Synta Pharmaceuticals has announced the publication of the company's first patent application covering its proprietary Hsp90-inhibitor drug conjugate (HDC) platform, which leverages the company's expertise in chaperone biology and medicinal chemistry to create a new class of anti-cancer therapies.
The patent application covers Synta's proprietary HDC technology, including composition of matter claims covering over 400 HDC compounds synthesized by Synta to date, methods for identifying therapeutically effective compounds, and methods of use against a wide range of diseases and conditions.
Hsp90 is a chaperone protein required by many cancer cells to maintain the stability and function of numerous proteins that drive cancer cell growth, survival, and metastasis.
Small molecule inhibitors of Hsp90, including Synta's drug candidate ganetespib as well as first-generation inhibitors such as 17-AAG and its derivatives, are retained in tumors for as much as 20 times longer than in blood or normal tissue.
These properties are believed to be due to overexpression of an active form of Hsp90 in cancer cells as compared to normal tissues, and have been recently applied for tumor imaging.
HDCs are drugs consisting of an Hsp90 inhibitor (targeting moiety) joined to an anti-cancer agent (payload) via a cleavable chemical linker optimized for controlled release of payload drug inside cancer cells.
Because HDCs are small molecules, they diffuse into the cell passively, avoiding reliance on cell surface antigens or transporters, as is required by other delivery mechanisms such as antibody-drug conjugates (ADCs).
The longer retention of Hsp90 inhibitors in tumors results in higher concentration and longer duration of active payload drug inside cancer cells than occurs with standard administration of unconjugated chemotherapy or other payloads.
This enhanced delivery creates the potential for greater cancer cell killing and reduced side effects.
Synta has developed over 400 HD-Conjugated chemotherapeutics, kinase inhibitors, hormone therapies, immunomodulators, and epigenetic modifiers, creating the potential for next-generation compounds in each of these categories.
Examples include HD-Conjugated bendamustine, temozolomide, doxorubicin, 5-FU, pemetrexed, SN-38, topotecan, vorinostat, panobinostat, fulvestrant, abiraterone, lenalidomide, pomalidomide, docetaxel, carboplatin, bortezomib, sunitinib, and sorafenib.
Proof-of-concept has been demonstrated in preclinical models of cancer, showing both improved delivery, including greatly increased concentration and duration of payload in tumors as compared to plasma and normal tissues, as well as significantly improved anti-tumor activity compared to administration of unconjugated payload in animal models of cancer.
Synta president and CEO of Dr Safi R Bahcall noted the company is excited about realizing the potential of this new class of anti-cancer therapies.
"We plan to selectively partner certain HDC therapeutic classes, in order to advance the potential to improve delivery of both approved and investigational anti-cancer agents across a broad range of oncology indications," Dr Bahcall added.
