MELBOURNE, Australia & NANTES, France—Telix Pharmaceuticals Ltd. has announced the completion of a product collaboration and purchase option agreement with Atlab Pharma SAS. Under the terms of the agreement, Telix will finance the manufacturing and clinical development of the huJ591 monoclonal antibody (mAb) radiolabelled with 177Lu (Lutetium) and 211At (Astatine), both promising “theranostic” products for the treatment of metastatic prostate cancer. The huJ591 mAb was originally developed by Dr. Neil Bander at the Weill Cornell Graduate School of Medical Sciences in New York and targets prostate-specific membrane antigen (PSMA), a well-validated target in prostate cancer.
The parties will collaborate to manufacture clinical material and work together to execute a multi-centre Phase 2b trial for the treatment of men with metastatic prostate cancer, with and without end-stage chemotherapy (standard care). In financing development, Telix also obtains an exclusive option to acquire Atlab under pre-agreed terms. The financial terms of the option exercise are not being publicly disclosed at this time.
Telix CEO Chris Behrenbruch stated, “PSMA targeting radiopharmaceuticals have shown great promise in both the diagnostic and therapeutic setting, dramatically increasing the interest in targeted radionuclide therapy by mainstream biopharma. The 177Lu-huJ591 program is the most clinically advanced PSMA program and has extensive patient experience, including in conjunction with anti-androgens and chemotherapy. We are very pleased to be working with Atlab to add this very promising program to Telix’s development pipeline.”
Atlab President, Dr. Jean-Marc Le Doussal commented, “As we learn more about the different strategies to deliver PSMA-targeting radiopharmaceuticals in the clinic, the advantages of antibody-directed approaches have become increasingly apparent. We are pleased to be working with the experienced team at Telix to further progress this very promising program.”
“Radioimmunotherapy is finally starting to hit its stride and garner the interest it deserves. In the clinic, we have seen targeted radionuclide therapy deliver impressive treatment responses, even in late stage patients,” added Prof. Jean-François Chatal, co-founder of and chief medical adviser to Atlab. “We are especially keen to use programs like 177Lu-huJ591 in conjunction with other immuno-oncology agents that have generally demonstrated lackluster performance in the mCRPC setting.” Chatal will also join Telix’s scientific advisory board.
PSMA is a cell surface antigen that has relatively little normal expression in normal tissues and represents a validated and highly promising target for a range of therapeutic strategies, especially radiopharmaceuticals. PSMA expression has been detected in a limited range of normal tissues including benign prostatic epithelium, renal proximal tubule, pancreas, small bowel and brain (a subset of astrocytes). However, these normal sites express PSMA at levels two to three orders of magnitude lower than that observed in prostate cancer.
Antibody-directed cytotoxicity (whether from conjugated radiation or other therapeutic payloads) offers several advantages over small molecule or peptide-based delivery approaches. Normal tissue PSMA sites are highly polarized to the apical/luminal aspect of the benign prostatic glands, renal tubules and small bowel, basement membrane and epithelial tight junctions, and as such are effectively inaccessible to circulating mAbs. PSMA expression by astrocytes is similarly sequestered behind the blood-brain barrier. Consequently, antibodies to PSMA are functionally tumor-specific, whereas small molecule PSMA ligands excreted via the renal tubular lumen are not. Small molecule and peptide therapies targeting PSMA, with various isotopes, have demonstrated serious off-target effects, such as pancreatitis, nephrotoxicity and permanent salivary gland ablation. These considerations are particularly important for developing PSMA-targeting agents with high-energy nuclides such as alpha-particle emitters.
The huJ591 (humanized) mAb is the most clinically-advanced anti-PSMA antibody, with several hundred patient doses for both imaging and therapy, both as a “naked” antibody and with a wide range of diagnostic and therapeutic payloads. Over 160 patients have been dosed with 177Lu-huJ591 at different dosing levels, and in combination with other standard care therapies in the metastatic castrate-resistant prostate cancer (mCRPC) setting. In over a dozen clinical trials, including with therapeutic radioimmunoconjugate forms, huJ591 has shown excellent immunogenicity, safety and tolerability, including with repeat dosing.