Micro-Partnerships With Academia Helping To Drive Bristol’s Pipeline Development

New agreement with Duke Translational Medicine Institute highlights Bristol-Myers Squibb’s particular approach to collaborating with academia – small, low-money partnerships that get pharma and university scientists working together in an atmosphere virtually free of corporate bureaucracy.

Recent years have seen the announcement of some major partnerships between big pharma and university researchers and medical centers, with companies like Pfizer Inc. and Sanofi at the forefront of developing such collaborations. While Bristol-Myers Squibb Co. also makes a priority of accessing the innovation available at the university level, it prefers to work through what it calls “micro-partnerships” that involve little or no money but also are almost free of bureaucratic red tape.

An example of this approach is a collaboration announced Feb. 28 between Bristol and the Duke Translational Medicine Institute (DTMI) at Duke University in Durham, N.C. Building on a decade of working together, the partnership will focus first on developing a Phase II protocol for BMS-986202, the pharma’s investigative compound for idiopathic pulmonary fibrosis (IPF), but also may extend to development of other compounds through proof-of-concept, improving enrollment in clinical trials and developing disease educational programs.

In announcing the collaboration, Bristol noted that it had worked with DTMI researchers in numerous areas in recent years, including cardiology, endocrinology and oncology. Most recently, DTMI assisted in patient and clinician education related to the ARISTOTLE trial for the Bristol/Pfizer-partnered novel anticoagulant Eliquis (apixaban). On March 1, the companies announced that FDA had extended the PDUFA date for Eliquis three months back to late June, sparking expectations that an advisory committee review might be necessary (Also see "Eliquis Delay Fuels Speculation About Advisory Committee Meeting" - Pink Sheet, 1 Mar, 2012.).

Brian Daniels, Bristol’s senior VP, global development and medical affairs, noted the agreement with DTMI does not call for any financial commitments on either side, but was driven by the company “noticing a lot of our scientists within BMS going down to Duke to have discussions about various types of projects.” The goal simply is to increase collaboration between the company and DTMI in a variety of areas, he said in an interview.

“In general, our observation has been that the optimal industry/academic relationships really occur where there is scientist-to-scientist interaction in areas of shared interest,” Daniels said. “That’s what this relationship represents to us, a broad focus all the way from potential discovery with a sweet spot in translational medicine further down into development and scientific exchange all the way to patient, physician, nurse practitioner education … it always is going be project-by-project based and driven by our scientist-to-scientist interaction model.”

Robert Califf, DTMI’s director, told “The Pink Sheet” that Duke’s involvement with Bristol drug-development projects is not about financial gain. The collaboration gives DTMI’s scientists an opportunity to conduct sponsored research in general, he explained, and some of the institute’s researchers particularly are interested in helping to find a cure for IPF, a build-up of fibrous tissue in the lungs for unknown reasons.

Agreement Centers Initially On IPF Drug

Current therapy for IPF is lung transplant, although InterMune Inc.’s Esbriet (pirfenidone) has been approved in Europe and is pending at FDA under a 2010 “complete response” letter. Esbriet, a dual inhibitor of TGF-beta and TGF-alpha synthesis, however, only addresses the symptoms of IPF, hopefully delaying advancement of the disease. Bristol and other companies including Gilead Sciences Inc. and Stromedix Inc.are working toward potential disease-modifying therapies for IPF.

Bristol acquired ‘202, an orally available lysophospahtidic acid 1 (LPA1) receptor antagonist, in its $325 million buyout of Amira Pharmaceuticals Inc. last year (Also see "BMS Bets On Amira's IPF Drug In $325M Acquisition" - Pink Sheet, 22 Jul, 2011.).

“We made the decision to get involved in fibrosis quite expeditiously,” noted Bristol Senior VP, Research, Francis Cuss, who oversees the micro-partnerships with academia. “We didn’t have a lot of expertise internally. In conventional terms, you’d say we need to go out and hire people, build a group, etc. But it became clear to us that the biotech was using outside people to enhance its capabilities. So why shouldn’t we do the same? Essentially, we’ve accelerated into this area by working with Duke. We’re really piggybacking on Duke’s expertise both about fibrosis and its ability to help us write a first-rate protocol.”

The Phase II program is slated to begin in late 2012. One of DTMI’s roles in advancing to that stage will be helping to identify biomarkers, both a pharmacodynamic biomarker that will help clinicians measure the amount of the drug in the patient’s blood or tissue and a patient-selection biomarker, Daniels said. Califf added that DTMI hopes to be involved in doing some of the clinical research “if the match remains good and the product is moving along.”

“Bristol is a diversified big pharma company [whereas Duke has] a large, integrated, academic health and science system that includes a very large health system, a medical school in Singapore, a university opening in China, a very big translational medicine effort,” he said. “We have a lot of expertise where across the board the match will be good. There also are matches in the areas of medical education, community implementation of health practices and development of global standards for research.”

Under the agreement, DTMI will get to publish its research but will hold no downstream rights to any revenues ‘202 might produce if it reaches market. Cuss noted that Bristol and DTMI have signed a “master agreement” that spells out rights and obligations, and will enable both parties “to accelerate into the science” as progress is made.

“You don’t want to have people sitting around waiting for the lawyers to do their job,” Cuss said. “Each step of the way here, we’re trying to minimize the amount of time it takes so that the academics and our scientists are spending their time thinking about the science and not the transaction.”

This master agreement won’t necessarily serve as a template for future collaborations between Bristol and other academic institutions, he admitted; there are just too many particulars to have a standard agreement that everyone could use. But what Bristol has learned in its work with DTMI is that if “you can get the senior scientists or physicians into this dialogue, you will very quickly understand what it is you want to get to and then it’s a matter of saying ‘how can we make this work,’” Cuss explained.

Micro-Partnerships: Narrow Focus, Small Investment

In general, Bristol’s micro-partnerships are more narrowly focused and involve small amounts of money, sometimes $100,000 of research funding. “Out in the industry, there are $10 million and $100 million collaborations, but the majority of ours are less than $100,000,” Cuss said. “That’s completely by design. About four or five years ago, I essentially set up an innovation fund to encourage what I like to call micro-partnering. And it’s focused on those relationships at the laboratory level – encouraging the scientists in our labs to make relationships directly with scientists or physicians in academia. This mainly encompasses discovery and translational science.”

The operating philosophy, he explained, is that “focus is good, but constraints are bad.” The micro-partnerships let the researchers involved go where the science takes them, in part because they are not bogged down by arduous approval or paperwork requirements, Cuss explained. “It’s not really a shots-on-goal approach but about getting real benefit out of modest sums of money,” he added.

Examples of this approach include a collaboration Bristol announced with the Gladstone Institutes last December to investigate novel targets in Alzheimer’s disease, with a focus on tau-mediated dysfunction (Also see "Deals Of The Week: Amgen/Watson, Baxter/Momenta, Takeda/Intellikine" - Pink Sheet, 2 Jan, 2012.). Cuss called it a “fairly conventional target identification and validation approach.”

Less typical is Bristol’s tie-up with , in which the school is serving as a mini small-molecule drug-discovery unit for the pharma. “They have a number of people who have worked previously in the pharmaceutical industry and they contribute something quite different to this partnership. They’re actually discovering the compounds and testing them,” Cuss said. “We work closely with them and complement them in the areas in which they haven’t built the infrastructure.”

No financial terms have been disclosed for either collaboration. Cuss could provide even less information about two very small arrangements that nonetheless might yield significant results for Bristol. In one, Bristol is working with a west coast university that cannot be named due to contractual reasons in a systems biology collaboration.

“There’s no money changing hands at all,” he said of the systems biology agreement. “They’re providing data that we can’t generate, and we provide data that they can’t generate or afford to generate.”

Finally, Bristol has had a micro-partnership around schizophrenia since 2008 with a single researcher at an eastern university that also cannot be named publicly. “[It involved] very modest sums of money, just enabling the work to continue,” Cuss explained. “It was renewed in 2010, and then in 2011 it graduated from the farm leagues up into the major leagues because the results had been so good. It then became a more formal, larger collaboration.”