Pharmaceutical giants Pfizer and Novartis were first to gain regulatory approval with drugs that block a pair of enzymes important to tumor growth in breast cancer. Clinical-stage biotech G1 Therapeutics has a different approach to those same enzymes and will ask investors in the public markets to get on board.
Research Triangle Park, NC-based G1 has filed for an initial public offering that could raise up to $115 million. G1 has yet to work out the number of shares it will offer and at what price. It has applied for a stock listing on the Nasdaq exchange under the stock symbol “GTHX.”
G1’s research focuses on two enzymes: cyclin-dependent kinases 4 and 6 (CDK4/6). Some cancers rely on these enzymes, so targeting them has become the basis for a new class of drugs. The Pfizer (NYSE: PFE) drug palbociclib (Ibrance) was the first CDK4/6 inhibitor to reach the market, approved by the FDA in 2015 to treat advanced breast cancer. Pfizer’s financial filings show that the drug accounted for more than $2.1 billion in 2016 sales, making it the company’s top revenue-generating cancer drug. Last month, the FDA approved the Novartis (NYSE: NVS) CDK4/6 inhibitor ribociclib (Kisqali) for advanced breast cancer.
G1’s lead drug trilaciclib is also a CDK4/6 inhibitor. But G1 has developed the intravenous drug not to kill cancer cells but to protect healthy cells in lung and breast cancer patients who are also taking chemotherapy. It would only be for patients with cancer that does not depend on the CDK4/6 enzymes.
Chemotherapy can be effective in killing cancer cells, but it also harms healthy cells. G1 wants trilaciclib to block CDK4/6 in these healthy cells, which would pause their division. If the cells don’t divide, they should be protected from the toxic effects of chemotherapy.
If all works according to plan, patients’ healthy cells would resume normal division after chemotherapy. G1 is currently recruiting cancer patients for two Phase 2 studies in small cell lung cancer, as well as one Phase 2 trial in triple negative breast cancer. The company expects initial data from these trials sometime next year, it says in its prospectus.
Trilaciclib is also being tested in combination with another class of cancer drugs called checkpoint inhibitors, such as Roche’s atezolizumab (Tecentriq).
A second G1 drug, G1T38, is in development for cancers that depend on the CDK4/6 enzymes. This once-daily pill would compete directly with the Pfizer and Novartis CDK4/6 inhibitors, and potentially the Eli Lilly (NYSE: LLY) drug abemaciclib, which is in a Phase 3 clinical trial. G1 says in its prospectus that it believes it can “improve upon and address the shortcomings” of drugs from Pfizer, Novartis, and others. Early data show the potential for continuous daily dosing compared to the Pfizer and Novartis drugs, which are administered on a schedule of 21 days on, then seven days off. G1 also says that in early studies G1T38 has shown promise of greater safety than its rivals in the areas of immunosuppression and liver toxicity.
G1 plans to start a Phase 2 study in 2018 in non-small cell lung cancer. A separate Phase 2 trial in patients whose breast cancers are dependent on CDK4/6 is also expected to start next year.
Late last year, G1 added on to its pipeline by licensing a compound the University of Illinois. The company expects this compound, called G1T48, would be used in combination with G1T38. G1 expects to file the application to start clinical trials on G1T48 in the fourth quarter.
G1 Therapeutics was founded in 2008 as G-Zero Therapeutics, spun out of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill. The company’s science is based on the research of Norman Sharpless, now the director of the Lineberger Center, and Kwok-Kin Wong, an oncologist and researcher at Dana-Farber Cancer Center and Harvard University. The company is led by CEO Mark Velleca, who previously co-founded and served as senior vice president of Connecticut-based CGI Pharmaceuticals until its 2010 acquisition by Gilead Sciences (NASDAQ: GILD). In 2012, G-Zero changed its name to G1 Therapeutics, a reference to the G1 phase of the cell cycle that the company’s drug pauses.
Last year, G1 spent $25.1 million on research and development, according to its filings. Its cash reserves of $47.3 million as of December 31 should be enough to fund the company for two more years, G1 says in its filings. G1 plans to use the IPO proceeds to continue clinical development of its drug pipeline. The company also says it may use the funds for acquisitions or licensing deals that complement its pipeline, though it adds that it has no such deals in place.
G1 has raised $95.8 million in equity financing, most recently a $50 million Series C round of investment last May. The company’s largest stockholders include Hatteras Venture Partners, MedImmune Ventures, Eshelman Ventures, RA Capital, and Lumira Capital.
Triple-negative breast cancer image by Kevin Janes of the National Cancer Institute.