The Treat FTD Fund

Background

Association for Frontotemporal Degeneration

Frontotemporal degeneration (FTD) encompasses a spectrum of neurodegenerative disorders (behavioral variant FTD, primary progressive aphasia, progressive supranuclear palsy, corticobasal syndrome, and FTD – ALS), which have in common degeneration of the frontal and temporal lobes of the cerebral cortex but present with varied biological mechanisms, clinical symptoms and prognoses. Although the most common form of dementia under age 60, FTD is considered a rare disorder, affecting approximately 50,000 – 60,000 people in the US. Clinical and pathological heterogeneity, low prevalence, the occurrence of both genetic and sporadic forms of FTD, and a limited repertoire of biomarkers collectively create unique challenges for FTD drug development. As a result, there are currently no approved treatments that delay or halt the progression of FTD disorders or that effectively treat symptoms. While there are increasing numbers of promising treatments entering clinical trials, the number remains small, and none have yet resulted in regulatory approval.

The Alzheimer's Drug Discovery Foundation (ADDF) and the Association for Frontotemporal Degeneration (AFTD) launched the Treat FTD Fund to provide critical funding for early-stage clinical trials to:

  • help address the challenges to drug development outlined above
  • build on emerging scientific understanding of biological mechanisms underlying FTD
  • stimulate the field to develop new disease-modifying and symptomatic therapies for FTD disorders
  • leverage previous research from related conditions to repurpose existing therapies for the benefit of FTD patients
  • advance the development, validation and adoption of informative biomarkers and clinically meaningful outcome assessments
  • Enable novel trial designs and technologies and develop improved methodologies and protocols to optimize clinical trial design for the FTD patient population

Goal

The Treat FTD fund aims to support the development of drugs or devices for FTD disorders while building a better understanding of FTD pathophysiology, biological mechanisms of disease, and analytically and clinically validated biomarkers with a well-defined context-of-use. The fund aims to de-risk clinical development programs by supporting clinical trial readiness activities or early/mid-stage clinical trials with clear go/no-criteria for later stage drug development. Programs will be considered that test novel or repurposed drug candidates or devices in phase 0, 1 or 2 clinical trials for FTD disorders, led by academic researchers or biotechnology companies, worldwide. Both disease-modifying and symptomatic approaches will be considered.

The RFP seeks to support clinical trials incorporating:

  1. biological mechanisms that have a sound scientific rationale for FTD
  2. biomarkers that would permit evaluation of target engagement, downstream pharmacologic effect, and biological effect
  3. trial designs aligned with constraints associated with a rare disease population
  4. clinical outcome measures that could provide a deeper understanding of the drug mechanism and disease progression
  5. therapeutics applicable to sporadic or genetic forms of FTD. Trials of treatments applicable in sporadic FTD are especially encouraged.

Although the strongest proposals will address all these aspects, all early-stage clinical trials with a sound biological rationale and well justified outcome measures for the patient population will be considered.

In 2019, the ADDF and the AFTD convened an advisory panel to generate recommendations on outcome measures and statistical considerations for value-generating exploratory trials in neurodegenerative dementias, including FTD. Prospective applicants are encouraged to review these recommendations for the design of informative early-stage trials before a submission to this program, which can be found here.

The value of considering the needs and priorities of study participants in the conduct of clinical trials is increasingly recognized by the research community as well as regulatory agencies. Applicants are therefore encouraged to utilize patient-relevant outcomes and patient-convenient protocols and study designs whenever possible.

Award Information

Up to $2,500,000 over 1 – 3 years, based on stage and scope of the trial. For studies requiring additional support, co-funding from other funding agencies or investors is encouraged. Payment structure will be negotiated and based on milestone achievements and patient enrollment.

Deadlines

Letter of Intent: Closed. TBD 2025.

Full Proposal: December 9th, 2024

Eligibility

Funding is open to researchers and clinicians worldwide at:

  • Academic medical centers, universities, or non-profits. Industry partnerships are encouraged.
  • Biotechnology companies. Existing companies and new startups are both eligible.
  • NOTE: All funding is provided through mission-related investments that require return on investment based upon scientific and/or business milestones (see Our Research Strategy for more information).

Funding Priorities

Clinical Stage: Funding can support phase 0, 1 or 2 studies, including prevention trials in presymptomatic individuals at risk for developing FTD due to a disease-associated pathogenic variants. This includes single ascending dose (SAD) and multiple ascending dose (MAD) studies to establish safety, brain penetration or target engagement in healthy participants. Phase 1 studies collecting biomarker data in patients will be prioritized. For Phase 1 studies that will not include FTD patients, it needs to be clear that FTD is the intended patient population in future studies. Funding can also support exploratory phase 1b or phase 2a trials designed to assess pharmacologic effects with shorter treatment duration and fewer patients than traditional phase 2 studies. These types of studies can serve as an important proof-of-principle to justify larger phase 2 clinical trials. Smaller studies that address one critical question or can further de-risk a clinical program will be considered. Studies that don’t align with any of these descriptions but fit the goals of the fund are also eligible.

Patient Population: Can include both genetic or sporadic forms of any FTD disorder, including behavioral variant FTD, primary progressive aphasia, corticobasal syndrome, progressive supranuclear palsy, and FTD/ALS, as well as healthy individuals for phase 1 studies or asymptomatic individuals at risk for developing FTD. A clear description of the rationale for the mechanism of action in the targeted population must be included in the application. Applicants must also provide information about the recruitment strategy in the target population to demonstrate (1) a sufficient number of patients are available to meet recruitment goals within the timeframe of the funding (particularly in genetic variants), and (2) participants have been accurately diagnosed at clinical sites with FTD expertise. Approaches for sporadic forms of FTD are especially encouraged.

Hypothesized therapeutic mechanism or mode of action: The strongest proposals will provide a clear rationale for targeting the proposed mode or mechanism of action in FTD disorders, compelling evidence that demonstrates a link to FTD, supportive preclinical data, and where available, human data. Proposals without an identified target will also be considered but a clear connection to FTD should be described. Biological areas of interest include, but are not limited to:

  • Genetic causes of disease (C9Orf72, MAPT, GRN, etc.)
  • Misfolded proteins (TDP-43, tau, FUS, etc.)
  • Inflammation
  • Autophagy
  • Mitochondrial & metabolic function
  • Epigenetics
  • Neuroprotection
  • Synaptic activity & Neurotransmitters

Other novel targets or pathways that are supported by compelling evidence that demonstrate a rational biological connection to the disease process will also be considered.

Drug that has completed IND-enabling studies (or international equivalent): The drug should have completed or be in the process of completing IND-enabling studies at the time of application. If IND-enabling work is in progress, any award would be contingent upon IND acceptance by the FDA and full review of the data package by the review committee. We encourage applications worldwide. Any applications from outside the U.S. would be expected to meet the country or regionally specific regulatory equivalent. Similarly, trials of devices should have an approved IDE or international equivalent.

Biologically relevant biomarkers: Where appropriate, proposals should include biomarkers that can measure pharmacokinetic/pharmacodynamic relationships and evidence of target engagement. Inclusion of novel, exploratory biomarkers that can provide insight into the biological effects of the intervention and/or advance validation of a promising biomarker are encouraged. Biomarkers used for participant selection or patient stratification are also encouraged, where relevant and available.

Study design: Studies should be designed around a clear, testable hypothesis with go/no-go decision points. Studies should be milestone driven, generate interpretable data and help with future decision making. Smaller, exploratory trials or trials that can de-risk or deploy new technologies or designs that enable smaller sample sizes and faster trials are also encouraged.

Ability to address unmet need: Effective interventions that can help manage debilitating symptoms as well as disease modifying approaches are both critically needed for FTD.

Data sharing: Applicants should address their plans for data sharing, including biomarker data, in the full proposal. The Treat FTD Fund encourages data sharing and will work with applicants during the diligence process to outline a clear sharing plan.

Type of therapy: Experimental and repurposed drugs, including small molecules, peptides, antibodies, gene therapies, antisense oligonucleotides (ASOs), and others. Non-pharmacologic interventions, such as devices, will also be considered. *For programs pursuing device-based interventions, please contact us before applying.

Selection process

Applicants will first submit a letter of intent (LOI) that includes brief information about the proposed mechanism or mode of action, the drug, supporting data, biomarkers and proposed clinical trial features. The top LOIs will be invited to submit a full proposal that includes a clinical trial protocol, budget, team biosketches, and business documents, if applicable. More detail provided in our Application Instructions . Applications will be reviewed confidentially by a panel of FTD experts. Applicants may expect to receive recommended revisions to their workplan or clinical trial design as part of the review process. In some circumstances, applicants may be offered access to a consultant with industry experience.

Recommended resources

Leveraging of existing resources, clinical coordination centers/networks, and patient registries are highly encouraged.

Relevant resources include:

APPLICATION SUBMISSIONS

Review the Application Instructions for steps on applying.

ADDF FUNDING PORTAL

 

We encourage you to contact us if you would like to discuss your proposed clinical trial and receive initial feedback. We have an iterative process and are happy to meet with you.

For scientific inquiries, please contact:
Meriel Owen, PhD, Director, Search and Evaluation, ADDF
mowen@alzdiscovery.org

Nicole Bjorklund, PhD, Director of Research & Grants, AFTD
nbjorklund@theaftd.org

For policies, contracts and terms, and IT related inquiries, please contact:
Grants and Mission-Related Investments Team
grants@alzdiscovery.org