At the Harvard Stem Cell Institute (HSCI), “Partnering is important at all levels,” emphasized Brock Reeve, executive director. That impetus is important not just in the sciences, but also among foundations, large and small companies and investors throughout the life sciences community.
“About two years ago, for example, we convened a meeting with the Harvard Business School,” Reeve said. It brought Harvard’s business and scientific experts together with investors, heads of disease foundations, and industry leaders from large and small companies to identify synergies and develop strategies to accelerate drug discovery and development.
Brock Reeve, Executive Director, Harvard Stem Cell Institute (HSCI)
Such meetings of the minds have led to new collaborative models throughout the life sciences ecosystem, as people realize they must work differently to achieve their goals. “That realization is behind big pharma’s new innovation centers, non-profits and creative research agreements,” Reeve said. “Here at Harvard, it led to the creation of HSCI, and other dedicated research centers such as the Broad Institute and the Wyss Institute.”
HSCI was formed about ten years ago as a virtual research organization to connect stem cell researchers across the Harvard healthcare system. It links nearly 1,000 scientists from Harvard’s schools and its nine affiliated hospitals.
Within this network, HSCI’s 300 principal and affiliated faculty members can take projects from basic research through clinical trials. “We have a big focus on collaboration, crossing organizational and disciplinary boundaries,” Reeve said.
Projects range from tightly focused research at any of the five core facilities (such as the iPS Core Facility) and other centers, to large scale, multi-year, cross-institutional projects in such major areas as diabetes, cancer, kidney disease and cardiovascular disease.
Focus: Translational medicine
“Our early focus was to fund work that wasn’t funded by the National Institutes of Health. The more we learn, the more we bring to the clinic, so the next decade will be more translationally focused,” Reeve said. HSCI will still tackle risky, early-stage research, though. As government funding becomes more difficult to obtain, it is important that HSCI and other institutes direct resources to basic research.
The expanding focus is a natural extension of the early research. “Early on, we built a therapeutic screening center to create human cells of interest and then to screen compounds against them to understand their mechanisms of action and to identify drugs that affect the cell of interest. Many drugs fail, even at Phase III, so this project helps researchers test drugs on human cells, at scale, early in a compound’s development,” he said. Therefore, drugs that will fail can do so earlier, enabling research to develop only the best candidates.
This approach also helps identify new uses for existing drugs. “Having stem cell models of disease makes it economically viable to test for drugs that affect motor neurons,” Reeve said. Because HSCI has cells from patients with amyotrophic lateral sclerosis (ALS), a joint project with GSK used this system to screen various drugs. “We found an epilepsy drug that kept the motor neurons alive longer than otherwise.
“The drug already was approved, so we could quickly move it into clinical trials for that new indication,” he said. The 120-person trial is being conducted in collaboration with GSK, the ALS Association and Harvard-affiliated Massachusetts General Hospital, one of the two coordinating centers for the Northeast ALS Consortium.
For such collaborations to work, Reeve said there must be joint scientific interest. “The scientists have to be interested in the problem and must want to work together. A successful collaboration can’t just be a contractual arrangement.” As he pointed out, the researchers at HSCI and GSK already had established rapport. “We had a five-year relationship with GSK in multiple areas before the ALS clinical trial.”
To help foster inter-disciplinary interactions, HSCI has created a community of researchers in a given field by hosting 30-minute “chalk talks” monthly. In the case of fibrosis research, scientists focused on the heart were able to interact with those focused on the lung or other organs. These talks identified commonalities in the research, and fresh perspectives helped them consider their own work in new lights. The insights from those meetings recently led to a project with a large pharmaceutical company.
“The most valuable interactions occur when the project is important and interesting to both parties,” Reeve underscored. When working with multiple teams and organizations, it’s important to align the program to meet joint interests.
That alignment is easier today than perhaps ever before. “Companies today are more flexible in their research agreements, and we have scientists who have worked in industry as well as academia and understand what’s important to each,” Reeve said.
Melding academic/industry needs
Because of increased flexibility and greater exposure to commercialization, the traditional academic/industry divide has dwindled. The conflicts between academic publication and intellectual property protection are being resolved. HSCI researchers, for example, meet the need to publish by working within a company’s library of compounds they are willing to discuss publicly while working privately on a subset of those compounds, which will remain proprietary.
Disease foundations are often less concerned about intellectual property, as their goals are to move effective compounds into the clinic quickly to benefit patients. Therefore, Reeve said, “disease foundations are a valuable partner to us and to biopharmaceutical companies—particularly those targeting smaller and orphan indications.”
For companies and foundations, partnering with HSCI has some distinct advantages. “Perhaps the greatest benefit relates to our organizational structure,” Reeve said. “We have research at all stages from basic through clinical and the underlying infrastructure that enables scale. As a result we have a breadth and depth of expertise in scientific and clinical knowledge that is unmatched in any other single organization.”
As an example, two of HSCI’s faculty—Doug Melton, HSCI co-director and co-founder, and Reeve—were listed as number 5 and 11, respectively, on the list of the world’s top 50 stem cell influencers released by the Annual World Stem Cells & Regenerative Medicine Congress.
Reeve, a management consultant before joining HSCI, understands the needs of the private sector as well as academia. “A large academic institution is different from a company, but understanding the perspective of the companies and of potential investors is important here. Our goal is not just to write papers but to make an impact through partnering, licensing and forming startup companies,” he said.
One of the traditional challenges of companies working with academia has been the higher level of risk associated with basic research. “You could argue that HSCI limits risks as we go along. Each experiment is a step in ‘de-risking.'” HSCI’s approach advances projects to a “reasonable” proof of concept and then structures the next step, often in consultation with potential partners.
HSCI works closely with venture capital firms and also may introduce faculty to potential investors. Reeve currently is helping some faculty members develop business plans for their newly-formed companies.
The list of companies that have been created by HSCI faculty include (among many others): Moderna Therapeutics, which uses modified mRNA to create and deliver a new class of therapeutics; CRISPR Therapeutics, which uses the CRISPR-Cas9 gene editing technology to develop novel medicines; Fate Therapeutics, which discovers and develops adult stem cell modulators to treat rare, life-threatening disorders; GenSight Biologics, which develops gene-therapies to treat retinal degenerative diseases; and, most recently launched, Semma Therapeutics, which is using stem cell derived beta cells for diabetes therapy. Other, ongoing, HSCI research includes resurrecting ancient viruses to improve gene therapy, developing hydrogels to treat inflammatory bowel disease and developing a new model for muscular dystrophy.
“HSCI doesn’t gain financially from its spinoff companies,” Reeve stressed. “The intellectual property is licensed from the institutions, and the principal investigators are shareholders.” Instead, the real benefit lies in translating research into the clinic and thereby fulfilling HSCI’s mission to use stem cells both as therapies and as tools to understand the treat the root causes of leading degenerative diseases.
Reeve will be moderating a panel on Gene and Cell Therapy during the Partnerships in Regenerative Medicine and Advanced Therapies sessions at BioPharm America™ in Boston, September 15–17.
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