Daniel Petrylak: How are you today?
Zachary Klaassen: I'm fantastic. So just give our listeners a background about this space, and where there's a need for additional agents.
Daniel Petrylak: So the urothelial carcinoma space has really dramatically changed over the last 10 to 15 years. With the use of checkpoint inhibitors and the use of enfortumab vedotin, this has really transformed the field. And we're seeing that, in the EV302 trial, that there's a 30% complete response rate, median survival of approximately 30 months. The same thing with the neoadjuvant study that's also showing a really high pathological complete response rate of 60%, and a survival benefit as well in favor of EV pembrolizumab.
So the question is of course, what are the side effects of EV pembrolizumab? Skin rash and peripheral neuropathy are the two most challenging things to take care of. Skin rash usually occurs early. Peripheral neuropathy occurs much later and sometimes can be cumulative.
A meta-analysis of five clinical trials looking at enfortumab vedotin demonstrated a rate of peripheral neuropathy of 40%, with about 3% of patients having severe neuropathy. There's a need for agents that have a better toxicity profile, as well of course we like to get 100% complete response rate, so more efficacy.
So a bicycle compound, the zelenectide peptide, is a compound that almost looks like a pretzel when it comes down to it. It's a small molecule. It's much smaller than ADC. It has a bicyclomoidity which recognizes nectin-4.
And you can design a bicycle compound to recognize anything. It can recognize PSMA, it can recognize F2, it can recognize nonactin. And this is linked to MMAE, very similar to enfortumab vedotin. So the DEVAR-2 study looked at patients who had received one prior therapy for metastatic urothelial carcinoma. And we found a comparable response rate. We looked at two different doses, five milligrams and six milligrams, and had a response rate of 28% and 30% respectively for both of those particular cohorts.
But what I thought was interesting was the neuropathy seemed to be a little bit lower, 20% overall for all patients, with about a 3% rate of severe neuropathy, which is what we see with enfortumab vedotin.
Now, of course, this is a small trial and it's very, very difficult to cross-compare trials, but I think it's something that's worthy of further study.
Zachary Klaassen: So that's fantastic. Leads into my next question. What do you see next for the bicycle targeting, and this technology that you can really specifically work with?
Daniel Petrylak: Well, I see that this can be used for a multitude of proteins to recognize different proteins. So for example, as I mentioned before, you can look at PSMA. There's a study that's looking at F2A, which is another target in urothelial carcinoma.
The advantage is, of course, as I mentioned before, that this is a much smaller molecule that potentially can bind to areas that the ADCs could not penetrate. So certainly I think that there's a bright future for this class of compounds, and I look forward to other studies looking at different targets.
Zachary Klaassen: Fantastic. Thank you, Dr. Petrylak.
Daniel Petrylak: Thank you.