Would proposals aiming studying basic mechanisms of recombinant AAV (rAAV) biology be appropriate for this funding mechanism? Examples include how does the recombinant virus genome and payload reach the nucleus, what is the role of the AAV ITRs in the cell, and what is the potential toxicity that they impose on the host?
Would proposals aiming to modify rAAV to mitigate rAAV toxicity and produce safer gene therapies be appropriate for this funding mechanism?
Proposals focused on optimization within these areas would be considered, excluding toxicity due to overlap with other programs. We are focused on optimizing AAV gene therapy in humans, not basic AAV Biology.
Proposals seeking to address host immunotoxicity would be considered outside the scope of this program. If a strategy to mitigate rAAV toxicity and/or increase safety was also producing an increase in vector production or therapeutic gene expression it would be considered for funding.
Regarding patent applications, we have already had the IP ready to file and will be filed before the grant starts. Will this conflict with the principles of this RFP/BGTC?
AMP principles primarily address new IP developed under the award. Pre-existing IP should be addressed in section 3 of the proposal and it will be evaluated by the reviewers accordingly.
Are there plans for RFPs in the coming years or is this a one-time opportunity?
Other than the invitations to submit RFPs for Clinical Trials, there are no plans for more RFPs unless additional funding is received or the BGTC is extended beyond the planned 5-year term.
How will proposals be reviewed? Will there be a NIH Special Study section?
All reviews will be done by the BGTC members and awards will be made by the Foundation for the National Institutes of Health, not the NIH.
How many awards will be made?
Around 10-12 awards are anticipated based on the available budget. Extensive proposals addressing multiple mechanistic steps may reduce that number.
Does the FNIH follow the NIH salary cap guidance?
Yes. Information about NIH salary cap guidance can be found here.
How are indirect costs calculated?
Indirect costs are calculated as a percentage of the total direct costs. Direct costs are not to exceed $250,000/year; indirect costs are not to exceed 15% of total direct costs.
Is FNIH funding transferrable if I move to a new institution?
FNIH awards are made to an institution with a named PI. If the PI transfers to a new institution, it is possible for the awarded institution to agree to a termination clause and the PI’s new institution to accept the terms of the FNIH award, enabling the PI to continue to access funds.
Should NCATS High-Throughput Screening services be included in our proposed budget?
No, any work done by NCATS will be funded separately from the FNIH research awards and should not be included in a budget proposal.
Disease Nomination Form and Clinical Trials Questions
Can I submit more than one disease?
Yes, interested parties may submit and/or be affiliated with more than one disease nomination.
Are the text boxes in the fillable PDF the recommended length of response for each question? Would it be acceptable to add references to an appendix or links to research papers, if it would be helpful?
Since we anticipate a large volume of submissions the text boxes are the suggested response space for each question, but it is fine to add references/links as appropriate. If selected to submit a clinical trial RFP a lengthier response will be permitted.
What if there is no industry partner post-trial due to lack of commercial viability? Is an industry partner necessary for disease submissions?
An industry partner is not necessary for submitting a disease. While the ultimate goal of the BGTC is to reduce the hurdles in starting an AAV clinical trial, we are hopeful that some of the work of the BGTC will enable AAV therapies in our clinical program to continue to move forward.
How do clinical trial costs impact the choice of disease? Is there benefit to minimizing costs and/or finding additional financial support?
We are not considering the costs of individual clinical trials until the RFP stage. Invitations to submit full proposals will be extended to Disease Nominations determined by the Steering Committee to have the highest likelihood of success. During the final selection we will balance clinical program costs within the BGTC available budget. We have not contemplated the possibility of co-funding, instead focusing more on choosing diseases on their scientific merits.
How does the ability to obtain manufacturing impact choice of disease?
BGTC partner organizations and/or CROs arranged by the BGTC will manufacture the vector. Disease Nominations need not be concerned with manufacturing, so long as the vector meets the technical criteria that would enable it to be manufactured.
Does the gene therapy candidate for IND-enabling studies need to be already identified at the time of the proposal submission or can candidate optimization work be ongoing?
Some optimization work can be ongoing at the time of submission of the Disease Nomination form. Submitters should present information about the timeline of any ongoing optimization work.
Is there any benefit or downside to working with a novel capsid?
We are looking for AAV serotypes that have been previously used in INDs. A new capsid that has never been used in an IND would not be considered for this program.
For the required criterion E, does the route of administration used in a prior IND have to be in the disease in question?
No, we are only seeking to ensure that the route of administration has been used in a prior IND for any indication; a novel route of administration would not be considered for this program.
Do we have to have at least 10 patients willing to participate in order to be eligible? If so, do they all need to be from the US?
You do not need to have a specific number of patients lined up in advance of submission. For the initial review we are simply looking for information that might increase the likelihood of enrolling patients in a reasonable amount of time. Patients do not need to be located in the US; if selected for an RFP submission the logistics of patient enrollment and dosing should be addressed at that time.
Is there a lower limit to the patient number (Criterion G)?
A study of one patient would likely not produce sufficient information for the overall BGTC goals, so an absolute lower limit would be two patients. While it will depend on the diseases selected, we are generally targeting an average of 8-10 patients per trial.
For the required criteria, must a disease meet ALL of them, or is MOST okay?
It is critical to address all points in the Disease Nomination form. We would like to see diseases that meet all of the required criteria, but if there is doubt whether all criteria are met, we would encourage to err on the side of submission. The BGTC has the ability to reach out to submitters if clarification is needed.
What do you prefer to see as a proof-of-concept study to support an AAV gene therapy?
Proof of concept simply needs to demonstrate that the therapy is likely to work in a patient, we have not expressed a preference for any particular type of study or model.
Are there plans to test AAVs and/or other delivery methods for their ability to target cells of the peripheral nervous system, in particular myelinating Schwann cells?
We have no specific plan to test any specific cell type, but it would be appropriate to propose a disease with these target cells with an appropriate AAV serotype. Data should be included that demonstrates the proposed capsid infects the target cell type.
Who will be the sponsor of the IND and Clinical Trials?
NIH will hold the INDs for all BGTC trials.
Where are the pilot clinical trials going to be conducted? At NIH? If selected to move forward with a clinical trial, will it be exclusively run by NIH? If it could also be run by a partner working with us, do you prefer to see a physician who is an expert in our disease or a gene therapy expert?
The exact locations will be dependent on the diseases selected but we expect that some trials will be conducted the NIH Clinical Center and some at external sites. At this stage of review, we do not have a preference for specific expertise for a potential PI but will favorably weigh if there is a willing PI who has already run a clinical study (of any type, not necessarily in the submitted disease).
A company is conducting some early-stage work on our disease, but we do not know if there will be commercial possibilities. Would this disqualify us from submitting a nomination?
This would not disqualify a submission from being considered, but submitters should be able to articulate the value the BGTC would be able to create or the hurdle the BGTC can help overcome that cannot be done by the company. In general, commercial work being done at a very early stage is less likely to limit a disease’s consideration than later stage work. The only firm disqualification when the BGTC is considering existing commercial interests is if a company has already started an AAV clinical trial in that disease.
A company may be designing proprietary vectors targeting our disease, should we still consider submitting?
A company potentially designing proprietary vectors would not disqualify a submission for consideration, but submitters should keep in mind that one of the goals of the BGTC is standardization of processes. For the final trials that are selected, manufacturing of vector and CMC testing would need to be done by one of the BGTC’s selected partners or to the consortium’s specific specifications to ensure that the process aligns across the trials and can be used in our AAV clinical development manual.
Will submitters receive individual feedback on their submissions?
The BGTC does not anticipate being able to provide feedback to individual proposals that are not selected. However, we are expecting to produce a white paper later in 2022 after the selection process is complete, to discuss the review/selection process and what made the diseases that were selected a good fit for the BGTC clinical program.
What is the deadline for the submissions?
RFP responses and Disease Nomination forms are due February 18, 2022 11:59 PM ET via email to [email protected].
Is international collaboration possible?
Yes, international organizations are permitted to apply to the RFPs and Disease Nomination process. As the BGTC is focused on streamlining the US regulatory process, proposals from international organizations would need to be aligned with this objective.
How many applications are expected?
We are not able to provide an estimated number of proposals or disease nominations at this time.
Does a company need to be a BGTC partner in order to apply?
No, a company does not need to be a member of the Consortium to submit a proposal or a disease nomination.