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High-Risk/High-Impact Grant Program in Osteosarcoma

Osteosarcoma Institute

Grantmaking involves balancing the potential impact of a successful research project with the risk of experimental failure. Traditionally, risk mitigation is accomplished during the research proposal review process in several ways, including heavily weighing preliminary data. While the historical balance point has proven broadly effective and successful, the stubborn lack of progress in osteosarcoma suggests that alternatives should be considered. Thus, the aim of this grant program is to place less emphasis on preliminary data in order to encourage projects exploring bold innovations that may fall within any stage of the drug development path, and that seek to deliver curative outcomes to patients with osteosarcoma. Proposals will be most valued based on their innovation and sound scientific hypothesis, and the likelihood that the approach will address a true dependency in osteosarcoma.

The desired criteria for this high-risk/high-impact osteosarcoma drug development research are:

• Bold ideas that will generate evidence of success or failure within 12 months.

• A new research direction rather than a continuation of ongoing funded research.

• While preliminary data are not required, the applicant must demonstrate feasibility of a persuasive research plan.

• Rigorous, quarterly interactive grant progress reviews to be used to guide ongoing direction and distribution of research support. A successful high-risk/high-impact grant proposal should have one or more of the following characteristics:

• A proposal that, upon successful conclusion of the project, may mature into a successful submission for a traditional OSI grant or launch a translational development plan with investigators, institutions, or commercial biopharma companies.

• An existing relationship that makes the development of a therapeutic asset in biopharma feasible.

BUDGET From $25,000 – $125,000 total over one year (inclusive of indirect costs not to exceed 10% of the requested project budget).

AI Based Application Success Predictor

1. Laser Focus on Osteosarcoma Patient Impact

OSI exclusively funds projects that meaningfully accelerate treatments, particularly for:

Relapsed or refractory osteosarcoma

Metastatic disease (especially lung metastasis)

Therapeutic resistance and relapse biology

Clinically actionable targets

Priority topics include:

Immunotherapy (T/NK cell, vaccines, IO combinations)

Target discovery & validation

Drug repurposing or novel small molecules

Precision medicine strategies (genomic, proteomic)

Biomarkers predicting response or relapse

Minimal residual disease (MRD) and monitoring tools

Metastasis inhibition

❗ Basic bone/sarcoma biology without a clear therapeutic implication rarely gets funded.

2. Fit With the OSI Mechanism

OSI offers mechanisms aligned to translational stage:

Mechanism	Best For	Key Criteria
Clinical Trial Grants	Investigator-initiated OS trials	Patient access, delivery timeline, safety & endpoints
Translational Grants	Bridging lab → clinic	Strong preliminary data + clear therapeutic pathway
Drug Development / Accelerator Funding	Industry or academia–industry	IND-enabling or near-clinical compounds

Predictor: Match your development stage to the mechanism: discovery → validation → translation → trial.

3. Robust Preliminary Data

OSI expects feasibility evidence:

Target expression/essentiality

Early efficacy in OS models

Pharmacokinetic/toxicity data (if drug-focused)

Proof of access to relapsed OS cohorts or samples

Pilot biomarker signals

Predictor: Strong preliminary data is a top determinant of success.

4. Osteosarcoma-Relevant Models

Models must clearly reflect human OS disease:

Patient-derived xenografts (PDX)

OS lung metastasis models

Canine OS as a translational bridge

CRISPR or humanized OS models

OS organoids or 3D cultures

Omics-driven subtype stratification

Predictor: OS-specific and metastasis-relevant models are critical for translational value.

5. Clear, Near-Term Clinical Trajectory

Winning proposals articulate a stepwise path toward patient benefit, including:

Defined translational milestones

Criteria for progressing to clinical trial

Endpoints that enable FDA engagement

Roadmap for CMC, toxicity, patient accrual (if applicable)

Predictor: “Therapy acceleration” must be undeniable.

6. Access to Osteosarcoma Patient Cohorts

Especially for clinical/translational awards:

Access to relapse and metastatic patients

Clinical sample biobanks

Imaging/pathology data

Partnerships with COG/SARC groups or major sarcoma centers

Predictor: Demonstrated access to relevant patients boosts feasibility.

7. Experienced Team & Necessary Partnerships

Top-scoring proposals include:

Clinician–scientist involvement

Experts in drug development, immunology, or metastasis biology

Cross-institutional collaborations

Industry partnership for IND/CMC/trial readiness

Predictor: Proven expertise + collaboration improves reviewer confidence.

8. Focused Aims with Measurable Milestones

OSI funding is milestone-driven.

Best proposals have:

2–3 focused, hypothesis-driven aims

Concrete deliverables (e.g., “IND submission-ready PK/PD dataset”)

Risk mitigation strategies

Clear timelines & go/no-go checkpoints

Predictor: Clarity + feasibility = higher scores.

9. Alignment With Unmet Needs

Highest priority for:

Relapsed/refractory disease

Rare OS subtypes

Therapies for patients with limited options

Early detection of metastasis or relapse

Reducing treatment toxicity in young patients

Predictor: Targeting urgent care gaps strengthens impact.

10. Clear Communication & Persuasiveness

Reviewers appreciate proposals that are:

Direct and well-written

Supported by compelling figures

Easy to follow for clinicians, scientists, and drug developers

Strong in statistical and regulatory rationale (if clinical)

Predictor: Professional-quality writing improves enthusiasm.

🏆 Summary Table — OSI Proposal Success Predictors

Predictor	Why It Matters
Osteosarcoma-specific focus	Core mission
Mechanism alignment	Expected progress level
Strong preliminary data	Demonstrates feasibility
Relevant OS models	Ensures translational relevance
Near-term clinical trajectory	OSI’s core goal
Patient access	Critical for clinical translation
Collaboration	Execution & expertise assurance
Focused aims	Fits OSI’s milestone-driven model
Address unmet needs	Aligns with mission urgency
Clear writing & rationale	Improves reviewer scoring

Specialties

Cancer

Eligibility Requirements

• Funds must be granted to nonprofit/charitable institutions or organizations. While we allow for any individual institution to submit multiple LOI submissions, we are unlikely to fund more than one grant per institution in any grant cycle.

• Grantee organization does not need to be based in the United States.

o However, in order to fund a foreign entity, the OSI requires documentation that if the entity were a United States-based organization, the entity would qualify as a charitable organization. This is usually relatively straightforward when dealing with entities in countries with a tax regime similar to the U.S. by way of a government-issued letter or other document designating the entity as a charitable institution or as performing a charitable purpose (for example, research or education). It might also be a determination from the relevant taxing authority that the entity qualifies for tax-deductible contributions.

• Applicants need not be United States citizens.

• Applicants must have an MD, PhD, MD/PhD, or equivalent and be appointed as faculty (or equivalent) at an academic institution.

• Applicants must have a track record of publication and funding productivity that demonstrates the project can be accomplished by the investigators.

• Research projects may be an extension of ongoing research but cannot overlap with any funded studies unless the applicant clearly demonstrates that new funding will not duplicate existing support.

• Applicants can submit only one (1) Letter of Intent (LOI).

• Applicants selected for funding will permit the OSI to publicize the grant for fundraising purposes, including, but not limited to a five-minute video discussing the research project, photos of lab, and photos of children participating in clinical trials, where applicable.

• Applications that do not follow the specific grant application instructions and/or submission process will not be considered.

• Applications received after the due date will not be considered.

• Applications which do not fall under the OSI mission will not be considered.

• Resubmissions: Only one resubmission of a previously reviewed application is permitted.

Sponsor Details

Sponsor Institute/Organizations: Osteosarcoma Institute

Sponsor Type: Corporate/Non-Profit

Address: 3963 Maple Avenue Suite 390 Dallas, TX 75219

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