By Rich Soll, Senior Advisor, Strategic Initiatives, WuXi AppTec (@richsollwx) and WuXi AppTec Content Team
The translation of academic discoveries into therapeutic products remains an issue despite passage of the Bayh-Dole Act (or Patent and Trademark Law Amendments Act) in 1980. That Act, for first time, allowed academic institutions to capitalize on discoveries that emerged from their faculty’s labs. Boston, San Francisco and San Diego nurtured cutting-edge entrepreneurial environments for spin-outs from academic science, but New York City, one of biggest recipients of NIH funding, lagged far behind the big-3 bioclusters.
Tri-institutional Therapeutics Discovery Institute (TDI) was born in New York City as a not-for-profit research center to explore the early steps of advancing scientific breakthroughs from bench to bedside. The goal of the Institute is to advance ground-breaking discoveries from scientists at the Memorial Sloan Kettering Cancer Center, The Rockefeller University and Weill Cornell Medicine through preclinical studies.
Leading TDI as the Sanders Director since 2018 is Dr. Peter Meinke, a 20+ year industry veteran from Merck Research Laboratories with broad experiences associated with multiple facets of drug discovery and development. He was a recipient of the coveted American Chemical Society’s Heroes of Chemistry team award in 2017 for his leadership in the discovery of the antiviral NS5A inhibitor found in the fixed-dose combination product known as Zepatier,® a therapy for the treatment of Hepatitis C.
Dr. Meinke recently sat down with Dr. Rich Soll and members of the WuXi Content Team to share his experience managing a unique organization like TDI as well as provide insights on drug development and observations of the industry’s dynamics and trends over the years.
Rich Soll: How does TDI work toward its goal?
Peter Meinke: TDI provides industrial-scale technical support for academic projects, making it possible to rapidly assess the utility of specific therapeutic targets in disease-relevant contexts in ways that are unprecedented in scale and scope for an academic environment. This is accomplished through a series of highly favorable academic-industry partnerships established through TDI, as well as our Innovation & Education Initiative, which provides community-wide training and support in order to maximize the impact of these partnerships on academic drug discoveries. We achieve our mission by leveraging the infrastructure, staff and intellectual capital of our academic and industry partners, as well as the generous support of philanthropists.
Rich Soll: How many projects do you have and what is the process for selection?
Peter Meinke: Currently, we have twenty-three therapeutic programs, almost equally split between biologics and small molecules, and our programs are structured as collaborations so we are able to leverage the expertise of the labs. And we have built an early portfolio of about twenty-five Early Stage programs, using about 10 percent of our resources, so we now have a pipeline of projects.
To decide which programs to undertake, we have an annual RFP process, but we also take in programs on a rolling basis over the course of the year. We have an independent scientific advisory board made up of people who are often former C-Level executives from Pharma and Biotech, all of whom have international reputations. Our SABs look at potential programs and use their best technical judgments, rank ordering them just as in an NIH grant review process, and then we set a funding line. We probably accept somewhere between a quarter and a third of all applicants on a historical basis. We also have project-specific advisory boards to provide technical expertise that we, or the Tri-I labs, lack.
Rich Soll: So what about the historical success rates?
Peter Meinke: We’ve accepted 60 biologics programs in just about six years, and 68 small molecule programs. Our total output to this date is we’ve contributed to two NewCos (new companies) and licensed six programs to biotech or pharma. We had one program where the PI declined to accept the license because he’s an MD/PhD with unique skills who recognized he could take it close to the NewCo stage and clinical validation before partnering.
We have three programs that are available for license, which we validated in animal models. We have 12 additional programs for which we have obtained animal proof of concepts for new mechanisms, five of these are under active licensing discussions and they’re split almost equally between small molecules and biologics. This is a pretty remarkable output. I think it’s about 20 percent overall.
Rich Soll: External collaborations and partnerships are vital, especially in today’s R&D. How is that implemented at TDI?
Peter Meinke: Because of the way we’re structured, we can only work with faculty from these three communities.However, many of the programs that we work on also have a collaboration with faculty from other New York, US or international universities. Takeda is our general partner, but many of the programs that we support do not align with Takeda’s interest and Takeda is happy for that because they get access to cutting edge research in areas that they are of strategic focus. For projects not within Takeda’s strategic interest, the institutions created a for-profit, virtual company called Bridge Medicines to continue translational development of the asset. Being a virtual development company, Bridge Medicines relies heavily on the use of providers, particularly WuXi AppTec.
Rich Soll: How has TDI used WuXi AppTec?
Peter Meinke: Currently, we have over 100 providers and platforms under contract with TDI and we have a wide range of specialists that we work with for new things. With respect to WuXi AppTec, we make very heavy use of chemistry services.
We do use a lot of biological profiling, but that ebbs and flows depending on the nature of the programs. We use WuXi AppTec very commonly to build assays and miniaturize them for high throughput screenings. WuXi AppTec has counterscreens for key off-targets which are very important to TDI because we learn more about our compounds’ profiles.
We also will perform animal pharmacology studies to support projects. For example, we encountered a situation on one mechanism where an off-target liability required a sophisticated animal study that is in the suite of experience that WuXi AppTec offered. We worked with WuXi AppTec senior scientists to make sure that we designed the study to de-risk this mechanism-based liability in animals as a key component of advancing the program. If that had been a negative result it would result in program termination, so it was important that study be done right and with appropriate standards. WuXi AppTec scientists were instrumental in ensuring that it was designed properly and appropriately controlled, so that we know it was executed to a high technical standard. Our molecules did not have the adverse signals. We couldn’t possibly do that internally.
And we have variations of that on the biologic side in terms of antibody generation, antibody maturation, and so forth.
Rich Soll: What is different leading an organization like TDI in comparison to previous positions?
Peter Meinke: Leading an organization like TDI has been very different, incredibly enjoyable and very rewarding for me. The environment here is filled with experienced and creative scientists in different scientific disciplines with diverse expertise. TDI is well-resourced, but it is not pharma, so everything we do matters. We continuously ask ourselves “what is the key impediment that stops a program or asset from progressing.” It’s all about quick decision-making and devoting resources to solve the problem, even if deemed risky.
We leverage our externalized networks to augment anything we can’t do internally. I can do that today because of the way industry has evolved. I have a working relationship with WuXi AppTec that goes back to its earliest days. I’ve seen the type of complexity that they can handle on both small molecule and biologic fronts. TDI has its internal labs but, importantly, does not need to build a large chemistry or biologics department because we can leverage the capabilities of WuXi AppTec.
Rich Soll: When you take a look at the world of R&D and pharmaceutical discovery, how has it evolved? What trends have you observed?
Peter Meinke: The growing role of biotech and academia is clear. There is an increasing amount of large pharma’s pipelines coming from small biotechs and academia. People with real talent and drug discovery experience who once worked for pharma have migrated to the sea of small companies that are doing innovative and highly risky programs that address a recognized unmet need.
These small organizations typically only have one, or a few, projects. They have very limited time and bandwidth to be successful, so they are incredibly focused on trying to show that “yes, this hypothesis has legs” and “yes, it will help treat some disease or another.” And then, when they get to a certain point, pharma, which has the resources and the wherewithal, will swoop in and often acquire/partner with these smaller organizations to really move it fast into clinical applications and real-world use.
Rich Soll: If you had access to one technology that could make a difference, what would that be?
Peter Meinke: One of the greatest challenges in the small molecule world is actually getting a suitable starting point of high quality. So, I pay a great deal of attention to computational technologies that allow me to generate this starting point. We pretty much have unrestricted access to Schrodinger’s software, and we have three full-time computational scientists using these tools, which lets you understand how valuable it is for TDI.
Rich Soll: Do you see opportunities here for cancer to go from treatment to cure?
Peter Meinke: It’s pretty clear to everybody that immuno-oncology, for example, is as profound a change for treating cancer as was the discovery of antibiotics, and you know the use of IO is extending past oncology applications. This has led to the development of the Car-T platform which you can view as the next generation, and from this are emerging even more and more changes. People are really starting to learn how the human body’s immune system actually controls disease states, so if you can modulate this in an appropriate fashion, it has really profound impacts, which are already extending beyond cancer treatments.