Children's Tumor Foundation establishes significant research initiative to combat NF2

On the occasion of World NF2 Awareness Day, the Children's Tumor Foundation has announced the establishment of a significant research initiative dedicated to finding effective treatments for NF2, along with a substantial investment of $2.3 million in this bold new effort. Called the 'NF2 Accelerator Initiative', this three-year undertaking will be dedicated to bringing active NF2 treatments to the clinic (and patients) by expanding the clinical drug pipeline for NF2, improving drug selection through the development of innovative testing models, and the development of gene therapy options that address the underlying genetic causes of NF2.

Neurofibromatosis, also known as NF, is an under-recognized genetic disorder that causes tumors to grow on nerves throughout the body and manifests in three distinct forms: NF1, NF2, and schwannomatosis. NF2 is the second most common type of NF and affects approximately 1 in every 25,000 people of all populations. It is caused by mutations in genes located on chromosome 22, and is a progressive disorder characterized by many different manifestations, including the development of tumors such as vestibular schwannomas, meningiomas and ependymomas. NF2 can lead to a variety of symptoms, including hearing loss, tinnitus, balance problems, and more. While the tumors are benign, their location in the body limits surgical options and can create serious health issues, with no effective non-surgical treatment options currently available.

As a global leader of NF research, the Children's Tumor Foundation is dedicated to developing cures for all three forms of NF. The Foundation and its partners have bolstered the NF2 research field through a team science approach, called Synodos. Launched in 2014, Synodos for NF2 brought together a multidisciplinary team of scientists from 12 world-class labs at academic and medical centers of excellence who pledged to work together. The Synodos teams shared information, datasets and results in real-time at every step of research development. (All that data is now publicly available at nfdataportal.org). That collaborative effort resulted in the identification of promising new clinical candidates for NF2, and today's announcement of the NF2 Accelerator Initiative leverages that new knowledge into a new and ambitious structure, with the goal of speeding up the drug discovery process.

The NF2 Accelerator Initiative will concentrate on opportunities in three areas:

1. Expand the Clinical Drug Pipeline for NF2

This effort will focus on discovering novel therapeutic targets and the development of preliminary biomarkers to help validate existing therapeutic targets for NF2. In order to expand the pipeline, CTF is planning to:

• Participate in and co-fund a phase 2 clinical trial using Brigatinib, a promising drug that came out of the Synodos for NF2 effort. Takeda Pharmaceutical Company has agreed to co-invest in the trial. Study protocol and clinical trial site selection is being developed. The trial is aimed to be open for recruitment soon.
• Offer Drug Discovery Awards to researchers and institutions focused on the next phase of NF2 clinical candidates. An RFA (Request for Application) is being launched today to support exploratory and development drug discovery projects. Information can be found at ctf.org.
• Offer Young Investigator Awards to early-stage researchers as an investment in basic research and the expansion of understanding of the processes that drive NF2. These awards will be available in 2020.

2. Improve Drug Selection for NF2

This focus is on the development of animal models to improve drug testing and efficacy within NF2.

• Based on the success of the Foundation's Synodos for NF1 pig models, the National Institute of Neurological Disease and Stroke (NINDS) recently developed similar animal models for NF2. This phase of the NF2 Accelerator project will expand research on these models and provide better understanding of how different manifestations of NF2 develop over time.
• Development of image-based animal models for vestibular schwannomas to combat the limited availability of preclinical resources that allow for efficient drug testing.

3. Gene Therapy for NF2

Much of NF2 drug discovery and development is primarily focused on inhibiting the processes that are activated as a consequence of the loss of the NF2 gene. CTF has invested in gene therapies in the past but has now received a very exciting gene therapy proposal that has the ability to be a real treatment option for patients with NF2.

Today on NF2 Awareness Day, we're proud to announce the next chapter of NF2 research aimed at bringing treatment options to those who are living with neurofibromatosis type 2 faster. By expanding the clinical drug pipeline, improving drug selection, and developing gene therapy options, we're pushing forward in the development of critical innovations to help solve the challenges of NF2, and most importantly, improve the lives of NF2 patients and their families."

Annette Bakker, PhD, President of the Children's Tumor Foundation

Lead funding for the NF2 Accelerator Initiative has been provided by Jim and Kathy Thoms; Nicole and Roland Thoms; Carol Harrison Kalagher; and Beth and John Morris. To support the NF2 Accelerator Initiative, please visit ctf.org/endnf2.