Avila Therapeutics: Exquisite targeting, compelling chemistry
Avila's CEO Katrine Bosley
With a platform to design and develop covalent drugs that have the depth and breadth to treat viral infections, cancers and autoimmune diseases, Avila Therapeutics in just three years has attracted USD 51 million in financing, and in July announced an option agreement with Novartis valued at USD 200 million in upfront payments and milestones.
Driving this rapid growth is a powerful therapeutic approach called ‘protein silencing’ that holds a promise for drugs that strongly and resiliently bond to specific disease-causing proteins, thereby ‘silencing’ them.
“Our Avilomics™ platform is proving to be even more productive than we initially believed it would,” Avila CEO Katrine Bosley told partneringNEWS™.
“Our chief scientist, Juswinder Singh, has significantly expanded the possible applications for covalent drugs” she explained. “From a strategic standpoint, there is no way that within the four walls of the company, Avila could develop all of this potential.”
“The agreement with Novartis represents a great first step on a strategic path where we plan to keep certain products in-house for our own development and will work in collaboration with a few, select partners on other programs,” Bosley added.
“We believe it is important in an alliance to establish solid relationships that will create value for our partners while at the same time retaining value for ourselves to continue building the long term potential of Avila” she said.
Two products Avila is developing in-house that Bosley confirmed are on track to move to clinical stages in 2010 are a small molecule Hepatitis C virus (HCV) protease inhibitor called AVL-181, and a Bruton’s tyrosine kinase (Btk) inhibitor for the treatment of B-cell malignancies and autoimmune diseases called AVL-292.
In October, Avila reported data at the International Symposium on HCV and Related Viruses in Nice, France, showing that AVL-181 bonds selectively and irreversibly to HCV protease (NS3/4A) to silence a key protein necessary for viral replication, and demonstrated the amount of HCV protease silenced by AVL-181 was measured in a dose- and time-dependent manner.
In April, Avila presented preclinical results from its Btk program at the American Association for Cancer Research (AACR) annual meeting. The data demonstrated that this approach may represent a best-in-class new therapeutic option. Avila’s product candidate was potent and demonstrated exquisite selectivity compared to previously reported Btk inhibitors, and did not inhibit other kinases, such as Lyn and Syk, that may cause toxicity.
Through their unique ability to completely ‘bond’ with a protein drug target, even during brief exposure, Avila’s drugs effectively ‘silence’ the targets, and these targets remain silenced until new protein is synthesized.
Avila expects that covalent drugs generated by the Avilomics platform can solve the critical therapeutic challenges of drugging difficult targets and addressing resistance mutations. In addition, the covalent mechanism leads to a prolonged duration of action, in contrast to most current drugs which need to maintain high exposure as the protein-drug interaction is transient. The benefits of this include the potential for better efficacy, less frequent dosing and less overall drug exposure that should improve safety.
In an interview with BioWorld Today, Henry Skinner, managing director of Novartis Venture Funds, explained the immediate attraction of Avila’s science. “They’ve taken a highly innovative approach to covalent inhibition, and there is some chemistry around that, which is very compelling,” he said . Skinner is a member of the Board of Directors for Avila Therapeutics.
Through its systematic approach to covalent drug discovery, Avila has developed a “core competency and proprietary know-how that others simply won’t have, primarily because while covalent inhibition has been around for decades, it largely has been an ad hoc approach,” Skinner said.
While other pharma developers have used the covalent approach “at moments of convenience and then gone on to other things,” Avila’s systematic and focused approach is “establishing the rules for covalent inhibition and how to be successful with it and all of the nuanced issues around it,” he said.
Avila knows, of course, that it has much yet to prove. With its most advanced programs still in preclinical development, there is much work ahead. But the vision of the team is ambitious. “To have the opportunity to create a whole new category of small molecule medicines is very rare,” said Bosley. “We believe we have a new way to develop drugs with improved profiles due to covalent bonding. This is an approach that builds on principles that pharma companies understand well and we think they’ll want to be a part of it.”
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