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Portola in the News

BioWorld Today
October 28, 2011
By Marie Powers

Fresh off a big score at the Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis conference in Amsterdam, the Netherlands, for its oral multiple sclerosis immune modulator BG-12, Biogen Idec has inked a multi-milliondollar deal with privately held Portola Pharmaceuticals Inc. (See BioWorld Today, Oct. 24, 2011)

The exclusive, worldwide collaboration and license agreement calls for the companies to develop and commercialize highly selective, oral spleen tyrosine kinase (Syk) inhibitors for the treatment of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The deal has some conventional terms as well as some interesting twists. Weston, Mass.-based Biogen will provide Portola, of South San Francisco, with an up-front payment of $36 million in cash and purchase $9 million in Portola equity. Biogen also will make additional payments of up to $508.5 million based on the achievement of development and regulatory milestones.

Biogen will lead the global development and commercialization efforts for the Syk inhibitor program in major indications such as RA and SLE, while Portola will focus on U.S. development and commercialization efforts for smaller indications and discovery efforts for followon Syk inhibitors. Portola retains an option to co-promote alongside Biogen in the U.S. in major indications.

The companies also will split worldwide costs and profits on a 75/25 basis for Biogen and Portola, respectively. Both companies touted the deal as a win-win and talked like a couple in love.

“Biogen is a true biotech innovator, both in immunology and in the area of B-cell disorders,” Portola CEO William Lis told BioWorld Today. “We got to know the executive team very well. We share a lot of the same DNA, and that sets the course for a collaboration that is somewhat unique: a worldwide co-development profit-sharing deal.”

For its part, Biogen was “very impressed with the science” underlying not only the lead Syk inhibitor, but also backup compounds, according to Biogen spokeswoman Naomi Aoki.

“Based on the preclinical and early clinical data that we’ve seen to date, we think the Syk inhibitor has the potential to be a best-in-class oral treatment for rheumatoid arthritis, lupus and other autoimmune diseases,” she said. “For us, this was a perfect strategic fit.”

The collaboration’s lead molecule, PRT062607, has been shown to be a potent and specific oral inhibitor of Syk in a broad panel of in vitro kinase and cellular assays and is currently in Phase I studies. Results, to date, suggested the compound is well tolerated and has a suitable profile for once-daily dosing.

Portola had been examining the potential to partner its Syk inhibitor program “for some time” and had been approached by multiple companies that were interested in the broad range of oral molecules that might emerge from the platform, Lis said.

“With that level of interest, we thought about partnering at an earlier stage than is fairly traditional,” he admitted, seizing the potential to negotiate terms that would favor Portola and put additional wind behind the company’s sails to advance its in-house programs.

That decision worked in Biogen’s favor as a suitor, since the larger biotech has been seeking to bulk up its early stage pipeline.

“We’ve got a tremendous number of programs in latestage clinical development,” but Phase I and II programs are lagging, Aoki told BioWorld Today. “It’s a priority for us to fill in our early and midstage pipeline.”

Both companies said the Syk inhibitor would likely move into Phase II studies next year.

In addition to the Syk clinical programs, Portola is developing oral specific inhibitors of Janus Kinase (JAK) and dual inhibitors of Syk and JAK for chronic autoimmune indications and oncology.

However, Portola’s most advanced programs involve antithrombotic agents. Earlier this year, the company took back rights to betrixaban, a Phase III-ready, long-acting, oral direct Factor Xa inhibitor, from Merck and Co. Inc., of Whitehouse Station, N.J., after the pharma giant reprioritized its late-stage investigational portfolio and failed to find a place for betrixaban. (See BioWorld Today, March 25, 2011)

Portola is now committed to progressing the betrixaban program internally, with Lis citing a 30-month timetable for the drug “potentially to be a first-to-market compound” to prevent clots in acutely ill patients in the hospital and subacute settings.

“Thus far, no one has been successful in demonstrating efficacy and safety for an anticoagulant” for that indication in both settings, he said. “We want to keep this in-house because we know this area of development and this market the best.” At this point, Portola intends to commercialize betrixaban in the U.S. and seek a marketing partner for global commercialization.

The company also has a partnership with Novartis Pharma AG, of Basel, Switzerland, to develop both intravenous and oral formulations of elinogrel, an antiplatelet that is a direct-acting, competitive and reversible P2Y₁₂ ADP receptor antagonist. (See BioWorld Today, Feb. 13, 2009.)

The compound, which is scheduled to move into Phase III in the coming months, could prove a formidable competitor to blockbuster Plavix (clopidogrel bisulfate, Sanofi -Aventis Group and Bristol-Myers Squibb Co.).

In addition, Portola has demonstrated in an animal model that a third agent, a recombinant Factor Xa inhibitor antidote known as PRT064445, can reverse the pharmacodynamic effects of anticoagulation by enoxaparin, a low molecular weight heparin, and fondaparinux, and reduce blood loss caused by those compounds.

Overall, the programs mesh nicely with Biogen’s strategic decision to focus on neurodegenerative diseases, immunology and hemophilia.

Portola plans to expand its work force selectively to explore some of the broader indications in its kinase platform.

“The cash, the milestones, the resources and the expertise that we get from Biogen sets up our company to advance the selective Syk inhibitor into Phase II into 2012, to advance betrixaban into Phase III independently, and to advance our other programs into the clinic,” Lis said.