Platform Start-Up Anaphore And Mitsubishi Tanabe Ink Deal For Autoimmune Therapies

Anaphore's novel Atrimer platform creates trivalent protein drugs to bind all three domains on trivalent ligands and receptors, a presumed advantage over two-armed antibodies.

Anaphore, Inc., a La Jolla, CA, start-up with a novel platform for developing trimeric proteins called Atrimers, has partnered with Mitsubishi Tanabe Pharma Corporation to work on autoimmune diseases.

The $5 million upfront on the deal reflects the current risk-sharing climate for early stage assets, but the validation that comes with a first industry partnership is solid gold for Anaphore.

"This first partnership does a great job of validating our technology platform," CEO Katherine Bowdish said in an interview. While the company plans to form additional partnerships that allow it to explore the potential of its platform in a variety of therapeutic areas, as well as to develop some candidates in-house, "we're excited to be working with a new partner," she said. Mitsubishi Tanabe is a mid-tier Japanese pharma with broad interests and global licensing relationships.

Under the terms of the deal, Mitsubishi Tanabe will make the upfront payment for an initial, undisclosed, target and contribute research funds. Tanabe Research Laboratories, in San Diego, has the option to nominate two additional autoimmune targets against which Anaphore would develop potential protein therapeutics. Anaphore is eligible for an addition $110 million in milestones and tiered royalties on sales if a product reaches market. The terms for the three potential candidates are substantially the same, Bowdish said.

Anaphore will work continuously with TRL on the early studies and with the parent pharma as the program moves into the clinic and into development, she said.

Anaphore's Atrimer Pipeline

Anaphore has a number of programs moving forward in various stages in oncology and in immunology, most of which are focused on a class of targets called the TNF super-family, a large class of trimeric proteins that binds to trivalent receptors, including, for example, the death receptors BAFF, APRIL and CD70. What makes Atrimers unique is their ability to bind all three receptors at once, creating a "full lock" on each of the three subunits of the target ligand or receptor.

Each of an Atrimer's binding domains has distinct amino acid loops that Anaphore can program to bind specifically to any target of interest and activate or suppress the target, differentiating Atrimer proteins from those created by other next-generation antibody or alternative scaffold programs, Bowdish said. Anaphore is particularly interested in using Atrimers to activate a receptor, such as the death receptor DR4, for example, to trigger cell death in solid tumors. The company has data suggesting Atrimers can do a better job at that than antibodies because of their trivalent binding ability, as opposed to binding by the two arms of an antibody, she said.

The company's most advanced candidate, ATX3105, antagonizes the interleukin-23 receptor, which is known to play a role in a variety of autoimmune disorders. The Atrimer has demonstrated potent and selective inhibition of the Il-23 pathway, according to Anaphore.

TRL, an independent subsidiary of Mitsubishi Tanabe, was founded in 1990 with a focus on small molecule drug discovery in metabolics and inflammation/immunology. Earlier in 2010, the reorganized laboratories began operating with a new focus on antibody and biological approaches to target specific immune cells and soluble factors, as well as investigating new methods for modulating immune cell functions - all aimed at developing biologic drug candidates for autoimmune diseases.

The deal appetite of Mitsubishi Tanabe and its peers, along with the industry trend toward risk-sharing deals, is making Japanese pharma attractive partners for U.S. biotechs. And the Japanese companies are more willing to enter these earlier-stage deals at a time when the number of large Western pharmaceutical companies is shrinking due to consolidation (Also see "Japanese Pharma, Hungry For Global Deals, Can Fill Gap of Shrinking Partners - PharmAsia Summit" - Scrip, 5 Nov, 2010.).

Partnering Is Part Of The Drill For Platform Start-Ups

Anaphore started out as a project of 5AM Ventures, which bought the technology and intellectual property from a Danish university spin-out that was failing to make a go of it, then brought Bowdish onboard in 2007 to run the company.

5AM and Versant Ventures had already put in $8 million in seed capital before the Series A, which initially closed in January 2009, pulled in $17 million from a syndicate that included Apposite Capital in addition to the two seed backers. A few months later the company announced a second closing that brought in an additional $13 million from SR One, Serono Ventures and Aravis SA, for a grand total of $38 million.

But biotechs, particularly platform-based ones, as well as their VC backers, are operating under a new capital-efficient reality these days. Even a lean, post-apocalyptic platform company is expensive to build, and a venture-backed company that has raised as much as $30 million or $40 million could still find its options severely limited without bringing in additional non-dilutive income.

According to Andy Schwab, a founder and managing partner at 5AM, platform companies are by definition partnering companies. 5AM, which has about a third of its portfolio in platform plays like Anaphore, sees partnering as a key driver of success for those companies.

-Shirley Haley ([email protected])