Seeding medical innovation: The Technology Development Fund

Monique Yoakim Turk Technology Development FundMonique Yoakim-Turk, PhD, is a partner of the Technology Development Fund and associate director of the Technology and Innovation Development Office at Boston Children’s Hospital

Since 2009, Boston Children’s Hospital has committed $6.2 million to support 58 hospital innovations ranging from therapeutics, diagnostics, medical devices and vaccines to regenerative medicine and healthcare IT projects. What a difference six years makes.

The Technology Development Fund (TDF) was proposed to Boston Children’s senior leadership in 2008 after months of research. As a catalyst fund, the TDF is designed to transform seed-stage academic technologies at the hospital into independently validated, later-stage, high-impact opportunities sought by licensees and investors. In addition to funds, investigators get access to mentors, product development experts and technical support through a network of contract research organizations and development partners. TDF also provides assistance with strategic planning, intellectual property protection, regulatory requirements and business models.

Seeking some “metrics of success” beyond licensing numbers and royalties (which can come a decade or so after a license), I asked recipients of past TDF awards to report back any successes that owed at least in part to data generated with TDF funds. While we expected some of the results, we would have never anticipated such a large impact.

Academic seed funds therapeutics

In the past five years, four startup companies have been created, collectively receiving $13.6 million in seed funding from venture capitalists, the Food and Drug Administration and foundations. The new companies include the recently announced Affinivax, a vaccine company started with $4 million from the Gates Foundation, and Epidemico, a population health-tracking company recently acquired by Booz Allen Hamilton. We’ve also launched 10 partnerships with academic institutions and biomedical companies and received $13.2 million in follow-on funding from the government and foundations that have continued to support many of the projects.

This year’s TDF projects are especially exciting, as 10 of the 11 recipients are first-time applicants, and all 11 eleven projects are new to TDF. The 2014 grant awards (totaling $1.15M) go to:

RNA interference (RNAi) was discovered over a decade ago and chemically synthesized siRNAs are emerging as a new class of pharmaceutical drugs. Lieberman, a pioneer in this field, has invented a method to make highly efficient and specific “recombinant” prokaryotic siRNAs (pro-siRNAs), which may be cheaper to produce than chemically synthesized siRNAs. She plans to optimize the production of pro-siRNAs for the industry setting.

  • Small molecules for ex vivo maintenance and expansion of hematopoietic stem cells (Derrick Rossi, PhD, PCMM)

Hematopoietic stem cell (HSC) transplantation is used to treat patients with a variety of life-threatening disorders, with 50,000 transplants performed each year worldwide. Boosting numbers of HSCs remains very challenging and has been a rate-limiting step to transplantation success. Rossi has discovered a cocktail of small molecules capable of expanding HSC numbers outside the body while preserving their functional potential. He plans on translating his discovery to human HSCs.

  • A high-throughput mouse model for optimizing therapeutic antibody specificity and affinity (Frederick Alt, PhD, PCMM)

Antibodies are among the most successful therapeutic drugs, but they currently do not achieve maximum potential in terms of affinity and specificity. Alt is developing a “high throughput” antibody producing mouse model that generates antibody variants with higher affinities or modified specificities.

Second-degree burns often cause significant scarring, and may require skin grafts. Current treatments typically involve an anesthetic and ointments, but there is no therapeutic on the market that specifically treats the burn wound. Carroll is developing a topical therapeutic peptide that works through a novel pathway of inflammation and may reduce destruction of surrounding tissue.

  • Use of ‘MAPS’ for the development of a tuberculosis vaccine (Richard Malley, MD, Infectious Diseases)

Mycobacterium tuberculosis is responsible for approximately 9 million new tuberculosis (TB) cases and 1.5 million deaths each year worldwide, with a rise in multi-drug and extensively drug resistant strains. The current BCG vaccine, while safe and reasonably effective in children, does not generate herd immunity as it does not offer protection for adults. The multiple antigen presenting system (MAPS) technology developed in the Malley laboratory will be used to create a TB vaccine eliciting a higher T-cell response.

Infections claim millions of lives every year, especially among the elderly and infants under 6 months of age, whose weak immune systems make them particularly susceptible. Vaccines are a highly cost-effective measure, but development of new vaccines is costly and slow. Levy and Sanchez-Schmitz are developing three-dimensional tissue-engineered constructs that accurately simulate age-specific human vaccine responses. These constructs will accelerate and “de-risk” vaccine development.

Pseudomonas aeruginosa commonly infects hospitalized patients, particularly those on ventilators, as well as cancer, burn, trauma and cystic fibrosis patients. Cases of antibiotic-resistant infections are on the rise, and no vaccine is currently available. This project aims to optimize a P. aeruginosa vaccine based on Priebe’s discovery of a protein called PopB that stimulates T helper cells to protect against pneumonia and wound infection in mouse models.

Systemic inflammatory response (SIRS) underlies a number of conditions, including sepsis, pancreatitis, burns and trauma. SIRS activates a number of cytokine pathways. McAlvin and Kohane are developing a novel hemofiltration device that selectively modulates the immune system to treat SIRS. TDF funding will allow testing the device in small and large animal models of SIRS.

Liu and Visner are developing a specialized magnetic suturing system for clinical surgeries, particularly in laparoscopic procedures where spaces are tight and access is limited.

Epilepsy is usually treated with medicines, but only cured when surgery can be performed to remove the region of the brain that causes seizures. Madsen and Park are developing an algorithm that allows surgeons to rapidly determine the sources of a patient’s seizures by analyzing brain network data between seizures, shortening monitoring time and reducing the risk and burden of epilepsy surgery.

  • Children’s Research Integration System (ChRIS) – a web-based medical image data and workflow platform (Rudolph Pienaar, PhD, Radiology)

Current image analysis software requires advanced computing expertise and is often non-collaborative. Pienaar is working to optimize the web-based Children’s Research Integration System (ChRIS) to facilitate the collection, management, analysis, visualization, and sharing of medical image data.

If I had to anticipate the ten year results for TDF,  I would predict an increasing number of collaborations (to advance promising projects) with both academia and industry and the development of new partnership models.  Just like academic collaborators join forces to tackle basic research problems, academic institutions and pharmaceutical companies will pool resources and expertise to effectively de-risk early-stage academic projects.