Episode 54: Ahmed Hamdy- CEO at Vincerx Pharma

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.

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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Transcript

Speaker 1: 0:07

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 connect with Dr Ahmed Hamdi, co-founder and CEO of Vincerex Pharma, to explore his journey in oncology, the development of groundbreaking cancer therapies and the transformative potential of Vincerex's bio-conjugation platform.

Speaker 2: 0:44

Hi, I'm Rich McCormick, executive Vice President of Clinical Strategy, here at Vile. Today, I have the pleasure of welcoming co-founder and CEO of Vincerex Pharma, dr Ahmed Hamdi, who is our first in-human podcast. Thanks for joining us.

Speaker 3: 0:59

Thanks, Rich, for having me.

Speaker 2: 1:00

So in your impressive career, you co-founded Asserta Pharma, played a key role in developing imbuvica and now lead Vincerex Pharma. Can you share the journey and milestones that led you to focus on oncology and drive innovation in these cancer therapies?

Speaker 3: 1:16

Absolutely Well. 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 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.

Speaker 3: 1:49

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 do we think of the prognosis for patients and I got even more involved in the cancer research, eventually got into the industry, worked on multiple programs and escalating level in my career, eventually became the chief medical officer at Pharmacyclics, where there were several very exciting programs, and first was the BTK inhibitor, which now proved called imbuvica. 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 and as we put it first in human 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 is really a horrible disease and only 57% of patients kind of have a response and they eventually succumb to the disease for multiple reasons. Btk made a difference. More than 87% of patients became responders. Their quality of life has improved and really that was very important for me to see that single oral pill can make a difference in patients' lives that dramatically.

Speaker 3: 3:26

But it also had its own problems. I mean, every rose has its thorns and as we continue developing it we realize there are issues with fatigue and bleeding and things like that. I was able to luckily find the next generation BTK inhibitor through my colleagues in the Netherlands which appeared to have much better profile than in Bruvica, specifically not hitting other kinases and therefore the safety profile. That's when, myself and my colleagues, we founded CERDA and we embarked on the development of the next generation BTK inhibitor, which now is approved, called Calqwens. But all in all the idea is to prevent the morbidity of medicine and to give patients treatments that has a better safety and efficacy profile. Recently, when we started Vincerex, we built a whole company on our bi-conjugation 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 and be happy to talk more about it, and the idea is focusing on patient benefit as our main goal.

Speaker 2: 4:49

Great Thanks for that. So you mentioned your Versaptix platform, which seems to be a game changer, and bioconjugation. Can you maybe elaborate on how the platform allows the company to tailor therapy?

Speaker 3: 5:00

So Versaptix. It's 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 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 molecule 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. We also have a very cool modification we call it the cell trapper, where we trap the payload inside the cell by a certain chemical modification that makes it hydrophilic.

Speaker 3: 6:00

The current ADCs they're all great drugs but yet have not delivered on the promise, basically because linkers cleave none, specifically usually by cathepsin, which is present in every cell. Also, payloads that are permeable payloads and specifically microtubulin inhibitors or DNA alkylators or chemo. Here we have a payload that only cleaves intracellularly by specific enzyme called legumaine 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 or prove that have quite a bit of toxicity profile and decreased efficacy potential.

Speaker 2: 6:59

You recently ran a phase one study in VIP 152 in combination with banana clacks and prednisone. Would you mind maybe just talking us through that combination and how you foresee that treatment possibly changing the landscape for non-Hodgkin's lymphoma?

Speaker 3: 7:15

Thanks, rich. Aside from our bi-conjugation platform, we have what we consider 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, thank you. So 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 double-hit, diffuse large B cell lymphoma, which is a really difficult disease to treat but by definition double-hit.

Speaker 3: 8:10

It has Bcl2, bcl, myck that are rearrange or overexpressed, or Bcl6. In our drug, cdk9 inhibitors inhibit myck profoundly, along with other messenger RNAs like MCL1. So by combining a Bcl2 inhibitor and a myck inhibitor in the population that do express or have those type 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 cell. 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.

Speaker 2: 9:22

How do you envision ADCs transforming cancer treatment, and what unique attributes does VIP943 bring to the table in that regard?

Speaker 3: 9:32

Coming back to the ADCs, like I said, we feel that our construct over antibody drug conjugate, 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 bystander defect, especially in hemolygenin Cs. You don't want bystander defect, 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 myeloid dysplastic syndrome, ball and others. It's expressed in a very high concentration.

Speaker 3: 10:32

Our antibody attaches to CD123, internalizes then our linker, cleaves only intracellarally. 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 tissue After it kills the cell. It doesn't leak outside and cause all kinds of toxicities. I think 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. We're very pleased with our profiles so far.

Speaker 2: 11:20

Drug development can be quite challenging. How do you motivate the people around you to do the work they're doing?

Speaker 3: 11:26

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, many years. Most of my Vincerex team have worked with me at Pharmacyclics, where we developed in Bruvica. Also, a large number of them have worked with me at Asurda, where we developed Calquins. I'm humbled that we are still together and still focusing in our science. We always challenge each other. We try to build a family of people that are united by 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 Vincerex and also trying to use the science to drive us forward as a team. I am quite humbled with my team's experience and moving forward with Vincerex.

Speaker 2: 12:39

That's impressive teamwork, thank you. 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?

Speaker 3: 12:57

Great question.

Speaker 3: 12:58

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?

Speaker 3: 13:10

You're always going to be thinking for what's best for the patient and, like I say to myself and to my team all the time is follow the science, follow the experiments that we have tell us and always challenge the assumptions. By doing that you're really asking the right questions. And I think 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 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. And 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 from the standard of care, and that by itself is really important to sort of balance between the commercial, the market conditions and the drug development and benefit for patients.

Speaker 2: 14:15

So, in the dynamic landscape of pharmaceuticals and specifically oncology, what trends do you find most exciting or transformative, and how do you see these trends shaping the future of cancer treatment?

Speaker 3: 14:29

The FDA has been doing and all the regulatory bodies around the world has 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.

Speaker 3: 14:44

In the past, you just throw the kitchen sink at them and give them all kinds of chemo and as much drug as you can tolerate, throw it at them. But in today's world, with targeted therapies, it is important to find minimally efficacious dose or biologically active dose. So 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. Like with chemo, you throw everything at them, 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 and also allowing early on combinations that are smart. For example, we mentioned the Venetoclax and CDK9 that hits two pathways at the same time, allowing you to use hopefully lower doses and therefore less toxicities. So it is important to keep all these pieces together and 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.

Speaker 2: 16:08

That's great. So, Dr Hamby, it's been a pleasure meeting with you today and thank you for being a guest on Biles First in Human podcast. The team here at Vial wishes you and your team at Benceric Sparma nothing but future success.

Speaker 3: 16:22

Thank you, Rich Pleasure to be here.

Speaker 1: 16:32

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