Computer modeling shows that ER-a36 protein is structurally unhindered by the lack of a stretch of helical chain present in ER-a66, resulting in a more open ligand-binding pocket in ER-a36.

Shenogen has found that ER-a36 is expressed in both ER-a66 positive and ER-a66 negative breast cancer, as well as Her-2 positive and Her-2 negative breast cancers. It proved, moreover, in a retrospective study of 700 cases of breast cancer, to be associated with the most severe cases of breast cancer.

Although tamoxifen has been a significant tool in the fight against breast cancer, patients eventually develop resistance to the drug. Shenogen thinks ER-a36 may be the cause of the resistance because it continues to function as an estrogen receptor in patients who are given tamoxifen. Cells that express only ER-a36 continue to proliferate, unhindered by the estrogen dampening effects of the drug, which affects only ER-a66.

“Three years ago, Professor Charlie Wang did the biology work that discovered ER-a36,” said Dr. Li. “He wondered if it was possible to find an NCE for this target. He gave many talks in China, and finally he met Dr. Meng.” Dr. Kun Meng, CEO of Shenogen and also a founder, received his advanced biological education in at Harvard and then worked for China pharmaceutical companies. He is an expert in TCM, with an extensive library of TCM compounds. “They talked about the aspects of the estrogen receptor, and after screening Dr. Meng’s library of TCM molecules, found several candidates for the target,” reported Li. That was the genesis of Shenogen.

The company’s lead molecule is SNG-162. It has been a part of TCM for many years, usually given for women-specific maladies. As a drug with a long history of use, it is not expected to have significant side-effects. All of the pre-clinical work has been completed, and Shenogen has submitted the compound to the SFDA for approval to begin human clinical trials. There is normally a long wait for a ruling at this stage, lasting from eight months to more than a year. Shenogen is filing its IND through the “Green Pass” category, which is given to innovative drugs for an unmet need. Because the “Green Pass” speeds up the process, Li hopes to hear from the SFDA within eight months.

Preclinical studies show that SNG-162 has considerable efficacy against the various forms of cancer in which estrogen is considered a cause: breast, ovarian, prostate, and tamoxifen-resistant endometrial cancer. So far, up to its highest dose, SNG-162 has not caused any dose-limiting toxicity.

Besides SNG-162, Shenogen is also working on NCEs that affect the ER-a36 receptor. In preclinical studies, these molecules are more effective than SNG-162, though their side-effect profile will be more open to question than the long-used, TCM-based, SNG-162.

Funding

Shenogen has reached this point in its corporate history with the backing of just $1.7 million in angel funding, most of it coming from fellow returnees. It is in the hunt for $5 million to $6 million in new money to carry the company forward and perform clinical trials..