Amendment_No._2_-_PHS-2018-1.pdf

AMENDMENT TWO (2)

Solicitation Number: PHS-2018-1

Date of Solicitation Issuance: 07/18/2017

Date of Amendment No.1 Issuance: 09/18/2017

Number of Pages 24

Point of Contacts:

George Kennedy, Contracting Officer Tiffany Chadwick, Procurement Analyst & Contracting Officer E-mail: kennedyg@mail.nih.gov E-mail: tiffany.chadwick@nih.gov Phone: 240-669-5170 Phone: 240-276-7293

OFFICE OF ACQUISITIONS

National Institute of Allergy and Infectious Diseases (NIAID) 5601 Fishers Lane, Room 3D35, MSC 9821 Rockville, MD 20852

PURPOSE OF SOLICITATION AMENDMENT

The purpose of this amendment is to respond to questions submitted by interested offerors.

The hour and date specified for receipt of Offers remains unchanged.

Except as provided herein, all terms and conditions of the solicitation remain unchanged and in full effect.

A recording of the pre-proposal conference and associated materials have been posted here:

https://sbir.nih.gov/engage/news#081817.

General Questions Question 1: Is OMB clearance required if the project will involve the collection of information from 10 or more public respondents?

Answer 1: No, OMB clearance in accordance with the Paperwork Reduction Act (PRA) is no longer required for NIH-funded research, in accordance with the enactment of the 21st Century Cures Act. SBIR offerors no longer need to restrict the number of surveys, interviews, etc. proposed for a project due to this concern.

Question 2: How often - how many times a year - does NIH announce the contract opportunity? What is the next contract announcement?

Answer 2: The NIH and the CDC issue one consolidated SBIR contract solicitation per year, generally sometime between June and August of each year. Solicitation PHS 2018-1 is this year’s consolidated SBIR contract solicitation – it was issued on July 18, 2017, and contracts will be awarded off of this solicitation in fiscal year 2018. These annual solicitations are for initial SBIR awards, and each awarding component independently manages the solicitation process for transitioning awardees from Phase I to potential Phase II.

Question 3: Will the next announcement have the same Topics as this announcement?

Answer 3: No, almost all Topics change from year to year. Occasionally, some Topics of great continuing interest will be repeated, although they may have revisions to the specifications. There is no guarantee that any Topic will be offered again.

Topics for each year are not released until a preliminary notice is issued, at least 15 days prior to the full solicitation being made available, on https://www.fbo.gov/ and on https://sbir.nih.gov/funding.

mailto:kennedyg@mail.nih.gov mailto:tiffany.chadwick@nih.gov https://sbir.nih.gov/engage/news#081817 https://www.fbo.gov/ https://sbir.nih.gov/funding

Question 4: How soon after completion of Phase I can an awardee begin work on a successful Phase II proposal?

Answer 4: For Phase I only submissions, the gap between a Phase I award and a successful Phase II award varies, as each awarding component independently manages the solicitation process for transitioning awardees from Phase I to potential Phase II – however, for NIH, the gap may be up to 1 year or so, as the Phase II proposal will need to go through external peer review technical evaluation, which can be a lengthy process to coordinate.

However, for Fast Track submissions at NIH that result in a contract award with a contractual option for Phase II, a successful Phase II project has the potential to begin immediately following the completion of Phase I, as the external peer review technical evaluation has already been satisfied during the Fast Track process.

Question 5: Can I propose collaboration with a specific NIH investigator in my proposal?

Answer 5: Only if the NIH investigator obtains all approvals required by standard operating procedures for intramural scientist collaboration on extramural funded grants and contracts, and the opportunity to collaborate with the NIH investigator was offered to all offerors on comparable terms as those offered to any one offeror.

Question 6: What is the difference between a contract and a grant?

Answer 6: Please refer to https://sbir.nih.gov/apply for general information on this topic. For this contract solicitation, it is important that you adhere to all the requirements set forth in the solicitation document PHS 2018-1 and its amendments, which provide all the information necessary to submit a successful contract proposal.

Question 7: If I am initiating an idea, which cannot "fit" into a solicitation topic, am I limited to a grant?

Answer 7: For a contract solicitation, it is very important that the proposal address how the proposed technology would meet the goals, objectives, and deliverables set forth in the Topic description, as one of the evaluation criteria set forth in Section 6 addresses whether the approach has a reasonable chance of meeting the topic objective. If you feel like your project may not be reviewed favorably under this evaluation criterion, you may be in a better position to submit a grant application, which allows for more flexibility. You may review grant opportunities on the https://sbir.nih.gov/funding website.

Question 8: Does the designated institutional official who will review financial disclosure statements from each

Investigator have to be a CPA or other licensed finance professional? Can you further clarify the part of the objectivity clause that defines the PI’s disclosure of Financial Interest in accordance to the 2011 vs. the 1995 standards?

Answer 8: Institutional responsibilities regarding investigator financial conflicts of interest are only required for Phase II SBIR contracts funded by Public Health Service appropriations. If your Phase II SBIR proposal is being considered for funding, you may discuss specific compliance concerns with the particular contracting officer who is responsible for your individual proposal’s negotiation and award, after reviewing the regulations found at 45 CFR Part 94 (available at https://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45:1.0.1.1.51&idno=45) as well as HHS guidance (available at https://www.hhs.gov/ohrp/regulations-and-policy/guidance/financial-conflict-of-interest/index.html).

Section 2.3 Fast Track Proposals (NIH Only)

Question 1: While acknowledging that the Government has complete discretion in making awards, does the statement

'Fast Track proposals will be accepted' for a particular Topic imply that funds are actually available to support a Fast Track if sufficiently meritorious?

Answer 1: Upon award of a Phase I contract with an option for Phase II, through the Fast Track submission process, an awarding component is not necessarily setting aside funds specifically for that specific potential Phase II award;

although, 3.2% of our agency’s extramural Research/Research & Development budget will be set aside each year for all SBIR awards, in general. The decision to fund or not fund the Phase II component of a successful Fast Track submission is based on all the factors set forth in Section 6.4 Award Decisions, which involves other factors outside of technical merit and availability of funds.

https://sbir.nih.gov/apply https://sbir.nih.gov/funding https://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45:1.0.1.1.51&idno=45 https://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&SID=0af84ca649a74846f102aaf664da1623&rgn=div5&view=text&node=45:1.0.1.1.51&idno=45 https://www.hhs.gov/ohrp/regulations-and-policy/guidance/financial-conflict-of-interest/index.html https://www.hhs.gov/ohrp/regulations-and-policy/guidance/financial-conflict-of-interest/index.html

Section 2.5 I-Corps™ at NIH

Question 1: We have completed NSF I-Corps. Shall we be eligible for NIH ICorps?

Answer 1: Companies that have already completed a different I-Corps program are not necessarily ineligible for the I- Corps™ at NIH program, as I-Corps programs can differ. When submitting an application in the second step of the I-Corps process, as described in Section 2.5 of the contract solicitation, the company should discuss the outcomes achieved under the previous I-Corps program and discuss the unique outcomes that they hope to achieve through this additional I-Corps™ at NIH opportunity.

Question 2: Is I-Corps restricted to only Ph.D.'s or could management of SBC also attend?

Answer 2: To be selected for I-Corps participation, the company must propose a specific 3-person team, which includes both scientific/technical, business, and industry representation, in accordance with the description set forth in Section 2.5 of the contract solicitation.

Question 3: Does the $50K for I-Corps come out of the max budget for Phase I?

Answer 3: No, the potential I-Corps funding (not to exceed $50,000), would be in addition to the basic Phase I project funding (not to exceed the specific amount set forth in the Topic description in Section 12).

Section 4.2 Offeror Eligibility and Performance Requirements

Question 1: I have a collaborator who is willing to perform necessary animal studies in Phase I; however, the costs might amount to more than the 1/3rd of the proposed project budget that is allowed for collaborators.

Would you have any suggestions?

Answer 1: One suggestion might be that the applicant company itself perform all the data analysis for the animal work, to reduce the cost of the subaward.

Question 2: If a proposed subcontract, such as a CMO for drug-scale up, does not do any ‘research’, does this work still count as part of the one-third effort that we are allowed to have completed by someone other than the applicant small company?

Also, if the applicant small company is doing software development, would this be included in the calculation of the applicant small company’s own ‘research or analytical effort’ in regards to Section 4.2 performance requirements?

Answer 2: For this solicitation, we have stated that we will be measuring the ‘two-thirds effort’ requirement for a Phase I (and the ‘one-half effort’ requirement for a Phase II) by using the total contract dollars allocated in the budget.

All dollars spent toward a subaward of any type will be counted towards the proportion of effort completed by someone other than the SBIR awardee itself. The Government will review the Appendix C budget and total all dollars that will be allocated to the small business applicant’s own effort versus all dollars that will be allocated to subcontractor and/or consultant effort, regardless of the nature of that effort.

Question 3: Does the number of employees of a subcontractor count against the 500 employee limit for “Small

Business Concern” if the Subcontractor IS NOT an Affiliate?

Answer 3: No, as long as the collaborating organization (performing a subaward) does not meet the definition of “Affiliate” (as established by federal regulation here: http://www.ecfr.gov/cgi-bin/text-idx?SID=b02d16dbfcddf646e5c0728d5e632a61&mc=true&node=se13.1.121_1103&rgn=div8), the subaward’s business size does not have any relevance.

Question 4: Can a foreign entity be involved together with a US company?

Answer 4: The research or R&D project must be performed in its entirety in the United States. Whenever possible, work outside the United States which is necessary for the completion of the project should be supported by funding other than the SBIR contract. In those rare instances where the study design requires use of a foreign site (e.g., to conduct testing of specific patient populations), the investigator must provide compelling scientific justification in the application for the need and use of a foreign site. Similarly, in those rare instances where it may be necessary to purchase materials from other countries, investigators must thoroughly justify the request.

http://www.ecfr.gov/cgi-bin/text-idx?SID=b02d16dbfcddf646e5c0728d5e632a61&mc=true&node=se13.1.121_1103&rgn=div8 http://www.ecfr.gov/cgi-bin/text-idx?SID=b02d16dbfcddf646e5c0728d5e632a61&mc=true&node=se13.1.121_1103&rgn=div8

NIH will consider these instances on a case-by-case basis. If requesting a deviation, please clearly state this in your business/pricing proposal AND your technical proposal, along with the scientific justification, to ensure that all parties review the request appropriately. You must receive a written authorization for this deviation at the time of your contract award to be in compliance with SBIR requirements.

Question 5: Does the Principal Investigator on the offer need to be a medical researcher? Does the Principal

Investigator need to have a Ph.D. or M.D.?

Answer 5: The Principal Investigator, and other significant team members, must demonstrate the training and experience necessary to carry out and lead the specific technical approach proposed. Technical personnel proposed will be evaluated for sufficiency to perform the technical approach proposed, and there is not a requirement for any one particular type of background or degree.

Section 4.19 Prior, Current, or Pending Support of Similar Proposals or Awards

Question 1: Can one company apply for two awards?

Answer 1: A company may submit only one SBIR/STTR application or proposal to a Department of Health and Human Services (HHS) component for each unique research project. Therefore, a company may submit more than one application/proposal for consideration as long as they are each for separate and distinct projects.

You may not submit an application/proposal for a project that is “essentially equivalent” to a project already submitted for consideration for any SBIR funding opportunity within the Department of Health and Human Services. See Section 4.19 of the solicitation document, as well as the definition of “Essentially Equivalent” in Section 3.1 of the solicitation document.

Question 2: If two contracts are awarded, can clinical studies overlap, as long as requirements of both contracts are met?

Answer 2: Two contracts or grants may not be awarded if the work would be essentially equivalent, as discussed above and in the solicitation document. If there is a component of work that could be leveraged for two different, successful research proposals, this should be communicated with Government staff during the pre-award negotiation phase for any affected proposal, so that the Government may incorporate safeguards into the award documents to avoid situations where services rendered could be charged under more than one award.

Question 3: If two contracts are awarded, are two PI's needed?

Answer 3: The PI on any SBIR proposal/application must be more than 50% employed by the small business applicant company; however, there is not necessarily a minimum percent effort that must be contributed by the PI on each project. During the evaluation process, technical reviewers will review whether the PI commitment to the individual project is found sufficient to successfully complete the work proposed. There is no rule prohibiting a PI 100% employed by the small business from applying 50% effort to one proposed, discrete project, and 50% effort to a separate project – however, each technical review panel will have the opportunity to evaluate whether the proposed effort is sufficient on each individual project, and weaknesses noted in technical evaluation will have an impact on the competitiveness of a proposal.

Note, as well: OFFERORS SHOULD ASSURE THAT THE PRINCIPAL INVESTIGATOR, AND ALL OTHER

PERSONNEL PROPOSED, SHALL NOT BE COMMITTED ON FEDERAL GRANTS AND CONTRACTS FOR

MORE THAN A TOTAL OF 100% OF THEIR TIME. IF THE SITUATION ARISES WHERE IT IS

DETERMINED THAT A PROPOSED EMPLOYEE IS COMMITTED FOR MORE THAN 100% OF HIS OR

HER TIME, THE GOVERNMENT WILL REQUIRE ACTION ON THE PART OF THE OFFEROR TO

CORRECT THE TIME COMMITMENT.

Section 4.22 Payment

Question 1: What schedule is in place for distributing monies? What are the Disbursement terms - are they upfront, installments, or reimbursement?

Answer 1: For general information on how payments are processed for federal contracting, review Section 4.22 of the solicitation document.

Individual contracting officers may use their discretion in setting up appropriate payment schedules. If you are notified that your proposal is being considered for award, you may begin discussing the potential payment schedule with the specific contracting officer point of contact named in that notification.

Section 5 Contract Requirements

Question 1: Who owns the intellectual property/technology/capabilities/source code developed under SBIR contracts?

Answer 1: Review Sections 5.5, 5.6, and 5.7 of the solicitation document in regards to Copyrights, Technical Data Rights, and Patent Rights. In general, the small business concern normally retains rights and ownership, while the Government is granted a royalty-free license.

You may review specific terms and conditions that will be included in any resultant contracts here:

https://www.law.cornell.edu/cfr/text/48/52.227-20 and https://www.law.cornell.edu/cfr/text/48/52.227-11.

The Government does typically require the delivery of source code and object code developed, modified, and/or enhanced under a Government contract; however, it will not be used in a way inconsistent with the rights discussed above.

Section 6 Method of Evaluation

Question 1: Can your proposal be technically acceptable and not awarded and if so, does that happen?

Answer 1: Yes, as stated in Section 6.1 of the solicitation document. This occurs frequently, as there are often more proposals deemed technically acceptable than there are funds available. Therefore, the Government will consider all of the evaluation factors for award stated in Section 6.4 of the solicitation document to make funding decisions that are deemed to be in the best interest of the Government.

Section 7.3 Limitation on the Length of the Technical Proposal (Item 1)

Question 1: Are links acceptable in the proposal?

Answer 1: Technical proposals shall not include links to internet web site addresses (URLs) or otherwise direct readers to alternate sources of information. Augmentation of the page limit through use of hyperlinks, etc. is not permissible.

Section 7.4 Submission, Modifications, Revision, and Withdrawal of Proposals

Question 1: Should registration in eCPS be done by a business leader or the research principal investigator?

Answer 1: There is no requirement about which company personnel should register or submit within eCPS.

Question 2: How do you get from eRA commons into eCPS?

Answer 2: Companies should access eCPS directly, using the instructions set forth in Section 7.4 of the contract solicitation. A company should be able to use its existing eRA commons log-in information to access eCPS;

however, no interaction or connection with eRA commons exists outside of this log-in capability.

Question 3: Do you need to use the same file name with a revised submission?

Answer 3: You may use the same file name if you revise your files uploaded to eCPS prior to the submission deadline;

however, you may also make a revision notation on the end of the file name, if desired, to assist with version control. Lack of compliance with suggested file naming conventions will not prevent submissions from being accepted – compliance merely assists the Government with the organization of submitted files.

https://www.law.cornell.edu/cfr/text/48/52.227-20 https://www.law.cornell.edu/cfr/text/48/52.227-11

Section 8 Proposal Preparation and Instructions

Question 1: Do all team members need to be identified by the end date of Oct. 20th or would members be added after the fact if their expenses are budgeted in the final financial worksheet? Do we need to submit anticipated costs for vacancies in the team during phase I? If our team is not complete, can we recruit after the submittal deadline for Phase I?

Answer 1: Team members can be added after the submission deadline, if their anticipated costs have been budgeted in the proposal submitted by the submission date. It is not required that all personnel be named at the time of proposal submission.

However, 20% of your technical evaluation score for a Phase I, and 15% of your technical evaluation score for a Phase II, will be based on “The qualifications of the proposed Principal Investigators, Project Directors, supporting staff and consultants.” The evaluation panel may note a weakness of varying degrees on proposals that do not have all significant personnel in place, depending on how critical and integral the unfilled position is to the particular, specific project. The evaluation panel will make the final assessment, in accordance with the scoring matrix in Section 6 of the solicitation.

In lieu of having an exact person named, you may at least discuss your intention to add this position to the team, the type of qualifications you will be looking for in filling that position, and a plan for how/when you will bring that position into the team, etc., to provide as much information as possible to the evaluation panel at the time of proposal submission.

Question 2: Could you clarify the requirement for a Business Proposal. Is this a proposal for commercialization of the product? The Pricing Proposal Appendix C - appears to be a standard research budget outline.

Answer 2: It is important to distinguish between the Commercialization component of the Technical Proposal and the Business Proposal. A Phase I Technical Proposal must address potential commercial applications of the product being proposed, as set forth in Section 8.8(A)(6). Likewise, a Phase II Technical Proposal must include a more thorough discussion as part of a Commercialization Plan, as set forth in Section 8.8(B)(9).

How your technical proposal addresses potential commercialization of your product is important, because it comprises 20% of your Phase I technical evaluation score, as set forth in Section 6.2, and 25% of your Phase II technical evaluation, as set forth in Section 6.3. Any discussion of how you propose to commercialize your product must be discussed within your Technical Proposal, and within the appropriate page limit set forth for the Technical Proposal in Section 7.3.

The Business Proposal should not address how you will commercialize your product. Your Business Proposal addresses your business’s eligibility to be considered for an SBIR award, and sets forth your requested budget to perform the work detailed in your Technical Proposal. The Business Proposal is not scored; however, it will be evaluated for compliance and cost/price reasonableness. The Business Proposal does not have a page limit, and for a Phase I SBIR award, it is not usually very long. The Business Proposal consists of a Pricing Proposal (Appendix C), a Venture Capital certification (if appropriate, see Section 4.6), Proof of Registration in the SBA Company Registry, and a Summary of Related Activities (Appendix F) form for each key personnel.

Please review Sections 8.3 and 8.4 for a high level outline of what is required for a Technical Proposal and a Business Proposal, in conjunction with Sections 8.5 and 8.6, which break down the details of the research plan (- the “Content of the Technical Element”).

Section 8.2 Fast Track Proposal Instructions (NIH Only)

Question 1: Do we need to include our CVs for both Phase I and II, if we submit a Fast Track submission?

Answer 1: As stated in Section 8.2 of the solicitation, a Fast Track submission must include a complete Phase I proposal and a separate, complete Phase II proposal. These proposals will be evaluated and scored separately and independently of each other. Therefore, Senior/Key Personnel and Bibliography of Directly Related Work should be addressed in your Phase I proposal in accordance with Section 8.8(A)(7), and Personnel should be addressed in your Phase II proposal in accordance with Section 8.8(B)(3).

Section 8.8 Content of Technical Element (Item 1)

Question 1: Is there a standard sectional breakdown of the Technical Element required or recommended for all offerors to use when generating and compiling their proposals? What should be included in the Technical Element?

Answer 1: For a Phase I proposal the Content of the Technical Element (or Research Plan) does not have any page limits for internal sections. For Phase II, the only such page limit is that the Commercialization Plan section must not exceed 12 pages. Companies may use their best judgement in addressing all content sent forth in Section 8.8 within the overall Technical Proposal page limit.

All Technical Proposals should include the material discussed in Section 8.8 (and follow the organizational structure set forth in Section 8.8). Further details are also provided in Sections 8.9 through 8.15, as applicable, depending on the particular considerations appropriate for the type of research being proposed.

Question 1: Can you clarify when letters of support are requested?

Answer 1: Letters of support are requested for proposals under all Topics in the following situations, as set forth in sections 8.8 A.9., 8.8 A.10., 8.8 B.3., 8.8 B.9.e., and 8.8 B.10: when a subcontractor or consultant collaborator is proposed, a letter must be included from each individual confirming his/her role in the project and extent of involvement; when facilities other than those of the applicant are proposed, a letter must be included stating that leasing/rental arrangements have been negotiated and will be available for the use of the SBIR applicant; and, for Phase II proposals under a Fast Track submission, letters should be included in the Finance Plan section of your Commercialization Plan.

In addition, some of the specific Topic Descriptions in Section 12 refer to additional and/or more specialized letter requirements, so check your individual Topic of interest carefully.

All of these letters should be included in your Technical Proposal to ensure that they are reviewed by all reviewers.

In addition, costs associated with collaborators should be addressed in Appendix C of the Business Proposal, and letters that discuss or confirm financial information for collaborators can also be included in the Business Proposal to support the evaluation of the proposed project budget. For NIH Topics, please note that information submitted in the Business Proposal, however, will not be seen by all evaluators, some of whom will only review the Technical Proposal.

Section 8.10 Human Subjects Research and Protection from Risk

Question 1: If a proposed project is regarded as Human Subjects Research, do I need a certain certification beforehand in order to submit the proposal?

Answer 1: Projects that will include Human Subjects Research must be compliant with relevant NIH/CDC policies prior to award, or in certain instances, prior to the conduct of the portions of the work involving human subjects research - not prior to the submission of the proposal. However, offerors are encouraged to address the human subjects research instructions set forth in Section 8.10 of the solicitation in as much detail as they are able to within their proposal, at the time the proposal is submitted, so that the proposal may be evaluated as comprehensively as possible, and any concerns noted may be resolved as efficiently as possible.

Section 8.16 Content of the Pricing Proposal (Item Two)

Question 1: Is profit/fee included in the budget capped at 7% of total costs, like it is for SBIR grants?

Answer 1: The SBIR Policy Directive states that SBIR awards are allowed reasonable fee or profit consistent with normal profit margins provided to profit-making firms for R/R&D work. Contract awards use a structured agency approach to determine reasonableness, in accordance with Federal Acquisition Regulation (FAR) 15.404-4 Profit, which can be viewed here: https://www.law.cornell.edu/cfr/text/48/15.404-4 . If contracting personnel are concerned about whether the fee/profit proposed is reasonable, this issue will be addressed in negotiations prior to award.

https://www.law.cornell.edu/cfr/text/48/15.404-4

Question 2: How do I know what is allowable as a direct cost for my SBIR contract proposal’s budget?

Answer 2: For SBIR contracts, costs that are reasonable to perform the work proposed and are 100% allocable to completing the SBIR project as set forth in the contract may be included as direct costs in the budget, as long as the same costs are not included in an indirect cost pool (for the creation/administration of G&A/F&A/Overhead rates), and are not expressly “unallowable” (prohibited) in accordance with the Federal Acquisition Regulation (FAR) Subpart 31.2 – Contracts with Commercial Organizations, which can be viewed here:

https://www.acquisition.gov/?q=browsefar .

Note that SBIR grants may have different policies on allowable direct costs, and this guidance applies only to SBIR contracts. Also, note that if your proposal is found to be competitive for award following initial evaluation, a contracting officer may discuss the appropriateness of certain costs with you in a pre-award negotiation phase, on a case-by-case basis, so budget concerns will have the opportunity to be resolved prior to a final award decision being made.

Question 3: Could the budget be used to provide lodging and subsistence allowance to bring together research team in one location?

Answer 3: Yes, a portion of the budget may be used to cover travel costs for this purpose, if justified and related to the needs of the project. The reason for travel, location of travel, number of travelers, and number of nights of lodging must be described in Appendix C.

Question 4: Is there a page limit for the Business Proposal?

Answer 4: No, the business proposal does not have a page limit. Information placed in the business proposal will not be considered during technical evaluation, and will be used only to consider cost/price reasonableness and general compliance with the SBIR program eligibility requirements.

Question 5: Can you give examples of how team members can be compensated for their efforts through an SBIR award?

Answer 5: Compensation could include salary, stipends, hourly rate, etc. The type of compensation and amount is determined by the applicant company, but must be in accordance with the salary rate limitation set forth in Section 5.1 of the solicitation. See https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/part- 352-solicitation-provisions-contract-clauses/index.html#352.231-70 for additional information on the Salary Rate Limitation.

Section 12 Component Instructions and Technical Topic Descriptions

NATIONAL CANCER INSTITUTE (NCI)

National Cancer Institute (NCI), Topic 370: Targeted Therapy for Cancer- and Cancer Therapy-Related

Cachexia Question 1: The Topic descriptions states “Activities not supported by this topic: Proposals involving supplements and food products will not be considered.” My intuition is that the intent of this was to prevent study of poorly-defined foods, herbs and preparations that are not drugs. If a project were to involve n-acetyl cysteine, which can be sold as a nutraceutical “supplement,” to enhance the activity of beta alethine, would this project be excluded from consideration under this Topic?

Answer 1: If the offeror can make a case that the drug/drug combination affects a target that is known to be involved in causing cancer- or cancer related-cachexia, it would be considered within the scope of what is appropriate for Topic 370.

Question 2: Our project does not address Cachexia specifically, although it is definitely a targeted therapy for cancer.

Can we still submit our proposal for this Topic?

Answer 2: Topic 370 is restricted to proposed technologies that would prevent or treat cachexia that is related to cancer.

Cancer therapies that are not proposed to affect a target that is known to be involved in causing cachexia will not be considered for funding under this SBIR Topic. You are encouraged to consider SBIR grant opportunities.

https://www.acquisition.gov/?q=browsefar https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/part-352-solicitation-provisions-contract-clauses/index.html#352.231-70 https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/part-352-solicitation-provisions-contract-clauses/index.html#352.231-70

Question 3: Our company has invented a new technology of making novel bispecific antibodies for cancer therapy. In order to compare our technology with the current approved drug, we used the same drug targets (CD3xCD19) as Amgen's Blincyto. My understanding is that the target therapy includes all agents hitting targets, no matter the agent is BsAb, Ab or chemical. Please clarify for me?

Answer 3: Topic 370 is restricted to proposed technologies that would prevent or treat cachexia that is related to cancer.

Cancer therapies that are not proposed to affect a target that is known to be involved in causing cachexia will not be considered for funding under this SBIR Topic. You are encouraged to consider SBIR grant opportunities.

National Cancer Institute (NCI), Topic 371: Drugs to Exploit the Immune Response Generated by Radiation

Therapy Question 1: We have engineered lymphocytes to target and eliminate cells specifically expressing a molecule induced after radiation therapy—hence this would be a combinatorial cellular therapy approach—to enhance radiotherapy. We see ‘cellular therapies’ listed within the broad range of agents although the title ‘drugs’ suggests more conventional approaches. Would this project be considered within the scope of this Topic?

Answer 1: The development of agents (including cell-based therapies) that can modulate responses (immune) induced by radiation, would be considered to fit within the scope of Topic 371. Regarding your specific aims, you are encouraged to look at the expected activities and deliverables set forth in the Topic description to get a sense for what sort of aims would be most appropriate, as aims that would match up with the expected activities and deliverables would be considered most competitive for award.

Question 2: Can we focus the Phase 1 activities on the use of non-ionizing energy- specifically ultrasound energy- as the immune modulating agent that is used in combination with Radiation Therapy? If so we suggest that the first sentence under the Project Goals heading be modified to address energy-based modalities.

Answer 2: NCI will not be revising the overall Topic description. However, the criteria for agents is quite broad. The two specific requirements for the topic are that: 1) The agents have to modulate the immune components; and 2) The agents have to be tested in combination with radiation.

National Cancer Institute (NCI), Topic 372: Development and Validation of Non-Mouse Reagents to Enable

Preclinical Development of Novel Therapeutics Question 1: Will the use of cell-based high-throughput/high content imaging assays be within the scope of this Topic?

For example, we work on an angiogenesis assay incorporating human genetic variability aiming for an identification of novel anti-angiogennic drug candidates and/or toxicity assessment. Will the use of a zebrafish model be within the scope of this Topic? For example, for toxicity assessment of novel anti-angiogenic drugs using high-content imaging for zebrafish vascular system.

Answer 1: The goal of the Topic is to enable a variety of useful assays in non-mouse, non-human animal models such as rat, rabbit, and canine by funding the development of reagents optimized to the selected model system. While the type of assay and non-mouse, non-human animal models are not restricted, the offeror must justify both the need for the assay and selection of the model system (animal chosen). If the scenario you propose first is focused on human assays, then it would not meet the topic goals. The scenario you propose second could meet the topic goals, but the need and value for both the zebrafish model and reagents optimized to the zebrafish would need to be fully justified in the proposal.

Question 2: I have developed and patented a canine scFv phage display library which enables one to isolate scFv of canine origin to target tumor associated antigens of interest in vivo in canine cancer patients with spontaneous disease. Does this project sound like a good fit for Topic 372?

Answer 2: The project describes appears to fit within the overall scope of what is intended for Topic 372. It will be important to adhere to the expected activities and deliverables listed in the Topic description.

Question 3: The Topic description notes that “A commercial supplier of reagents resulting from this topic is advantageous…” I am a basic science researcher and a veterinarian, so my interest would be in developing the clones and validating the target. Would it be acceptable to state that once my antibodies were validated, I would license them to a commercial company and get a letter of support from that company? Or is a letter not necessary for a Phase I proposal?

Answer 3: Identification of a commercial supplier of reagents would be advantageous in a Phase I proposal – however, it is not a strict requirement and lack of this component would not exclude you from consideration.

National Cancer Institute (NCI), Topic 373: Tools and Technologies for Monitoring RNA Modifications Question 1: Researchers investigating modified RNAs are interrogating structural effects resulting from the modification. The first step in determining whether a modification causes a structural perturbation is to determine the secondary structure. Would a software that enables a user to: (1) upload NMR and other biophysical data of a modified RNA, (2) upload NMR and other biophysical data of the control unmodified RNA, and (3) analyze both sets of data to accurately determine the secondary structure of the RNAs be of interest to the NCI under the SBIR Topic?

Answer 1: No - the focus of this SBIR topic is on the development of assays or tools to detect or monitor covalent modifications of eukaryotic RNAs. Determining the structural perturbations induced by RNA modifications is not within the scope of this Topic. You are encouraged to consider SBIR grant opportunities.

National Cancer Institute (NCI), Topic 375: Diagnostic Imaging for Cancer Immunotherapies Question 1: We are unsure whether our project would be a better fit for Topic NIH/NCI 375 or Topic NIH/NCI 376.

Answer 1: If the specific aims of your proposed research focus on immunotherapy, Topic 375 would likely be more appropriate. If the specific aims of your proposed research focus on the tumor microenvironment, Topic 376 would likely be more appropriate. Also, it is recommended that you read through the Questions & Answers provided for both Topics to assist you in making this determination.

Question 2: We are considering submitting a proposal on development of imaging tracer for imaging PD-L1 on tumor cells. If successful, this tracer will be used for selection of patient for therapy with approved drugs for stimulating immune response. However, we are in doubt about whether to apply under Topic NIH/NCI 375 or under Topic NIH/NCI 376.

Answer 2: Based on the description you have provided, we believe Topic 375 would be the better fit for your potential proposal.

Question 3: Acceptable imaging modalities listed in the Topic description include but are not limited to: "optical imaging, PET, SPECT, or MRI." Will sample-driven histological imaging modalities (e.g. multiplex immunofluouresence or immunohistochemistry on tissue biopsies) be considered on equal footing as the non-invasive methods listed in the solicitation?

Answer 3: Innovative projects based on sample-driven histological imaging modalities will be considered as within the scope of this Topic if they can be used to identify patients who are likely to respond to cancer immunotherapies, evaluate the efficacy and potential toxicities of the treatment, and/or monitor cancer patients’ prognosis.

Question 4: Would a proposal that used a mouse cancer model be appropriate for this topic?

Answer 4: Yes, using a mouse cancer model is appropriate for this Topic.

Question 5: Would a proposal to develop an optical microscopy solution for diagnostic and/or mapping tumor micro-environment in prostate cancer be appropriate for this Topic?

Answer 5: Topic 375 is focused on diagnostic imaging for cancer immunotherapy. The development of an optical microscopy solution for diagnostic and/or mapping tumor microenvironment in prostate cancer would not have enough of a focus on immunotherapy to be considered within the scope of this Topic, unless the focus on immunotherapy were increased.

National Cancer Institute (NCI), Topic 376: Imaging-Based Tools for Longitudinal and Multi-Dimensional Mapping of the Tumor and its Microenvironment

Question 1: We are unsure whether our project would be a better fit for Topic NIH/NCI 375 or Topic NIH/NCI 376.

Answer 1: If the specific aims of your proposed research focus on immunotherapy, Topic 375 would likely be more appropriate. If the specific aims of your proposed research focus on the tumor microenvironment, Topic 376 would likely be more appropriate. Also, it is recommended that you read through the Questions & Answers provided for both Topics to assist you in making this determination.

Question 2: If we propose an imaging tool for mapping specific cancer, for example lung cancer, would it still fit the objectives of this Topic? Or you are looking for “platform” solutions that would work for every cancer?

Answer 2: This topic is not limited to platform development and proposals to map a specific cancer through an imaging tool would be considered within the scope of this Topic, provided the proposal meets the other goals and deliverables listed.

Question 3: Our measurement technique works on tissue biopsy samples (in-vitro). Is that a conflict with the goals of

Topic 376?

Answer 3: Topic 376 solicits the development of in vivo assays so this proposed in vitro assay would not fit the Topic goals.

National Cancer Institute (NCI), Topic 377: Bridging the Guideline Implementation Gap: Clinical Decision-

Support to Improve Cancer Symptom Management Question 1: I would like clarification on the management of 8 common cancer-related symptoms that have associated national CPGs. Besides the 11 Clinical practice guidelines for cancer supportive care one of the guidelines cover 15 sub-categories that will have similar weight to the other 10 clinical practice guidelines if they were listed separately. Can more than one cancer related symptom be selected from the same clinical practice guideline?

Answer 1: The proposed project should focus on the management of symptoms caused by cancer and/or its treatment.

While symptom management is a component of survivorship care, the decision support proposed for development is specifically for guideline-based symptom management, including the management of symptoms in cancer survivors, rather than decision-support to implement guideline-based survivorship care more broadly (e.g. screening, risk reduction, exercise, surveillance).

Question 2: Are the sponsors of this Topic interested in responses that focus on treatment identification and management in addition to or instead of symptom management?

Answer 2: No. The focus needs to be on translation of symptom management guidelines into computable algorithms for decision support to improve management of cancer and treatment-related symptoms.

National Cancer Institute (NCI), Topic 378: Mobile Application for Surveillance of Post-Radiation Therapy

Health-Related Quality of Life Question 1: It indicates that a biostatistician would need to be involved. Would you be able to explain their role in this project?

Answer 1: A biostatistician is explicitly mentioned in the context of statistical justification of the planned sample size for usability testing/validation in Phase II. However, in addition, a statistician may be of value throughout the project to help interpret usability testing and workshop results, especially in Phase II.

Question 2: The Topic Description specifies that a Phase I activity is to “perform small scale usability testing with at least 25 cancer patients.” For the purposes of Phase I activities on this specific contract topic, does NCI consider this usability testing to be an activity requiring a Human Subject Protection plan? Or is the required usability testing exempt under one or more of the HHS exemption categories?

Answer 2: NCI does require IRB review for any project involving usability testing of software, which is required under Topic 378. The IRB may decide the project is exempt, or may opt for an expedited IRB review, and either one of these IRB outcomes is acceptable with NCI. For these reasons, NCI does feel it is appropriate to affirmatively address Human Subjects Research through a section within your proposal, in accordance with the instructions set forth in the solicitation – however, in this section, you may address why you feel an exemption is appropriate, if applicable. If NCI feels your justification is not appropriate, you will have an opportunity to resolve any concerns prior to a final award decision being made.

Question 3: We are planning to get primitive data from a hospital's database without identifiable or private information on patients. Since this is a Phase I application, and data is not obtained through the interaction/intervention of patients nor any identifiable or private information on patients, would this be considered Human Subject Research?

Answer 3: See Answer 2, above. Also, note that whether or not a project involves human subjects research is not tied to whether the project is in Phase I or Phase II.

Question 4: Which medical record systems must the final app be able to interface with?

Answer 4: Topic 378 does not require compatibility with specific named medical record systems. However, compatibility with at least one of the major electronic medical record systems is encouraged, and would be a significant strength.

Question 5: Regarding the workshop required in Phase I to deliver a report of issue toxicities on the proposal: Is there an anticipated form for the workshop to take? Is there a deliverable for this workshop?

Answer 5: There is not a required format for the workshop, offerors may use their professional judgement, in accordance with the stated goals listed in the Phase I Activities and Deliverables description. The deliverable for the workshop would be to describe its outcome in the first quarterly technical progress report.

Question 6: Question regarding the use of the CTAE: Can we supplement the NCI instrument with follow up questions and perhaps even pictures or other recording devices?

Answer 6: It is fine to supplement PRO-CTCAE as you suggest. Topic 378 does not prohibit that.

National Cancer Institute (NCI), Topic 379: Software Enabling Data Integration from Wearable Sensors to

Generate Novel Analytics for Cancer Patients Question 1: Is there a particular sensor (e.g., fitbit or apple watch) or sensor signal (e.g., PPG, GSR, accelerometry, biochemical measures) on which you would prefer initial efforts (e.g., Phase I work) to focus, that could then be expanded on as the effort progresses?

Answer 1: NCI is interested in initial work with sensor signal(s) from bimodal wearables (HR+accelerometer, Apple, Fitbit, etc.) and any other wearable or implantable device currently used to measure biochemistry (e.g., Profusa, Dexcom, etc.).

Question 2: Is real-time information delivery to the patient desired?

Answer 2: Not initially, although ultimately this may be a desired target audience. For now, the focus should be on targeting clinicians and cancer researchers looking to implement their respective cohorts and/or solutions in a “bring your own device(s)” approach.

Question 3: What is the desired level of fidelity of information delivered to the patient, as this might have implications for FDA approval (e.g., your heart rate is high, which with your doctor vs. you may be having an adverse reaction to therapeutics, seek immediate help)?

Answer 3: The desired level of information to the patient should not be the focus of the initial prototype. It is desirable to have the ability to eventually open up more information to the patient, at the discretion of the clinical researcher or clinicians utilizing the platform.

Question 4: Is real-time availability of information to clinicians a goal?

Answer 4: Yes, or at a minimum, continuous, in a “fit-for-purpose” manner (e.g. measurement device 1 data per hour and measurement device 2 per 3.5 hours, etc.). The optimum goal will be to have a platform that can uptake data from multiple external/passive/wearable sources as they stream and integrate together relative to time (e.g., multiple data streams by which could be processed with novel predictive analytics). Subsequently generated data streams and analytical predictions/assessment could then be used by 1) researchers to understand progression and the implications / deviations in patient behavior or other biological parameters that are not currently understood at the temporal granularity necessary to utilize in support of clinical decisions; or 2) by clinicians whom already have clear prognostic understanding of particular biological parameter(s) and need a convenient tool to monitor in aid of the current standard of care.

Question 5: The topic indicates that completely passive monitoring is the eventual goal. Is any interaction with the participant acceptable? If so, how much interaction with the patient is acceptable (e.g., cross-daily requests for symptom ratings vs. no interaction)?

Answer 5: Complete passive monitoring possibly, yet without removal of caregiver / patient interactions necessary for optimal delivery and patient outcomes (i.e., not for patient isolation solely because they are passively monitored by multiple metrics). As far as acceptability of patient interactions, yes, caregiver / patient interaction of symptoms through platform is encouraged.

Question 6: Would you like to see a user…