jfm1330 wrote: What you need is not scientists knowing how to make these PDCs with radioisotopes. This science is pretty straightforward now, and well known. What you need is scientists able to run good preclinical studies and then clinical trials with these compounds, because the toxicity risk is a real issue. You need to be sure that you have a good index between receptor expression on tumors and receptor expression in healthy tissues. You cannot go with probability of receptor expression like Thera is doing right now. Confirmation of receptor overexpression is mandatory.
I gave the example of salivary gland problems with Ac225-PMSA, but with Lu177-Dotatate, there was also a major toxicity issue with the kidneys because of proximal tubular reabsorbtion of the PDC that exposed the kidneys to too much radiations. The solution they found to avoid this and favor rapid clearance by the kidneys is to give an infusion of two positively charged amino acids, arginine and lysine, before injecting the PDC, during injection and three hours after injection of the drug. This is just an example, but the more toxic the warhead is, the better understanding you need to have and the more careful you need to be in phase I dose escalation. And with actinium 225, the main problem is the availibilty of the radioisotope with the proper purity level.
Also, the company that got Lu177-Dotatate approved in the US and Europe did not developped the drug in itself. They did the phase III clinical trial necessary to get it approved, and they don't have a patent on the PDC, but on a specific patent involving the manufacturing process. This drug was developped in Europe and Australia well before it was approved. Before formal approval it was used under research protocols in many European countries. It was a way to give patients access to it. Doctors knew it was effective, but since neuroendcrine cancers are rare, and that there was no patent on the molecule itself, and that the phase III study involved 229 patients, it took time to have a company willing to get it formally approved. But as it is often the case, a first approval in a class of drug pushes other to follow suit. It was followed by Lu177-PSMA (Pluvicto) for prostate cancer, and you will see many other in the coming years. Lu177-PSMA is not considered a PDC because PSMA is not a peptide, but it is a ligand to a receptor, so it acts in the same way as a PDC.
Wino115 wrote: Advanced Accelerator is the company that developed Lutathera PDC that JFM knows well. They were bought by Novartis for a tidy sum. Guess the non-competes are over! Typical.....
qwerty22 wrote: Guess what, they didn't just pull this technology out of thin air. There's a tonne of expertise here that THTX just doesn't have.
John Valliant, Ph.D.
CHIEF EXECUTIVE OFFICER
Dr. Valliant is Founder and Chief Executive Officer of Fusion Pharmaceuticals. Dr. Valliant has been instrumental in securing both investment and scientific and medical collaborations with the industrial and academic partners of Fusion.
Prior to Fusion, Dr. Valliant founded the Centre for Probe Development and Commercialization (CPDC), a radiopharmaceutical research and development centre of excellence established in 2008 through funding from the Federal and Provincial governments, industry and academic partners. The CPDC is focused on discovering, developing and distributing the next generation of molecular imaging probes. The CPDC also plays an important role in Canada’s health care system, manufacturing and delivering a reliable, daily supply of imaging probes to hospitals and clinics nationally and internationally.
Christopher Leamon, Ph.D.
CHIEF SCIENTIFIC OFFICER
Dr. Leamon was most recently executive director, radioligand drug discovery at Novartis. Prior to Novartis, he was vice president, discovery research at Advanced Accelerator Applications, a subsidiary acquired by Novartis in 2018. Before that, he held several positions within Endocyte, including vice president of research and most recently, president. At Endocyte he contributed to the research and development of the company's PSMA-targeted radioligand therapy program for metastatic castration-resistant prostate cancer prior to the acquisition by Novartis.
jfm1330 wrote: Another Canadian company mentionned in the article is Fusion Pharma. They work on PDCs where the cytotoxic agent is actinium 225 (Ac225). That's the warhead I would like to see coupled with TH19P01. Very powerful stuff, bye bye resistance. It breaks both strands of DNA. That being said, toxicity can be an issue if the target receptor expression is too high in some healthy tissue.
https://fusionpharma.com/
Wino115 wrote: Really encouraging to see TH1902 is highlighted up front. We are jaded when Paul & Co say they have a "first-in-class" novel approach ---but it is. Articles like this that review the entire market place for a market research consulting paper bolster that claim.
Good find TH1902.
TH1902 wrote: TH1902 mentioned, from a few days ago but interesting
Neeraj Chawla, Kuick Research
https://www.medgadget.com/2022/09/peptide-therapeutics-market-to-surpass-usd-75-billion-by-2028.html