Ever wondered about the people who are leading the fight against cancer, developing groundbreaking treatments, and changing lives? Meet Frank Boriello, the mind behind SUPLEXA cell therapy, and the CEO and founder of Alloplex Biotherapeutics. In our conversation, Frank his personal backstory that sparked his quest to revolutionize cancer treatment and frames the scientific journey that led to SUPLEXA. 

Richard McCormick: [00:00:00] Hi, I’m Rich McCormick, Executive Vice President of Clinical Strategy here at Vial. Today, I have the pleasure of welcoming Frank Borriello, CEO and Founder of Alloplex Biotherapeutics, to our First In Human podcast. Hi, Frank, would you mind telling us a little bit about yourself?

Frank Borriello: My name is Frank Borriello. I’m trained as an MD, PhD. I’ve been in this profession for over 30 years. Originally born in Italy, grew up in Brooklyn, New York. Now, I live in the Boston area.

Richard McCormick: It’s a pleasure to have you on today. Can you share the inspiration behind founding Alloplex and developing SUPLEXA cell therapy?

Frank Borriello: The inspiration came from a personal loss. I was a business development professional in a pharmaceutical company up until 2015 when my brother died at the early age of 56 from colorectal cancer. At about the same time, the company I was working for was purchased by a larger rival. The senior management team, including myself, was given the opportunity to stay on or to go away with a package. I opted for the latter.

The reason I did is because there had been an idea gelling in my mind for a while, but I never really had the opportunity to work on it. I thought it was a chance to get back to my first passion, immunology, to see if I couldn’t do something more relevant to what I thought was important, which is treating patients. 

The first order of business was to go to the library and flesh out the idea. It was only after I confirmed that no one else was working on it did I roll up my sleeves and actually do some experiments in the lab again to see if it would work. Almost immediately, the lab experiments showed the approach was not only feasible, but readily executed. That was seven years ago. Things have been going so fast ever since. I’ve never really looked back

Richard McCormick: Balancing roles as a scientific founder and CEO can be challenging for some. It sounds like you have a great balance of both. How do you manage guiding the scientific direction of the company while overseeing the business development side as well?

Frank Borriello: I never thought about it that way when I started. In a small company, you don’t have structure and layers of management you find in a large organization. This can be both good or bad, depending on how you look at it. On the bad side, is the pressure that comes from having to juggle many tasks and always feeling like you’re behind. On the positive side, however, there are no layers of management to slow things down and absolutely zero politics.

It’s you against Mother Nature and who will win. Well, we know who will win. We just hope she agrees with our idea. It helped, of course, to have had experience, as an immunologist, a medical doctor. I also had experience in the financial industry, and running clinical trials. So it seemed this job brought to bear every skill set I had accrued through 30 years of working.

Richard McCormick: Meant to be. So, digging into the science a little bit, can you explain the significance of ENLIST training cell lines in SUPLEXA therapy? How did you identify the need for simultaneous activation of multiple immune pathways to achieve such a strong anti-tumor response?

Frank Borriello: The ENLIST cells are central to our technology and they contain what we call the secret sauce. Since, ENLIST cells can be made in many different varieties and you have to get the variety that gives you the results you want. It may sound simple-minded, but it originally started with the realization that the immune system is complicated. It takes many components talking to one another to get it to work correctly. Yet, despite that common perspective, the drug industry still involves developing drugs that affect one pathway or one cell at a time. Everybody is still looking for that magic bullet.

The advent of cellular therapy as a field offered a different starting point from which to launch a program. I realized if multiple signals were required to impact immune cells to do what you wanted them to do. We would have to have a platform by which those signals can be provided all at the same time. It turns out the one [00:05:00] solution we came up with was to use another cell, the ENLIST cell, which has the ability to express many immune modulating proteins at the surface. We can engineer into the training cell as many signals as we want to be delivered. 

It was through a process of systematically exploring this combinatorial space, we finally came up with a recipe that causes immune cells to become highly activated. We know this because they proliferate very much, they differentiate into different flavors of cells, they make copious amounts of cytokine, and finally, most importantly, they acquire the ability to kill all tumor cells they touch without harming normal cells.

 Once we came up with that recipe, we locked it down, and that’s what we went with into the clinic.

Richard McCormick: Immuno-oncology is quite competitive. How does SUPLEXA stand out from some of the existing CAR T therapies and other cellular treatments on the market? How do you envision its role within the evolving landscape of treatments, including potential, combination options with checkpoint inhibitors?

Frank Borriello: It is a very complicated field and it’s constantly evolving. It’s hard to stake out a unique point of view, a unique approach. But, that’s exactly what we’ve done. I scanned the literature and other companies constantly looking for who might be our competitors. And basically, I don’t see any. There are many people trying to cure cancer, that’s to be sure, but they’re all using different technologies.

CAR T Cells have done a great service to mankind because it showed that cells could be used as a drug. But the CAR is an engineered artificial protein. While it accomplishes what you want the cell to do, it also disturbs an equilibrium in the immune system. That’s why you get some serious side effects.

With SUPLEXA cells, there is no engineering involved. The cells are simply trained to reawaken their inherent qualities. One of these inherent qualities is the ability to detect and kill tumor cells. Rather than coming up with a novel engineering approach, which can be quite tantalizing, many of us are engineers at heart, if the system is already in place by Mother Nature to be able to do that, maybe we would have luck in simply reawakening this inherent ability. And that’s what we did.

Richard McCormick: Great. SUPLEXA therapeutic cells are designed to target a wide range of tumor types. You mentioned earlier they had the ability to leave healthy cells alone. So can you maybe explain how you’re able to ensure specificity and safety?

Frank Borriello: Yes. We have now been in the clinic and our cells demonstrate no adverse events whatsoever that we can detect. That is already proof the cells are safe. But why are they safe? There’s a primordial part of the immune system called the innate immune system which existed before the days of T-cells and B-cells. Vestiges of it, more than vestiges, continue to operate today. There are proteins that can be considered pattern recognition proteins. They can detect abnormal patterns like you would find on a tumor cell. You don’t find it on normal cells. 

There are well-understood and well-studied receptors on immune cells that can detect tumor cells, or cells that are deranged in some way. They could be possibly infected by a virus or they could just be getting old and dysfunctional, but they are somehow deranged and not normal. The cells with this receptor have the ability to discriminate between the two.

Richard McCormick: With the recent advancements in your second generation manufacturing process for SUPLEXA cells, how do you envision these improvements enhancing the therapy’s potency and potential impact on patient outcomes?

Frank Borriello: Manufacturability of a cellular therapy is essential. It doesn’t [00:10:00] help if you’ve got a great idea, but you can’t manufacture it. The first generation manufacturing method we used was an extension of our laboratory methods, which worked. Not every element of the manufacturing process was completely standardized. 

As we are seeing the light at the end of the tunnel with an approach to treating many patients, we want to industrialize the process. Strip away any variables that would confound the results. We want to make it possible to make sure that all the patients get the same number of doses, with the same number of cells, each having the capacity we say they have against tumors.

That’s what our second generation process has done for us. It’s stripped out a lot of the variables that could be confusing and pose an impediment when we get in front of regulators who like, if nothing else, to see consistency in safety and efficacy. If we want to see this turn from a good idea to a good product, we have to satisfy those manufacturability issues. We think we have.

Richard McCormick: Given Alloplex’s private funding, what lies on the horizon regarding partnerships, expansion, and the extended development of cell therapies beyond SUPLEXA?

Frank Borriello: Private funding has been a lifeline for Alloplex. Without our passionate and supportive investors, the Alloplex idea would almost certainly have died on the vine. I have to give a big shout-out to those investors (if they ever hear this) to say I appreciate you. They know who they are.

 We now have promising clinical data emerging. We are entering a rarefied space. Not all companies get to generate good clinical data. With that, we are beginning to approach the larger pharmaceutical partner companies and the professional pharmaceutical biotech investors. These efforts have met with some headwinds, mostly because we live in difficult times. Interest rates are going up, market capitalizations are going down, and basically biotech companies have not performed as promised over the past several years. Put that all together and it’s the perfect storm when I knock on the door and say, “I have something different. Really. Believe me.” Of course, investors can be a very jaded group, if nothing else. 

The onus has been placed on me, the bar has been raised, to generate more data than what we already have. Years ago, what we have would have gotten us a deal. We would be quickly moving forward in clinical trials. But, as things stand today, even positive data is considered not positive enough until you’ve stripped out a lot of the risk for those pharmaceutical executives who have to champion your product in front of a committee. Similarly, for the funds who have to convince their investors they can make money off of your company.

Richard McCormick: That’s a great answer summing up the current biotech landscaping. Alloplex’s journey from concept to clinical trial is really impressive. Can you describe some of the key challenges you’ve faced along the way, both in scientific development and navigating the business aspects of what it takes to bring a novel therapy to market?

Frank Borriello: The biggest challenge for us has been that we pursued an unorthodox approach. Why did I choose an unorthodox approach? While I was an immunologist, I was not an oncologist. I never treated cancer patients before. I wasn’t informed enough to develop a negative opinion of this approach, which many others have adopted.

Now that we’re getting good results with this approach, against all odds, I have to spend a lot of time counteracting firmly entrenched prejudices even among the experts because they’ve already discounted this idea from long ago. To see a positive result emerge requires a major rethink. Anytime one has to reach back into their psyche to think, “Why did I not like this idea to begin with?” it causes an [00:15:00] unsettling psychological dilemma. 

That’s what I’m interested with. The best results are when I find people who are willing to put all their prejudices aside and just look at the data. Forget about everything you think you know about cells and just look at the data and see if that shouldn’t trump what you want the answer to be.

Richard McCormick: Frank, it’s been a pleasure meeting with you today. I want to thank you for being a guest on the First In Human podcast. The team here at Vial wishes you and your team at Alloplex Biotherapeutics nothing but future success.

Frank Borriello: Thank you very much, Rich. It’s been a pleasure spending a little time with you. I hope this message resonates with your listeners.

Richard McCormick: Thanks, Frank.