An experimental lung cancer drug discovered at Boston’s Dana-Farber Cancer Institute is currently at the center of a lawsuit involving Dana-Farber, Swiss drug giant Novartis, and Millbrae, CA-based Gatekeeper Pharmaceuticals. But while that complicated case continues to unfold, Waltham, MA-based biotech startup Avila Therapeutics is working on a similar molecule, which is designed to treat certain drug-resistant forms of lung cancer.
Avila, founded in 2007, has gained wide attention for its covalent drug chemistry, which enables drug molecules to form strong bonds with disease proteins and block their activity. Its lead molecules target hepatitis C virus as well as a protein involved in certain B cell cancers and autoimmune diseases. The durable bonds its drugs are designed to form with disease proteins offer potential advantages such as reducing the dosages patients need to take for the therapy to be effective and limiting treatments’ toxic side effects.
Since this spring, Avila has been applying its covalent drug technology in a $209 million partnership with Boulder, CO-based Clovis Oncology to discover new treatments for non-small cell lung cancers that are resistant to Roche and OSI Pharmaceuticals’ blockbuster cancer pill erlotinib (Tarceva) and AstraZeneca’s gefitinib (Iressa). The cancer’s resistance to those existing therapies is often linked to a mutation (called the T790M mutation) in the gene for a protein called an epidermal growth factor receptor (EGFR).
There’s a huge amount of interest in new lung cancer treatments among drug developers. Lung cancer is the leading cause of cancer deaths among men and women in the U.S., according to the National Cancer Institute. Non-small cell lung cancer, the most common type of lung cancer, is fueling a lot of the activity; New York-based drug giant Pfizer and German drug maker Boehringer Ingelheim both have drugs for this type of lung cancer in late-stage clinical trials, for example. There are many more companies at earlier stages of developing drugs against non-small cell lung cancer.
Even though Avila’s and Dana-Farber’s efforts in this crowded field are relatively young, both are notable because they aim to produce drugs that target tumor cells with a specific mutation of EGFR linked to drug resistance while sparing healthy tissues. Studies indicate that most patients who take erlotinib or gefitinib develop resistance to the drugs most often after a year, and the T790M mutation is involved in half of those cases of resistance. “That’s a real motivator to try to develop a drug candidate as soon as possible,” said Katrine Bosley, Avila’s CEO. “I think that’s why there is such a strong interest in this area—because it’s such a real clinical problem.”
Avila and Clovis are hoping to ask the FDA for permission to begin human studies with a drug from their ongoing research collaboration by the end of 2011 or early 2012, Bosley said. It’s unclear when the Dana-Farber molecule is going to begin being tested in humans; the case is pending, and the parties involved in the case at Dana-Farber, Gatekeeper, and Novartis have declined to comment on the program.
Dana-Farber’s researchers’ work in this area predates the collaboration that Avila and Clovis announced in May, however. The Dana-Farber scientists and their colleagues published their findings about a molecule against drug-resistant lung cancer in a 2009 paper in the prestigious journal Nature. The group showed its molecule could bond covalently with mutated forms of the EGFR protein while having limited effects on the normal form of the protein in lab experiments. Since the normal EGFR protein plays important roles throughout the body, limiting a drug’s interaction with it could potentially reduce side effects on healthy tissues.
“The Nature paper from the Dana-Farber folks certainly brought more attention to the area in terms of demonstrating the possibility of hitting this profile that really matches up with the clinical need,” Avila’s Bosley said.
In March 2009, Dana-Farber researchers and others co-founded Gatekeeper to commercialize their molecule and related ones as treatments for resistant lung cancer. The firm gained an option to license the technology in June 2009 from Dana-Farber. In August, however, Dana-Farber informed the startup that it believed the technology was subject to the cancer institute’s collaborative research agreement with Novartis. The Swiss drug maker has the first option to license discoveries at the cancer institute that are funded through that agreement. In September, Dana-Farber filed suit against Gatekeeper, asking the court to declare that it has “complied with its obligations under the Gatekeeper Option Agreement” and to excuse the cancer institute from “any further performance under” the agreement.
The dispute calls into question which company will take Dana-Farber’s molecule into clinical trials. Yet the rival program at Avila appears to moving ahead with financial support from Clovis.
Avila’s drug is designed to block multiple mutations of EGFR, including T790M, with a single molecule, making it a potential first-option treatment for non-small cell lung cancer as well as a potential treatment for patients whose tumors have developed resistance to erlotinib or gefitinib. Avila’s potential edge over others in developing such a molecule is that it has a broad platform and proven track record discovering covalent drugs against specific targets, Bosley says, and its partner, Clovis, has extensive experience in cancer drug development.
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