Collaboration catalyzes industry progress
By Seth Kroll
(BOSTON) — Launched in 2019 as an ambitious idea, the Wyss Brain Targeting Program was designed to address a critical challenge in neuroscience and brain health: how to safely and effectively deliver drugs across the blood-brain barrier (BBB). The BBB is a tightly regulated gateway that protects the brain from toxins and pathogens but also prevents nearly all large-molecule drugs from reaching brain tissue in therapeutic concentrations.
In response to this longstanding problem, which has contributed to the high failure rate of treatments for Alzheimer’s and other neurodegenerative diseases, Jim Gorman, M.D., Ph.D., Senior Director of R&D and PI for the Brain Targeting Program, and Wyss Founding Director Don Ingber, M.D., Ph.D., envisioned a pre-competitive model of collaboration that brings together academic innovation and industry insight. In this model, experts from both worlds collectively concentrate on how to enable drugs to more efficiently cross the BBB and propel the development of brain-targeted therapeutics to treat an array of diseases. Initial sponsor Bristol Myers Squibb, joined by Alnylam, Eisai, Eli Lilly and Company, Lundbeck, Merck, and Visterra, worked with the Wyss team to establish a collaborative research framework for multi-company participation, based on the philosophy of, “collaborate on tools, compete on compounds.”
Through this pre-competitive model, the Brain Targeting Program has accelerated its progress and made critical inroads into the problem of brain drug delivery. Over the past year, Wyss scientists and engineers, with the support of industry sponsors, and in collaboration with the Harvard Office of Technology Development, have:
- Welcomed four new industry sponsors: ABL-Bio, GSK, Leal, and one additional company.
- Completed the first six licenses of brain shuttle technology to ABL-Bio, GSK, Leal, Lundbeck, and Visterra.
- Continued to make our brain transport mouse models available, now totaling 18 agreements.
- Initiated brain shuttle discovery projects with new antibody discovery partners OmniAb and Alloy Therapeutics.
- Initiated a project to optimize brain delivery of oligonucleotide therapeutics, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs).
- Hosted two meetings at the Wyss Institute with industry sponsors and partners.
- Drafted two peer-reviewed scientific manuscripts on the brain delivery program, for planned submission in the fall.
Recognition at international meetings
The Brain Targeting Program, its leaders, and its scientists have assumed prominent roles at several international meetings. PI Jim Gorman served as one of three organizers for the 2nd Keystone Symposium on Drug Delivery to the Brain in February, in Keystone, CO, where scientists and stakeholders from academia, industry, and non-profits convened to present talks and posters, and participate in workshops to discuss progress and plans for further innovation.
Jim Gorman presented a main session talk unveiling results showing that combining two of our lead shuttles in the same brain-targeted therapeutic provides a significant increase in brain uptake. He also described exciting new findings regarding a third, yet-to-be-disclosed brain transport target shuttle with differentiated features compared to our two current lead shuttles binding TfR and CD98hc.
Gorman also co-chaired a workshop focused on identifying emerging principles of engineering anti-TfR brain shuttles. Principal Scientist Liqun Wang, Ph.D., presented on the BTP shuttle platform in the workshop on TfR shuttle engineering, and presented a poster, “Brain transport platform for precision drug delivery of large molecule therapeutics.”
Wyss Technology Development Fellow Ana Raquel Santa Maria, Ph.D., and Scientist Sanjid Shahriar, Ph.D., presented a summary of their work. Drawing on transcriptomic and proteomic datasets, they found that expression levels of key brain transport targets are consistent across diseases and demographics, but vary meaningfully between individuals, supporting both the broad utility of these targets and the importance of understanding individual receptor expression levels. This work will be published in a forthcoming manuscript.
In July, Gorman organized and co-chaired with Joy Zuchero, Senior Director and Staff Scientist at Denali Therapeutics, the Featured Research Session on drug delivery to the brain at the Alzheimer’s Association International Conference. BTP team members Liqun Wang, Ana-Raquel Santa Maria, and Sanjid Shahriar also presented posters on their progress on solving drug delivery challenges in this important disease area.
The Power of Pre-Competitive Industry Collaboration
From its inception, the Brain Targeting Program has been structured as a pre-competitive sponsored research program built on scientific transparency and the collaborative development of new solutions. Our nine active industry sponsors include ABL-Bio, Bristol Myers Squibb, Eli Lilly and Company, GSK, Lundbeck, Visterra, and three additional companies. In many cases, our sponsors have voluntarily helped to shape the research roadmap and guide early validation efforts based on their industry, clinical, and regulatory experiences. At our sponsors meeting in June, we gathered with representatives of our sponsors and partner companies to review progress, discuss plans, and exchange ideas on the path forward for the brain transport field. Finding value in this collaborative model, most sponsors have extended their sponsorship once their initial sponsorship period has passed.
Five companies have now licensed Wyss shuttle technologies: ABL-Bio, GSK, Leal, Lundbeck, and Visterra. Harvard’s Office of Technology Development enabled these licenses to further develop the research toward a range of potential biologic drugs, including antibody, oligonucleotide, and protein therapeutics.
The Wyss Institute’s Brain Targeting Program’s collaborative model accelerates the research toward achieving real-world results. The Office of Technology Development is committed to building opportunities with industry, and this program showcases the possibility of medical breakthroughs when industry collaborates with academia.
What’s Next?
We know breakthroughs do not happen overnight but are the result of months and years of relentless and dedicated work of collaborating teams. As discussed during the annual sponsors meeting, the next priorities for the program include:
- Further optimization of shuttle-enabled drug delivery to enable treatment of important diseases for which no therapies are available.
- Completion of new engineering and shuttle discovery campaigns to augment existing lead shuttles, and generate new novel shuttles.
- Acceleration of a search for new BBB targets that could enhance uptake and retention of drugs in the brain.
For the first time, it seems truly within reach to transport large molecule drugs into the brain safely and effectively. The momentum behind the Brain Targeting Program gives us real hope for turning scientific insight into meaningful clinical impact.
Open Invitation to Innovators with a Passion to Defeat Brain Disease
For companies exploring treatments for brain diseases but struggling with delivery barriers, the Brain Targeting Program offers a flexible platform backed by world-class science and a collaborative structure. By joining, sponsors and partners not only gain access to transformative technology but also help set a new standard for collaborative development of enabling technologies.
Delivering biologic drugs across the blood-brain barrier now seems achievable. Our industry sponsors are bringing focused pre-competitive support to address this critical bottleneck. Working with partners who share this passion, we aim to help make brain transport technology highly effective, adaptable and available, enabling many more novel brain-targeted therapeutics to enter the development pipeline.
To learn more or arrange a visit to the Wyss Institute, contact Jim Gorman at james.gorman@wyss.harvard.edu.