By Rich Soll, Senior Advisor, Strategic Initiatives at WuXi AppTec (@richsollwx)
Crossing the “valley of death” between discovery and development has been a longtime leap between university labs and the commercial market. For the past decade, the Blavatnik Biomedical Accelerator at Harvard University has been working to help close that gap between innovative, early-stage life science research and development of high-impact biomedical products, and with much success. The critically acclaimed program has an integrated approach that combines essential funding with development and business expertise, leading to commercial partnerships that bring forth new biomedical discoveries that create value and benefit society.
Funded technologies have included therapeutics for oncology, metabolic disease, diabetes, immuno-inflammatory disease, infectious diseases, and neurodegeneration; diagnostics/biomarkers, instruments; and other biomedical technologies. What makes the Accelerator unique is that nearly half of all completed projects have been partnered with industry either through collaborations and licensing transactions with existing pharmaceutical and biotech companies, or through the formation of new startups. These alliances have already resulted in more than $25 million in commercialization revenue and $40 million in follow-on industry-sponsored research funding for Harvard. Moreover, startups based on technologies supported by the Accelerator have raised over $475 million to date.
Leading the Accelerator’s valiant efforts is its founding chief scientific officer Curtis Keith, who joined the program, which is part of Harvard’s Office of Technology Development, in 2008. Before that, the trained chemist co-founded CombinatoRx, where he directed research programs in multiple therapeutic areas, including rheumatoid arthritis, psoriasis, osteoarthritis, oncology, metabolic, neurodegenerative and infectious disease, and helped the company to advance a pipeline of several clinical and preclinical drug candidates.
I recently spoke with Keith, who explained the Accelerator’s winning strategy of de-risking university research and bringing creative biomedical concepts to the market, as well as why the center adds value to the overall life science ecosystem.
Rich Soll: What is the mission of the Blavatnik Biomedical Accelerator?
Curtis Keith: The Accelerator exists first and foremost to support Harvard’s public service mission, ensuring that the important biomedical research being carried out at Harvard makes it out of the University to benefit society.
We advance Harvard’s most promising biomedical technologies to the stage where they are ready for partnership with industry, either through formation of new companies or through licensing to existing biotech and pharma. It’s imperative that we form alliances with strong industry partners in a timely manner, since they have the expertise and resources to further develop Harvard’s nascent technologies and bring them to the market as quickly as possible. In most cases, such partnerships will also help support research at Harvard in the future. In addition to our “bridging the gap” goal, the Accelerator also has a broader mission of supporting translational research and entrepreneurship here at Harvard.
Rich Soll: What is the Accelerator’s history and how has is evolved overtime?
Curtis Keith: Harvard’s Chief Technology Development Officer and Senior Associate Provost, Isaac Kohlberg, oversaw the launch of the original Harvard Accelerator in 2007 as a $10 million philanthropic fund. I arrived at the beginning of 2008 as the Chief Scientific Officer.
We relaunched the program in 2013 coinciding with a major gift from Len Blavatnik and the Blavatnik Family Foundation and at that time, we also created the Blavatnik Fellowship in Life Science Entrepreneurship.
Over time, we’ve increased the number of projects we fund per year, and in some cases, we’ve increased the amount of money spent per project. This has allowed us to develop technologies to a more advanced stage than was possible in the early years of the program. To a certain extent, the nature of funded technologies has also changed over the past decade, which is to be expected as our faculty research evolves over time.
Rich Soll: What kind of support do your team and the Accelerator provide? What is the process?
Curtis Keith: Generally speaking, we aim to fund key proof-of-concept and de-risking studies for Harvard’s biomedical technologies. Exactly what that looks like, i.e. the specific type (and stage) of PoC experiment, is highly dependent on the nature of the technology.
Twice a year we issue a request for proposals, open to all life science researchers around Harvard University. In many cases we become aware of potential technologies for funding via Harvard’s business development team, who alert us to promising opportunities they know of from their interactions with faculty. Project evaluation is done in a series of stages through a combination of internal and external diligence, as well as with the assistance of our independent advisory committee of experts from the local life sciences community
At the initial stage of our project development process, we collaborate with Harvard investigators to help them determine what additional work is needed for their technologies in order to advance them to a point where they are ready to be partnered. This involves extensive discussions with potential investors, companies, and experts with technical expertise in areas that are relevant to the technologies. We then develop more detailed project plans that if successful, should enable partnership within a few years.
After extensive review, we select a subset of the proposals for funding. This is done with the help of our independent Accelerator Advisory Committee, comprising individuals from the local life sciences community, including venture capitalists, CSOs and CEOs from biotech, and Harvard faculty who have previously started companies or have significant experience working with industry. Project funding is provided in the form of grants that are given within the Harvard financial system.
By design, studies funded via the Accelerator are intended to reflect what we’ve heard from investors and companies regarding the next critical steps for our specific Harvard technologies. Having said that, in most cases the gaps we’re trying to bridge are the ones you would expect would be the case for university-stage technologies, especially in the domain of therapeutics – more extensive target validation, hit discovery, hit-to-lead, lead optimization, and in vivo proof-of-concept in pharmacology/disease models.
We manage the projects collaboratively with Harvard investigators. Most projects involve a significant amount of work that needs to be done at CROs and we’re particularly involved in those aspects. We use outside consultants as well at this stage, including for the management of medchem activities at CROs. At later stages of Accelerator projects, as a critical mass of results are generated, we work more closely again with other members of Harvard’s Office of Technology Development team to initiate business development activities and eventually secure partnerships. The core BBA team includes myself, Su Chiang and Leandro Vetcher, but it’s important to understand that the Accelerator leverages many other people at Harvard, including attorneys, financial administrators and so on.
Rich Soll: How many projects does the Accelerator have today?
Curtis Keith: Over the past 10 years we’ve funded 103 projects. There are approximately 25 projects still on-going, many of which are now in their final stages. There are additional projects for which business development is underway. The Accelerator does not have a specific therapeutic emphasis; our portfolio of projects reflects the areas of biomedical research in which Harvard researchers are active. We’ve had projects in almost every therapeutic area you can imagine, as well as projects focused on biomedical technologies such as diagnostics, drug delivery, vaccines, instruments, and medical devices.
Rich Soll: Does this center differ from other Blavatnik centers from around the world?
Curtis Keith: It’s important to understand that we do not have labs ourselves, in contrast to, for example, the Blavatnik Center for Drug Discovery at Tel Aviv University, which has labs for HTS, modeling, synthesis and other activities. Harvard’s Blavatnik Biomedical Accelerator is virtual in that sense – the work in our projects is done within the funded investigators’ own labs, other facilities around Harvard, or at contract research organizations. The Blavatnik Family Foundation has also now funded a program at Yale, the Blavatnik Fund for Innovation at Yale, and I believe there are strong similarities to our Harvard program.
Rich Soll: Can you describe some of the hottest and challenging projects the Accelerator is working on today?
Curtis Keith: Historically, the majority of our projects have been in therapeutics space, including, in some cases, platforms or enabling technologies for therapeutics discovery.
A major trend for us in recent years is that we’ve funded a lot of very exciting stem cell technologies. Just last year, we had three projects from leading stem cell researchers at Harvard; from Lee Rubin in the Department of Stem Cell and Regenerative Biology, a new method for generating clinically relevant quantities of muscle satellite cells for muscle repair; from George Church at Harvard Medical School, a new method for rapidly and efficiently differentiating iPS cells into a wide variety of different cell types; and from David Scadden and David Mooney, a biomaterial-based bone marrow cryogel to improve hematopoietic stem cell transplantation (HSCT). All of these stem cell technologies will be tested in vivo for proof-of-concept over the course of their Accelerator projects, to give you a sense of their stage.
Rich Soll: How have the companies formed at the Accelerator evolved over time?
Curtis Keith: A few examples of Accelerator startups from recent years include Macrolide Pharmaceuticals, based on a platform technology for creating fully synthetic macrolide antibiotics from the lab of Professor Andy Myers; Magenta Therapeutics, formed in part around a bone marrow conditioning technology from Professor David Scadden; Incro, which Denali acquired in 2016 for a Rip1 kinase inhibitor program; and FOG pharma, a next generation peptide stapling technology from Greg Verdine. There are a handful of other startups currently in the works and we expect to announce at least three of these in the coming months.
Rich Soll: How do companies graduate from the Accelerator? And, what is their life like after the Accelerator?
Curtis Keith: Regarding our startups, the funding provided to projects comes in the form of a grant given within the Harvard financial system, not through an equity investment. The exit for us is startup formation and licensing of the Accelerator-funded Harvard technology. In some cases, our office (Harvard Office of Technology Development) brings the founding entrepreneur to the table, while in other cases, the VCs we work with drive the process of assembling the initial management team. More often than not, there will be an on-going collaboration between the new startup and a Harvard founder’s lab for many years to come.
Rich Soll: Have you tracked success rates of companies through the Accelerator?
Curtis Keith: In terms of success rates for projects, we’ve seen that between a third and a half of our completed projects lead to some form of industry partnership. This includes not just startups, but also licenses to existing companies and major industry-sponsored research agreements that arise as a result of an Accelerator project. In terms of other metrics more generally, Accelerator projects have brought in more than $25 million in license revenue, and $40 million in sponsored research funding. In terms of impact on the biotech ecosystem, Accelerator startups have raised over $475 million in equity financing and employ hundreds of people.
Rich Soll: What do you see as the key impact of the Accelerator on industry trends such as transition probabilities (success/failure rates) and why?
Curtis Keith: Much has been said about reproducibility issues for university technologies. We think our Accelerator projects are de-risking Harvard’s technologies in a way that increases the probability they will succeed in the hands of our industry partners. There are other cases in which an Accelerator project provides the support needed for studies that demonstrate breadth of applicability of a nascent technology, providing evidence for embodiments and applications that were otherwise speculative.
We should be mindful of the fact that the differentiating strength of universities with regards to therapeutics lies in their highly innovative science and the powerful technologies this can give rise to. This is where universities are really adding something unique, and defines our place in the ecosystem. In certain cases it may make sense for universities to develop to a relatively advanced stage a ‘conventional’ drug (albeit on a new target with new chemistry), but our uniqueness is ultimately with true breakthrough unconventionality.
Rich Soll: Can you describe the Accelerator’s entrepreneurial program and what is it designed to do?
Curtis Keith: As part of the 2013 gift from the Blavatnik Family Foundation, we launched the Blavatnik Fellowship in Life Science Entrepreneurship. Recent Harvard Business School MBAs spend approximately one year working with the Accelerator and the Office of Technology Development with the goal of launching a new venture based on a Harvard biomedical technology. The Fellows reside at the iLab on the Harvard Business School campus. The program really has a dual purpose – to train future generations of entrepreneurial leaders in life science industries, and to help Harvard launch more startups around our biomedical technologies.
Rich Soll: How many entrepreneurs have been developed through the program?
Curtis Keith: There are five Fellows selected per year, and the program is now entering its fifth year. A couple of recent successes for our Fellows include Akouos and has raised over $50 million in its first two years. Another success story is Gemini, started by James McLaughlin, focused on age-related macular degeneration and other ophthalmology and complement-mediated rare diseases. Overall, the Blavatnik Fellows have created 17 companies and raised over $200 million in equity financing.
Rich Soll: What are your top priories for the Accelerator?
Curtis Keith: It’s important to remember that the role of the Accelerator is ultimately to support our faculty and to help them see their science translated for public benefit. As their research programs move in new directions, we move in those directions as well. Increasingly over the time I’ve been here, the proposals we receive from faculty have moved away somewhat from conventional small molecule therapeutics and biologics, and toward new modalities such as stem cell-derived regenerative medicine technologies, AAV gene therapy, etc. It’s critical that we make sure we have the expertise and external relationships – such as CROs, consultants, KOLs, and potential industry partners – in order for these technologies to be moved forward effectively.
Rich Soll: What are the toughest challenges you face today?
Curtis Keith: A key challenge is that we’re working with relatively modest budgets of a few hundred thousand dollars per project, so we have to be careful about what kinds of projects and goals we take on; we need to be realistic about what we can accomplish. We’ve seen that this challenge can also be an opportunity for us by entering into risk-sharing arrangements with CROs and other companies at an early stage – something we’ve done in the past and will look to do more of in the future.
Rich Soll: What attracted you to the Accelerator?
Curtis Keith: Prior to this, I had been in biotech at a drug discovery company called CombinatoRx, which I had co-founded with a few Harvard colleagues in 2000. I did my PhD at Harvard with Stuart Schreiber in the 1990’s, so coming back here to run the Accelerator felt like a return of sorts. It appealed to me to work Harvard faculty—many of whom I already knew—in a different capacity, and to give back to the University in some small way. My role at the Accelerator allows me to have an involvement at the very earliest stage in helping shape technologies based on some of the most innovative science in the world. It’s hard to beat that.
Rich Soll: What has been the most rewarding experience to date?
Curtis Keith: There have been many promising startups that have come out the Accelerator over the past decade. Every time a new one is launched, I enjoy seeing the sense of promise and optimism that all involved clearly experience at the outset. Separately, it was particularly rewarding when two years ago, Harvard licensed Professor Matt Shair’s acute myeloid leukemia program to Merck. Since the early days of the Accelerator, we had made the assertion that it should be possible in certain special cases to advance a Harvard therapeutic technology to a stage comparable to what a small biotech company has when they partner with a larger company. With Accelerator support over a period of four years, we helped Professor Shair advance his AML program to a stage where it resulted in one of Harvard’s biggest ever licensing deals, with the most significant upfront payment we’ve received ($20 million), as well as other downstream financials.