2018-19 Grant Guidelines
Table of Contents About HeritX... 3 The HeritX Path to Cancer Prevention... 3 2018-2019 Funding Priorities... 5 The Application and Review Process... 5 Letter of Intent Sections and Requirements... 7 Full Application Sections and Requirements... 9 2
About HeritX HeritX is a 501(c)(3) nonprofit whose mission is to prevent cancer, starting with cancers caused by inherited cancer gene mutations. Our goal is to first develop a therapy that prevents inherited cancers and then expand to the general population. HeritX was formed in 2015 by medical, biopharmaceutical and business leaders whose families and friends were affected by inherited cancer. The shared passion for improving cancer prevention led to the HeritX mission and strategic plan to engage scientists around the world to help understand inherited cancers as a route to development of cancer prevention therapies. HeritX uses its resources to overcome the historic barriers to the development of cancer prevention drugs, to enable innovation, and to shorten therapy-development timelines. Research funders traditionally support individual research projects to increase knowledge of a disease the R in R&D. Knowledge is vital but cannot alone prevent cancer. Research must from the beginning be linked with the activities required to turn this new knowledge into an approved therapy for patients the D in R&D. HeritX connects the R and D into one integrated program that can transform basic research into an FDA-approved cancer prevention therapy. As a start, our programs focus on how to prevent cancer in families with cancer gene mutations and with a goal to address all components required to bring a prevention therapy to the clinic. One of HeritX's goals is to prevent cancer caused by inherited BRCA1/2 gene mutations. Unlike sporadic cancers, cancer with an inherited BRCA1 or BRCA2 mutation has a known origin, the inherited BRCA mutation. These mutations and mutations in other cancer genes provide a unique opportunity to identify and test ideas for how to stop the earliest steps in cancer development. For more information about HeritX and our mission to prevent inherited cancer visit www.heritx.org. The HeritX Path to Cancer Prevention To accomplish the goal of preventing cancer, HeritX has put together with the input from our scientific advisers a Roadmap to define the tasks needed to achieve an approved preventive therapy. From the start, this focuses on the patient need and attempts to address all necessary components, including fundamental knowledge, drug screening, drug safety, drug delivery, and FDA requirements. The activities in the graphic below describe HeritX s initial research priorities in this Roadmap: 3
Roadmap to Cancer Prevention With Milestone Goals First Programs for Support Basic Research to Identify New Therapeutic Targets Proof of Target Mechanism Therapy Discovery & Delivery Proof of Clinical Concept Clinical Studies & Safety FDA Approval Preventive Therapy 1. Review and establish the current state of BRCA1/2 research models (assays) 2. Establish research models (assays) to study the early development of BRCA1/2 mutated cancers 3. Test Candidate Therapies to Ø Fix the decrease in BRCA1/2 gene activities Ø Provide BRCA1/2 proteins by alternative means Ø Protect BRCA1/2 mutation carriers from developing cancer 4. Identify biomarkers that can serve as surrogate endpoints for inherited BRCA1/2 cancer risk in clinical studies 5. Find compounds that increase the function of the nonmutated BRCA1/2 gene Acceleration Projects Research Priorities 6. Develop vaccines to target BRCA1/2 mutated cancers The Roadmap research questions are: 1. How can we FIX the decrease in BRCA1/2 gene function? a. Increase the activity of the functional BRCA1/2 gene copy b. Identify compounds that increase genomic stability (including natural compounds, repurposed drugs, and others) 2. How can we PROVIDE the missing BRCA1/2 protein? 3. How can we PROTECT healthy BRCA1/2 mutation carriers from developing cancer? a. Identify the earliest steps in the development of inherited BRCA1/2 mutated cancers (any type including breast, ovarian, prostate, pancreatic and melanoma) b. Identify BRCA1/2 mutated pre-cancer targets for possible preventive therapy c. Develop a vaccine against BRCA1/2 mutated pre-cancer antigens d. Stimulate immunity against BRCA1/2 mutated pre-cancer cells in other ways (specific or non-specific immunity) 4. How can we ACCELERATE the development process? a. Develop faster clinical/regulatory strategies (e.g., through using novel surrogate endpoints/biomarkers) b. Generate more predictive preclinical assays for effective and efficient screening of potential therapies c. Facilitate availability of clinical tissue samples for use in preclinical experimentation d. Develop faster clinical enrollment methods 4
2018-2019 Funding Priorities For the 2018-2019 funding cycle, we will accept applications representing innovative approaches to prevent any BRCA1/2 mutation-related cancer (breast, ovary, prostate, pancreas or melanoma) with a preference for projects that are directed at preventing more than one type of BRCA1/2 mutant cancer. All proposed projects must be aligned with the HeritX Research Roadmap above. Funding priority will be given to proposals focused on the following: 1. Proposals for research to define new approaches to enhance immunologic surveillance and destruction of cells that have lost the wild type BRCA1/2 gene or gene activity in patients who carry an inherited a BRCA1/2 mutation in one chromosome. 2. Proposals for research to define new agents that demonstrate cytotoxicity specifically to cells that have lost the corresponding wild type BRCA1/2 gene in patients heterozygous for an inherited a BRCA1/2 mutation. These agents should have a benign safety profile in cells that retain at least one functional BRCA gene. 3. Proposals for diagnostic tests / biomarkers that identify BRCA1/2 mutation carriers at the earliest transition from normal cellular function to pre-malignancy. Ideally a biomarker would predict transformation to a detectable malignant tumor within two (2) years (or another short-term period). The Application and Review Process Our goal is an iterative and efficient application process. We are happy to discuss ideas and assess if and how they may support the our mission to develop a cancer prevention therapy. If you have any questions, please contact us at Grants@HeritX.org. Letters of Intent are required and will be evaluated for alignment with HeritX goals before a full application can be submitted. This process is designed to allow us to interact with you and provide input in advance of the preparation of a full application. We sincerely appreciate your interest and work in this field. The LOI application steps are: 1) Application: We invite you to apply through proposalcentral, our platform for receiving and reviewing your application. 2) The LOI template (which is outlined in full below) will lead you through our key questions, which include: a. What is the scientific goal of your proposed research? b. How will the project achieve this goal? 5
c. How does this project bring us closer to an available prevention for inherited BRCA1/2 mutated cancers? d. How does this project align with one of the three 2018-2019 Funding Priorities? e. Budget Note: Awards are limited to a maximum of $300,000 total for either two (2) or (3) years. 3) Submission: Once you have completed the LOI and all required attachments, submit your application through proposalcentral. 4) Administrative Review: The submitted LOI will be reviewed by the HeritX scientific team to ensure that the application is complete and that it aligns with HeritX s funding priorities. Applications that do not directly focus on inherited cancer prevention will not be reviewed. You will be notified if your project as described in the LOI does not fit with the programmatic goals of the RFP. 5) Iteration: HeritX may contact you with questions about your proposed research or to make suggestions to strengthen the proposed research based on our experience and expertise. 6) Peer Review: At the LOI stage, our review process focuses on whether the proposed research advances the R&D Roadmap to Cancer Prevention and whether it addresses one or more of our funding priorities. The review criteria include: a. Does the research address one or more of the funding priorities? b. Does the research question advance the HeritX Roadmap to Cancer prevention? c. Is the research plan feasible? d. Does the proposed research have the potential to benefit the development of a preventive therapy for people at risk for BRCA1/2 mutated cancers? 7) LOI Decision: If your LOI is approved, you will receive an invitation to submit a full application. The Full Application steps are: 1) Invitation: If your Letter of Intent is approved, we will invite you to apply for research funding through an email with a link to the HeritX Research Grant Full Application ( Application ) through proposalcentral, our platform for receiving and reviewing your application. 2) Application: The Application template (which is outlined in full below) will lead you through completing the application. 3) Submission: Once you have completed the Application and all required attachments, submit your application through proposalcentral. 4) Review: Once complete, your application will be submitted to an independent grant review committee for review. At the Full Application stage, all applications will receive an administrative review that focuses on whether all application elements are complete and whether the proposed research advances the R&D Roadmap to Cancer Prevention. Following administrative review, applications will be peer reviewed for scientific merit and feasibility. The review criteria include: 6
a. Does the research question address a milestone or research issue in the HeritX R&D Roadmap to Cancer Prevention? b. Does the research have scientific merit? c. Is the research plan feasible? d. Does the proposed research have the potential to benefit patients at risk for inherited cancers through the development of a preventive therapy for BRCA1/2 mutated cancers? 5) Decision: You will be notified by email if your Application is approved. Should you have any issues using the proposalcentral portal please contact proposalcentral customer service by email at pcsupport@altum.com or by phone at (800) 875-2562 or (703) 964-5840. For all other grant application questions contact our HeritX Grants team at Grants@HeritX.org. Letter of Intent Sections and Requirements All Letters of Intent must be submitted through proposalcentral. Mandatory sections of the application are identified in proposalcentral with as asterisk. Once you start a Letter of Intent, you will see the following sections: 1. Title Page: a. Title: You must enter a title for the project, a total budget, and start and end dates for the project before you will have access to the other sections of the application. b. Budget: A detailed budget is not required for the LOI but the total budget as well as the proposed start and end date for the project must be entered on the title page. The default start date is April 1, 2019. You may propose a two (2) or (3) years project. Budget Note: Indirect costs are not allowed. HeritX will consider exceptions to this policy for research projects with a budget of more than $120,000 on a case-by-case basis but indirect costs may never exceed five percent of the total budget. Requests for indirect costs must be approved in advance and must be justified based on the research necessitating increased organizational overhead. c. Research type: Please select the type of research from the drop-down menu. 2. Download Templates and Instructions: All templates and instructions can be downloaded from this page. Please download these documents, save them to your computer and complete them. Once complete, please save them as a PDF and upload them to your proposalcentral application (Step 8). 3. Enable Other Users to Access this Proposal: Optional. 7
4. Applicant/Principal Investigator (PI): Information in this section will populate from your proposalcentral profile so please check to be sure that your profile is complete and accurate. Enter any additional information for the PI directly into proposalcentral. 5. Institution: Enter PI s institution information. 6. Key Personnel: Enter additional key personnel (beyond the PI) and collaborators. Add new contacts by entering the email address of the person you wish to add. Click Add. Select the appropriate Role from the dropdown and add Key Personnel information for the person selected. a. Involving Patient Advocates: If the research team includes a Patient Advocate please include them in the Key Personnel section. HeritX believes that the voices of patients are important to the research process but does not require the inclusion of a trained patient advocate on the research team. If you would like assistance finding a patient advocate for your project please contact us. 7. Abstracts: A scientific abstract is required with your LOI. A lay abstract or general audience summary is optional. Abstracts are limited to 3,000 characters. 8. Upload Attachments: Please upload the following documents in PDF Format. Name each document in the Describe Attachments field. Please name the documents with the name of the PI followed by the name of the document. For Example Dr. Smith s proposal narrative would be Smith_LOI Narrative. a. Biosketches for all Key Personnel: Name each biosketch with the last name of the person followed by the name of the document. For example, the biosketch of Dr. White would be named White_Biosketch. Please use your current NIH Biosketch. b. LOI Narrative: Please follow all formatting requirements listed in the Template Instructions. The LOI Narrative is limited to four (4) pages and must include all of the following required sections: A. Research Question: Hypothesis and Objective (brief, no more than one page) B. Background and Significance 1. Background 2. What funding priority or HeritX Roadmap research question will this proposal address? 3. Describe how successful completion of the proposed research will provide an answer to this research topic. 8
C. Feasibility: Briefly describe the scientific basis for the proposed research and the feasibility for achieving a successful outcome. D. Specific Aims & Timeline: Describe the research aims and timetable for completion, including intermediate milestones. c. References: Please include only the most relevant references. References are limited to two (2) pages. 9. Validate: This step checks to see if all elements of the application are complete. If not, proposalcentral will indicate the sections that need attention. You will not be able to submit the application until all required sections and all required attachments are complete. 10. Submit: Once you submit your application through the submit link you will receive an email confirmation. Under the Manage Proposals tab of proposalcentral the application will show submitted. You may view the application at any time through the manage proposals tab. Full Application Sections and Requirements All applications must be submitted through proposalcentral. Mandatory sections of the application are identified in proposalcentral with as asterisk. Once you start an application, you will see the following sections: 1. Title Page: The Title and Budget total will prepopulate from your approved LOI. 2. Download Templates and Instructions: All templates and instructions can be downloaded from this page. Please download these documents, save them to your computer and complete them. Once complete, please save them as a PDF and upload them to your proposalcentral application (Step 12). 3. Enable Other Users to Access this Proposal: Optional. 4. Applicant/Principal Investigator (PI): Information in this section will populate from your proposalcentral profile so please check to be sure that your profile is complete and accurate. Enter any additional information for the PI directly into proposalcentral. 5. Institution: Enter PI s institution information. 6. Key Personnel: Enter additional key personnel (beyond the PI) and collaborators. Add new contacts by entering the email address of the person you wish to add. Click Add. 9
Select the appropriate Role from the dropdown and add Key Personnel information for the person selected. a. Involving Patient Advocates: If the research team includes a Patient Advocate please include them in the Key Personnel section. HeritX believes that the voices of patients are important to the research process and recommends but does not require the inclusion of a trained patient advocate on the research team. If you would like assistance finding a patient advocate for your project please contact us. The inclusion of a patient advocate will be viewed favorably in the grant review process. 7. Abstracts: A general audience summary and a scientific abstract are required with your Application. These will be public documents and should not contain any proprietary information. If your project is funded, the general audience summary may be shared on our website. Abstracts are limited to 3,000 characters. 8. Budget Period Detail: Please enter the budget details for each period with decriptions for each expense. Note: Indirect costs are not allowed. HeritX will consider exceptions to this policy for research projects with a budget of more than $120,000 on a case-by-case basis but indirect costs may never exceed five percent of the total budget. Requests for indirect costs must be approved in advance and must be justified based on the research necessitating increased organizational overhead. 9. Budget Summary: Budget amounts entered in the Budget Period Detail section will be summarized on this page. You will need to upload a Budget Justification in Section 12. There is no particular format for the Budget Justification, but it should justify all personnel expenses and explain the percentage of effort for all personnel. Please prepare the Budget Summary as a Word document and convert it to PDF format before you upload it in Section 12. 10. Other Support: Please list other research support information including, funder, title, award number, status, amount of support, project dates and summary of the major goals of the project. Please also specifically identify any overlap with the proposed research in the application. 11. Organizational Assurances: Please provide all requested assurances including IRB approval, IACUC approvals if applicable. Note that Human Subject and Animal Welfare assurance numbers cannot be entered on this screen. HSAS and AWSA information must be entered in the organizational profile. Please contact your organizational administrator for help with this information. 12. Upload Attachments: Please upload the following documents in PDF Format. Name each document in the Describe Attachments field. Please name the documents with the name of the PI followed by the name of the document. For Example, Dr. Smith s proposal narrative would be Smith_Application Narrative. 10
a. Biosketches for all Key Personnel: Name each biosketch with the last name of the person followed by the name of the document. For example, the biosketch of Dr. White would be named White_Biosketch. Please use the NIH biosketch format. b. HeritX Narrative and Scientific Plan: Please follow all formatting requirements listed in the Template Instructions. The Application Narrative must include all of the following required sections: A. Research Question: Hypothesis and Specific Aims (brief, no more than one page) B. Background and Significance (2-3 pages) 1. Background 2. What funding priority or HeritX Roadmap research question will this proposal address? 3. Describe how successful completion of the proposed research will provide an answer to this research topic. C. Feasibility: Briefly describe the scientific basis for the proposed research and the feasibility for achieving a successful outcome. (1 page) D. Scientific Plan: Please describe the scientific plan for the proposed research (activities and timetable), including intermediate milestones for assessing progress. (3-5 pages) c. References 1. Specific Aims 2. Experimental Design and Methods 3. Potential Pitfalls and alternative strategies 4. Timeline and Milestones (Describe the research timetable for completion, including intermediate milestones.) d. Budget Justification e. Letters of Commitment from All Collaborators f. Letter(s) of Institutional Support: What support will the institution provide for the proposed research project? g. Signed Cover Sheet: For the signed signature page, you will need to go to section 12) Print Application Attachments to download and print the Cover Sheet through the Print Signature Pages link. You will need to sign it and get it signed by the institution Signing Official and Financial Officer. Once you do 11
that, scan it in as a PDF file and upload it under the Signed Cover Sheet attachment type. 13. Validate: This step checks to see if all elements of the application are complete. If not, proposalcentral will indicate the sections that need attention. You will not be able to submit the application until all required sections and all required attachments are complete. 14. Print Application Attachments: This is where you can print the Application Cover Page for signatures. You can also download and print a copy of the full application for your own files. 15. Submit: Once you submit your application through the submit link you will receive an email confirmation. Under the Manage Proposals tab of proposalcentral the application will show submitted. You may view the application at any time through the manage proposals tab. 12