Join Dr. Ahmed Hamdy, CEO of Vincerx Pharma, on a compelling journey through oncology. From co-founding Acerta Pharma to pioneering patient-centric innovations, Dr. Hamdy shares his impactful career. Explore the groundbreaking VersAptx
bioconjugation platform, designed to elevate cancer therapies and uncover the delicate balance between clinical excellence and commercial viability in the dynamic landscape of pharmaceuticals.
Rich 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 co-founder and CEO of Vincerx pharma, Dr. Ahmed Hamdy to our First in Human podcast. Thanks for joining us.
Ahmed Hamdy: Thanks, Rich for having me.
Rich McCormick: In your impressive career, you co-founded Acerta Pharma, played a key role in developing Imbruvica, and now leads Vincerx Pharma. Can you share the journey and milestones that led you to focus on oncology, and drive innovation in these cancer therapies.
Ahmed Hamdy: Absolutely. Thanks for giving me the chance. As a physician, it is important for me to find cures for patients. I started my career as a urologist, nevertheless. I veered into oncology and oncology research earlier in my career. I always had the concept of morbidity of medicine and trying to find treatments for patients that are safe and effective and doesn’t have a lot of side effects. As my career developed through working research at the CDC, working on a PhD in experimental pathology, focusing on prostate cancer at the University of Colorado, I’ve always been focused on how we think of the prognosis for patients?
I got even more involved in the cancer research. Eventually, I got into the industry, worked in multiple programs, escalating the level of my career. I became the chief medical officer at Pharmacyclics, where there were several very exciting programs. First, was the BTK inhibitor, which, now proved, is called Imbruvica. The neat thing about it, it was an oral drug that can inhibit a specific receptor on the B cells that are causing different types of leukemia and lymphoma.
As we put it in first in human (trials), and we saw responses, it was super exciting to be able to navigate the landscape and where to position it for the patient benefit. At the time, chronic lymphocytic leukemia was really a horrible disease, and only 57 percent of patients had a response. They eventually succumbed to the disease for multiple reasons.
BTK made a difference. More than 87 percent of patients became responders. Their quality of life have improved. That was very important for me to see that a single oral pill can make a difference in patients’ lives that dramatically. But, it also had its own problems. Every rose has its thorns. As we continued developing it, we realize there are issues with fatigue, bland things, things like that.
I was able to, luckily, find the next generation BTK inhibitor through my colleagues in the Netherlands, which appeared to have a much better profile than Imbruvica, specifically with not hitting other kinases and therefore the safety profile. That’s when myself and my colleagues, we founded Acerta. We embarked on the development of the next-generation BTK inhibitor, which now is approved called, Calquence.
All in all, the idea is to prevent the morbidity of medicine and to give patients treatments that have a better safety and efficacy profile. Recently, when we started Vincerx, we built a whole company on our bioconjugation platform in hopes to deliver on the concept of antibody drug conjugates, where you have a targeted therapy with a specific profile that doesn’t have a whole lot of toxicities. I’d be happy to talk more about it. The idea is focusing on patient benefit as our main goal.
Rich McCormick: You mentioned your VersAptx platform, which seems to be a game changer in bioconjugation. Can you elaborate on how the platform allows your company to tailor therapy?
Ahmed Hamdy: VersAptx is a versatile, adaptable platform where we can combine and link different types of targets with different types of payloads. We can link small molecule drugs to a payload that would enter in the cell and kill it. Or, we can link it to an antibody that targets a specific antigen that’s expressed on the cancer cells, release the payload intracellularly, and have the payload trapped inside the cell. We have the capability of different types of targets, whether small molecules or antibodies. We have different types of linkers that cleave intra or extracellularly, we have different types of payloads that can modulate the disease quite dramatically.
Ahmed Hamby: We also have a very cool modification. We call it the cell trapper, where we trap the [00:05:00] payload inside the cell by a certain chemical modification that makes it hydrophilic. The current ADCs, they’re all great drugs, but yet have not delivered on the promise. Basically because linkers cleave non-specifically, usually by cathepsin, which is present in every cell. Also, payloads that are permeable payloads and specifically microtubule inhibitors or DNA alkylators or chemo.
Here we have a payload that only cleaves intracellularly by a specific enzyme called legumain that’s highly expressed in the tumor tissue. The payload that we’re using is a kinesin spindle protein that basically inhibits the cell during mitosis. We have a cell trapper moiety that traps it inside the cell. By that design, the sum of all parts is designed to solve problems of the current ADCs that are in the market for approval that have quite a bit of a toxicity profile and decreased efficacy potential.
Rich McCormick: You recently ran a phase one study in VIP152 in combination with Venetoclax and Prednisone. Would you mind talking us through that combination and how you foresee that treatment possibly changing the landscape for non-Hodgkin’s lymphoma?
Ahmed Hamdy: Aside from our bioconjugation platform, we have what we consider is a best in class CDK9 inhibitor. CDK9 is an important target that people have been trying to target for quite some time. Our compound is an IV compound that can be given once weekly and has a wide therapeutic index. By not hitting other kinases, you’re not having the toxicities that are seen with other kinases.
With our CDK9 or VIP152, we inhibit the kinase CDK9, profoundly, and long enough to describe an oncogenic shock where the cell reprograms, inhibits the protein, and induces apoptosis. In certain malignancies like doublehead diffuse large B cell lymphoma, which is a really difficult disease to treat, but by definition doublehead has BCL-2 Myc that are rearranged or overexpressed or BCL-6. In our drug CDK9 inhibitors inhibit Myc profoundly along with other messenger RNAs like MCL-1. So by combining a BCL-2 inhibitor, and a Myc inhibitor in the population that do express, or have those types of mutations, double hit lymphoma, you’re really hitting it from different angles.
We have monotherapy activity with our VIP152 in double hit diffuse large B cells in a monotherapy setting. Those patients were complete responders for many years. Nevertheless, the responses came in after five or eight cycles. When we combined it with Venetoclax, we’re able to get the responses much faster because there’s synergy between the two pathways and inhibiting the two pathways, especially in double hit diffuse large B cell, which is a very difficult disease and currently doesn’t have sufficient treatments out there with a duration of response that we would like to see.
Rich McCormick: How do you envision ADCs transforming cancer treatment and what unique attributes does VIP943 bring to the table in that regard?
Ahmed Hamdy: Coming back to the ADCs, like I said, we feel that our construct over antibody drug conjugates, where the sum of all parts improves the safety and efficacy of our antibody drug conjugate. As I mentioned earlier, antibody drug conjugates, they can cleave non-specifically, they have permeable warheads. Therefore, they can have a bystander effect, especially in heme malignancies you don’t want bystander effect. You want to hit the cells that express that antigen and kill that cell and not anything around it.
VIP943 is a unique antibody drug conjugate where we are targeting CD123, which is an antigen that is expressed specifically on different types of leukemia cells, specifically acute myeloid leukemia and myelodysplastic syndrome, BLL, and others.
It’s expressed in a very high concentration. Our antibody attaches to CD123, internalizes, then our linker cleaves only intracellularly. It doesn’t cleave in circulation before getting to the cancer cell. It only cleaves inside the cancer cell, releasing the payload, which is a kinesin spindle protein, that inhibits the spindle formation as the cell undergoes mitosis.
It also gets trapped inside the cell, therefore, it doesn’t go into neighboring [00:10:00] tissue and after it kills the cell, it doesn’t leak outside and cause all kinds of toxicities. With this construct, hopefully we’ll be seeing quite a bit of benefit for patients. We are currently dosing our patients in our second dose cohort, and we are very pleased with our profile so far.
Rich McCormick: Drug development can be quite challenging. How do you motivate the people around you to do the work they’re doing?
Ahmed Hamby: It is important to have a cohesive team. I’m super lucky to be working with the best of the best. I call it the dream team. I’m also quite humbled that my team has been together for many years. Most of my Vincerx team have worked with me at Pharmacyclics where we developed Imbruvica. Also, a large number of them have worked with me at Acerta, where we developed Calquence. I’m humbled that we are still together, and still focusing on our science. We always challenge each other. We try to build a family of people that are united by a common cause which is doing better for patients.
We always try to stick with The Four Agreements. I don’t know if you’ve read that book, but it’s a very important book, where you always do your best. You speak impeccably. Don’t make any assumptions. We’ve been using the concept of The Four Agreements, in our relationship at Vincerx, and also trying to use the science to drive us forward as a team.
Rich McCormick: That’s impressive teamwork.
Ahmed Hamby: Thank you.
Rich McCormick: How do you strike a balance between the clinical aspects and the commercial demands in your role as the CEO of a pharma company? What considerations are essential in developing those therapies that are not only going to be effective, but then they’re also commercially viable too.
Ahmed Hamdy: Great question. Thank you for that because in what we do, again, if you put the patient first, and you think of the morbidity of medicine, you ask the question, would you put your mother on that drug you’re always going to be thinking about what’s best for the patient. I say to myself, and to my team all the time is follow the science. Follow what the experiments that we have, tell us. Always challenge the assumptions. By doing that, you’re really asking the right questions.
The commercial space is very important because there’s no drug that’s going to fit all, but you have to design it where it helps a specific group of patients. Of course, everybody wants the larger market, but, there are ways of developing it where you can have a bigger market, and help a lot more patients than a single group of patients. That’s by following the science and trying to position it in the standard of care where it’s beneficial for the patients and differentiated it from the standard of care. That by itself is really important to balance between the commercial, the market conditions, the drug development, and benefits for patients.
Rich McCormick: In the dynamic landscape of pharmaceuticals, specifically oncology, what trends do you find most exciting or transformative? How do you see these trends shaping the future of cancer treatment?
Ahmed Hamdy: The FDA, and all the regulatory bodies around the world, have been doing a great job in partnering with pharma and designing ways to be able to have better treatments for patients. For example, cancer patients, in the past, you just threw the kitchen sink at them and gave them all kinds of chemo and as much drugs as they can tolerate, throw it at them.
But, in today’s world with targeted therapies, it is important to find the minimally efficacious dose or biologically active dose. In partnerships with the FDA and regulatory bodies, now, there’s multiple initiatives that can help getting to more efficacious treatment without the severe toxicities that cancer patients have. With chemo, you throw everything at them with all kinds of toxicities.
But now, with the targeted therapy, we have to focus on patient benefit without having toxicities that are unneeded and finding the minimally efficacious dose. Also, allowing early combinations that are smart. For example, we mentioned Venetoclax and CDK9 that hits two pathways at the same time, allowing you to use, hopefully, lower doses and therefore less toxicities.
It is important to keep all these pieces together. In today’s world, the collaborations with the regulatory bodies is super-beneficial and also helping us to move drugs to earlier lines of therapy and therefore more patients and also, hopefully, in pediatric indications the same way.
Rich McCormick: That’s great. Dr. Hamdy, it’s been a pleasure meeting with you today. Thank you for being a guest on Vial’s First In Human podcast. The team here at Vial wishes you and your team at Vincerx [00:15:00] Pharma nothing but future success.
Ahmed Hamdy: Thank you, Rich. It was a pleasure to be here.
