Brigatinib Now in the NCCN Guidelines for NF2-SWN

BREAKING NEWS - FOR IMMEDIATE RELEASE

A landmark moment for NF2 -SWN patients - Brigatinib is now part of national treatment guidelines - giving doctors, patients, and insurers a major new recognized treatment option for NF2-related schwannomatosis.

CTF brought the right people together, at the right time, in the right place - and changed what is possible for people living with NF2-SWN.

The National Comprehensive Cancer Network (NCCN) - the gold standard in oncology treatment guidelines - has included brigatinib as a recommended treatment for NF2-related schwannomatosis (NF2-SWN). For a condition with no FDA-approved therapies, this is transformative. It reflects years of CTF's scientific leadership and persistence, including our role in identifying brigatinib's promise and ensuring that critical data was shared, understood, and advanced through collaboration with our research partners and the NF2 community.

NF2-SWN patients live with tumors that grow relentlessly - on their hearing nerves, in their brains, and along their spines. Without treatment options, they face complete deafness, paralysis, and death. There has never been a single drug approved for NF2-SWN. Until now, there were no national guidelines for insurance companies to use in approving medication requests for patients.

The NCCN guidelines mark a major turning point for NF2-SWN. Physicians across the United States can now point to a national clinical guideline. Patients and families can point to published evidence. Insurers can be asked to recognize the weight of both. This milestone reflects years of CTF's scientific leadership, funding, persistence, and coordination, including CTF's role in catalyzing the collaboration and data-sharing that helped move brigatinib from promise to practice, in partnership with extraordinary researchers, clinicians, government agencies, industry, and the NF2 community.

The Road to NCCN: A Story Only CTF Could Tell

This is a story about bringing the right people together at the right moment - and refusing to let science move slowly when patients cannot afford to wait. Five milestones. CTF driving every one.

Step 1 - Synodos for NF2: Assembling the Dream Team

In 2014, CTF launched Synodos for NF2 - the first-of-its-kind collaborative research platform ever created for this disease, led by four world-class PIs: Dr. Jaishri Blakeley, Dr. Wade Clapp, Dr. Jim Gusella, and Dr. Scott Plotkin. Nothing like it had ever existed for NF. CTF drove it forward.

Synodos NF2 Dream Team, 2014

Synodos brought together 12 world-class laboratories - basic scientists, translational researchers, clinical trialists, and patients - all working in a shared data environment, in real time. The scientific leaders were handpicked for their complementary expertise and their willingness to approach science differently.

In each Synodos collaboration, CTF assembled "dream teams" of doctors, scientists, and patients who work together to solve problems that are simply too complex for any individual lab to solve alone. Every dataset was shared openly through the NF Data Portal, which is maintained by several partners across the NF community. No siloes. No territorial withholding. Just committed experts working together, with science advancing as fast as patients need it to.

Step 2 - NCATS Partnership: The Screen That Changed Everything

CTF, together with Dr. Jaishri Blakeley, forged a landmark partnership with the National Center for Advancing Translational Sciences (NCATS) at the NIH. Together, they deployed a high-throughput screening platform testing over 1,900 FDA-approved oncology compounds against NF2-deficient schwannoma and meningioma cell lines developed by the Synodos team.

The result was remarkable: brigatinib, a drug already approved for lung cancer, emerged as a potent inhibitor of NF2-deficient tumor cells. What made it truly extraordinary was that it was working in a way no one initially expected. The CTF research team dug deeper and discovered an entirely different mechanism driving its effect - one specific to the biology of NF2-SWN tumors. The skeptics were wrong. A drug built for lung cancer was, against all odds, hitting the right target in NF2.

This is drug repurposing at its finest - and it happened because CTF built the platform and the partnerships to make it possible.

Step 3 - INTUITT-NF2: The First-Ever Platform-Basket Trial for NF2-SWN

Dr. Scott Plotkin

CTF co-funded with Takeda, and together with Dr. Scott Plotkin, created something that had never been done before in any form of NF - a platform-basket clinical trial - a unique trial design that tests multiple therapies across multiple tumor types simultaneously within a single "always on" clinical trial, slashing the time and cost of clinical development in rare diseases.

The INTUITT-NF2 trial was built to solve the central challenge of rare disease trials - too many tumor types, too few patients, too little time. It simultaneously tests therapies across vestibular schwannomas, non-vestibular schwannomas, meningiomas, and ependymomas in a single adaptive trial. People without benefit from one drug arm can seamlessly enroll in the next arm with a new drug. This is how you run science when your patient population is potentially small and time is not on your side.

Dr. Scott Plotkin of Mass General Hospital and Harvard Medical School - serving as Principal Investigator - led the charge. Six clinical sites joined forces: University of Miami, Johns Hopkins, NYU, Mayo Clinic, UCLA, and Indiana University. Takeda Pharmaceuticals stepped in as a co-funder, underwriting the platform alongside CTF. This is what happens when you show the world a credible, rigorous, connected ecosystem: pharma follows. And investors should, too.

Step 4 - The

New England Journal of Medicine

In June 2024, the results of the brigatinib sub-study were published in the New England Journal of Medicine, a most prestigious medical journal.

The findings were striking:

• Patients experienced benefits that truly mattered: approximately one-third of patients with vestibular schwannomas had hearing improvement, and patients reported less pain over time.
• Tumors shrank at rates far above those historically observed in NF2 -SWN. The historical tumor shrinkage rate was approximately 2%; in this study, 10% of the main tumors being tracked shrank, and 23% of all 153 tumors evaluated shrank.
• The tumor-shrinkage results were seen in meningiomas and non-vestibular schwannomas - two serious NF2-SWN tumor types. 25% of meningiomas shrank, and 20% of non-vestibular schwannomas shrank, with results sustained at 12 and 24 months.
• The treatment was generally well tolerated, with manageable side effects.
• The trial moved fast: 40 patients enrolled, results analyzed and published, all in under four years

The NEJM publication was the proof the world needed. It validated the science. It validated the model. It put NF2-SWN on the map of conditions that medicine can treat.

Step 5 - NCCN Guidelines: The Moment We've Been Building Toward

Today, brigatinib has been included in the NCCN Clinical Practice Guidelines in Oncology for NF2-related schwannomatosis. The NCCN guidelines are a backbone of oncology treatment decisions across the United States and around the world. Inclusion here means real physicians treating people with NF2-SWN today can act on this evidence - with institutional support, with insurer justification, with clinical authority.

From the dream team to the data portal, from the drug screen to the first-ever innovative trial for NF2-SWN, from a world-class publication to a treatment guideline approval - every single step was enabled, funded, and catalyzed by CTF in partnership with an extraordinary community of believers (scientists, clinicians, industry, patients, donors and government partners). That is what we do best. That is what we will keep doing until NF is defeated.

Recognizing the Heroes

Breakthroughs like this do not happen in a single lab. They happen when the right people commit to working together, when funders are bold enough to invest before proof exists, and when a driver organization refuses to let bureaucracy slow down patients who cannot wait. CTF salutes:

• The CTF Synodos for NF2 Dream Team - the 12 research labs that identified brigatinib's true mechanism and gave us a molecule worth taking to patients.
• National Center for Advancing Translational Science (NCATS at the National Institutes of Health) - for bringing the full power of the NIH drug-screening platform to bear on this rare disease.
• Dr. Scott Plotkin, Mass General Hospital - Principal Investigator of INTUITT-NF2, whose clinical vision and scientific rigor made this trial a model for the field.
• The six trial sites of the first-ever platform-basket trial (INTUITT NF2) and their teams - University of Miami, Johns Hopkins, NYU, Mayo Clinic, UCLA, and Indiana University - whose investigators, coordinators, and nurses enrolled patients and executed a complex multi-arm trial with excellence.
• The INTUITT-NF2 patients - who enrolled with hope and courage and whose participation has now changed treatment guidelines for everyone who comes after them.
• Takeda Pharmaceuticals - for their co-investment in the INTUITT-NF2 platform trial. Companies that partner with patient-driven science accelerate what government and philanthropy alone cannot complete.
• The CTF team, board of directors, and donors - whose conviction that CTF must build pipelines and platforms, not just fund individual grants, made every step of this journey possible. This is your victory too.

What This Means Right Now

NCCN inclusion is not the end of the story - it is the beginning. Brigatinib is now a recommended option that oncologists and neuro-oncologists across the United States can prescribe with guideline backing. Insurers can be compelled to cover it. Doctors can offer a new evidence-based treatment to their NF2-SWN patients.

This is the power of drug repurposing. Because brigatinib was already approved, already manufactured, already proven safe, CTF's model bypassed years of early-stage development and went straight to the question that matters most: does it work for NF2-SWN patients? For a community that has waited decades for more answers, that shortcut is not a technicality - it is years of patients' lives.

This is the power of platform-basket trials. NF2-SWN isn't one tumor - it's vestibular schwannomas, meningiomas, non-vestibular schwannomas, and ependymomas. A traditional approach would test each one separately, in sequence, over the course of decades. The platform-basket design tests them all simultaneously, and patients who don't respond to one arm can move to the next without leaving the trial. You need a smarter, faster architecture - and CTF catalyzed it.

What Comes Next - The Opportunity for All Forms of NF

We have proven the model. And we know exactly how to do it again.

Patients living with NF1 and non-NF2 schwannomatosis are waiting. The same playbook, the same team science infrastructure, the same platform-basket trial architecture - applied to all other forms of NF, a disease affecting 1 in 2,000 births - is within reach. CTF has the expertise, the relationships, and the platform.

We have done it. We know how to do it again. The path is mapped, the team is ready, and the science is there. All NF patients deserve their own NCCN moment. CTF is ready to deliver it. Are you ready to invest in it?