A non-traditional team
sanofi-aventis and Avila Therapeutics sign $800 million-plus deal to develop targeted covalent oncology drugs
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WALTHAM, Mass.—Seeking to expand its oncology pipeline—and proving that it isn't afraid to think outside of the box to realize that strategy—sanofi-aventis has signed a worldwide strategic alliance with Avila Therapeutics Inc. to discover targeted covalent drugs for the treatment of several types of cancer.
The deal, valued at more than $800 million, centers around Avila's Avilomics platform, which Avila uses to design and develop strong, durable covalent bonds that silence challenging disease targets like cancer, autoimmune diseases and hepatitis C.
In a statement released Dec. 20, Dr. Debasish Roychowdhury, senior vice president and head of sanofi-aventis' oncology division, said Avila's expertise in designing targeted covalent drugs "offers a new way to solve difficult pharmacological challenges in oncology and to address important cancer targets."
"We believe that Avila's approach adds to our growing portfolio of research capabilities that will provide medicines which substantially improve patient outcomes," Roychowdhury added. sanofi-aventis did not respond to interview requests.
According to Avila President and CEO Katrine Bosley, the Avilomics platform enables the company to create targeted covalent drugs "to achieve best-in-class outcomes that cannot be achieved through traditional medicinal chemistry." This, Avila says, gives drug developers the power to "treat diseases in new and better ways."
While current drugs are able to inhibit disease-causing proteins, Avila notes that they are generally only able to form transient binding interactions with disease targets. Targeted covalent drugs, Avila says, can do this but also "silence" disease-causing proteins completely by forming a durable bond that shuts down the protein's activity throughout the life of the protein—which typically lasts between a few hours to a few days.
This unique covalent bonding mechanism, Avila says, leads to two primary benefits that sanofi-aventis found particularly attractive: precise selectivity and retained efficacy against mutations. Indeed, sanofi-aventis' CEO, Chris Viehbacher, has spoken quite publicly about the company's strategy of turning to outside partners to increase innovation, particularly in its cancer research efforts.
"sanofi-aventis has a clear vision to transform cancer research, and its commitment to innovation has been very tangible to us as we worked together to establish this alliance," Bosley says. "In any environment where innovation is cultivated, the most quirky and unusual insights usually come from someplace else. That is the environment we have built here at Avila."
Covalent drugs have been developed by pharmaceutical industry in the past and have even included major blockbusters such as omeprazole for acid reflux, clopidogrel for blood clotting and penicillin, but these drugs were discovered "by chance," Bosley says. Avila is the first company to focus on the development of covalent drugs, she says.
While Bosley admits that "some companies have been a bit closed-minded about what we're doing because it challenges conventional wisdom," she says sanofi-aventis was actually attracted by Avila's unique capabilities.
"Quite rapidly, they saw what our potential was, and our discussion turned to what problems we could solve together," she says. "They brought an understanding of different biologies to the table, and we had ideas for programs and suggested them. The process was fun in that we focused on how we could work together."
Under the companies' alliance agreement, which initially spans three years, sanofi-aventis will obtain a worldwide exclusive license to develop and commercialize the compounds resulting from the discovery collaboration. The deal includes $40 million in upfront and research support payments, plus development and regulatory milestones of up to $154 million spread across six different cancer programs, one of which Avila will retain. While the companies are not yet releasing details on the programs, Bosley says, "being that this is a strategic research area for sanofi-aventis, you can imagine that our work has the opportunity to touch diverse tumor types across the six programs."
Avila's lead program, AVL-292, selectively targets Bruton's tyrosine kinase (Btk), an important target in B cell signaling and proliferation and is currently in Phase I development. The company also has a preclinical program centered on inhibitors of the HCV protease. In September 2009, Avila entered into an option agreement with the Novartis Option Fund to advance an undisclosed covalent drug program from Avila's research pipeline in conjunction with an equity investment. In May 2010, Avila inked a deal with Clovis Oncology Inc. to develop and commercialize Avila's epidermal growth factor receptor (EGFR) mutant-selective inhibitor program.
"The past year or so has been very exciting for our company, and we think the tide is turning as far as the industry's interest in covalent drugs and the unique capabilities of our platform," Bosley says. "We were a bit of a lone voice out there for a while, but we knew we had to do things the right way and take our time in creating data to show people that we can address many scientific concerns. Ultimately, that is very exciting for patients who might benefit from these drugs."
The deal, valued at more than $800 million, centers around Avila's Avilomics platform, which Avila uses to design and develop strong, durable covalent bonds that silence challenging disease targets like cancer, autoimmune diseases and hepatitis C.
In a statement released Dec. 20, Dr. Debasish Roychowdhury, senior vice president and head of sanofi-aventis' oncology division, said Avila's expertise in designing targeted covalent drugs "offers a new way to solve difficult pharmacological challenges in oncology and to address important cancer targets."
"We believe that Avila's approach adds to our growing portfolio of research capabilities that will provide medicines which substantially improve patient outcomes," Roychowdhury added. sanofi-aventis did not respond to interview requests.
According to Avila President and CEO Katrine Bosley, the Avilomics platform enables the company to create targeted covalent drugs "to achieve best-in-class outcomes that cannot be achieved through traditional medicinal chemistry." This, Avila says, gives drug developers the power to "treat diseases in new and better ways."
While current drugs are able to inhibit disease-causing proteins, Avila notes that they are generally only able to form transient binding interactions with disease targets. Targeted covalent drugs, Avila says, can do this but also "silence" disease-causing proteins completely by forming a durable bond that shuts down the protein's activity throughout the life of the protein—which typically lasts between a few hours to a few days.
This unique covalent bonding mechanism, Avila says, leads to two primary benefits that sanofi-aventis found particularly attractive: precise selectivity and retained efficacy against mutations. Indeed, sanofi-aventis' CEO, Chris Viehbacher, has spoken quite publicly about the company's strategy of turning to outside partners to increase innovation, particularly in its cancer research efforts.
"sanofi-aventis has a clear vision to transform cancer research, and its commitment to innovation has been very tangible to us as we worked together to establish this alliance," Bosley says. "In any environment where innovation is cultivated, the most quirky and unusual insights usually come from someplace else. That is the environment we have built here at Avila."
Covalent drugs have been developed by pharmaceutical industry in the past and have even included major blockbusters such as omeprazole for acid reflux, clopidogrel for blood clotting and penicillin, but these drugs were discovered "by chance," Bosley says. Avila is the first company to focus on the development of covalent drugs, she says.
While Bosley admits that "some companies have been a bit closed-minded about what we're doing because it challenges conventional wisdom," she says sanofi-aventis was actually attracted by Avila's unique capabilities.
"Quite rapidly, they saw what our potential was, and our discussion turned to what problems we could solve together," she says. "They brought an understanding of different biologies to the table, and we had ideas for programs and suggested them. The process was fun in that we focused on how we could work together."
Under the companies' alliance agreement, which initially spans three years, sanofi-aventis will obtain a worldwide exclusive license to develop and commercialize the compounds resulting from the discovery collaboration. The deal includes $40 million in upfront and research support payments, plus development and regulatory milestones of up to $154 million spread across six different cancer programs, one of which Avila will retain. While the companies are not yet releasing details on the programs, Bosley says, "being that this is a strategic research area for sanofi-aventis, you can imagine that our work has the opportunity to touch diverse tumor types across the six programs."
Avila's lead program, AVL-292, selectively targets Bruton's tyrosine kinase (Btk), an important target in B cell signaling and proliferation and is currently in Phase I development. The company also has a preclinical program centered on inhibitors of the HCV protease. In September 2009, Avila entered into an option agreement with the Novartis Option Fund to advance an undisclosed covalent drug program from Avila's research pipeline in conjunction with an equity investment. In May 2010, Avila inked a deal with Clovis Oncology Inc. to develop and commercialize Avila's epidermal growth factor receptor (EGFR) mutant-selective inhibitor program.
"The past year or so has been very exciting for our company, and we think the tide is turning as far as the industry's interest in covalent drugs and the unique capabilities of our platform," Bosley says. "We were a bit of a lone voice out there for a while, but we knew we had to do things the right way and take our time in creating data to show people that we can address many scientific concerns. Ultimately, that is very exciting for patients who might benefit from these drugs."
sanofi-aventis in two R&D deals with UCSF
SAN FRANCISCO—sanofi-aventis also recently signed two research and development collaborations with the University of California, San Francisco (UCSF): One that seeks to promote innovative research in pharmacological science and in multiple therapeutic areas, such as oncology, aging, diabetes and inflammation; and a second oncology partnership that will focus on project-based collaboration to accelerate the progression of research through the clinical proof-of-concept stage.
sanofi-aventis will be the first industry partner for UCSF's Program for Breakthrough Biomedical Research (PBBR), which awards funding to projects of potentially high impact, greater creativity and with an innovative approach to scientific discovery.
Under the terms of the agreement, a joint steering committee will choose from among UCSF-generated proposals identified for their scientific excellence. sanofi-aventis will fund up to five grants a year, with additional funds being available for students or fellows to intern at sanofi-aventis to conduct collaborative research. sanofi-aventis will also fund an annual research forum that will bring together researchers from both parties to share knowledge and perspectives on relevant scientific matters and to review progress of research projects funded through the collaboration.
Currently entering its 14th year, PBBR provided $42 million in these grants during its first decade alone, which now are credited with drawing more than $300 million in external follow-up funding, as well as generating 900 scientific papers, 30 filed patents, licensed technologies and three startup companies.
