POINT Biopharma Global Inc. (NASDAQ:PNT), a company accelerating the discovery, development, and global access to life changing radiopharmaceuticals, today released additional preclinical data from its fibroblast activation protein-alpha (FAP-alpha) inhibitor program called PNT2004. The new data demonstrates best-in-class characteristics including rapid and persistent tumor targeting with very low retention in normal tissues. Over the duration of the preclinical study, complete tumor regression and prolonged survival were observed. Based on this exciting preclinical data, the Company exercised its option on the technology and amended the exclusive global licensing agreement with Bach Biosciences providing the Company with the opportunity to further expand uses with the highly FAP specific D-Ala-boroPro inhibitor as a targeting warhead.
FAP-alpha is a serine protease highly expressed in over 90% of epithelial tumors on cancer associated fibroblasts (CAFs) which drive tumor progression and resistance to chemo and immunotherapy. FAP is expressed during development but is absent in adult tissues, making it a compelling target. The clinical candidate in the PNT2004 program, PNT6555, is a D-ala-boroPro based FAP targeting radioligand. D-ala-boroPro is a potent and selective FAP inhibitor that has superior tumor retention and normal tissue clearance. In animal studies PNT6555 has successfully delivered large doses of radiation to tumors while limiting dose to non-target tissues. PNT6555 showed >26,000-fold selectivity for FAP over the closely related enzyme DPP4, which is broadly expressed in normal tissues, including kidneys. The Company believes the high level of selectivity will result in very precise delivery of radiation to tumors during treatment.
“We believe Pan-cancer radiopharmaceuticals like our PNT2004 program are going to play a key role in the future of precision oncology,” said Dr. Joe McCann, Chief Executive Officer of POINT Biopharma. “For over a century radiation has been used to treat cancer. A precision radiopharmaceutical that can deliver radiation directly to most solid tumors, while sparing healthy tissue, would be a game changer with both mono and combination therapy opportunities. We are therefore very enthusiastic about the new data and expanded licensing agreement with Bach Biosciences. Looking ahead, we are well underway with the IND enabling studies and clinical design and expect to submit an IND in 1H2022.”
“An ideal radiopharmaceutical “sticks” to tumors but is flushed out of healthy tissue quickly,” said Dr. Neil Fleshner, Chief Medical Officer of POINT Biopharma, “as the longer the radioisotope stays in the tumor, the more DNA damage it can inflict. The tricky part is getting the radioisotope to remain in only the tumor tissue – and that is where PNT2004 really shines. PNT2004’s preclinical data demonstrates the desirable quality of sticking in tumor tissue while being flushed from healthy tissue. This is a tremendously exciting program, and we look forward to continue working with leading physicians and scientists to develop a Phase 1 protocol.”
“We are proud to expand our agreement with POINT and believe they are well-equipped to leverage our FAP-alpha inhibitor-targeting technology to develop the next generation of safer and more efficacious radiopharmaceuticals,” said Dr. William Bachovchin, Chief Executive Officer of Bach Biosciences and Professor of Molecular & Chemical Biology at Tufts University. “I believe that this technology holds great potential for the precision treatment of a variety of solid tumor cancers, as it is differentiated from others with respect to having superior FAP-selectivity and in vivo PK/PD properties, and POINT is the right partner to make it happen. I look forward to a continuing collaboration with POINT to develop PNT2004 and as well as other radioligand treatments to achieve our mutual goal of bringing effective therapies to patients.”
Data Summary:
68Ga-PNT6555 demonstrated fast tumor targeting and good tumor retention with low accumulation in other organs. 177Lu-PNT6555 demonstrated prolonged tumor retention and rapid clearance in normal tissues. 177Lu-PNT6555 showed compelling dose responsive anti-tumor efficacy, with 100% (6/6) of mice dosed at 60MBq and 50% (3/6) of mice dosed at 30MBq achieving tumor free survival at 80 days post-injection. Similarly, 225Ac-PNT6555 also showed anti-tumor efficacy, with 67% (4/6) mice dosed at 50kBq achieving tumor free survival at 70 days post-injection.
