By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL
At this year’s BIO International Convention in San Diego (June 19 – 22), I moderated a session, Navigating A Clear Path To Public-Private Partnerships, and we talked about the good, the bad, and the ugly of P3s. After a brief introduction, the first question was posed, resulting in the following edited dialogue.
Close to zero.
That’s the probability of one company or researcher successfully finding cures for the likes of ALS, Alzheimer’s, or any of the other horrible diseases that continue to ravage humanity. To develop therapeutics of the future will most likely require the launch of a number of P3s (public-private partnerships) — today. But just getting a cadre of participants even interested in participating in a P3 can be a challenge, not to mention the process of launching and managing a P3 all the way through to conclusion. For example, the $230 million Accelerating Medicines Partnership (AMP) that was launched in 2014 involves two government organizations, 10 biopharmaceutical companies, and a dozen nonprofits. And while P3s are intended to be part of the solution, if not properly managed they could become part of the problem. How does one prevent such a scenario?
Which P3s Are You Involved With?
STACEY ADAM, FNIH: One P3 that’s just coming out of a design phase is the Partnership for Accelerating Cancer Therapies (PACT). It’s one of the 41 projects proposed by the Cancer Moonshot initiative, and its purpose is to establish a P3 to help coordinate the ongoing immunooncology (IO) efforts with those of the National Cancer Institute (NCI). There are approximately 1,300 IO trials taking place, but some people fear there are not enough cancer patients to actually complete all of these trials, which tells us that we need to improve how we rationally design and coordinate these efforts. Fellow panelist Chandra Ramanathan, along with 41 of his scientific colleagues from 14 separate companies, the NCI, FDA, and a number of academic leaders collaborated on a six-month design phase. The process included 35 separate teleconference meetings and two face-to- face meetings with all participants assembled. We hope PACT to have about $210 million in funding, split equally between the public and private sectors.
An example of a more thoroughly developed project is the Lung Master Protocol (Lung-MAP), a clinical trial for patients with advanced squamous cell carcinoma. Lung-MAP is a P3 involving government (NCI), physicians (SWOG, a cooperative group within the National Clinical Trials Network), patient advocacy (Friends of Cancer Research), seven pharmaceutical companies, and Foundation Medicine (FMI). Thus far we have successfully tested five separate drugs and enrolled over 1,300 patients into the trial, with 500+ of those being allocated to separate substudies. We are expanding that trial to include IO combinations for PD-L1 refractory patients by adding three trial arms in the next year and bringing in six additional corporate partners.
CHANDRA RAMANATHAN, BAYER: We developed an open innovation platform along with a Grants4Targets initiative, which has two arms — pharmaceuticals and crop science. The global research grant program for pharmaceuticals supports research on novel drug targets for application in Bayer’s focus areas (oncology, cardiovascular, and gynecological therapies) through funding, expertise, and technologies in drug discovery. Thus far, our open innovation platform has been in place for the last seven years, generated 3,575 ideas from 60 countries, and has funded 285 (and counting) projects.
One of the successful P3s we developed at Bayer was with the American Association for Cancer Research (AACR). The collaboration (AACR-Bayer Innovation and Discovery Grants) promotes the key tenets of the Bayer Grants4Targets initiative, providing new treatment options for cancer patients with high unmet medical need, encourages innovation and translation of ideas from basic research into novel drugs, and fosters collaboration between academia and biopharma. This innovative partnership brings out the best of two worlds — couples the scientific excellence of AACR with drug discovery expertise of Bayer to enable translation of scientific ideas to address patient unmet needs. In addition to funding, there is a mentorship component to educate scientists in principles of drug discovery and development.
ISSI ROZEN, THE BROAD INSTITUTE: The Broad Institute engages in P3s, like the one we have with Bayer, to allow us to propel treatment forward. In seeking to participate in P3s, we look for partners that first, share a specific scientific vision. Second, we look for P3 participants who are willing to share in the commitment, not just the excitement. Sometimes partners of P3s, while enthusiastic, may be a little naïve about the level of resources, timelines, and effort that will be required. The third component we look for is a cultural fit (i.e., organizations we think we can work with effectively). Biopharmas are typically driven by goals, timelines, or bonuses at the end of the year tied to moving “X” number of programs. Academic institutions generally don’t think this way and do research until they solve the problem and then publish a paper. Successfully executing a P3 involving biopharma and academia involves finding likeminded people who understand these differences and are willing to work together to bridge them. The Broad Institute will never take a drug into the clinic or into the market because we simply aren’t built to do so. But we do have significant capacity to understand biology and targets, and we have a lot of interesting early-stage drug discovery capabilities. So partnering with a company that actually knows how to take a drug to the clinic, design clinical trials, and market a drug is very important to us, as it helps us toward fulfilling our mission.
How Do Government Organizations Measure P3 Success?
ADAM: I think of the FNIH as being the neutral third party that helps broker deals and get the companies and government organizations what they need out of P3s (e.g., drugs progressing into the clinic, moving forward with the FDA, creating guidance documents), while still being able to retain all the IP and licensing rights for our academics to publish. If you are going to establish a partnership with the FNIH and the NIH, all of the data has to be made public. There can’t be exclusive licensure to any one person/entity, because the NIH wants the broadest possible use in the clinic or anywhere else. Another metric for us is adherence to all the federal regulations and guidelines.
What Can A City Or Economic Region Do To Promote The Development Of A Regional Cluster?
ROZEN: We have a cluster in Kendall Square near Boston. From my perspective, the success of this cluster began with first having super academic institutions. On one side of the square there is MIT, while on the other side you have Harvard. Just across the river there is Harvard Medical School, Mass General Hospital, the Dana-Farber Cancer Institute, and five other teaching hospitals. So there is an incredible amount of fundamental research happening within a very short distance, leading to a lot of advancement in understanding of basic science. As the world started to believe in biotechnology, we saw the formation of different biotech companies in the area (e.g., Biogen, Genzyme, Vertex). These early successes attracted VCs seeking to invest in opportunities arising from the area universities. Big Pharma saw what was happening in Boston and wanted to figure out how it might benefit. The first Big Pharma to move into Kendall Square was orchestrated by Mark Fishman. Back in 2002, Fishman, the head of the Novartis Research Institute, decided to move the company’s research headquarters from Basil, Switzerland, to Kendall Square, and other Big Pharmas soon followed. And while this created a bit of a snowball effect, I don’t think the success we have seen in Boston would have happened without the surrounding academic institutions serving as a pipeline for ideas.
RAMANATHAN: While there are public and private institutions that can drive investment, what is also needed is a catalyst (e.g., Massachusetts Biotechnology Industry Organization [MassBIO], Massachusetts Life Sciences Center) to make sure the stakeholders interact and work with each other.
ADAM: There are other cities that have done this that don’t necessarily have the big-name institutions. For example, Kansas City has been trying to recruit people to build a bio hub around the University of Kansas Medical Center, and it has been the Kansas Department of Commerce that has been the catalyst.
ROZEN: Phil Sharp is a Nobel laureate professor at MIT and the founder of Biogen. Back in the 1970s, people in Cambridge, MA, where Biogen was started, were very worried about this industry, as they didn’t really understand what biotech did. Sharp helped explain to the city council that what would be happening in the labs of biotechs would be no different from what was already happening in the labs at MIT and Harvard. He has a clip from a city council meeting that shows there were a lot of questions. As he responded to their challenges they became more comfortable with the idea of biotech. That was a critical moment for Cambridge. For had he not been able to convince people that the work of biotech was okay, the cluster may not have ever gotten started. Local politicians and governments play an important role in the success of a hub.
Have You Ever Been Involved In A P3 That Started Going Sideways, And What Did You Do To Get It Back On Track?
RAMANATHAN: To avoid a P3 from getting off track in the first place, you need to establish value and flexibility. Understand the value drivers for each partner in a P3, and allow for flexibility throughout the life of a P3, as these often run for many years. For example, how researchers currently approach drug discovery and therapeutic strategy could be very different from what is being done five years from now, and you want to be flexible to adapt to such changing conditions.
ROZEN: If I think about all of the P3s that did not go so well for us, it was often a result of a leadership change on the biopharma side. This is one thing we have found to be very frustrating. A lot of time has been spent creating excitement, aligning scientific visions, building relationships, and working together, and then about a year in one person leaves. A new person comes in, and they have very different ideas of how the P3 should look. Such situations can be very challenging, and I don’t have a good solution other than asking biopharma to be more consistent in their strategy involving a P3.
ADAM: In addition to the company leadership, we find it beneficial to have a company champion. Often, that champion is somebody with boots on the ground. So even if there is turnover at the leadership level of a P3, having a company champion can be helpful toward preventing such a change from slowing the P3 down. As for flexibility, I don’t think the goals of the P3 have to be overly flexible. However, there should be flexibility in the parameters used to drive successful execution of the P3 and transparent and frequent communication among P3 partners.
How Do You Manage Extremely Large P3s With A Wide Variety Of Participants?
ADAM: It is essential to define the value each P3 player brings. What is it you need to do together? Why does each partner need to be there? If they don’t have a need or a value to be at the table, they have less incentive to stay for the long term. Next, you need to define the parameters for P3 stakeholders (i.e., shared benefit and shared risk). Again, everybody is taking on some amount of risk, and so your hope is that a rising tide will raise all boats, as far as the benefit being gained from participating in the P3. The certain amount of risk in a P3 has to be balanced by the idea one partner could possibly have done it faster or better by going it alone. Make sure the P3 has concrete goals and parameters outlined in the very beginning.
We encourage infinite amounts of transparency in the partnerships we run. The first time you start having isolated conversations with any one of the partners, the P3 can begin to get away from you. The FNIH has very clear parameters and guidelines for people interested in working with the NIH, which have to be agreed to up front. If considering doing a P3, consider taking a similar approach of making sure all goals and guidelines are defined in advance.
In getting a P3 off the ground, we prefer in-person meetings. Having everyone sitting across a table from each other and engaging in clear dialogue can work wonders. If you have to do a P3 via telecom, that’s where somebody like me comes in. To make sure everyone gets their say, I ask questions of each partner during the call, and do a lot of email follow-up to make sure each partner got what they needed from the teleconference. In addition, I want to make sure we have the right parameters and that these are agreed upon and locked down before moving forward. The last thing I or the P3 needs is for someone (e.g., a financial investor) to say, once we are well underway, that this is not what they wanted.
If A P3 Achieves Its Defined Objective, Should It Be Disbanded?
ROZEN: My experience is that if the partnership is successful, it doesn’t die; it morphs, and it can morph in a number of ways. For example, four years ago we started an oncology collaboration with Bayer. It was going so well that we expanded it to include cardiology and basically copied the exact blueprint of what we had in place for oncology. Here is another situation. Over 10 years ago we started the RNAi consortium, which recently entered its fourth iteration. It started out as a three-year consortium with one set of companies. We expanded the consortium two times by adding additional companies. But between the third and fourth iterations, the world changed, and RNAi was no longer the hottest thing, and we had pretty much exhausted this field of study. But we felt that all of the players were getting a lot of value from the consortium. So, instead of disbanding, we changed our focus toward the new hot thing — CRISPR, and changed the consortium name to the Functional Genomics Consortium. It’s now generating new value in a different scientific area.
Who Should Someone Call If Interested In Starting A P3?
ADAM: If you would like to start a partnership with the NIH, consider contacting the FNIH first. The advantage of coming to us is that we know the ins and outs of NIH and can usually get you to the right people pretty quickly. If you’re doing a P3 with the NIH and it is not a one-company-and-NIH scenario that a simple cooperative research and development agreement (CRADA) can handle, the FNIH will end up helping you navigate it anyway. If you don’t know who to contact at either the FNIH or NIH, a good place to start is with the chief of staff of the institute director. These people have the broadest perspective of what’s going on within any of the 27 institutes at the NIH. For example, if you want to do a P3 in cancer, get to the chief of staff of the National Cancer Institute (NCI). There is also a P3 panel within the Office of the Director at the NIH that can assist you.
How Should Someone Approach Developing A P3 Within A Biopharmaceutical Company?
RAMANATHAN: There is no magical formula for determining how to make a P3 successful within a biopharmaceutical company. However, when thinking about the various partnerships in which I have been involved, there are five things that you can do to help set you on a path to success. First, be very clear on the business objective. What exactly do you want to get out of the partnership and the timeline? I think that should be really clear before you even initiate the process. Second, you’ve got to have a champion in the company. This person needs to be passionate about the cause and really believe in what you’re trying to do. Third, set expectations well in advance. When you are working with the FNIH and some 40 other people, you have to set an expectation that is similar to doing precompetitive research, and sometimes things take time. Fourth is communication. Keep communicating within the organization so people do not forget what you are trying to do. It can take six months to a year to get a P3 to move from the genesis of an idea to the point where something is actually being done, and if you don’t communicate routinely, when you approach the eighth or ninth month, people can forget what exactly you are trying to do. Lastly, whenever you go to meetings and talk about the P3, anchor it to the value — the business objective for why you’re doing it in the first place. P3s provide wonderful opportunities to learn from people outside of your own organization and to work on projects too big for one company to handle.
Is There A Good Example Of An Effective International P3?
RAMANATHAN: There is a P3 called Innovative Medicines Initiative (IMI) in Europe, which is a $5.3 billion P3 lasting over 15 years. It is probably the biggest P3 in the world, with 50 percent of its funding coming from the EU, while the remaining 50 percent comes from different companies. IMI focuses on trying to make the drug discovery and development more efficient and targets its priorities by first looking at the priorities of the WHO. Companies can participate in IMI by giving money, sharing compound libraries, or providing people to work on projects.
Parting Pearls Of Wisdom
At the end of the session, each panelist was invited to share a parting pearl of wisdom.
ROZEN: The Broad Institute has looked at many P3s between academic institutions and for-profit entities, specifically pharma and biotech. To be honest, many of these have failed because they were not managed appropriately within the academic institutions or pharma companies, or the structure was not optimal. Structures where one party does all the work while the other comes in every few months to provide feedback don’t work because one party isn’t fully invested and doesn’t understand the challenges. We believe the structure that allows you to increase the probability of success requires all parties of a P3 to have an ownership stake. Our most successful collaborations are those having scientists on both sides with joint responsibility for success.
RAMANATHAN: Power of partnership. For example, there has been lots of buzz around immuno-oncology. However, the reality is, IO currently benefits about 15 to 20 percent of all cancer patients, while the other 80 percent still don’t have an option. One company alone cannot address this huge unmet medical need. There is power in collaboration, and the forming of P3s will not only enable the development of new innovative options, but will do so quicker.
ADAM: A shared vision and a shared goal are probably what you want more than anything else. A P3 benefits from strong management and clear parameters for how to achieve the goal. Finally, you need transparent communication from start to finish among P3 partners. If you can hit those factors all along the way, you should be successful.