Episode 45: Frank Borriello- Founder and CEO at Alloplex Biotherapeutics

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 shares the personal backstory that sparked his quest to revolutionize cancer treatment and frames the scientific journey that led to SUPLEXA.

First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder. Episodes launch weekly on Tuesdays. To view the full transcript of this episode, click here.

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Chapters

• 0:06 Suplexa Cell Therapy for Cancer Treatment
• 17:13 First Human Podcast Pleasant Meeting

Transcript

Speaker 1: 0:06

You are listening to First In Human, where we interview industry leaders and investors to learn about their journey to in-human clinical trials presented by Vile, a tech-enabled CRO hosted by Simon Burns, ceo and co-founder. Featuring special guest host, rich McCormick, evp of Clinical Strategy and Head of Oncology. In this episode, we chat with Frank Boriello, founder and CEO at Alloplex Biotherapeutics. Find out more about the inspiring journey behind developing suplexa cell therapy and the challenges faced in bringing this innovative cancer treatment to market.

Speaker 2: 0:45

Hi, I'm Rich McCormick, executive Vice President of Clinical Strategy, here at Vile. Today I have the pleasure of welcoming Frank Boriello, CEO and founder of Alloplex Biotherapeutics, to our first in-human podcast. Hi, frank, would you mind telling us a little bit about yourself?

Speaker 3: 1:02

Absolutely. My name is Frank Boriello. I'm trained as an MD, PhD, and I've been in this profession for over 30 years, originally born in Italy, grew up in Brooklyn, new York, and now I live in the Boston area.

Speaker 2: 1:18

Awesome pleasure to have you on today. Can you share the inspiration behind founding Alloplex and developing suplexa cell?

Speaker 3: 1:25

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

Speaker 3: 2:00

The reason I did that 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 this is a chance to get back to my first passion, which was immunology, and see if I couldn't do something that was 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, and almost immediately the lab experiments showed the approach was not only feasible but readily executed. That was seven years ago and things have been going so fast. Ever since that, I've never really looked back.

Speaker 2: 3:03

So balancing roles as a scientific founder and CEO can be challenging. For some 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 by?

Speaker 3: 3:15

law. I can tell you that I've really never thought about it that way when I started. In a small company, you really don't have structure and layers of management that 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's no layers of management to slow things down and absolutely zero politics. It's you against the mother nature, and who will win? Well, we know who will win. We just hope she agrees with your idea. It helped, of course, to have had experience as an immunologist, a medical doctor, and I also had experience in the financial industry and running clinical trials. It seemed that this job brought to bear every skill set I had accrued through 30 years of working it meant to be.

Speaker 2: 4:23

So, digging into the science a little bit, can you explain the significance of enlist training cell lines in suplexa therapy? And then, how did you identify the need for simultaneous activation of multiple immune pathways to achieve such a strong anti tumor response?

Speaker 3: 4:41

Excellent question. The enlist cells are central to our technology and they contain what we call the secret sauce. 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 and that it takes many components talking to one another to get it to work correctly. And yet, despite that common perspective, the drug industry still involves developing drugs that affect one pathway or one cell at a time, and everybody is still looking for that magic bullet. So the advent of cellular therapy as a field offered a different starting point from which to launch a program.

Speaker 3: 5:40

I realized that if multiple signals were required to impact immune cells to do what you wanted them to do, then we would have to have a platform by which those signals can be provided all at the same time. And it turns out the one 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, and it was through a process of systematically exploring this combinatorial space that 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, and most importantly, they acquire the ability to kill all tumor cells they touch without harming normal cells. And once we came up with that recipe, we locked it down and that's what we went with into the clinic.

Speaker 2: 7:07

So in renal oncology it is quite competitive. How does Suplexa stand out from some of the existing CAR-T therapies and other cellular treatments on the market? And then, maybe, how do you envision its role within the involving landscape of treatments, including potential combination options with checkpoint inhibitors?

Speaker 3: 7:28

Yes, it is a very complicated field and it's constantly evolving, and so it's kind of hard to stake out a unique point of view, a unique approach. But I think that's exactly what we've done. I scan 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. You mentioned CAR T-cells.

Speaker 3: 8:05

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 that, while it accomplishes what you want the cell to do, it also disturbs an equilibrium in the immune system, and that's why you get some serious side effects. The thing about suplexa cells is that there is no engineering involved. The cells are simply trained to reawaken their inherent qualities and it turns out one of these inherent qualities is the ability to detect and kill tumor cells. So rather than coming up with a novel engineering approach, which can be quite tantalizing I think 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 Reawakening this inherent ability, and that's what we did.

Speaker 2: 9:19

Great. So suplexa therapeutic cells are designed to target a wide range of tumor types, and you mentioned earlier the bad the ability to leave healthy cells alone. So can you maybe explain that a little bit and how you're able to ensure specificity and safety?

Speaker 3: 9:36

Yes, we have now been in the clinic and our cells demonstrate no adverse events whatsoever that we can detect. So that is already proof that the cells are safe. But why are they safe? It turns out that there's a primordial part of the immune system called the innate immune system, and the innate immune system existed before the days of T cells and B cells, and vestiges of it more than vestiges continued to operate. Today, it turns out that there are proteins that can be considered pattern recognition proteins. They can detect patterns that are abnormal, like you would find on a tumor cell, and you don't find it on normal cells. So 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 they're not normal, and the cells with this receptor have the ability to discriminate between the two.

Speaker 2: 11:02

So, 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?

Speaker 3: 11:16

Well, manufacturability of a cellular therapy is essential. It doesn't help if you've got a great idea but you can't manufacture it. So the first generation manufacturing method we used was an extension of our laboratory methods, which worked, but not every element of the manufacturing process was completely standardized. So, as we're seeing the light at the end of the tunnel and an approach to treating many patients, we want to industrialize the process. We wanna strip away any variables that would confound the results. We wanna 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. And so 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. So if we want to see this turn from a good idea to a good product, we have to satisfy those manufacturability issues, and we think we have.

Speaker 2: 12:52

So given Alloplex's private funding? What lies on the horizon regarding partnership expansion? The extended development of cell therapies beyond Suplexa.

Speaker 3: 13:03

Well, first of all, 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. So 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, and with that we're entering a rarefied space. Not all companies get to generate good clinical data, so with that we are beginning to approach the larger pharmaceutical partner companies and the professional pharmaceutical biotech investors.

Speaker 3: 13:49

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 like the perfect storm. When I knock on the door and say that I have something different, really believe me. And of course, investors can be a very jaded group, if nothing else. And so 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 a sad deal and 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 really stripped out a lot of the risk for those pharmaceutical executives who have to champion your product in front of a committee and similarly for the funds who have to convince their investors they can make money off of your company.

Speaker 2: 15:14

That's a great answer in summing up the current biotech landscape. So well said there, alloplex's journey from concept to clinical trials it is really impressive. Can you describe some of the key challenges you faced along the way, both in scientific development and navigating the business aspects of what it takes to bring a novel therapy to market?

Speaker 3: 15:36

The biggest challenge for us has been that we pursued an unorthodox approach. And why did I choose an unorthodox approach? The answer is because, while I was an immunologist, I was not an oncologist. I never treated cancer patients before and therefore 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. So to see a positive result emerge requires a major rethink, and any time one has to reach back into their psyche to think why did I not like this idea to begin with? It causes an unsettling psychological dilemma, and that's what I'm interacting with. The best results are when I find people who are willing to put all their prejudices aside and look at the data. And just look at the data. What 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.

Speaker 2: 17:12

Yeah, that's a great answer. So, 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 Bio wishes you and your team at Alloplex Biotherapeutics nothing but future success.

Speaker 3: 17:28

Well. Thank you very much, Rich. It's been a pleasure spending a little time with you and I hope this message resonates with your listeners. Thanks, Frank.

Speaker 1: 17:44

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