Charles J. Ryan: Howard, great to have another opportunity to sit and talk about TACTICAL. We now have sent out the RFAs. So we have scientific teams being formed, hopefully all over the world and we're expecting some applications. I thought it'd be a good opportunity for us to explain what TACTICAL is about and a little bit of the logistics around it.

Howard R. Soule: Yeah. Thanks, Chuck. I personally am very excited to have this opportunity to watch the global research community come together, as they did years ago around the dream teams, and come up with new ideas to intercept the lethal form of prostate cancer. While the field has made immense progress in the last, really decade, lots of new drugs, doctors, and patients have lots of new choices. Unfortunately, we're not finished yet and we're hoping that the TACTICAL Awards, putting together large teams to do big, thoughtful projects is the way to go forward.

Charles J. Ryan: Do you think that people are going to focus on drug resistance mechanisms? For example, if you go back and you look at the literature of the last five years and you did a PubMed search on enzalutamide resistance, you're going to see a huge upswing in that term in the literature.

Howard R. Soule: Yes.

Charles J. Ryan: Is that what we think we're going to find from people, or do we think we're just going to see totally different mechanisms that may have nothing to do with resistance?

Howard R. Soule: I'm hoping that we will see a diversity of ideas. Certainly resistance is a killer. It's a big problem and unfortunately resistance occurs for every treatment I know of maybe some that don't, but all of the new anti-androgens, even the highly regarded radioligand therapies, they all end up with some treatment resistance. We're hoping people will find a way to break through that. But I'm also really enthusiastic about some of the new targets that have poured into my telephone and email from around the world. Even being here at ASCO, just in the last few days, people have floated numerous ideas. They're all good. We'll see which ones float to the top.

Charles J. Ryan: Right. It's all going to boil down to the logistics and the feasibility and the tactics of the whole process.

Howard R. Soule: Right.

Charles J. Ryan: I mean, I think that one could focus on enzalutamide resistance. That's obviously, a really... I just say AR targeted therapy resistance, obviously very important, but that underscores the notion that we're going to continue to treat prostate cancer sequentially. We'll give a drug until it's resistant or something along those lines. Whereas the identification of completely new targets, as we're hearing about, offers a completely different paradigm to replace the AR targeted therapies, maybe

Howard R. Soule: You're absolutely right. And when you think about it, we have learned so much about the changes in prostate cancer as it becomes more and more lethal, that allow us to target. Delta-like ligand 3 is just one of many ideas that I know we're going to see a churn around, and that's a good thing.

Charles J. Ryan: Let's speak a little bit about how this fits in with the legacy of PCF, because I think one of our greatest strengths as an organization has been, A, fostering team science across multiple institutions and, B, fostering career development in young investigators. This award, through your input, has created an opportunity for both of those ideas to move forward. So speak to that.

Howard R. Soule: Yeah. We want senior led teams. We also want young investigators as a meaningful part of the team, not just as a thumbtack in the bulletin board. So we're asking for that and as we and our external advisors read these applications, we'll be focusing on that. Idea, team, it's all about the people.

Charles J. Ryan: Yeah, absolutely. And that's what makes PCF special. The other part is that we are actively seeking and hope to see applications that will address problems in prostate cancer, but that could be translated to other cancers, as well.

Howard R. Soule: Yeah. That's a big one. And I know of already two ideas that have been floated to me. And by the way, that doesn't mean anything.

Charles J. Ryan: Right.

Howard R. Soule: Yeah. I always tell people, Chuck, "You can talk to me all you want about your idea, but we don't make the final decisions. The external advisory board does."

Charles J. Ryan: Right.

Howard R. Soule: But numerous ideas have percolated through my email, through my telephone, about targets that will not only address prostate cancer, but many other cancer.

Charles J. Ryan: Yeah.

Howard R. Soule: So stay tuned for that.

Charles J. Ryan: Right. So we're excited about that. And then the final piece that we should talk about is the process is a little bit different than what we've done in the past. It's not just submit a grant and have a review committee give a score. We're going to do a little bit more of a stepwise process.

Howard R. Soule: We are.

Charles J. Ryan: That I think we'll make better applications. We

Howard R. Soule: In fact, letters of intent are due later this month, in June. We will announce who gets the privilege of writing a full proposal. All of this is defined in the RFA. And then we're going to peer review these applications and our team will choose those that we think meet the criteria of TACTICAL and we'll invite these people to these teams, to a Zoom interview, which is something we have done in the past, selectively, as well. So it's a slightly longer process, but it's a whole lot more resource than the foundation has typically provided.

Charles J. Ryan: And hopefully the beginning of perhaps three trenches of that resource, we hope maybe more over time or we'll just keep doing it until we solve the problem. Let's just put it that way.

Howard R. Soule: Correct. Could I just say one thing?

Charles J. Ryan: Yeah.

Howard R. Soule: It would be there are several things we stayed in the RFA that are advantageous. How about bringing a partner to the table? If you are studying a new drug, if you are proposing a clinical trial and we're going to fund the extensive, correlative science to understand how this drug works and how it does work or it doesn't work. If you brought resources from the company, more than just a drug, that would be highly advantageous.

Charles J. Ryan: Right. So that's a key point is that it doesn't need to be wholly within the TACTICAL framework, is what you're saying, is that we could have companies supplying drugs, companies even supplying other support.

Howard R. Soule: Yes.

Charles J. Ryan: There may even be other trials done through other mechanisms, governments and whatever that we could utilize and that might make for better science, ultimately. So great. Well, I'm really excited to be working with you on this. I know you're excited and we're looking forward to seeing all of these applications down the road. And I really like the process, also, because one of the things it's doing is by doing the iterative selection, we're not asking people to spend a lot of time, if they're not heading down the right path, we can tell them, "Maybe try next year, save your time, go back and think through things." We're only selecting a few to move forward with the full application.

Howard R. Soule: That's correct.

Charles J. Ryan: And I think that's really good. Saves people some time, so.

Howard R. Soule: Well, we're excited and this is all about the patients.

Charles J. Ryan: Yeah.

Howard R. Soule: So we're going to do something big here, Dr. Ryan.

Charles J. Ryan: All right. Yes. I agree. Let's do it.