“Two years ago, when I decided to come back to China, I wanted an opportunity to change people’s lives and to help China’s pharmaceutical industry,” said Dr. Jin Li, COO of Shenogen Pharma Group, in an exclusive interview with ChinaBio® Today. Dr. Li was speaking in highly personal terms of his professional odyssey as a returnee, or Hai Gui (literally, “sea turtle”). “If many of us who have an understanding of Western pharma invest and work in China’s companies, we can do that. I will add a little bit, and everybody will add a little bit,” he continued. “But if we do just what Western pharma does, we won’t develop a unique China pharmaceutical pathway.”

Those words say a great deal about Dr. Li. But they also describe his company, Shenogen Pharma Group, which is a combination of Western practices and traditional Chinese medicines. It is also a highly innovative company that, despite its small size, is taking on a very large goal: small molecule and biologic drugs that are potential treatments for breast cancer and obesity.

The story has proved to be compelling. At the recently held ChinaBio® Investor Forum in Shanghai, 21 young companies presented their business plans to the over 80 venture capitalists in attendance, and Shenogen was one of two presenters selected by a panel of 12 of the VCs to win a “Most Promising Company” award. The Investor Forum was organized by ChinaBio® Accelerator, a sister organization to ChinaBio® Today, and hosted by ShanghaiBio Corporation, a rapidly growing CRO in Zhangjiang Hi-Tech Park. (See www.ChinaBioLLC.com and www.shanghaibio.com.

Drug Research

To trace a short history of this young company, about three years ago, one of the four founders of Shenogen, Zhao-Yi (Charlie) Wang, discovered ER-α36, a novel variant of the estrogen receptor, as part of his research at Creighton University in Omaha, Nebraska. Previously, ER-α66 had been considered the main estrogen receptor that mediated estrogen signaling and estrogen-stimulated cell proliferation in estrogen-caused breast cancer. Wang showed that ER-α36 was also a significant participant in the estrogen signaling process. ER-α36 is situated in the membrane. Membrane mediated estrogen signaling had been thought to exist, but its mechanism was never proven until Dr. Wang completed his research.

ER-α66, the long-characterized estrogen signaling receptor that is located in the nucleus, is also the target through which the breast cancer drug tamoxifen works. Tamoxifen, in use for 30 years, is a very successful drug that still produces several billions of dollars of annual revenues for its manufacturers. Generally, it is given for five years following successful cancer treatment to prevent relapse.

According to Shenogen’s website, ER-α36 has considerable sequence homology with ER-α66, but distinguishes itself by a unique C-terminal 27 amino acid sequence. It appears to function through a totally different mechanism. Computer modeling shows that ER-α36 protein is structurally unhindered by the lack of a stretch of helical chain present in ER-α66, resulting in a more open ligand-binding pocket in ER-α36.

Shenogen has found that ER-α36 is expressed in both ER-α66 positive and ER-α66 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-α36 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-α36 continue to proliferate, unhindered by the estrogen dampening effects of the drug, which affects only ER-α66.

“Three years ago, Professor Charlie Wang did the biology work that discovered ER-α36,” 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-α36 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..

Speaking of the process of raising capital for an early project, Dr. Li was very upbeat. “People are willing to talk to us. We have been having discussions [with investors] for the past three to four months,” he said. “The ChinaBio Investment Forum helped get the word out, and the [Most Promising Company] prize will make the process go more quickly,” he added.

The new funding certainly takes Shenogen further than the same amount of money would do in the US. Besides the obvious China advantage, Shenogen makes its money go further by using the virtual model of biopharma development. Shenogen has a strong management team as well as a scientific advisory board. “Professor Elwood Jensen, V. Craig Jordan and Sohaib Khan are distinguished scientists in the ER and breast cancer field. Our R&D will progress rapidly with their help,” Li said. As employees, the company has only the four principals and then 15 managers, who oversee the out-sourced development of Shenogen’s various programs.

Prospects

SNG-162 will be initially investigated as a treatment for tamoxifen-resistant breast cancer, and it will eventually be tested as a first-line breast cancer therapy. However, it has its best chance of becoming a first-line treatment in endometrial cancer, because tamoxifen is known in some cases to cause endometrial cancer.

Dr. Li thinks that SNG-162 could be on the market in as little as five to seven years, if the early clinical tests prove to be positive. He anticipates 14 months to complete Phase I trials and two to three years for Phase II. Phase III trials are too far in the future to fully anticipate.

Besides SNG-162, Shenogen is working on a biomarker that will identify patients with high counts of ER-α36 receptors. This will help characterize the type of breast cancer in an individual patient, and it will also be predictive of the probability for success of tamoxifen.

In addition, work will continue on SNG-162 for the other types of cancer in which estrogen plays a part. Because of the significant of ER-α36 for estrogen signaling, Shenogen feels that monoclonal antibody and siRNA attempts to prevent or treat breast cancer can best be targeted at membrane associated ER-α36. Shenogen owns the IP for this, as it does for most of the ER-α36 centered therapies.

Shenogen is also developing an MTP (microsomal triglyceride transfer protein) inhibitor for obesity. In an early three-week study, SNG-5075 lowered food uptake by 70%.

Summary

Even the company’s name, Shenogen, reflects the commingling of East and West. “Shenogen” was formed from three syllables: Shen Nong Gen. Shen Nong is the name of a famous practitioner of TCM, while Gen connotes the world of modern westernized medicine, once again tying together the pharmaceutical worlds of West and East.

Shenogen is an innovative China biopharma that is using a TCM molecule as a way of treating diseases that affect both patients in both the West and the East. Despite the great advances made in treating breast cancer, much remains to be done. With its new target and new compounds, Shenogen is contributing to Dr. Li’s goal of potentially helping people and China’s biopharma industry. Shenogen is a blend of the East and the West, precisely the goal of Dr. Li when he returned to China.


Disclosure: none.