bit of that and then maybe the efficacy could be increased and ultimately it's sort of improving the cytotoxicity is sort of the ultimate promise of these?
Mark Frohlich:So I mean, I think you know well, obviously as we go through clinical development we'll get a sense of how effective these cells can be and how it compares to CAR-T. But I think because of this ability for it to be given in the, you know, community setting, I think it really provides an opportunity for many more patients to benefit from this type of therapy. And you know, ultimately potentially being positioned, you know, before these other therapies, because as long as you're not leaving anything on the table, if you can have your patient, you know, benefit from something that's very safe, then you can save in your arrows, in your quiver. You know things that maybe have more risk, maybe great benefit, but also risk. And you know, I think in general patients, physicians, always like to, you know, do the safer options first.
David Washburn:And the company now can you talk about, of partnerships or sort of the investor side or some of the clinical trials, to the extent that you can. Where are you on a number of those fronts?
Mark Frohlich:Yeah. So let me start with where we are in the clinic. So we're in the clinic now it's a very exciting time. We're in our first in human Phase 1. Now it's a very exciting time. We're in our first in human Phase 1 trial. We were putting ourselves into patients with lymphoma and multiple myeloma and we initially had a safety run- in per agreement with the FDA, where we did a single dose and then multiple doses and then we added interleukin-2 to help the cells be more active in vivo in the patient and we reported that at the Society for Immunotherapy of Cancer last November and we were very encouraged. Most of the patients responded.
Mark Frohlich:So for myeloma in particular, you look at this tumor marker, the M protein that you can measure in the blood, and most of the patients had dropped, some of them quite dramatic, more than 90%. And when you look at the prior experience with natural killer cells in multiple myeloma, there was some activity but it was very limited, much less than we were seeing, so small numbers. But it really encouraged us that this thesis that these cells were more active looked like it was bearing out. And now we're enrolling in the cohorts where we're adding monoclonal antibodies to help target the cells specifically to the cancer. So we use FDA-approved antibodies anti-CD30, antibodies for myeloma, anti-CD20 for lymphoma and we're just now beginning to treat patients there. So we're very excited that we can potentially get you know even deeper and more durable responses with that.
Mark Frohlich:So that's one is. We're in the clinic, if we have time, happy to tell you about it. Our cells also have a very differentiated approach for treating autoimmune disease, for actually specifically deleting these autoreactive T and B cells that lead to autoimmune disease, and there's increasing evidence in the literature that this is the case. And so we've embarked and have an IND cleared in multiple sclerosis and autoimmune disease to test our cells there. And finally we haven't announced it yet but we've gotten some funding from the Focus Fund, which is an investment group affiliated with MD Anderson, to do a treatment in acute myelogenous leukemia, aml, in combination with an eight immune engager. So we basically have three different programs. We're very excited about the data we'll be reading out in part later this year, and we also announced at the latter part of last year that we have a collaboration agreement with Sanofi, the French pharmaceutical company.
Mark Frohlich:They were encouraged by the myeloma data that I just described.
Mark Frohlich:They have an FDA-approved antibody Sarcleza approved for myeloma, that is, you know, getting increasing label indications, and they wanted to work together with us to test the combination of our cells plus the antibody. So that's very exciting. They're providing both drug and some financial support for that trial. And then, finally, to get your question about investors obviously we can't do any of this without, you know, significant financial resources to do the process development, to do the manufacturing and to execute the clinical trials. And so when I joined in January of 2022, we announced a Series A investment of $60 million very good investors RE Capital, Leaps by Bayer, Pontifex, Vertex Ventures, the Myeloma Investment Fund, and MSU's research group research investment team I'm sorry also and persistent in that which we're very appreciative of. And so that really gave us the runway to really get into the clinic, figure out the manufacturing. And we just announced at the end of last year that we did what we call a series A extension, where we raised another $22.5 million to give us a runway to really get to those data readouts that I just mentioned.
David Washburn:Fantastic progress. And the lymphoma and myeloma is that related to the FDA fast-track news that you all published earlier?
Mark Frohlich:Yeah, so we had applied for, and were granted, fast-track designation for our program, our cancer program, and that's, I think, was nice recognition by the FDA that this was fulfilling an unmet need. And what that provides for is basically more frequent and more accelerated interactions with the FDA so that you know we can move this through the development process and ultimately to approval more quickly with that designation.
David Washburn:Well, so many great opportunities on those three, those three fronts. How many um individuals are in the company today?
Mark Frohlich:You know, uh, it's interesting. Uh, we, we have made a conscious decision to, to, to take a very streamlined approach, uh, to how we build out the company. Uh, I've had, um, you know, you know, the opportunity- slash- misfortune to be part of companies that had a had to downsize significantly, and that's always, you know, painful and it often, you know, means that you're burning through your cash more quickly than you might otherwise. So we are currently about a dozen full time employees. We're supplemented by a number of, you know, highly experienced individuals as consultants who really function very much integrated with our team. You know, I think if you sat on teams you wouldn't know who is and is not a consultant. But that just gives us a lot of flexibility. So, if we have any delays for any reason, we're not burning through cash as quickly and, you know, I think that's a positive thing for investors to know that we can execute, get an incredible amount accomplished with a very lean, lean team.
David Washburn:Great and is most of the work on the West Coast, or are you spread all over the country?
Mark Frohlich:You know we're pretty virtual, so our physical space is located in Houston, Texas, where our research lab is, and we do, you know, screening of donors, some early process development work, and then, you know so folks who need to be involved in that are physically located there. And then most other folks are spread mostly throughout the West Coast, some in Seattle, some in the Bay Area, some in Southern California.
David Washburn:If I'm not mistaken, I think there may be an IP license from MSU and to the company, and that's correct. Yes, I was curious if there, if there's other IP from other universities that are in there, is it mostly sort of...?
Mark Frohlich:So the foundational IP was the IP developed by Sungjin Kim and licensed from MSU. And then you know, we have been steadily building out and complementing that with additional IP, particularly around things like how we manufacture and selectively expand these cells, what the particular uses are in the clinic and what diseases and what types of combinations. So we filed and have some additional granted IP both in the US and ex-US know ensure our competitive position with these very unique subset of cells.
David Washburn:Yeah, fantastic. The other thing I read about were these sort of immune checkpoint inhibitors. I guess those sort of along the sort of CAR-T cells are sort of kind of be can be looked at as sort of incumbent or I don't know, competitive technologies. Are they, are those sort of technologies a would you, would you call those, and CAR-T sort of the alternative methods that you all are sort of...?
Mark Frohlich:Interesting. I, you know, I think these different products all have their uses and applications and I think as we gain more experience we'll figure out the right setting where to use these different drugs. Yeah, I would say that one of the things we're quite interested in is, you know, is how these different types of therapies may complement each other and may in fact be sequenced. Therapies may complement each other and may in fact be sequenced. So, you know, for example, we think that, you know, ultimately, to get to the best outcome for patients, it will be really advantageous to harness not just the innate immune system so our natural killer cells are part of the innate, kind of naturally sensing and able to kill abnormal cells with the adaptive immune system, which is, you know, really referring to T cells that have specific receptors that recognize specific pieces of proteins or peptides. And the elegance of the adaptive immune system is that it has this feature called long-lived memory and has proven efficacy with, you know, things like CAR-T or checkpoint inhibitors that harness them.
Mark Frohlich:And we think that there's a real opportunity to kind of synergize these two therapies. So, for example, we have emerging data from our trials, that these, and from other trials from other folks doing NK cell therapy, that NK cells can really remodel a tumor microenvironment, that they secrete cytokines, that they can draw T cells in, that they can present some of these antigens to T cells, and so we're very excited about the possibility of kind of using our cells and then following that with something that augments a T cell response, whether that be a cytokine, whether that be a T cell engager or a checkpoint inhibitor. And we're actively discussing with companies that have those reagents about potentially collaborating on those types of things.
David Washburn:My guest today has been Dr. Mark Frohlich. He is the CEO of Indapta Therapeutics, and Indapta is working to improve the cytotoxicity of antibiotic therapies, enabling healthcare providers to treat patients suffering from cancer and other diseases. Mark, thank you very much for being here today.
Mark Frohlich:Great pleasure. Thanks so much, Dave.
