Alicia Morgans: Hi, I'm so excited to be here with Dr. Phil Kantoff, who is the CEO, CMO, and co-founder of Convergent Therapeutics. Thank you so much for being here with me today.

Phil Kantoff: Great to see you, Alicia. Thanks for having me.

Alicia Morgans: It is always a pleasure to talk to you, Phil, and I'd really love for you to introduce everyone to Convergent Therapeutics. What is this company that we've been hearing so much buzz about?

Phil Kantoff: Thank you. So I made the jump from academic medicine into industry, we'll say, and specifically in biotech, a little over a year ago. I had been, as you know, at Memorial Sloan Kettering as the chair of medicine and before that, at Dana Farber for many, many years. And I loved my academic career, but I thought it was time for changing directions. And I looked at pharma initially and then looked into biotech and examined a lot of different opportunities, a lot in the early detection space, some in the therapeutic space.

 But I really was intrigued by what was started at Convergent Therapeutics. The company had formed in late 2020, and it was based on work that Neil Bander, a Cornell Urologist and Physician Scientist had been working on. He had been working on the biology of prostate specific membrane antigen, PSMA, I'll refer to from now on, and had been developing antibodies as therapeutics for prostate cancer for a long time.

So he developed antibody drug conjugates, he developed other therapeutics, including radionuclide, the anti-antibody. Initially started out with Lutetium 177, which is a beta emitting radionuclide, attached to his antibody, which was previously known as J591. And then when alpha particles or alpha emitting radionuclides became available through the Department of Energy, he began to look at those as conjugates to the antibody J591. And that's the basis of Convergent Therapeutics.

 So what was exciting to me was some phase work that Scott Tagawa had done as the initial first in man study of what we now call Convo One Alpha, which is the antibody attached to Actinium-225, which is sort of an ideal alpha emitting radionuclide in that as a half-life of 10 days. Alpha emitting radionuclides, as you know, are much more powerful than beta emitting radionuclides by 1,000 fold.

Their path length is much more narrow, so they don't cause as much collateral damage as do beta particles, and they cause double strand breaks in DNA as opposed to single strand breaks. And as you know, Alicia, double strand breaks are very hard to repair as opposed to single strand breaks. So the potential for targeting PSMA with an antibody and attaching it to an alpha particle was a very exciting possibility.

And Scott did a single dose escalation study that was presented at ASCO last year, and the results were really quite spectacular. And that's what got me really excited about the company, also working with Neil Bander, who had been working in this field for a long time, so I joined in July of last year. And what we are trying to do is be the first in class first to apply Alpha radionuclides in prostate cancer targeted at PSMA, and so far the results are fantastic.

So I've spent the last year developing a clinical development plan, raising money for the company, building out the company, we're still a company of only four people. As you said before, I'm both the CEO and CMO. I need some help to advance our program, but it's been a fantastic learning experience for me. Academic medicine is very different than biotechnology, and I think this is where true drug development takes place in biotech and ultimately in pharma, so that's been a great learning experience for me.

Alicia Morgans: Well, I would say that you must draw so much on your academic experience too, which really makes you the ideal person to be a CEO and CMO. But as you think about this alpha particle strategy, we have alpha particles in Radium-223 that we've been using for a number of years. What makes this so different, beyond the very simple, we can target PSMA so we can get to soft tissue and bone?

Phil Kantoff: Yeah, Radium-23 was a surprising but noteworthy advance in the radiopharmaceutical area. And the way it works is not clear as it's a bone targeting agent because it is divalent cation and seeks bone. But I think we learned over time, that it doesn't directly affect the cancer cell. It affects the bone, the microenvironment, and in some way inhibiting the microenvironment around the cancer cell, it has a beneficial effect in prostate cancer.

 The direct approach of using an antibody directed PSMA attached to an antibody is the direct way to kill cancer cells. And in fact, we see that. We see tumors shrink, we see PSAs go down. It's a much more powerful therapeutic than Radium-223. So I think it's going to have greater traction than Radium-223 has had. There have been a number of radio pharmaceuticals that have been developed over the years. There were a couple back in the 2000, Zelin and Bexar, for non-Hodgkin's lymphoma and they used beta particles and they worked quite well, but they didn't gain a lot of traction.

And then Radium-223, which was an advance in prostate cancer, unfortunately it's not used that often anymore. I think maybe 5% of patients now get radium-223, when you look at population based work. The work that Endocyte and Novartis did in bringing the beta emitting Lutetium-177 attached to a ligand small molecule was really a breakthrough.

 And so we are trying to take that to the next level by using an antibody, which is retained by cancer cells much better than ligands when they get internalized, they stay in the cell for a longer period of time. And in addition, using an alpha particle, rather than a beta emitting radionuclide, is a much more powerful way to kill cancer cells. So that is why we're excited about Convo One Alpha.

Alicia Morgans: Wonderful. Well, what should we be on the lookout for in the next months to years, when it comes to Convergent Therapeutics?

Phil Kantoff: So our phase I work is ongoing. We're developing the optimal dose in schedule for delivering it to patients with advanced prostate cancer. And I think we're moving into a registrational trial toward the end of 2024, early 2025, in patients with advanced prostate cancer.

Alicia Morgans: Well, that's definitely something to look forward to. We are excited to continue to hear updates. Thank you so much for sharing your expertise and keep up the good work.

Phil Kantoff: Thank you so much, Alicia.