Teaming Up to Drive Drug Discovery for Rare Disease Patients: Rationale for Nonprofit Patient Foundations and Pharma/Biotech to Collaborate

Paul R. August

For many years now, I have been a staunch advocate for non-profit patient foundations and pharmaceutical companies to work together to advance drug discovery efforts that support the objectives of both organizations. Along these lines, I have worked to forge relationships between these types of disparate non-profit patient organizations and the drug discovery industry with one goal in mind. That goal being to advance drug discovery for patients, especially children that have no therapeutics available for their disease. There have been many challenges on both sides of the aisle to justify the rationale of working together. Often times, patient foundations perceive pharmaceutical companies as well financed, research machines with unlimited need in research funding or even expertise to advance their strategic missions. In addition, there may even be the perception that there is little interest in rare diseases or collaborating with patient foundations in the first place. On the flip side, some drug discovery research organizations may lack the fundamental concept of what it means to collaborate with patient foundations, may see patients foundations as interfering with their scientific objectives and may also be unwilling to disclose the strategic focus of their early stage research portfolio. Navigating the lines between these two sides has been challenging but there are some clear opportunities to reflect on successful interactions and this highlights the need for enhanced collaboration between the non-profit and for-profit sectors going forward.

To begin to build a foundation of understanding across the landscape there are several myths that need to be dispelled. First of all, there is a myth that pharmaceutical R&D organizations have access to sufficient R&D budgets to address the needs of their strategic portfolio. It is important to state that today pharma R&D researchers have very limited access to funds to explore new ideas or therapeutic opportunities that are not in direct alignment with strategic objectives. In fact, even for those that are in alignment there are many challenges to obtain the resources and budgets to support internal research activities. Many research activities in the pharmaceutical industry are being outsourced and large swaths of R&D budgets have been oriented outside of the R&D budget in an effort to advance therapeutic development. One example of this is the investment in Regeneron by Sanofi in recent years. A large percentage of the Sanofi R&D budget has been diverted to support therapeutic antibody development at Regeneron. This leaves less funds and less scientific resources internally to an organization like Sanofi compared to 10-15 years ago. In addition, in recent years many pharmaceutical R&D budgets have been significantly reduced as a function of cutbacks and efforts to increase value to shareholders. This financial pressure has resulted in closures and divestitures of research sites across the globe. Therefore, funding mechanisms which can subsidize pharmaceutical research investments in rare diseases can have a powerful impact on driving the development of therapeutics specifically for these diseases.

Another myth that needs to be dispelled is that the pharmaceutical industry has the most experienced scientific staff in the world in a specific disease indication. As indicated previously, the pharmaceutical industry has undergone enormous changes in the last few decades. Scientific expertise in pharma across the globe has been lost due to divestitures, closures, R&D reorganizations and the stampede of scientists to management positions out of science with apparent greater job security. This has resulted in many changes where the expertise of specific scientists may not directly correlate with their functional responsibilities or the areas in which they were professionally trained. Importantly however, operationally they do often possess the management expertise and technical understanding in the discipline of therapeutic drug discovery or advancement to make substantial contributions and provide important insights. Thankfully however, patient foundations and the closely affiliated academic and clinical researchers have significant depth of knowledge that can overcome these deficiencies.

One other myth which addresses the mechanism whereby academic research is funded globally is the tenet that academic researchers should be funded to advance therapeutic discoveries. Many pharmaceutical scientists have the experience of being approached by an academics laboratory which have been funded to perform drug discovery project. Often times the project involves a model organism (yeast, fly, worm, or fish), or a small molecule that a medicinal chemist would have nightmares about. Obviously this is not the case all the time but the majority of academic small molecule opportunities do seem to be very poor starting points for optimization and development. This leads to the suggestion that academic and industry representatives collaborate to bring the strengths from each area together in order to identify and develop a therapeutic opportunities.

So the question is if industry and academia both face significant obstacles to therapeutic discovery, what is the solution? Well after many years of working in this space my observation I have seen that there is a clear opportunity for patient foundations and the pharma industry to work together to advance solid, scientific approaches towards their common goal. There are several examples where this type of reciprocal partnership has worked well. One example recently has been the efforts at Vertex that were supported by the Cystic Fibrosis Foundation and have lead to several transformative therapeutic opportunities for cystic fibrosis patients. My own personal experience at Sanofi and Icagen has been through funded programs with the Muscular Dystrophy Association (MDA), Charcot Marie Tooth Assocation (CMTA), and the Michael J. Fox Foundation. Each of these publicly disclosed partnerships have been structured and funded slightly differently. However they share a common unified, laser focused goal of developing therapeutics for rare diseases. These Sanofi collaborations are not as advanced as the Vertex efforts but these efforts are advancing rapidly to a point where it will be known if there is a clinical path forward in the near future. The support from non-profit patient foundations has been instrumental in their progression and their continued viability.

Although there are many different types of collaborations possible, the approach by which the CMTA is advancing industry collaborations should be considered as a potential model for collaborations between industry and patient foundations. Under the the leadership of a CMT patient, Patrick Livney (CEO) has strove to build an external team with foundation expertise from target to clinical development. Although the CMTA STAR team has the capabilities to build assays and perform pilot drug discovery screens in collaboration with NCATS, it lacked some expertise found only in industry. These areas are access to a pharmaceutical company drug collection, ultra high throughput screening with follow-up, drug development medicinal chemistry expertise and clinical drug development experience. The blending of these two strengths and financial support has established a solid foundation for therapeutic advancement for this program. Importantly, each team brings their unique expertise, key opinion leaders and physical assets to advance a highly collaborative endeavor. Time will tell if the therapeutics under development in the CMTA Sanofi programs advance to the clinic. Regardless however, this type of non-profit and industry collaborative model sets a standard for the future of rare disease patient foundations and industry collaborations.

In summary, although it would seem unexpected for non-profit foundations to fund research efforts in pharmaceutical and biotechnology laboratories there are many benefits to all the parties involved, especially the patients. First, limited donor dollars can be leveraged to influence the direction of drug discovery towards diseases with unmet needs, i.e. rare diseases. Second, the funding can secure the viability of a research program within a large organization where many disease areas are competing for limited resources. In some instances, the funded partnership may even keep a program from being eliminated during the incessant rounds of realignment and reorganizations in the pharmaceutical industry every year. Third, the agreements with the pharmaceutical industry partner can be crafted such that there is a payback option of all the funds invested at some predefined multiplier if a therapeutic from the project is successfully approved or advanced to some agreed upon milestone. This type of return on investment can actually create a potential evergreen fund that can be reinvested in other disease sub-types in the foundation portfolio or used to support patient focused programs. The fourth and most important reason is that by combining efforts the probability to of success to generate a therapeutic is dramatically enhanced then by what can be achieved by one partner alone. Drug discovery is a challenging endeavor, fraught with many obstacles along the path. The probability of success from starting with a new drug target to clinical approval is approximately one percent. By sharing resources, challenging scientific paradigms, aligning objectives and sharing tools the probability of success could increase to two or three percent. Although this is still low, it represents a significant increase of two to three fold in the possibility of a therapeutic developed for a rare disease with an unmet need. As a foundation donor, parent and scientist, I think that this is a return and a strategy that makes financial and scientific sense to bring therapies to those who need it the most. My hope is that future funds can be invested in these type of joint programs in order to bring forwards more therapies to patients out of options. Although I am no longer at Sanofi (due to a recent divestiture), I will strive to advance this concept at Icagen in order to leverage our integrated drug discovery capabilities and with the sincere desire to bring new therapeutics forward for rare diseases.