Michael Morris: Thank you for having me, Oliver. It's always a pleasure.
Oliver Sartor: You're going to be talking about a really interesting topic, Mike, but one that people may not know much about. We're going to talk about, CONV01-alpha. What is CONV01-alpha? What does it mean? And tell us a little bit about the background, before we get to the results.
Michael Morris: Sure. There's a long and rich history to CONV01-alpha. It's based on the targeting molecules based on an antibody that those of us like ourselves who've been working in the PSMA field for a long time, this molecule actually was used in the original studies. These were academic studies of PSMA-targeting. This product is now commercialized by a company called Converge, and the targeting agent is CONV01-alpha.
It's an antibody, not a small molecule. It's different than the Lutetium-based targeting molecule that is Pluvicto, which is, commercially available. That's a peptide. It's a small molecule. There's uptake in the normal organs, in the salivary glands. There's some in the kidneys as well. There's uptake in the lacrimal glands.
On the other hand, the antibodies really don't have very much in the way of salivary gland uptake. There's no renal uptake. There is some hepatic and GI uptake, but in previous trials, that's never really been a clinical issue. There's no hepatotoxicity or colitis from this.
The other differentiating issue from Pluvicto is that this is radio labeled with actinium, so it's an alpha emitter instead of a beta emitter. In contradistinction to what patients receive today, it's got quite a different behavior both in terms of the targeting molecule and the payload. I should mention that Actinium as a payload on an antibody is a very good companion set. Because, actinium has a long half life of 10 days, and it's matched with an antibody which also has a longer half life than a peptide. So, as the biologic sense of the molecule, it's got a good match of payload and targeting agent.
Oliver Sartor: Well, one of the things I think it's attractive about the antibody is, less salivary-
Michael Morris: Yes.
Oliver Sartor: ... less renal.
Michael Morris: Yes.
Oliver Sartor: And if there are two of the concerns we might look at with a small molecule with actinium, it's salivary and renal, and this obviates that issue.
Michael Morris: Yes, it does. Yep. I agree. I think we all hope to mitigate a lot of the Xerostomia that is seen with PSMA-617 or I&T based. These are the peptides that are conjugated to Actinium, because Xerostomia is really an issue and limits the amount of therapy that patients can get with Actinium.
Oliver Sartor: Enough background. Let's talk a little bit about the data you're presenting here at ASCO.
Michael Morris: Sure.
Oliver Sartor: A little bit about the trial design, a little bit about the background to the prior treatments of the patients, and then moving on to some of the results you've seen.
Michael Morris: Sure. The CONV01-alpha has been in a phase two study that's pretty broad. It covers a wide range of patients. What we'll be talking at ASCO this year is, that cohort of patients examined who have received an ARPI, have received Pluvicto before. Actually, it was broader than that. They could have received any lutetium-177-PSMA-617, it could have been I&T, it could have been 617, and could have seen chemotherapy as well.
When you look at this patient population is quite heavily pretreated. The 35 patients I'll be presenting, all of them obviously received an ARPI. 80% of them received chemotherapy. And the median number of Pluvicto cycles that the patients had received were six.
Oliver Sartor: Oh, wow.
Michael Morris: So, we're talking about patients who really don't have too many other treatment options, and who already have some of the side effects of radioligand therapy. About 49% of the patients have already had, and were going into the trial having already had Xerostomia. I think it's a very challenging patient population, but it is probably the patient population with the greatest need for a new therapeutic choice.
I should also point out that eight of those 35 patients, were refractory to Pluvicto. They received fewer than four doses, because they either were primarily refractory or primarily resistant, or they had acquired resistance very early on in their treatment course. Not only were these patients very heavily pretreated, but some of them also were radioligand therapy resistant, before going on study. So, I think it was a bold patient population, but in point of fact, the drug was really quite active in these patients and so, it looks good.
Oliver Sartor: Let's talk a little bit about dose and schedule Mike.
Michael Morris: Sure.
Oliver Sartor: Just so people understand how it was administered or what intervals had.
Michael Morris: This is a very interesting dose and schedule so, unlike Pluvicto, which is given every six weeks for a total of what's on the label of six doses, this through a whole series of studies that were conducted by Scott Tagawa in an academic setting, the best way to deliver this agent, both in terms of safety, efficacy, and what looked like durability in those early trials, which involved over 100 patients, was a single fractionated dose.
So you got two doses, those were the two fractions. One was given on day one, the other was given on day 15, and that was it. And so, if you can get good anti-tumor activity that's durable with just basically two doses that are separated by two weeks, that would be a major achievement in terms of reducing the treatment burden on a very advanced patient population.
Now, originally the dosing was based on body weight. That was, 45 and 55 kilobecquerels per kilo. But now like many radioligand therapies in development, it is moving to a fixed dose. And so, the data that I'll be presenting will actually be converted into the fixed dose that they would've received. That will be what that's intended to be, the phase-three dose, at the next phase of drug development, and the intended dose will be nine megabecquerels.
At nine megabecquerels, this really did look active. 40% of the patients had a PSA50 response. And remember, this is in the post Pluvicto setting. And in terms of safety, remember that half of these patients went in with Xerostomia. At the day's end, there was no high grade Xerostomia in terms of the post-Actinium treatment. 62% of the patients in total had Xerostomia. So, that would be an uptick of around 14% from where they were going in. And then of those 62%, around 23% were grade two, which we would consider to be notable, because the patients are now moistening their food and making adaptive changes in order to be comfortable in terms of eating.
So, the durability, of course, is quite important. There are patients who even with just those two doses, had durable responses between eight and 12 months. I think for a really heavily pretreated patient population, this looks pretty good in terms of efficacy and in terms of safety as well.
Oliver Sartor: I think this is a important potential advance. Obviously we need to get to the more extensive trial testing, phase-three. Very delighted to know that phase-three will be proceeding. And Mike, I'll simply say, thank you for all your contributions to the field-
Michael Morris: Oh, thank you Oliver.
Oliver Sartor: ... for making a difference for our patients, and thank you for being on UroToday.
Michael Morris: Thank you for having me, Oliver, and thank you for being such a terrific collaborator in so many different studies in this arena. It's such a privilege to work with you.