Mark Frohlich: A ‘Natural’ Leader

Mark Frohlich, MD, CEO, Indapta Therapeutics

When asked why they got into the life sciences industry, it’s common for most professionals to say that they wanted to help people. For Mark Frohlich, MD, he takes that answer a step further. He began his career in medicine, working with patients and conducting clinical trials. However, he eventually realized that he wanted to work in a position that allowed him to help people on a much larger scale.

Today, as CEO of Indapta Therapeutics, he says he’s doing just that. When asked about his company’s achievements, he tells Pharm Exec, “we’ve identified a very potent immune cell. It’s a subset of what’s called natural killer (NK) cells, that arise in people who’ve been exposed to a very common virus called cytomegalovirus. The immune response to the virus generates these biologically programmed cells that are highly potent. These cells are particularly effective at killing abnormal cells when they’re combined with an antibody, but they also have important non-antibody dependent mechanisms.”

Indapta is a biotechnology company that is focused on developing immunotherapies for cancer and autoimmune disease. This work involves the administration of large numbers of NK cells, although Frohlich says that Indapta takes a unique approach to this.

“There are a dozen or so companies that are developing natural killer cells. NK cells can be produced from a variety of sources,” Frohlich explains. “Some companies manufacture them from induced pluripotent stem cells, cord blood, cell lines, or peripheral blood. We derive ours from the peripheral blood, but from a unique subset that we call G-minus NK cells that have very differentiated properties. We have shown this in the laboratory and the early clinical data are consistent with the best-in-class properties of these cells.”

According to Frohlich, Indapta is developing an “allogeneic” product that uses cells from healthy donors as the starting material for the manufacturing process. They then preferentially expand the G-minus NK cells using feeder cells and growth factors. Since the product is made from healthy donors, even patients who don’t have a healthy immune system can be treated. Because many cells can be produced from a single donor, a large number of patients can be treated at a fraction of the cost of currently approved “autologous” cell therapies that are manufactured from cells collected from the patient to be treated, says Frohlich.

“Our cells can be given immediately as soon as the physician feels it’s appropriate for the patient,” he explains. “One of the other really important features of these natural killer cells is that they have been very well tolerated to date. You don’t have any of the cytokine release syndrome or neurologic toxicity that has been seen with currently approved autologous CAR T-cell therapies. And there also is no risk of graft-versus-host disease that you might see from an allogeneic off-the-shelf T-cell product.”

Indapta’s cells, according to the company, have been well tolerated to date, especially compared to similar treatments. Frohlich explains that Indapta has used these cells to treat about a dozen patients in the clinic, and so far, the main adverse reactions that they’ve noted are ones that are associated with the conditioning chemotherapy given prior to the delivery of the cells or the low-dose interleukin-2 administered to support the cells in vivo. These adverse reactions have included lower blood counts and low-grade fevers.

Frohlich tells Pharm Exec that he spent most of his career focused on T-cells, which he says were historically thought to be the most important cells of the immune system for fighting cancer.

“I became very intrigued by natural killer cells, which I saw as having the potential to overcome some of the challenges of autologous CAR T-cells, which currently are really only given in specialty medical centers where they have the experience to deal with the potential life-threatening toxicities,” he says. “I was encouraged that natural killer cells could really democratize access to cell therapy because they can be administered in the community oncology clinic, given the favorable safety profile. I was also very encouraged by the emerging efficacy data being generated by other companies and became convinced that NK cells will become part of the FDA-approved armamentarium of therapies.”

The shift to CEO

Indapta is Frohlich’s first experience as a CEO. Named to the post in February 2022, he says that, so far, it’s been a very gratifying experience. One of the aspects that Frohlich enjoys the most is having to deal with both clinical science and business aspects and figuring out ways to integrate those areas together. During his time as CEO, Indapta has seen a string of successes, including getting its investigational new drug (IND) application cleared; reporting encouraging early clinical data in cancer; obtaining fast-track designation from the FDA; securing a second IND cleared in autoimmune disease; establishing a collaboration with Sanofi in multiple myeloma in December 2024; and raising additional funds to support its development programs.

“I’m very pleased with the progress we’ve been able to make,” says Frohlich. “Our immediate goals are to demonstrate clinical proof of concept in our cancer trial, which is currently enrolling patients with multiple myeloma and lymphoma. We have some very encouraging early data from the safety run-in portion of the trial, where we were testing, first, a single dose, then multiple doses, but without the addition of a targeting antibody. We weren’t really expecting to see a lot of clinical activity, but in the patients who received cells plus interleukin-2, four out of five multiple myeloma patients had an objective response, which is much better than has been seen historically with natural killer cells.”

Of course, CEOs don’t typically just talk about what their organizations have already done. They need to have a plan for the future. This is especially true in the pharma and biotech sectors, where the timeline for getting products to market is longer and more complex than other industries.

“We’ve raised some additional funding and look forward to treating more patients and getting additional follow-up to get to clinical proof of concept,” Frohlich tells Pharm Exec. “The second major objective is to demonstrate biological proof of concept in our trial in multiple sclerosis. There are a number of different mechanisms that we think our cells bring to bear on the treatment of autoimmune disease, and we aim to demonstrate that in our Phase I clinical trial, where we’re doing very intensive biomarker analysis.”

Fortunately for Frohlich, this isn’t his first experience in the C-suite. While Indapta marks the first time he’s been responsible for functions such as business development and financing, his past experience did expose him to those aspects of the industry. According to Frohlich, the real challenge in moving up the leadership ladder is becoming responsible for decisions in areas where one isn’t already a subject matter expert.

“For me, the areas where I am most comfortable are clinical trial design, regulatory interactions, and reviewing clinical and scientific data,” says Frohlich, who has roots as a medical oncologist following earning an MD at Harvard Medical School. “But this is the first time I have been directly responsible for raising money to support the business or structuring business relationships with other companies. It’s been a steep learning curve for me on some of those aspects, but we’ve pulled in excellent consultants to help in those areas. The board has also been a great resource for me, especially on the financing side. It’s been fun to live or die by our decisions, and so far, I’ve been pleased that we’ve been able to make good decisions and execute on them.”

Making leadership personal

Part of being a leader is being able to provide feedback to the people working for you. For Frohlich, he says this was something he struggled with earlier in his career. He says he often worried about how his feedback would be received.

In the years since, however, that’s something he’s been able to get better at, Frohlich says, adding that he considers his ability to work with employees and build them up as one of his strengths today.

“I would say that my leadership style is one where I really embrace the personal and career development of the people that report to me,” he explains. “I try to give very honest, real-time feedback with a goal for this person to become the best that they can possibly be. If you frame it that way, it gets a lot easier to give feedback. The change has been liberating for me as a manager and hopefully empowering for the people that report to me.”

Mark Frohlich, MD: At a Glance

(Click to enlarge)

As is often the case, Frohlich says that he initially expected to work in academic medicine, seeing patients and doing research. However, he eventually felt that he might be able to do more good for a greater number of people working in biotech. Those early experiences shaped the way he approaches his current business strategy.

“Early in my career, I was spending most of my time in the laboratory doing experiments, and one day a week in the clinic seeing patients and conducting clinical trials,” he reflects. “I really enjoyed understanding the biology and working on translating it into therapies for patients. I began to appreciate that this translation primarily happens in biotechnology companies more so than in academia. When I had an opportunity to join a small company working on immune therapy, I made the transition to industry.”

While in medical school, Frohlich participated in a very research-oriented program. At the time, his plan had been to apply his BS degree in engineering from Yale to medicine. However, he says he ended up working in a cancer lab and became fascinated by the biology of cancer. That interest extended into his clinical training and oncology fellowship program at University of California, San Francisco.

“It was really that cross-talk between gaining scientific insights in the lab and treating patients on clinical trials that ultimately made me decide that that’s what I wanted to focus my career on,” he says. “I was passionate about taking scientific insights and translating those into new and better therapies for cancer patients. At the time I trained, clinical research in oncology consisted of mixing and matching toxic chemotherapies with the hope that we could extend a patient’s life by a month or two and calling it success.”

After changing course, Frohlich, as chief medical officer with the biotech Dendreon, saw early success with prostate cancer drug Provenge, the first therapeutic cancer vaccine to receive approval from the FDA. According to Frohlich, Provenge launched a new era of immunotherapy. While younger clinicians today may take it for granted that immunotherapy is now part of standard care in cancer treatment, Frohlich was proud to be involved at the beginning of the change.

“When I was working in the lab, one of the things I appreciated was that our scientific understanding was exponentially increasing,” he says. “I realized that it could be an incredibly exciting career to help translate these new scientific developments into therapies for patients.”

For Frohlich, such opportunities to advance therapies that could impact hundreds or thousands of patients has been the guiding light of his career and his road to CEO.

Mike Hollan is Pharm Exec’s Assistant Managing Editor. He can be reached at mhollan@mjhlifesciences.com.