Targeted Cancer Therapies and the Fight to Make Treatment Less Fearful featuring Stanley Lewis

ChatGPT asked me to let y'all know that no AI was used in the crafting of this teaser. How could honeybee venom help you get to the tops of the bottom of cancer? Find out today. Welcome to The Connect Current, the flow of innovation in San Diego. We bring you the founders, investors, and leaders building the future across life science, tech, climate, defense, AI, and more. This is where San Diego's next chapter takes shape. Welcome to the Connect Current, the flow of innovation in San Diego. I'm your host, James Zanewicz, and this episode is being recorded at the UC San Diego Park and Market building. UC San Diego Park and Market, located in the heart of downtown San Diego, offers an event venue with cityscape views and state-of-the-art technology. It's available for meetings, conferences, and special events, and it's conveniently located near hotels and the convention center. And I can testify to that as we just did a big event here last week, and their courtyard is an amazing reception space. But you can get more details for yourself at parkandmarket.ucsd.edu. All right, now onto the show. I am joined by Stanley Lewis, MD, MPH, founder and CEO— you actually have a couple more letters than I do, and I like that because people make fun of me, and I feel like this is good now— of A28 Therapeutics. And one of Connect's 2026 cool companies, A28 Therapeutics is a clinical stage biopharmaceutical company developing targeted oncolytic peptide therapies for the treatment of multiple cancer types. The company's lead candidate, AT-101, is being advanced as part of a broader platform designed to target cancer cells while limiting damage to healthy cells. Stanley brings a deep background in medicine, clinical research, drug development and biotech leadership. Before founding A28, he held senior clinical development roles across the life sciences industry and helped guide programs through important regulatory and clinical milestones, which is why this conversation is going to be so much fun because it pulls together not just the science, not just patient need, but company building and the realities of moving a therapeutic platform through development, which is way more than we often realize. It's also a great example of why A28 is one of Connect's 2026 Cool Companies. So I'm excited to dig in and talk more about what you're building, what approaches you're applying, and why they matter in cancer, and how you think about building a clinical-stage biotech company in San Diego, as well as what investors, partners, and collaborators should know about you. Welcome to the show.

Thank you, James. I appreciate that wonderful introduction.

I know. Well, now I can take a breath. Trey does all the hard work and writes it, and I just get to show up and sound smart. It's amazing.

You're doing it. You're knocking it out the park.

I know, right? Trying, trying. But Stanley, so for folks who are just meeting you, Maybe this is the first time they've heard of A28 because they haven't been paying attention to cool companies and that kind of stuff yet. But what are you building? What problem does it solve? And why does this mission feel so important right now to build a company around it?

Well, thank you for asking. So we are building targeted oncolytic peptides, or TOPs as we call them, for treatment of cancer. And it's a new way of thinking about cancer where you have the targeting moiety binding to the Surface receptors found on cancer cells, and a payload that's actually a peptide, not a drug. So it's a lot like an ADC as a construct, but different. And the thing I love about this approach is the tolerability, the ability to actually fight cancer and to leave healthy cells unharmed.

Mm-hmm.

So patients don't experience so much by the way of side effects. So that's really the motivation behind pursuing this course at this time. And I have a lot of other sort of personal reasons why I believe that everyone has a cancer story in their family or their friends. I'm no different. And this is a really cool way to help patients who are suffering from this disease. And like I said, preserve some of their quality of life as we attempt to extend their lives.

Well, I imagine what you just referenced is perhaps the beginning of the answer to this question, but you've moved from physician to founder because your background spans patient care, public health, clinical research, and biotech leadership. So how has that pathway shaped how you think about cancer treatment and the kind of company you wanted to create?

To me, patients are always first. It's always been that way since I was a medical student and since I became a physician too many years ago to count. And it's always been difficult for me To sometimes explain why I went into drug development versus continuing to see patients in clinic. And ultimately, that really sort of boils down to the fact that I felt physicians were outgunned. We didn't have enough medications that were safe and tolerable that could treat patients for all the different diseases and presentations and conditions that they show up with. And so I felt like someone needs to do something about this. Someone needs to develop medications That don't cause so many side effects or so many toxicities. And I kept saying that over and over and over again while I was there in my clinic. And I realized, hey, you know what? That someone is me.

Someone's me. Yeah.

I got to take up that call. And so that's how I sort of transitioned into drug development and cancer specifically. I lost my dad to cancer. It was, you know, several years ago, but he had gastric cancer that had metastasized to his liver. And we took him to the doctor and they looked over his scans. They actually tried to do a surgery and they opened up and got inside. They realized that there was, there was really nothing they could do and they had to close him up. Now, fast forward, my wife's grandfather had the exact same cancer, gastric cancer, went to the same institution, MD Anderson, saw the same exact doctors. as my dad did. They were able to cut his cancer out. He lived almost 30 more years. So that really got me to thinking, you know what? These liver metastases in particular, being able to catch cancer before it spreads to that vital organ is hugely important.

Mm-hmm.

So I sort of kept that in the back of my mind, sort of a corner of my mind. And when I came across AT101 and this particular platform, I knew that I hadn't found this drug, this drug has found me. And I really wanted to be able to dive into that, to be able to develop it, and to help patients, particularly those late-stage patients who are suffering from metastases that often end up being the reason that they don't survive.

How did AT101 find you?

AT101 found me because I was doing diligence for a company that I was working for out here in San Diego. And we were looking for a new product to insert into our pipeline because we were a single asset company with a lot of money, but a drug that we couldn't move forward given the fact that we were in the middle of a COVID epidemic and it was for treating hospitalized influenza. Well, nobody was getting the flu.

Nobody was going to the hospital. Nobody was going to the hospital.

You scared you'd get COVID?

I had worked in a medical center at that point. I know that stuff wouldn't happen. No, that was not happening.

So we couldn't enroll that trial to save our lives. So my CEO asked me to go out and find something else for us to develop. Ran across this molecule, and I thought it was really interesting because it was a lot like an antibiotic in that it was a lytic peptide. And I had developed drugs for treatment of HIV and had worked in infectious disease space for a long time. So I was naturally drawn to this molecule that looked familiar, but it was different though. They had asserted a targeting unit so that it binds to the receptors on cancer cells. And I said, wow!

And to nothing else, from what it sounds like, that's how it works.

Well, interestingly enough, it can bind to healthy cells that have this same receptor. It's a hormone receptor called LHRH. It used to be called gonadotropin-releasing hormone.

You may have heard of it as that.

Well, somewhere along the way they changed the name of it, probably just to confuse me. But LHRH or GnRH Receptors are found on the surface of healthy cells as well as cancer cells. However, cancer cells have a unique property due to the Warburg effect. They are negatively charged on the outside, and that negative charge is what we exploit when we use our payload.

So that activates your payload in a way where the healthy cells then don't have the negative, they don't activate your payload.

It's really—

You have destruction. Very cool.

It's super cool.

It's like a—

I call it the new IO, right? Because it's really an ionic oncology instead of—

But through peptide chemistry, which was like— and peptides go way back. Like Dr. Andrew Shalley years ago won so many, you know, his Nobel Prize for that. It's at Tulane, the institution I came from. And like, if you can get a peptide to work in this way, you have decades of data behind you showing how it works.

Absolutely. That's Andrew Shalley, bro.

Smart.

Some of the papers that we've based this molecule on.

Yes. I love when the world is small and things fit together.

It's so cool.

Because I did not realize that connection would be there walking into this room. It's awesome.

You know what other connection you might not realize would be there? This molecule is actually— was invented at the LSU, at the Pennington Biomedical Research Center, right there in Baton Rouge.

Yeah.

So the Louisiana folks. Yeah.

My good friend Patrick Reed, who is now at Auburn, did a lot of the tech transfer from there. So I wonder if he was the person who did your deal for this.

It's amazingly small.

That's amazing.

Amazing small world. Yeah.

I love it. Well, this is really cool and I love hearing about the science. I want to dig a little more back into patient need and treatment because also having been very affected by so many people by cancer, and I, you know, understand how you feel about your dad. I've lost 2 friends in the last year and a half, family members beyond that, but it's way more about whether a therapy works. It's about, can you tolerate it? How's your quality of life? Can you stay on the treatment? Do you want to be on the treatment because of how it makes you feel? So how do you incorporate that patient reality and shape that in how you're thinking about A28's platform and impact and, quite honestly, quality of life for the patient as they go through the process?

That's an excellent question. I base my approach to drug development around really 3 principles. The first is first do no harm. I took a Hippocratic oath. That I swore I would do that. And that's very important to me. And I usually, I try to keep it at the sort of the center of everything that I do is we're going to make sure that no matter what we do, we're not going to make patients worse off or feel worse than they did before they came here.

Mm-hmm.

The second thing I believe is that nature will give us clues. I think that everything that we need to solve the problems that we have is actually already here. We just have to find it. Yeah, maybe we'll have to tweak it. Maybe we'll have to put a targeting unit on it or whatever, but it's already here. And this molecule actually is inspired by nature. Turns out that honeybees have lytic peptides in their venom. And we've known for decades that honeybee venom was anti-cancer.

Right.

But, you know, just go around injecting honeybee venom into patients, that could, you know, that could cause some other problems. But what was done here is we essentially teased out all the parts that you'd be allergic to and then left the parts—

Left the good parts.

That would be anti-cancer. And so that's sort of the scaffold upon which AT-101 and our entire platform was built. And then the final thing is what I call the KISS principle: keep it simple and straightforward.

You used to say something else. Different S at the end. Different S at the end. My dad would have said— Keep it simple, stupid, when he was talking to me. I like your version better. But we have evolved.

A kinder, gentler world we are living in now. But yeah, no, keep it simple. I mean, I love the great stories about CRISPR and gene therapy and cell therapy and all this wow, cool, sexy science. But I'm from Texas. I also like to keep it simple.

Yeah.

Right? And this molecule is really, really simple. It binds to a hormone receptor that's found on the surface of cancer cells. The positive charge of our payload attracted to the negative charge of the surface of the cancer cells causes an interaction that ultimately causes this cancer cell to disintegrate. It pokes holes in it.

You know how it works and you know what it does, which is unusual in science many times.

Exactly. And it's just like 1, 2, 3, bind, assess if it's a negative cell, If it is, you destroy it. And then in that destruction, you get one more bonus. So you get this direct killing, this direct cytotoxicity, but when you kill cancer cells in this manner, you also cause the release of tumor-associated antigens.

Yeah.

So you ultimately can recruit the immune system to join in this fight and ultimately treat cancer throughout the body. So it's a wonderful one-two punch, direct and indirect, That allows us to derive the efficacy from the molecule. And you mentioned safety, and I know the—

Yeah.

Your question was really rooted in safety. It's really cool because for this molecule, the only really noteworthy side effect we've noted is a rash. And that rash is transient and it's very treatable. It's the same vancomycin, which is also a lytic peptide. This is the vancomycin flushing syndrome. It's the same rash that you get with that. You can use Benadryl or some other antihistamine, a prednisone.

Nice and easy.

Doctors know exactly what to do about this, and most patients actually may develop the rash while they're getting their infusion, but it's gone before they leave the infusion center, and they don't have to be treated at all. So this is the kind of medication that I want to develop, the kind of medication that is really tough on the tumor but really easy on the patient.

We're close to the patient with what you're doing because you're not an idea-stage company. You're working through Realities of clinical development, data regulatory strategy, capital. He likes money, y'all, give him money. And partnerships. But what has been most important in moving from that scientific promise towards that more mature clinical stage technology for you?

The most important part, you touched on it, right, is how do we find the resources to develop molecules like this, right? When you're thinking about what's hot, what's cool, what's sexy, AI or crypto or whatever investors find themselves drawn to these days. You know what? We didn't cure cancer. It's still here. You know, it's still a very important part of what we're trying to do. It's a deadly disease that we really need to get a handle on. It's been taking too many of our loved ones. And it's a huge burden on society, both from the personal, but as well as the cost of this disease on our healthcare system. So for me, it's really about pushing this approach forward and sort of getting folks to jump on board and understand that there's a different way, I believe very strongly, a better way of approaching this disease that we can tap into and add it to the armamentarium that physicians have to treat patients. I, for one, would love to see this drug in the world as an option if anyone is diagnosed with cancer. And pretty much any kind of cancer. It's relatively tissue agnostic.

That's amazing. So let's talk about how we make it more of an option for folks, because again, you're one of our cool companies, A28, and that's designed to spotlight venture-ready companies in the region. So are you raising right now? If so, what kind of round and what kind of fund are you raising? What will that capital help you accomplish and what should investors understand about you in this time?

Wow. So yes, we are raising, we're in the process of raising a Series A, $20 million for our next clinical trial. We'll need those funds to manufacture our next round of drug, to prepare and conduct the clinical trial, which will look at dose optimization and proof of concept in what's really our new indication, our lead indication, which is hepatocellular carcinoma. Without going into too much detail, the reason why we've selected hepatocellular carcinoma is because it's a huge problem worldwide, even though it's an orphan indication here. But our drug has this unique biodistribution. It has a very short systemic half-life, about 15 minutes, which is why it probably is so safe. But it accumulates and persists in the liver for 3 days.

Wow.

So where you see this high exposure and this long residence time, that's where you really see its activity. So in a previous clinical trial, in patients who had ovarian cancer, They didn't see a real difference between the drug versus, in paired with standard of care versus standard of care alone. But when you looked at that subset of patients, those who had ovarian cancer with liver metastases, wow, the effect size was huge, really 69% of those patients' ORR versus only 17% of the patients who had standard of care alone. So we believe that in patients who are in late stage, who've develop some liver involvement, whether it's from the cancer starting there, which is what we're going to look at first, or whether it's from metastases from a distant primary. If you have liver involvement, I think this drug is really going to work wonders for those patients. So we want investors, we want everyone to know that this is really what we're trying to accomplish. Dose optimization and proof of concept in this indication will set us in the right direction for value creation.

So investors, strategics, you know, whether they got cash, network leverage, whatever, it is, come to your door. You're open for conversation.

Call us. I'm open.

Nice. I like it. Well, we always close out on a much more personal note in a way. We like to ask at the Connect Current, what drives your innovative flow?

Ooh, it sounds like I should break out into a verse or something.

Well, I'm here for it. I have sung on podcasts before, I won't lie. Oh my God. I don't know if Trey's gotten to experience that yet. My last podcast, I did it all the time. Let me start now.

Well, you know, I think, James, that I'd have to still go back to patients, man. That's what really drives my— it really drives my innovative flow. I was talking to my wife the other day. I was drawn to this that I, that I often say, that biology is undefeated. You know, we have tried to chemistry our way out of disease, and it has left us with chemotherapy and, right, and all those side effects and other problems, toxicities that you develop.

Mm-hmm.

With chemical interventions. And now I think we sort of turn to technology. Hey, can we technology— can we tech our way or AI our way out of disease? Eh, I'm not sure that's going to work either. Biology is very personal. It is very, very personal.

Absolutely.

You've got to continue to put the patient first. And I believe that when we think about our interventions, when we think about these things that we're going to bring to the patient, Please keep in balance that you are trying your best to get rid of this disease, but you want to preserve this person's quality of life. So when I think about my innovative flow, I go straight back to the source. I go straight back to the patients, and then I use that to drive whatever I'm trying to— and guide whatever I'm trying to develop.

I love that you basically just said the individual human does it. It's like it boils it down to what should matter.

What should matter.

I love it. Well, thank you so much, Stanley. This is like, it's one of the most thoughtful conversations we've had, and we've had many. And I think it's a powerful reminder why some of the most important aspects of innovation start with that human need and, and quite honestly, looking at patients and helping them face difficult diseases with better options. And it's funny, I wish more physicians would have your mindset and step out from behind the clinic and into a CEO role to bring more of that perspective. I think it adds a lot. excited about how A28 Therapeutics sits at that intersection of cancer biology, clinical development, and let's be honest, the founder's persistence. For investors and partners, it's a reminder that he's open for business. Call Stanley. And that meaningful biotech is built through a combination of science, timing, execution, and that clear understanding of patient need. And again, so proud to have A28 as one of our 2026 Cool Companies.

Thank you so much, James. I appreciate this opportunity.

Thanks for listening to The Connect Current. If you want to learn more about Connect and explore resources across San Diego's innovation ecosystem, follow us on LinkedIn or visit connect.org. We'll see you next time on The Connect Current, where San Diego's innovation story keeps moving forward.

This podcast was edited by Resonate Recordings.