The Crucial Role of Nonprofit Risk-Tolerance
Annette Bakker, PhD, President, Children’s Tumor Foundation
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Introduction
Motivated by a vision to eliminate obstacles hindering the journey from discovery to clinical advancements and to enhance the likelihood of transforming noteworthy academic findings into improved treatments for patients, I decided to transition from the pharma/ biotech industry. I joined the Children’s Tumor Foundation in 2012. I performed a landscape analysis of the other creative patient-centric research foundations, and I learned that foundations like the Cystic Fibrosis Foundation, Leukemia Lymphoma Society, Alzheimer’s Drug Discovery Foundation, Multiple Myeloma Research Foundation, and others were also transforming from mere program managers and advocates into active participants in the Research and Development (R&D) ecosystem. I redesigned the Children’s Tumor Foundation (CTF) operations, and today, its proactive approach and risk tolerance have become a blueprint for others in the nonprofit sector. CTF has successfully positioned NF as a prototype for rare diseases.
Consequently, the overall awareness of NF has massively increased, and the science is ready to be translated into treatments for our patients. In collaboration with the entire community, we brought the first drug to the market, and we have two other drugs that just entered phase 3, many clinical trials, gene therapies, and new scientific analysis modalities. The time is now to end NF!
Nonprofits as Unconflicted Stakeholders
With their unique attributes, research foundations play a distinctive role in the R&D ecosystem. Their connectivity to all stakeholders, unparalleled understanding of diseases due to proximity to patients, and a shared sense of urgency make them unconflicted stakeholders capable of challenging the status quo. Unlike other entities bound by the need to publish or patent, nonprofits, like the CTF, possess a fiduciary responsibility to invest in research and activities that advance care and cures. This autonomy positions them as critical drivers of change in a system sometimes hampered by reluctance to take risks.
As valuable contributors to the R&D ecosystem, nonprofits have a dual obligation and opportunity to address challenges. The belief that foundations should be willing to take risks on a diversified portfolio of activities is not merely a strategic choice but an ethical imperative. Despite the often-uncomfortable solutions proposed, patients, resilient in the face of disease, tend to support unconventional approaches that promise quicker solutions to their conditions.
Collaborative Approach to Stakeholder Engagement
A fundamental belief in the goodwill of stakeholders in the healthcare sector forms the foundation of the CTF’s philosophy. Rather than attributing blame, the organization commits to collaboration with all stakeholders willing to contribute to a better future for patients. However, a nuanced understanding acknowledges that stakeholders may unintentionally act against the acceleration of cures and care.
The roadblocks include delayed science advancements due to grant issues, lack of collaboration and data sharing, pharma’s reluctance to invest in rare diseases, and patient’s hesitancy to participate in clinical trials. They underline the healthcare sector’s complexity. As posited by the CTF, effective change necessitates identifying incentives and disincentives driving behaviors that either catalyze or hinder progress.
Children’s Tumor Foundation: A Model for Change
The CTF’s theory of change serves as a guiding framework for their transformative initiatives. Case studies aligned with this model shed light on the foundation’s endeavors to address challenges systematically, illustrating the efficacy of their risk-tolerant approach.
Case Study #1: Accelerating Science Advancement
The first case study addresses the sluggish pace of scientific advancement attributed to low success rates in securing large NIH/CDMRP grants. By understanding that government institutions require solid preliminary datasets, the CTF initiated a pilot program funding small grants to de-risk promising ideas. Despite challenges, the organization has invested significantly in investigator-initiated grants, showcasing the impact of supporting pioneering research. Recent adjustments, such as offering additional bridge funding for promising studies, demonstrate the commitment to ensuring that great science never halts.
Case Study #2: Overcoming Collaboration Barriers
The second case study delves into the issue of inadequate collaboration and data sharing among researchers. Recognizing the scarcity of funding and competition, the CTF launched SYNODOS in 2014, emphasizing multi-disciplinary collaboration, patient participation, immediate data sharing through the NF data portal, substantial funding, and project management by CTF. Although the outcomes were phenomenal, it highlighted the importance of ongoing adjustments, including patient education and further incentivizing data curation and user-friendliness.
Case Study #3: Addressing Reluctance in Rare Disease Research
The third case study confronts the reluctance of companies to invest in rare diseases, characterized by their complexity and small markets. Through the Preclinical Consortium, SYNODOS-NF2, and participation in global NF platform trials, the CTF has made substantial contributions to identifying treatments for neurofibromatosis (NF). These remarkable successes led to the creation of the NF Preclinical Hub, which aims to scale up preclinical testing capacity and make NF more attractive to pharma and biotech.
Case Study #4: Repositioning Shelved Assets
The fourth case study explores the issue of pharma and biotech shelving assets for strategic reasons, rendering them unavailable to patients. CTF successfully collaborated with the Pfizer leadership to reposition the MEK inhibitor from Pfizer into the spinoff company SpringWorks. CTF now recognizes the need to design new approaches to incentivize even more companies to release their shelved assets.
Persistence and Dedication: Catalysts for Change
The journey of the CTF, marked by persistence and dedication, underscores the importance of challenging the status quo. Despite the exhaustion inherent in swimming against the stream, the foundation’s achievements are remarkable. With 67 trials involving ten companies dedicated to NF, the first approved drug and gene therapy in development, the CTF has fostered a highly collaborative community involving ten pharma companies and over 800 funded research projects.
Next Main Projects: Charting the Future
The CTF’s vision encompasses crucial projects that exemplify their commitment to innovation and patient-centric care. The development of the Preclinical Hub, improvements in data experience, expansion of clinical trials consortiums and platform trials, incentivizing pharma to release shelved assets, education and engagement through CTF Engage, strengthening clinic networks, and establishing standardized clinical care guidelines are all testament to the organization’s holistic approach to transforming healthcare.
My humble view on the future of NF science
Regarding neurofibromatosis (NF), there are several significant opportunities. Since it is crucial to persist in addressing the needs of current patients, we should continue the different treatment approaches, including repurposed small and large molecules, repositioned, and exploring novel chemical modalities like PROtaq and DUBtaq. With regard to treatment for patients today, incorporating RNA treatments is strongly recommended. Continued investment in gene therapy, focusing on refining delivery systems and mitigating systemic toxicity, is essential.
From a scientific standpoint, a substantial opportunity exists to explore the microenvironment. This involves studying inflammation for pain, understanding macrophage and immune cell infiltration for other tumors, and delving into the role of vascularization in the malignant transformation of peripheral nerve tumors (PN). To ensure a seamless translation from basic discovery to clinical benefit, validating identified biomarkers for clinical use is crucial. Developing new endpoints that account for the complexity of pain, learning and social challenges, and bone, I would advocate for developing and validating comprehensive, objective measurement, incorporating imaging, multiparametric data collection, and artificial intelligence (AI).
A significant investment in standardized clinical care and imaging, enhancing the synergy between engineering and biology, will be imperative to advance the field and make NF more predictable. Although I am very excited about the approval of the first MEK inhibitor, exploring the non-MEK biological pathways are exciting and essential avenue for further research and discovery in the field of NF and schwannomatosis.
Conclusion
In conclusion, the Children’s Tumor Foundation serves as a paradigm for nonprofits seeking to drive change in the healthcare sector. Their risk-tolerant approach, illustrated through comprehensive case studies and ongoing projects, highlights the transformative power of nonprofits in overcoming challenges. By persistently challenging the status quo and embracing innovation, organizations like the CTF are accelerating the development of cures and care and shaping a future where collaborative efforts triumph over inherent complexities in the medical research landscape. The imperative question posed at the beginning resonates: If nonprofits don’t take risks, who will?
About Annette Bakker. Annette first got a teaching degree in physics, mathematics, and chemistry, studied chemistry, and obtained a PhD in Biochemistry/ cell biology. After a 15-year tenure in the academic enterprise in Belgium (Univ Antwerp), Paris (La Salpetriere), and New Haven (Yale Med School), Annette joined Janssen Pharmaceutica (J&J) as an oncology preclinical development group leader in Belgium. She led numerous R&D projects. After six years, she was recruited to design and lead a new neuro-oncology division in a biotech in Italy. She led a group of approx. fifteen scientists, developed novel GBM-relevant screening such as neurosphere and co-cultures, new imaging-based animal models, and led the clinical development group. She was part of their executive leadership for seven years, building a solid neurooncology pipeline and many national and international collaborations. Throughout her scientific career, she mentored 3 Ph.D. students and numerous interns, co-authored patents, and published her work in peer-reviewed papers. In 2012, she joined the Children’s Tumor Foundation (CTF) in NYC as lead scientist, and in 2014, the Board of directors nominated her as president of the foundation. In 2018, the board also approved her role as chairperson of CTF Europe.
