IGNITE and CREATE Bio Programs with a focus on Non-Addictive Pain Therapies Webinar

IGNITE Q&A

Estimate of success: how many grants will be funded relative to applications?
We typically have about 30 applications per round and we typically fund about 5. Although there is some variability.

I submitted once a couple years ago. Will this one count as my last submission?
You can resubmit an application if it’s within 37 months of the original application. You can resubmit to the new R61/R33 IGNITE FOAs even if your original application was an R21/R33 IGNITE as long as you haven’t already put in an A1.  Here is more information on resubmissions: https://grants.nih.gov/grants/policy/resubmission_q&a.htm

How much preliminary data is required for the IGNITE assay development grants?
Does early feasibility matter, or is innovation/significance more important? Both are important. You need enough preliminary data to support the biological rational of the project. Depending on the FOA, other data may also be needed. All preliminary data should be from well-designed and rigorous experiments. Please look carefully at the FOA and contact us with questions.

When is the next due date?  
The remaining submission dates are: February 20, 2019, June 19, 2019, October 17, 2019, February 19, 2020, June 17, 2020, October 20, 2020 and February 17, 2021

A brief review of NIHReporter suggests that there is a fair number of projects that do not transition to R33. Can you speak to some common reasons for "failure to transition" beyond just "did not meet Go criteria"?
This could help applicant avoid pitfalls. Since the program has only been around for 3 years, the majority of projects are still in the first phase. Most projects that have gotten to the R33 transition have progressed. There aren’t enough failures for me to comment on common reasons.

Please recommend FOA for early development of a device & procedure at NINDS?
For advice on device development, please contact Nick Langhals:  nick.langhals@nih.gov. IGNITE doesn’t support device development.

What do you like to see in the preliminary data for PAR-18-762 assay development?
It can vary. You want to convince reviewers that your assay and screening plans are feasible. Perhaps you have an assay but need to miniaturize it to make it high throughput. Maybe you have your primary assay done but need to create your secondary assays. These are successful examples I’ve seen, but of course not everyone has this. I’ve seen cases where a pilot screen has been done. But also many that haven’t done this. All preliminary data should be from well-designed and rigorous experiments.

What is the difference/similarity between PA-18-575 and PAR-18-761?
PA-18-575 is the STTR Omnibus solicitation. You will need to partner with a small business to apply here. The STTR (and SBIR) programs have set aside funds, so if you are eligible, this is probably your best bet. The Omnibus has a much broader scope of allowable science as well, so you will have more flexibility. For more information, please contact Stephanie Fertig: fertigs@ninds.nih.gov

For PAR-18-763, if Biomarkers are out of scope, does that include Biomarkers that will be monitored as part of the model development?
Development of biomarkers is out of scope. If you are monitoring existing biomarkers as part of developing a new animal model, that is ok.

Is PAR-18-761 restricted to in vitro testing? 
Will optimization of delivery + evaluation of other compounds related to a lead (validated) compound in animal model fit in for 761 or 762? PAR-18-761 is for Neurotherapeutic Agent Characterization and In vivo Efficacy Studies. Yes, optimization of delivery and evaluation of compounds in an animal model would be appropriate. It is not limited to in vitro testing.

Can PAR-18-762 be used to develop the in vitro on-target and off-target screening tree to identify a back-up candidate for a project that has a lead compound with in vivo efficacy, but the exact mechanism and best on-target in vitro assays are unknown?
Using PAR18-762 to screen for back-up compounds would be allowable, but you could run into an issue with convincing reviewers that a back-up is innovative and a significant need. I’d be happy to discuss the specific project on a call.

In contacting you about whether a project fits, what should we share:  general concepts, specific aims and potential milestones? Other key information? A specific aims page is most helpful. This can include a general intro, significance, and aims. This helps me make sure you’re talking to the right person before we have the call. On the call I will likely ask you additional questions on things like milestones, the therapy development plan or IP. This is so I can help you think about how to head-off potential review concerns.

Phenotypic assays are supposed to be target-agnostic. Do reviewers have expectations that "targets" are identified/validated/known/etc?
I wouldn’t anticipate reviewers would expect you know the target going into the screen- that’s what makes it phenotypic. I would suggest having some plan (within the grant or beyond) to figure out what the hits are doing and how you can do future optimization and development.

PAR-18-761 - total period of grant support is 3 yrs between the two phases?
Yes.

Is a timeline of 1.5 years each for R61 and R33 acceptable?
Yes, that is allowable. Many people choose to do the milestone at the end of a budget year so that the R33 can serve as the progress report. But if 1.5 makes the most scientific sense, I would recommend going with that.

What is the minimum time frame for the R61 stage?
1 year.

May I have a list of mechanisms that would support Biomarkers and Device-mediated interventions?
Our translational programs are available at: https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research. Please see the Biomarker Program and the Translational Device Program.

With regards to "neurological disorders" would that umbrella description include neuropathic pain?
Generally, yes, but there are exceptions, such as diabetic pain (supported by NIDDK). Take a look at NIH RePORTER to see which institutes typically support the science you propose. You can also check with us to confirm.

Does a proposal for the assay development program need to be disease-specific?
It’s not required, but it might be helpful if the goal is a therapeutic that can be further optimized in BPN or CREATE. I’m happy to talk about the project specifics on a call. 

What you would expect as preliminary data for PAR-18-761?
You will need to convince reviewers that you have a compound/therapeutic that’s worth testing and that you have a good, therapeutically relevant model to test them in. All preliminary data should be from well-designed and rigorous experiments. Often people have in vitro data to support going to an in vivo model. Sometimes the therapeutic is the result of a screen, but sometimes it’s the product of rational design. Regardless, I recommend you tell reviewers about it. Evidence that using the model is feasible is helpful if it is a new model. Even if it isn’t, I’d recommend demonstrating or referencing that you have experience with it. Again, I’m happy to discuss your specific project on a call.

For an academic and small business team, is it better for applying SBIR or IGNITE?
If you are eligible for the STTR or SBIR program, that is probably the best path for you. There are set-aside funds available for SBIR/STTR applications that are not available for IGNITE application. If you are eligible for an SBIR or STTR, please contact Stephanie Fertig: fertigs@ninds.nih.gov

Is it necessary to have a lead compound? Is it an advantage to have one?
I’m not sure which FOA you are referring to. For PAR-18-761 (Efficacy Studies FOA), you would need a therapeutic to test. For PAR-18-762 (Assay FOA), no, you don’t need a lead compound. I can see the advantage to having a known compound that could be used as a control when setting up your assays, but often there are other ways to do this if such a compound isn’t available. For PAR-18-763 (Model Development FOA), I wouldn’t recommend using an experimental therapeutic to validate your model. A well-known and commonly used therapeutic would be a better way to go. 

Are there any restrictions with Non-US based collaborators or PIs?
In order to get a foreign component grant funded, you will need to convince NIH that there is no way to get the same work done in the US.

Is there a unique resource or expertise at the foreign location that does not exist domestically?
If you have a candidate that could be useful for a wide range of indications on a similar condition (eg., pain), how important is it to have indication-specific assays, as opposed to general assays that speak to a common mechanism across indications? That depends. I think I would need to know more about the particular project to answer that fully. But I’ll make a general attempt here. I’m assuming the question refers to the assay development FOA. It sounds like the assay measures a target that could be used for a number of different kinds of pain. If that’s the case, you might not have indication-specific assays. But you can discuss in the therapeutic development plan a specific indication. Again, I’m happy to discuss the project specifics on a call.

Would 18-761 be appropriate if my lead compound has cleared Phase I trials for one neurologic disease but I want to broaden its therapeutic potential by demonstrating efficacy and MOA in a different animal model of neurodegeneration?
You can pursue a second indication. But be prepared to describe to reviewers why this is significant, innovative and not just an add-on. You could also run into an issue with reviewers wanting to see if your first indication works before supporting a second. These issues can sometimes be prevented with a good rational in the application. Again, I’m happy to discuss the project specifics on a call.

You just mentioned that neuropathic pain generally would fit these mechanisms, but not diabetic pain. This is an important point. What about pain that is due to neuropathic condition of the peripheral nervous system and not CNS? Why are those off-mission?
Take a look at NIH RePORTER to see which institutes typically support the science you propose. You can also check with us to confirm.

Why would you recommend SBIR before IGNITE?  Are the funding chances higher for the SBIR? There are set-aside funds available for SBIR/STTR applications that are not available for IGNITE applications. So, yes, the chances are higher for the SBIR.

Do rare genetic neurological disorders fall within scope for PAR-18-761? We support any rare disease within the NINDS mission. Again, take a look at RePORTER and talk to us to find out if your project is a fit for NINDS. You can also check with us to confirm.

For PAR-18-761, can we use a tool compound from literature to establish assays and efficacy? Do we have to have novel compound?
The FOA states it’s to “to encourage the translation of research discoveries into new treatments for disorders that fall under the NINDS mission.” You might have a hard time convincing reviewers that a published tool compound can be developed into a therapeutic in the future. However, it is perfectly fine to use a tool compound to validate your assays and models or to use the tool compound as a control when testing the experimental therapeutic.

Reframing the question: will re-purposing an existing drug be under the 761 opportunity?  Who should I send the Aim/milestone for advice?
Yes, you can propose to re-purpose. Send the aims page to me (Becky Roof, Rebecca.roof@nih.gov). I will likely also bring in a second program director who knows your disease and we can discuss your project with you.

Coming back to neuropathic pain, and condition-specificity, would the use of several different models that are relevant to different conditions, be appropriate in the R33 phase?
It sounds like you have some project-specific questions that are going to be hard for me to answer here without more detail. It comes down to what the goals of the project are and where you are going in the future. It is generally good to have models that as best as possible reflect the human condition. If you get more confidence out of more models because none of them are prefect, then doing more might strengthen the proposal. But doing a bunch of models in a non-focused way might raise questions about whether or not you have a clear path and might weaken the proposal. Perhaps it would be best to discuss this on a project call where we can talk about specifics.

For the PAR-18-762, can the HTS assay development and screen be part of the R61 and then hit optimization/SAR for the R33?
This is allowed, but generally people do the HTS in the R33 phase. This way, you can have milestones demonstrating that your assays are ready to go before doing the screen.

It seems that for PAR-18-762, it is important to have a lead compound (positive control), but not a potential development candidate. Is that a fair assessment?
Yes.

Does the project with human noninvasive brain stimulation (with TMS) for pain treatment qualify for this program?
For advice on device development, please contact Nick Langhals:  nick.langhals@nih.gov. IGNITE doesn’t support device development.

What is A1 resubmission possibility?
Yes, you can resubmit an application one (1) time, even if the prior application was an IGNITE R21/R33. https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-197.html

If one has already has demonstrated in vivo efficacy of a new therapeutic, how do you balance applying to IGNITE vs CREAT/Blueprint?
I would encourage you to take a look at the entry criteria for BPN/CREATE. If you feel that you can meet the entry criteria (which includes in vivo proof of concept but also other things) then please contact Chuck Cywin (charles.cywin@nih.gov, BPN) or Chris Boshoff (christoffel.boshoff@nih.gov, CREATE) about an application. Otherwise, IGNITE is the way to go.

Can the first phase be used for in vitro and animal model assay development to be used for PK/PD measurement in to help lead optimization?
For PAR-18-761, Neurotherapeutic Agent Characterization and In vivo Efficacy Studies, yes, you can do PK/PD work in the first phase.