Double the Hope: A Conversation with Annette Bakker, CEO, the Children’s Tumor Foundation

Dr. Annette Bakker, CEO of the Children’s Tumor Foundation (CTF), spent the last decade passionately devoted to finding impactful therapies to treat all forms of NF, which includes neurofibromatosis type 1 (NF1) and all forms of schwannomatosis (SWN), including NF2-related schwannomatosis (NF2-SWN). These genetically driven rare diseases cause tumors to grow on nerves. Under her leadership, CTF has built global, patient-centric research networks that not only benefit NF patients but have broadened awareness of NF. The Foundation also engaged in two novel drug approvals for NF1 and drugs in clinical testing for NF2-SWN, and continues to advocate for a blueprint for accelerating rare disease drug development. In this interview, Dr. Bakker shares her insights on the role of patient organizations, key factors for successful partnerships, and her call to action in rare disease drug development.

Annette, great to see you again! For neurofibromatosis patients, the Children’s Tumor Foundation has become central to drug development. How do you see the role of patient organizations evolving in catalyzing research and accelerating new therapies?

Annette Bakker: Thank you so much for inviting me—it's always an honor to connect with my friends at WuXi AppTec. I believe our role, and that of similar research foundations, is critical. For instance, when I spoke with the company behind the first drug approval for NF1, I asked why they were interested in partnering with the Children’s Tumor Foundation. Their response was clear: we stand at the nexus and have the trust of the patients and the broader research community. We have built strong relationships with patients, clinicians, researchers, pharma, and regulators alike.

They view us as a convener and partner, with a singular ethical obligation—to invest every donor dollar in delivering treatments to patients. This position reinforces our clear mission in the NF1 and schwannomatosis research and development ecosystem.

Two drugs have been approved for NF in the past five years. What advances do you expect to see in the future?

Annette Bakker: We now have two drugs approved for NF—both for plexiform neurofibromas, with one approved exclusively for children and the other for both children and adults. While this progress is significant, it addresses only one manifestation of NF. Currently, there are over 60 ongoing clinical trials in the United States exploring various aspects of the disease. The inherent challenge with NF, and many rare diseases, is its heterogeneity: these disorders often affect multiple organs and manifest in diverse, progressive ways. Each manifestation essentially behaves as an independent disease, which means that separate drug approvals are necessary. For example, we saw the approval of Koselugo for plexiform neurofibromas, followed by SpringWorks' approval for Gomekli. Our current goal is to secure approvals for all NF and schwannomatosis indications, including cutaneous neurofibromas, vestibular schwannomas, meningiomas, ependymomas, pain management , and cancer, just to name a few.

Looking forward, one promising advancement is the emergence of platform basket trials for rare diseases. We have two platform-basket trials up and running and a third one being evaluated at the European Medicines Agency. These trials enable a long-term, continuous clinical study—potentially lasting up to 10 years—into which companies can integrate their drugs as they become available. This approach could significantly accelerate the development process, addressing one of the key challenges in rare disease research.

The Children’s Tumor Foundation has established numerous successful collaborations. What critical factors have contributed to building these effective partnerships?

Annette Bakker: I have a very simple definition of a partnership: it’s a collaboration between people. I believe that when you bring the right people together—a coalition of the willing—the commitment to step out of one's comfort zone makes breakthroughs possible. That's where discoveries translate into clinical benefits.

For example, our Synodos consortium brought together patients, clinicians, researchers, pharma representatives, and members from organizations like NCATS to tackle challenges in NF1 and schwannomatosis. When the patient is in the room, it truly motivates everyone to push beyond conventional boundaries. Another successful initiative is our NF Data Portal. By curating and sharing unpublished data, researchers can see what works and what doesn’t, accelerating our understanding of NF and preventing redundant efforts. This open sharing has proven invaluable. These examples illustrate that effective partnerships are built on a shared commitment to innovate and a willingness to invest in transforming patient care.

Considering the unique challenges in rare disease drug development, how can we overcome these hurdles to ensure every patient has access to innovative treatments?

Annette Bakker: That’s a big question. One major challenge I see is that even if we successfully develop a prototype for NF, it represents only one relatively common rare disease. There are around 11,000 rare diseases, and we simply can’t replicate the same prototype for each one individually. We need to really start thinking about clustering these rare diseases together so that they can benefit from similar therapeutic assets. For example, can we group conditions like Rasopathies, muscular myopathies, and others in a way that remains attractive to the pharma sector and yields sizable, meaningful trials? That’s one legacy I hope to leave behind, and we are working with partners from EFPIA, Sanofi, NCATS and the Myhre Syndrome foundation to untangle the challenge of how to cluster rare diseases efficiently.

Another critical area is what I call the “repositioning conundrum.” Many pharma companies are shelving promising assets for commercial and marketing reasons. For instance, when a biotech with multiple assets is acquired by a large pharmaceutical company, they may only pursue one asset while the others—sometimes already in advanced stages with FDA data packages—are left dormant. We need to develop a business model that rescues these valuable assets, ensuring that data from IND-enabling studies isn’t wasted and that drugs can be brought back into commercial to the clinic without unnecessary repetition of studies.

Addressing these issues will require collaboration among a wide range of stakeholders—from policymakers and legal experts to finance professionals and drug discovery scientists. I hope the FDA will engage in real conversations with rare disease groups to ensure we don’t inadvertently "kill" drugs that still hold promise for patients. By tackling these challenges, we can pave the way for a future where every patient with a rare disease has access to innovative and effective treatments.

Thank you so much for your insights. As we conclude, could you share your vision for the key technologies on the horizon for NF research and drug development?

Annette Bakker: One critical area on the horizon is making NF more predictable. Although only 10-15% of patients experience the transformation of benign tumors into highly malignant sarcomas, current prediction methods are suboptimal. We are investing in liquid biopsies and blood markers that can distinguish between benign tumors, suspicious lesions, and malignant peripheral nerve sheath tumors (MPNST). Once validated, these markers will become crucial tools in clinical decision-making. By integrating clinical and liquid biopsy data with advanced imaging techniques, we aim to develop artificial intelligence methodologies to accurately predict which tumors are at risk of malignant transformation, allowing for personalized treatment strategies—whether initiating aggressive chemotherapy or opting for vigilant monitoring.

Also, there is tremendous potential in leveraging new technologies to discover novel biological insights. Embracing the complexity of the biological pathways, advances in spatial omics, transcriptomics, and proteomics allow us to analyze subcellular populations within tumors, study the tumor microenvironment, and identify new markers and therapeutic targets. We are also exploring the roles of metabolism, neuron-tumor interactions, and the secretome. Coupling these findings with emerging treatment modalities—such as small molecules, PROTACs, DUBTACs, kinase inhibitors, biologics, nucleotides, and innovative delivery systems—offers immense promise. The energy in the field is remarkable, and I am confident that these breakthroughs will lead to the identification of new targets and the development of transformative treatment modalities for NF.