Brain Tumor Initiative

Request for Letters of Intent

January 2026

The Gilbert Family Foundation (GFF) is pleased to announce a Request for Proposals (RFP) for developing novel effective treatments for neurofibromatosis type 1 (NF1) associated high grade gliomas. The overarching goal of this funding opportunity is to increase treatment options for NF1 patients diagnosed with High-grade Astrocytoma with Piloid Features (HGAPs) or Glioblastoma (GBMs). This RFP would support the development of single or combinatorial treatments that have transformative potential to impact disease progression or recurrence.

BACKGROUND

NF1 is an autosomal dominant, genetic disorder that affects approximately 1 in every 2,500 births throughout the world. Hallmark features of NF1 include multiple café au lait (light brown) skin spots, neurofibromas (small benign growths) on or under the skin, and tumors on nerves that can lead to disfigurement, blindness, and cancer. NF1 can also result in cognitive disability, skeletal deformity, and cardiovascular complications. The course of the disease is both unpredictable and variable among individuals. Even within the same family, patients may experience vastly different symptoms with varying degrees of severity.

NF1 is caused by germline mutations in the neurofibromin 1 (NF1) gene, which encodes neurofibromin protein. Neurofibromin is primarily characterized as a GTPase-activating protein, catalyzing the conversion of active Ras-GTP into inactive Ras-GDP and thereby negatively regulates Ras/MAPK pathway activity. In NF1 disease, NF1 haploinsufficiency is thought to underlie vasculopathy and cognitive symptoms. The remaining majority of NF1 clinical manifestations require a separate mutational event in the somatic NF1 allele (a ‘second hit’). Tumor manifestations are typically benign; however, the accumulation of additional pathogenic mutations leads to progression to a more aggressive and/or malignant state.

GFF is a private nonprofit foundation founded by philanthropists Dan Gilbert and Jennifer Gilbert. One of GFF’s missions is to develop effective treatments and ultimately a cure for NF1. At present, its major research initiatives include its (1) Gene Therapy Initiative, developing innovative therapies that address the underlying genetic abnormalities in NF1 patients, (2) Vision Restoration Initiative, developing vision protection and restoration therapies in patients with NF1-associated optic pathway glioma, (3) Brain Tumor Initiative, focused on identifying and developing therapeutic strategies to effectively treat NF1-associated high grade gliomas, (4) Next Generation Models initiative to utilize cutting edge technologies to accelerate discoveries and their validation in more human-relevant systems and thereby facilitate translation to the clinic, and (5) FAIR Data initiative to promote data sharing, research, and tools to accelerate research into NF therapeutics.

SCOPE AND KEY REVIEW CRITERIA

The focus of this RFP is to develop a pipeline of therapeutics to treat patients with NF1-associated high grade gliomas and improve their clinical outcomes.

• Support would be provided for projects from lead optimization up to first-in-human clinical trials.
  • Lead optimization stage: Projects in this stage would have identified one or more lead agent(s) and demonstrated preliminary efficacy in a relevant disease model. The goal of the lead optimization stage is to identify a candidate for further development. Activities in this stage would include (but are not limited to) in vivo testing, medicinal chemistry, exploratory pharmacokinetics (PK), metabolism and toxicology, blood brain barrier penetrance, and candidate selection based on the outcome of these activities. Availability of scientifically sound assays and models to support lead optimization and candidate selection would be considered. Following 2-3 years of optimization, projects are expected to move to development stage.
  • Development stage: This stage would bridge the lead optimization stage and pilot clinical trials. Clinical candidate(s) would have been selected with no further optimization required. Candidate would have demonstrated suitable PK, PK/PD, in vivo efficacy, and preliminary safety/tolerability with the planned route of administration. Activities in this stage would include (but are not limited to) scale-up and formulation, PK, ADME and GLP toxicology, efficacy studies using the clinically intended route of delivery, and IND filing.
• Treatment strategies including combinatorial and emerging therapeutic modalities may be proposed. This includes studies to assess combination(s) of new agents with standard-of-care chemotherapy and/or radiation therapy.
• Studies testing combinations of multiple existing therapies or drug re-purposing studies would need to include strong preliminary data to be considered.
• Development of functional biomarkers to demonstrate target engagement and predictive biomarkers to guide early-stage clinical studies may be included.
• While preference would be given to projects studying NF1 associated high grade gliomas (germline NF1 mutation), projects focused on sporadic glioblastoma with NF1 loss would be considered provided relevance to NF1 associated high grade gliomas is addressed.

ELIGIBILITY CRITERIA

• Principal investigators must be independent researchers at the level of Assistant Professor or above at their respective institutions.
• Collaborations are encouraged between teams with complementary expertise and capabilities. Applying teams may consist of investigators from the same or different institution and may be international. One PI should be designated as the Administrative PI and is responsible for administrative leadership while scientific leadership is shared by all PIs on the team. Applications must include a rationale for the proposed collaboration, the specific role of all PIs, and synergistic opportunities.
• Applicants may include expertise from contract research laboratories.
• Clinical trials are not eligible.

AWARD LENGTH AND BUDGET

GFF expects project timelines of up to 5 years with up to $400,000 per year in direct research costs. GFF will allow indirect costs of up to 10% of the total direct research cost minus travel and equipment expenses. Pilot awards may be considered at the discretion of GFF.

REVIEW AND SELECTION PROCESS

All LOIs will be reviewed by GFF and invited full proposals will undergo rigorous review by an external peer review panel. Applications will be evaluated according to the Key Review Criteria (above), scientific merit, and team synergies (if applicable). GFF will provide summaries of reviewer critiques and evaluations to full proposal applicants. Based on peer review and GFF priorities, GFF will work with selected applicants to modify submitted project plans and/or budgets prior to award execution. GFF anticipates inviting 3-4 LOIs to submit full proposals and funding up to 2 full awards.

APPLICATION INSTRUCTIONS

The application process entails 2 stages:

1. 1.2 Page letters of intent (LOIs) are due by 5:00 PM Eastern Time on February 27, 2026.
2. 2.For LOIs selected to advance, full-length proposals are due by 5:00 PM Eastern Time on May 15, 2026.

Guidelines for preparing the full application will be included with the invitation to submit full proposal. All full applications must be submitted online via GFF’s application portal.

LETTER OF INTENT

All applicants must submit a LOI to GFF prior to submission of a full proposal.  The LOI application consists of the following components and must be formatted in Arial 11-point or Times New Roman 12-point font with no less than ½ inch margins. To submit your LOI, please submit a combined pdf of the requested components via the form/link below.

1. 1.Project Title
2. 2.Applicant/PI Information: Team Science applications must identify one PI for administrative purposes (the Administrative PI for the proposal). This is the Applicant.
3. 3.Organization/Institution Information: This is the Administrative PI’s institution.
4. 4.Key Personnel Information: Identify other PIs and other key personnel on the team. All PIs share authority for project leadership. Please describe the nature of and rationale for the proposed collaboration, and the specific roles of each key personnel, including the Administrative PI.
5. 5.LOI: 2-page maximum that includes:

1. 1.specific aims
2. 2.preliminary data including figures and tables
3. 3.overview of proposed studies including key assays and models, and their availability
4. 4.key milestones and timelines
5. 5.up to 5 references

KEY DATES

*Timeline is subject to change at GFF’s discretion

GFF CONTACTS

For questions regarding GFF and/or this RFP, please contact Dr. Poornima Venkat, Scientific Program Manager, BTI, at PoornimaVenkat@GilbertFamilyFoundation.org

If you have any questions, technical issues, or need to change your application after submission, please reach out to Caroline Poole at carolinepoole@rock.com  or 313-771-3082.

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