Synthon Biopharmaceuticals Reports Positive Early Results With Its Second Generation HER2-Antibody-Drug Conjugate

Best-in-Class potential with improved therapeutic index compared to other armed antibodies

Synthon Biopharmaceuticals, a subsidiary of specialty pharma company Synthon, has reported promising results with its lead program of antibody-drug conjugates (ADCs). In pre-clinical xenograft studies using patient-derived breast cancer and non-small-cell lung cancer material, Synthon has reported complete tumor remission. Toxicity experiments conducted to-date have revealed Best-in-Class potential with a greatly improved therapeutic index compared to other armed antibodies, due to an impressive safety profile. The company has also opened a state-of-the-art GMP facility in Nijmegen for the production of ADCs up to phase III clinical trials and early launches.

ADCs are a new type of targeted therapy that combines a specific anti-cancer antibody or antibody fragment linked to a potent anti-cancer therapeutic. The aim for this class of therapy is to combine better tumor penetration and killing properties with lower side effects for cancer patients. 

Dr. Marco Timmers, chief scientific officer at Synthon Biopharmaceuticals said: "Synthon's first ADC program incorporates the HER2-binding antibody trastuzumab. The primary objective is to develop a broad therapeutic spectrum by targeting tumors that over-express HER2, such as metastatic breast cancer and non-small-cell lung cancer.  As a result of our unique linker-drug technology, this ADC program is delivering on its promise and giving us exciting preclinical results with the opportunity to become a Best-in-Class therapy."

In several xenograft models, including primary human breast cancer and non-small-cell lung cancer xenografts, Synthon's HER2-ADC dosed alone induced complete tumor remission, whereas with the antibody alone there was no effect. Toxicity studies conducted to-date have revealed that clinically effective doses are not likely to show serious side-effects since the difference between effective and toxic doses, the so-called therapeutic index, has been improved with at least one order of magnitude compared to competitor ADC technologies.

Synthon's proprietary ADC linker-drug technology is based on duocarmycin analogs. The differentiating design of Synthon's linker connecting the antibody to the duocarmycin drug, leads to high stability in circulation and also induces efficient release of the cytotoxin in the tumor cell. A key feature of Synthon's duocarmycin technology involves disruption of the DNA of (solid) tumor cells at any phase of the cellular cycle unlike many other ADCs which only attack tumor cells in a mitotic state. Another feature of duocarmycins is that these cytotoxins can also be effective against tumor cells that are multi-drug resistant. 

With the newly opened GMP facility available, Synthon will enter its drug candidate into clinical trials in 2014. Dr. Timmers added: "We strongly believe that advancing this second generation ADC technology will lead to a new class of effective, targeted medicines in oncology. Our GMP plant will also accelerate future patient access to oncology products based on this pioneering technology."

In addition to its ADC directed against HER2, Synthon is currently developing two other ADC programs for multiple indications in oncology. Depending on the indication, projects will be progressed independently until registration or will be co-developed/licensed out at an appropriate (pre-)clinical stage. Synthon also offers its linker-drug technology and manufacturing capabilities to external partners for conjugation to their own proprietary monoclonal antibodies.