Below quotes and information from
Oliver Sartor at the Telix Investor day. - TLX 591 advantages over the small molecule approach like Claritys CU67 SAR bisPSMA.
**Safety** **Reduced Salivary and Renal Toxicity:** -- "One of the real advantages of the antibody is the two doses, which are pretty simple, just 2 weeks apart... Really, really good tumor uptake... no salivary, no kidney. You're going to be able to see it in the tumor. You'll see hepatic uptake... But it's not [dangerous]. And it turns out there are very few in the way of liver function tests that are going to be problematic."
- "The limitation on the small molecule has been built around these two organs, salivary and kidney. The salivary toxicity on the small molecules is probably rate limiting... the limitation on the dose on lutetium with a small molecule is related to the renal dosimetry... And the antibody is going to avoid that problem. And that's going to have another potential DLT. But nevertheless, the renal dosimetry problem is solved with the antibody." - "This is an advantage of the antibody, which simply doesn't have [dry mouth]."-
**Hematologic Toxicity:** - "The issues really revolve around the hematologic toxicity. And you can see the anemia that is present but in terms of grade III, grade IV, didn't see it in this study. Lymphopenia, which, by the way, is not really clinically relevant... Neutropenia, you can see is grade IV, only a very small percentage of patients. Neutropenic fever is not a problem. It doesn't particularly last that long when it does occur... Thrombocytopenia, you do see some thrombocytopenia in the grade IV, you're probably running about 6% or so." -
- "If you end up with a grade 4 [platelet drop], you see that there can be a little bit of a delay getting back to kind of 100,000. But I'm unaware of any bleeding that's actually occurred and there have been some platelet transfusions given. I think that's going to be a rare event."-
**Lower Total Radiation Dose:** - "Here, the actual amount of the radiation administered is much lower than with the typical RLT peptides like 617... The lower dose of radioactivity is going to be a little bit easier on the patient from that perspective, minimal safety requirements. So it's actually a pretty dramatic difference between 152 millicuries as opposed to 1,200 millicuries."###
**Efficacy** **Outstanding Survival Data:** - "You'll see that the survival outcomes have been outstanding, but of course, that needs to be verified in the Phase III trial. This is the survival outcomes that are outstanding. Again, this was with the two doses of the antibody. And there were some sort of eye-popping overall survivals 42.3 months supported for castrate-resistant disease, and that's like rather phenomenal. These are patients who had pretty high burden. And there does seem to be this survival benefit that attracts people's attention, certainly attract my attention."
**Tumor Uptake and Retention:** - "That retention within the tumor is really, really, really good. And you, again, don't see the salivaries, you don't see the kidneys. You don't see anything in the bladder, but you do see the liver. When I first saw the liver, like I said, I had kind of alarm bells go off but it turns out there's really no liver toxicity and look at the dosimetry limits. It's nowhere near the dosimetry limits within the liver."
**Advantages of TLX591 (Antibody) Over Small Molecule Approach** **Avoids Dose-Limiting Toxicities of Small Molecules:** - "The limitation on the small molecule has been built around these two organs, salivary and kidney... the antibody is going to avoid that problem."
- "The renal dosimetry problem is solved with the antibody."
- "This is an advantage of the antibody, which simply doesn't have [dry mouth]."
**Simplified Dosing and Patient Experience:** - "You have a 2-dose regimen that's 14 days apart. You have the hepatic clearance, which really solves dosimetric problems, and you also avoid the salivary uptake."
- "The infusion goes in over about 5 to 15 minutes, pretty short infusion. This has real advantages compared to some of the RLTs, which are going to be using higher doses of the activity... You can have a very rapid discharge. You can also turn over your chairs a lot quicker and not occupy the chairs as often. That's advantageous for patients, advantageous for the treating physician."
**Lower Radiation Burden:** - "The lower dose of radioactivity is going to be a little bit easier on the patient from that perspective, minimal safety requirements. So it's actually a pretty dramatic difference between 152 millicuries as opposed to 1,200 millicuries."-
**Better Dosimetry Profile:** - "The antibody looks pretty good... the salivary is getting right up around the threshold [with small molecules]... If you look at the kidneys... you're approaching the kidney limits when you're given the 200 millicuries times 6, and that's what's prevented people from going higher with the small molecules. The salivaries and the kidneys are the 2 kind of areas of concern."
Oliver Sartor Quotes"One of the real advantages of the antibody is the two doses, which are pretty simple, just 2 weeks apart... no salivary, no kidney [uptake]. You're going to be able to see it in the tumor... very few in the way of liver function tests that are going to be problematic."
"The limitation on the small molecule has been built around these two organs, salivary and kidney... the antibody is going to avoid that problem... the renal dosimetry problem is solved with the antibody."
"This is an advantage of the antibody, which simply doesn't have [dry mouth]."
"Survival outcomes have been outstanding... eye-popping overall survivals 42.3 months supported for castrate-resistant disease, and that's like rather phenomenal. This was presented by Scott Tagawa. Scott Tagawa, by the way, Cornell's close collaborator, close friend, and we've worked together for many years.This data is very reliable. I trust Scott completely.""That retention within the tumor is really, really, really good... you, again, don't see the salivaries, you don't see the kidneys... there's really no liver toxicity."
"The lower dose of radioactivity is going to be a little bit easier on the patient... pretty dramatic difference between 152 millicuries as opposed to 1,200 millicuries."
"You have a 2-dose regimen that's 14 days apart... hepatic clearance, which really solves dosimetric problems, and you also avoid the salivary uptake."
(20min delay)