Thank you for the opportunity to share with you some of my preliminary thoughts and plans in early translational research at UCSF.
A very brief introduction I joined CTSI just 3 months ago as the Director of Early Translational Research from Genentech where I worked in clinical development for the last 7 years in varying capacities. My most recent role was in early clinical development heading up programs in infectious diseases, cardiovascular/metabolic diseases, and respiratory diseases. Prior to Genentech, I was at UCSF for 9 years as a clinical and research fellow and on faculty.
This is an exciting time to be working on translational research which has been referred to as “valley of death” in the past. It’s an exciting time for many reasons. At UCSF, above all else, we have really top notch, amazing science and scientists-the fundamental building blocks of good translational research. Translational research is an important and complex multidisciplinary endeavor that we and others are trying to figure out how to do better. UCSF is an institution with demonstrated commitment and intent to making this happen. The faculty and the leadership are clearly committed to this endeavor and there is evidence of this commitment throughout the campus…Decade of Human Biology, QB3, CTSI, Cancer Center with its translational core, CVRI, to name a few. Outside of UCSF, the whole of scientific community very keenly recognizes the need to translate our science to better health solutions better than we are doing now. Funding agencies, regulatory bodies, and the industry are responding and as a result, the landscape is quite dynamic and exciting and presents many potential opportunities In my new role, my goal and commitment is to facilitate/enhance/and accelerate early translational research at UCSF. The specific tactics on how this will be done will continue to evolve over time. Today, I will share with you the framework that I am using to think about translational research at UCSF and some near term plans.
Since arriving back at UCSF 3 months ago, I have been on a listening tour…meeting with many folks involved in various aspects of translational research across the campus to better understand What are the ongoing T1 efforts across the campus? What works well What could work better What is missing? What’s being done at other places? With this information, I am starting to work on a business plan
I have put together this framework to help me to simplify and think through the processses in translational research. And this has been useful to me in identifying the key gaps and potential needs. We have what is called early or T1 and later T2 translational research. Under T1, the work of translating science to invention/discovery occurs. Here, I will use the term invention to be synonymous with patent filing while acknowledging that there are discoveries that are not filable which can result in development of products that impact health. Under the T1 umbrella is also where this invention/discovery gets translated to a product that then can be used to impact health and to modify outcomes. I will use the term product to refer to a therapeutic/diagnostic/device/or an entity that can then be used for health benefit. This process is not quite as linear as this graphic would suggest. In an ideal world and in reality, there is feedback from the bedside to bench, from community to bedside and community to bench which informs the science (many would argue we can do better in that regard). In terms of where the resources and focus for the work at the various stages has traditionally been, academia has focused more on the science and discovery. Once there is an invention, start up companies moved the work along towards creating a product. At some point in this continuum, larger companies/pharmas then became involved as strategic partners or through acquisition. I should also mention that large pharma companies also invested significantly into in-house science and discovery work in the past. All analysis would indicate that this investment has been costly and not nearly as productive as hoped for. More recently, esource gaps have been growing. Venture funding for starting up and sustaining biotech/startups is becoming more scarce and the high failure rate of inventions/discoveries in the later phases of development among other reasons have led to large companies/ pharmas being less willing to take on molecules that others have developed at high valuations until substantial development has taken place (reducing the risk that lies ahead). Because internal R& D as well as startups/biotech have become a less reliable source for pipeline, large pharma/companies have been making a concerted effort at reaching directly into academia to get engaged early with the science and to populate, at least in part, their development pipeline in this mechanism. And of course, funding for academic research has been more challenging than ever before. And with the gaps in translational research widening, more is expected with less. In that regard, this new paradigm in which pharma is actively looking to invest in academia and to partner with academia is an opportunity.
Within this framework, the gaps in early translational research can be defined in multiple layers. Not clear how much science with invention potential is left on the table or on the shelf. What keeps science from leaving the confines of a particular lab or the walls of UCSF? Invention to product…what happens to the patents that are filed? What are the challenges beyond patent filing? Why don’t more patents get licensed? What are the challenges in moving a research program from bench to bedside? Do we infrastructural support for this type of translational research to occur? How does what we learn at the bedside then get fed back to bench to inform the science? How are we connected to the community? How does what is learned in the community make it back to the scientists and the clinicians working at the bench and bedside? Are we sufficiently leverating the resources, capabilities, and experience that industry has in turning inventions to products and beyond? If not, why not? These are questions that many are asking and thinking about. And understanding these better will be important in helping us to develop specific strategy and tactics to address these gaps. And in doing so, the opportunity is that of leading, influencing and driving the acceleration of research to improving health.
One of the programs T1 traslational catalyst award is a program which was initiated a year and a half ago to address the gap of invention to product. It is intended to identify projects with diagnostic, device, or therapeutic potential The program then provides a customized panel review and in some cases, provided a customized consultation award for the program.
T1 catalyst award program is a unique awards program in that the value of participating in the program goes beyond the development award. Bob Nussbau/s proposal and the evolution of his program nicely demonstrates how a program can benefit from some of the aspects of the T1 catalyst program. Bob Nussbaum applied for a T1 Catalyst program to further develop his pre-clinical work to assess the role or alpha-synuclein in PD pathogenesis. Hypothesis: lowering aSyn would benefit clinical manifestations of PD. There was already in vitro using which showed treatment with posiphen which led to reduction of in vitro expression of a-Syn. Proposal was to do a POA study in murine model of PD using posiphen. Posiphen is a small molecule inhibitor shown to reduce amyloid precursor protein in development at QR pharma for Alzheimer’s disease. His collaborator also had pre-existing relationship with QR. Bob did not. Phase II panel discussion: Posiphen is being developed for AD by QR pharma. Unclear on QR’s plans on PD. Engage OTM to help clarify relationships between Nussbaum and collaborator and Nussbaum and QR pharma. He was then provided time with a pharma development consultant with significant expertise and experience in neurodegenerative diseases to work with. They contacted QR pharma and with the help of OTM and the consultant, were able to define clear working relationships with each of the collaborators including QR pharma. They applied for a MJFox grant together with the help of a translational grant writer with the funds provided by CTSI and was invited to submit a full proposal which is currently being done. And Nussbaum/UCSF are in the final phases of negotiating a MOU with QR pharma whereby UCSF’s investment into the development of Posiphen for PD indication would be paid back in some form should Posiphen program in PD reach certain milestones. So, while he did not receive the final Phase IV award, through the support provided by the T1 Catalyst award program, he was able to navigate a complex IP situation with opportunity to leverage external resources for funding and collaboration to hopefully move the program forward.
My thoughts on this early assessment are that the award program only helped to identify a small proportion of the science and invention here at UCSF. And while it’s important to identify the inventions that are ready for support in becoming products, it’s perhaps equally as important to identify the early program to help science to become inventions. And that providing access to the customized consulting and small pilot grants can be a mechanism by which we can identify some of the promising earlier science.
We are starting the discuss how we might be able to offer the components of T1 Catalyst award thought to be most valuable to more investigators…in particular the pilot grants and the consultation program. Preliminary thoughts around this is that we would create a more comprehensive T1 transalational catalyst program which would include the T1 catalyst award but would also include a freestanding consultation program and pilot-micro grants program for investigators whose programs are less mature and might need a more limited one time consult or a small pilot grant to do that experiment which then can help determine human relevance for the program. Both the consultation and micro grants program would be designed to be minimal process with a quick turn-around on the order of 1-2 wks for decision. Stay tuned for more on this. This can also then be used as a mechanism by which we identify science which have the potential to become inventions. In that way, it can also serve as a funnel to identify programs that can then apply for a full T1 Catalyst Award.
Also discussing the expansion of the award program to create different tracks (with different expert review panels) and hopefully increase the number of awards. Currently in active discussion with a number of potential partners and affiliates to help fund some of these awards.
Early translational research is a complex, multidisciplinary, and in places capital intensive endeavor. The goal is to build innovative partnerships that is fit for purpose in such a way that the scientists at UCSF can continue to do what they do best while leveraging the capabilities that reside in the resources that surround us in the industry and other partners/ collaborators. This might mean that we enter into a collaboration that is more of a co-development model in the way the Pfizer CTI program is set up. This might mean we engage the a venture company to help us get a company started as QB3 has done with great success. We are in active discussions with many of these entities to set up partnerships that are fit for purpose. UCSF/Academia Cutting edge science Deep subject matter expertise and experts Industry partners Development experience Process capabilities Access to resources Potential source for funding
Early Translational Research at UCSF-CTSI: Programs, Plans and Partners
Early Translational Research July 28, 2011 June Lee, MD Director, Early Translational Research CTSI Associate Professor, Department of Medicine
Prior experience <ul><li>Joined CTSI on 4/26/11 </li></ul><ul><li>Title: Director of Early Translational Research </li></ul><ul><li>Prior experience: </li></ul><ul><ul><li>2004-2011 Genentech Inc </li></ul></ul><ul><ul><ul><li>Head of Infectious Diseases, Cardiovascular/ Metabolic Diseases, Respiratory Diseases in Early Clinical Development (Pre-clinical to end of Phase II) </li></ul></ul></ul><ul><ul><li>1995-2004 UCSF </li></ul></ul><ul><ul><ul><li>Pulmonary/Critical Care Faculty </li></ul></ul></ul><ul><ul><ul><li>Director of High Risk Asthma Clinic, SFGH </li></ul></ul></ul><ul><ul><ul><li>Pulmonary Critical Care Fellow/ Research Fellow </li></ul></ul></ul>
Why now? <ul><li>UCSF </li></ul><ul><ul><li>Science/scientists </li></ul></ul><ul><ul><li>Intent and commitment </li></ul></ul><ul><ul><li>Leadership </li></ul></ul><ul><li>External to UCSF </li></ul><ul><ul><li>Funding agencies (NIH-NCRR, NCATS) </li></ul></ul><ul><ul><li>Regulatory agencies(e.g. FDA) </li></ul></ul><ul><ul><li>Industry </li></ul></ul>Goal: Facilitate/enhance/accelerate early translational research at UCSF
What I’ve been doing <ul><li>Listening tour </li></ul><ul><li>Assessing current T1 activities/efforts at UCSF </li></ul><ul><li>Working on a business plan </li></ul>
Translational research Early (T1) Late ( T2) Bench Bedside Community Outcomes/ Impact Better Health Academia Start up company/ biotech Large pharma/company Academia Start up company/ biotech Large pharma/company
Early translational gaps <ul><li>Science to invention </li></ul><ul><li>Invention to product </li></ul><ul><li>Bench to bedside </li></ul><ul><li>Bedside to bench </li></ul><ul><li>Community to bench/ bedside </li></ul><ul><li>Academia to industry </li></ul>Lead, Influence, Drive…Improve Health
T1 Translational Catalyst Award <ul><li>Identify the best projects </li></ul><ul><ul><li>Diagnostics, devices, or therapeutics </li></ul></ul><ul><li>Bring in missing pieces </li></ul><ul><ul><li>Panels include people from industry and academics </li></ul></ul><ul><ul><li>Panels review and provide individualized feedback </li></ul></ul><ul><li>Leverage limited resources </li></ul><ul><ul><li>Identify partnerships if appropriate </li></ul></ul>Gap: Invention to Product
Phased award approach <ul><li>Attractiveness </li></ul><ul><li>Ease of Implementation </li></ul><ul><li>Intellectual Property </li></ul>Gap: Invention to Product
T1 Catalyst Award program assessment <ul><li>Status </li></ul><ul><ul><li>Completed 3 cycles of funding to date </li></ul></ul><ul><ul><li>Number of proposals submitted was limited </li></ul></ul><ul><ul><li>Initial target: “Invention to product” stage but many proposals were “science to invention” stage </li></ul></ul><ul><li>Feedback </li></ul><ul><ul><li>Pilot grants helped advance programs </li></ul></ul><ul><ul><li>Customized consulting service very useful </li></ul></ul>
T1 translational catalyst program Identify & Enable Science Invention Invention Product Gap: Science to Invention, Invention to Product
T1 Translational Award Program <ul><li>Planning for multiple tracks </li></ul><ul><ul><li>Therapeutics </li></ul></ul><ul><ul><li>Diagnostics </li></ul></ul><ul><ul><li>Devices </li></ul></ul><ul><ul><li>mHealth </li></ul></ul><ul><ul><li>Orphan/ rare diseases </li></ul></ul>
Innovative partnerships <ul><li>Critical to extending the T1 translational capacity in academia </li></ul><ul><li>Non-traditional models and re-defining the boundaries of private/public partnerships </li></ul><ul><ul><li>Pharma/academia </li></ul></ul><ul><ul><li>Early stage investors (e.g. Venture capital) </li></ul></ul><ul><ul><li>Foundations and venture philanthropy </li></ul></ul><ul><ul><li>Others </li></ul></ul>
Near term focus <ul><li>Enhancing T1 translational catalyst program </li></ul><ul><li>Build/enhance innovative partnerships to support T1 translational research efforts </li></ul><ul><li>Continue to assess for opportunities </li></ul><ul><ul><li>Multidisciplinary cross fertilization </li></ul></ul><ul><ul><ul><li>Bench to bedside </li></ul></ul></ul><ul><ul><ul><li>Bedside to bench </li></ul></ul></ul><ul><ul><ul><li>Community to bench/bedside </li></ul></ul></ul><ul><ul><li>Education (T1 focused) </li></ul></ul><ul><li>Definition of success </li></ul>
How you can help me <ul><li>Please let me know if what has worked well in the past at UCSF and what could work better </li></ul><ul><li>If you’re aware of interesting/successful programs in early translational space, please let me know </li></ul><ul><li>If you have a project/program/issue that CTSI may be able to help with, please call/contact </li></ul><ul><li>Other inputs/perspectives/constructive feedback are all welcome </li></ul>
Accelerate research to improve health <ul><li>Identify and address gaps </li></ul><ul><li>Be agile </li></ul><ul><li>Take smart risks </li></ul><ul><li>Collaborate </li></ul>UCSF SOM/ SON/ SOD/ SOP, CTSI, QB3, NIH, NCATS, Pfizer, Sanofi, Bayer, Genentech/ Roche… many more