AMENDMENT 4_75N91024R00006_CO executed.pdf

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75N91024R00006 x x

1 copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted ; or (c) By separate letter or electronic communication which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGEMENT TO BE

RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR

OFFER. If by virtue of this amendment you desire to change an offer already submitted , such change may be made by letter or electronic communication, provided each letter or electronic communication makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

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NCI-EXEC

Bethesda, MD 20892-7511 National Cancer Institute National Institutes of Health

13. THIS ITEM ONLY APPLIES TO MODIFICATION OF CONTRACTS/ORDERS. IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

12. ACCOUNTING AND APPROPRIATION DATA (If required) is not extended.is extended, Items 8 and 15, and returning

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended , by one of the following methods: (a) By completing

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

FACILITY CODE CODE

10B. DATED (SEE ITEM 13)

10A. MODIFICATION OF CONTRACT/ORDER NO.

9B. DATED (SEE ITEM 11)

9A. AMENDMENT OF SOLICITATION NO.

CODE

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP Code)

7. ADMINISTERED BY (If other than Item 6)CODE 6. ISSUED BY

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4. REQUISITION/PURCHASE REQ. NO.3. EFFECTIVE DATE2. AMENDMENT/MODIFICATION NO. 5. PROJECT NO. (If applicable)

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AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

CHECK ONE A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority) appropriation data, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

E. IMPORTANT: Contractor is not is required to sign this document and return ______1____________ copies to the issuing office.

ORDER NO. IN ITEM 10A.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

The purpose of this amendment is to respond to questions regarding Solicitation No.

75N91024R00006 that were received by the applicable due date and time. In addition, a replacement Appendix A Technical Proposal has been provided to correct a typo in one of the

"Objectives". See attached Q&A under General for further details. The due date for the submission of proposals is unchanged.

Offerors are required to acknowledge EACH Solicitation Amendment by including EACH Standard

Form 30 (SF-30) signed by your organization's signature authority and are required to be submitted with your proposal.

PROPOSAL DUE DATE: FEBRUARY 29, 2024, 5:00PM EDT (Unchanged)

16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)15A. NAME AND TITLE OF SIGNER (Type or print)

15C. DATE SIGNED 16B. UNITED STATES OF AMERICA 15B. CONTRACTOR/OFFEROR 16C. DATE SIGNED

(Signature of person authorized to sign) (Signature of Contracting Officer)

MANDIE S. WHITE

STANDARD FORM 30 (REV. 11/2016)

Prescribed by GSA FAR (48 CFR) 53.243

Previous edition unusable

Except as provided herein, all terms and conditions of the document referenced in Item 9 A or 10A, as heretofore changed, remains unchanged and in full force and effect .

2/23/20244

To all potential offerors

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Solicita�on 75N91024R00006 Amendment 4 2

ARPA-H SBIR SOLICITATION 75N91024R00006

Amendment #4 Questions and Answers

General:

• For Topic ARPA-H 03 under Phase I Final Exams (#3) has been revised to

“200kbps” from “200nkbps”. The rest of the topic remains unchanged.

• The response to Question #29 in Amendment #1 (dated 2/7/2024) has been revised from "We are not looking for existing biomarkers.” to “will be prioritizing existing approaches that have already demonstrated retrieval of predictive biomarkers.”

• The Appendix A, Technical Proposal, Objectives has been revised from “State the specific objectives and anticipated end results of the proposed Phase II effort.” to “State the specific objectives and anticipated end results of the proposed Phase I effort.” The corrected document has been provided as an attachment with this amendment.

• Please note, Amendment 5 is forthcoming and will include the final batch of questions from the Q&A period. Amendment 5 is anticipated to be the final amendment for this solicitation.

1. QUESTION: If we submit early and Amendments come out after the submission, are we able to pull it back? Our concern is if we submit early and more Amendments come out we won’t have the signed Amendments signed and attached. If we do submit prior to the 29th and another amendment comes out can we pull it back? This is our first submission to ARPA H and we don’t want to submit early if it can be replaced or pulled back.

ANSWER: Please refer to the eCPS FAQ page. However, we recommend organizations submit their proposals once they are finalized only. Please see above regarding future amendments.

2. QUESTION: The solicitation closes Feb. 22, 2024. What is the expected time to complete review/evaluation and make award decisions? Also, what would be the approximate time from an award granted to when funding began?

ANSWER: It typically takes a few months to complete evaluations and make awards decisions. The anticipated award date is on/around late September 2024; therefore, you could assume this as the estimated start date for work.

Solicita�on 75N91024R00006 Amendment 4 3

Small businesses may invoice within a month upon contract award. In addition, the Due Date for proposals has been extended. See Amendment 3 of the solicitation.

3. QUESTION: I have a couple of questions regarding the SBIR announcement, in particular Topic ARPA-H 05 - Saving Baby Hearts.

• Can a non-U.S. resident person (Canada) be a consultant on the proposal?

ANSWER: Please refer to Section 6.2 Offeror Eligibility and Performance Requirements of the solicitation.

• The announcement mentions travel (e.g. conferences) is only allowed with

Contract Officer approval. Does this restriction also include travel between clinical sites (e.g., the P.I. traveling to a clinical site at study start)?

ANSWER: Please see Section 8.13. Costs for travel funds. Travel related to the needs of the project can be proposed but need to be justified in the Business Proposal.

Can the 500 health + 100 CCHD (600 total) clinical study be used for AI training? Are there any restrictions on how the study data should be used in validation (any thoughts on study design)?

ANSWER: We are open and flexible on the study design and happy to consider various study design approaches. The key goal is to create confidence that the approach has been validated to some extent. In general, the training and validate data sets should be separate, however.

Can the UI for the ultrasound device provide initial placement guidance (e.g. not enough gel, move left/right) prior to beginning the 5-minute scan?

ANSWER: Yes, the UI ideally would create the best chance for a high quality and successful scan, and the “5 minutes” applies to the scan time, not to the placement time.

Solicita�on 75N91024R00006 Amendment 4 4

The announcement mentions "concluding with a go-to market strategy", Is that something to be included in a final report? Is development of that strategy funded by the SBIR or is it to be developed with external funds (i.e.

are there parts of a go-to market strategy that are not part of the restriction that there shall be no market research)?

ANSWER: The goal here is to ensure that there is some line-of-sight to commercialization and broader access to the technology. This can be satisfied by ensuring that there is a commercial partner or other approach to ensuring the technology has a path to being used widely.

4. QUESTION: Our company is excited to be preparing a Direct to Phase II submission for the ARPA-H SBIR 05 - Saving Baby Hearts: Fully Autonomous Neonatal Echocardiography for the Diagnosis of Critical Congenital Heart Disease.

• We understand SBIR 05 to be a firm-fixed price contract, and budget to be built around $3.5M including Direct and Indirect costs. Would the 7% SBIR fee be added on top of the proposed budget?

Regarding TABA, would the $50,000 be expected to be included in full budget amount, or on top of it?

ANSWER: Proposed Fee and TABA is included within the maximum budget ceiling of $3.5M.

• Is there a “pricing form” on the eCPS portal?

ANSWER: The pricing proposal can be found within the Business Proposal Appendix (either Appendix B or D depending if it’s a Phase I or II submission).

5. QUESTION: We want to propose a clinical trial to validate our diagnostic tool to help with ICI treatment efficacy based on a patient's circadian rhythm status.

Is that fundable as a phase II within Topic 4? Two of our preferred collaborators are academic institutions and companies in Germany. Are they permissible as sub-contractors or consultants for this grant?

ANSWER: As per the solicitation: “Applications focusing solely on basic science research such as: biomarker identification in in vitro and/or animal models, generation of new animal models and/or mechanistic studies, are not

Solicita�on 75N91024R00006 Amendment 4 5 considered responsive.” Hence, the proposed trial would not be considered responsive.

In addition, please refer to Section 6.2 of the solicitation, "For both Phase I and Phase II, all research or research and development work must be performed by the SBC and its subcontractors in the United States. Based on rare and unique circumstances, deviations from these performance requirements may be considered on a case by case basis. Deviations must be approved in writing by the funding agreement officer after consultation with the agency SBIR Program Manager/Coordinator."

6. QUESTION: Topic area -04 lists the following: Proposers must identify an appropriate number of clinical partners able to collect data in patients treated with neoadjuvant immunotherapy alone (as opposed to the standard of care chemotherapy + immunotherapy). Does this mean that the clinical partners must be identified in the course of phase one (i.e., as a deliverable) or that the data collection itself is a deliverable and the clinical partner must already be identified?

ANSWER: The identification and confirmation of clinical partners sufficient for phase two platform validation is the phase 1 deliverable.

7. QUESTION: Below are our questions for ARPA-H SBIR SOLICITATION

75N91024R00006, ARPA-H 04 - Personalized medicine platform for predicting response to immunotherapy:

• Is the Phase II clinical trial intended to cover patients with different types of cancers? Or is it sufficient to do a trial in just one of the cancer types for which the platform has previously validated utility/performance in Phase I?

ANSWER: One cancer type is sufficient.

• While the solicitation states "It is strongly suggested that proposals adhere to the above budget amounts", will applicants be disqualified for requesting optional budget amounts to fully fund the appropriate level of prospective clinical trials required? Or are

Solicita�on 75N91024R00006 Amendment 4 6 applicants expected to seek out how they intend to obtain the additional funding.

ANSWER: Applicants are not disqualified for technical review if their proposal submission is over the stated ceiling; however, no subsequent awards shall be made above the stated ceiling. Therefore, applicants who seek out additional funding shall address this in their proposal where additional information will be sought during the negotiation phase, if moved forward. Please also reference the SBIR Life Cycle Certification and SBIR Funding Agreement Certification Forms.

• The prior Q&A #20 stated that "The term "neoadjuvant" was included accidentally and has been removed under this Amendment. The main aim of the topics refers to all uses of immunotherapy, to reduce instances when immunotherapy is given to patients who will ultimately not respond." (emphasis added). As the prior question noted, Immunotherapy is used in many settings: neoadjuvant, adjuvant, perioperative, and as definitive treatment. Does this answer mean that proposals must address "all [of the] uses of immunotherapy" listed above or will a single treatment setting be sufficient?

ANSWER: A single treatment setting may be sufficient if it is rationally justified. However, proposed technologies capable of predicting response across a number of treatment settings is preferable.

8. QUESTION: We are interested in applying for ARPA-H 04 - Personalized medicine platform for predicting response to immunotherapy. We are a small business developing a Mass-spec Proteomics data analysis platform that significantly increases data quality and number of hits. We believe we can greatly contribute to the ARPA-H Personalized Medicine Initiative.

We have the following questions:

• Would this be in the scope of your proposed areas under ARPA_H 04?

ANSWER: The technology itself is responsive. However, as per the solicitation: “Applications focusing solely on basic science research such as: biomarker identification in in vitro and/or animal models, generation of new animal models and/or mechanistic studies, are not

Solicita�on 75N91024R00006 Amendment 4 7 considered responsive.” If the proposers have sufficient preliminary data from known responder animal models, then their submission would be considered responsive.

• Would we be able to access patient/proteomics data from any ARPA-H or other government projects?

ANSWER: At this time, we are not able to offer this.

• If we plan to collect data and samples, at what phase in the application process do we need to disclose a confirmed partner/data source or is there flexibility to change that data source if/once the application moves forward?

ANSWER: At the end of phase 1.

9. QUESTION: I would like to submit a few questions in regards to H-03 Continuous Monitoring of Vascular Health using Smart Biometric Implantables.

• In the Objectives section it states: “the stent will be powered by and transmit data to a health app wirelessly, and continuously monitor CV biomarkers including vessel occlusion, flow, arterial pressure, and troponin levels”. But later in the Activities and Deliverables there is no mention of occlusion or any requirements related to it or restenosis measurement. Can you please clarify if occlusion measurement is specifically related to restenosis for the requirement, or should we also consider thrombosis as occlusion?

ANSWER: Consider both restenosis and thrombosis.

• In Phase 1 Final Exams #3 the data transfer rate is given as

>200nkbps. Is this a typo? Should it be >200kbps?

ANSWER: Yes, >200kbps

• On page 23, Proposal Fundamentals, 6.2 Offeror Eligibility and Performance requirements it states that all R&D work must be performed by the SBC and its contractors in the US. But then goes on to

Solicita�on 75N91024R00006 Amendment 4 8 say: “Based on rare and unique circumstances, deviations from these performance requirements may be considered on a case by case basis. Deviations must be approved in writing by the funding agreement officer after consultation with the agency SBIR Program Manager/Coordinator.” There is no mention of the deviation request timing. If we would like to seek a non-US based contractor for a very specific need, should that be done prior to proposal submission?

ANSWER: A deviation request would take place at the negotiation stage if the proposal was selected for potential award. However, prior to the Contracting Officer even requesting a deviation, the offeror would be asked to go back and rework their proposal to be in compliance. If the offeror cannot come into compliance with the rule set forth in the solicitation, a detailed justification would be requested of the offeror as to why it cannot be met and efforts made to come into compliance.

Deviation requests would have to be supported by the NCI SBIR Development Center. IF it were approved at this stage, it would then get sent for review with no guarantee of approval.

10. QUESTION:

• The original solicitation (Jan 23) states that "Due to the urgency of this public health need, projects supporting the validation of an already existing approach will be prioritized." However, the answer to question #29 in the Amendment (Feb 7) states that "We are not looking for existing biomarkers". Can you clarify the goal of prioritizing existing approaches while not utilizing existing biomarkers?

ANSWER: This answer was added to the Feb 7 amendment by mistake and has been corrected. We will be prioritizing existing approaches that have already demonstrated retrieval of predictive biomarkers.

• For example, multiple PD-L1 targeted antibodies have been approved for use as an IHC based companion diagnostic to predict ICI response in patients. There is variation in the predictiveness of this approach based on limitations in IHC workflows. If we are proposing a method for

Solicita�on 75N91024R00006 Amendment 4 9 enhancing the workflow for PD-L1 detection, is this considered an appropriate fit for ARPA-H04?

ANSWER: Yes, this technology appears appropriate for ARPA-H 04.

• Phase I Activities and Deliverables include "IRB submission and approval (pilot study in adult population)". We understand this to mean that the IRB can be obtained during Phase I and is not a prerequisite for the submission. Is our understanding correct?

ANSWER: This is correct.

11. QUESTION: Does the patent stay with the company that's formed (us) or will ARPA-H have the patent for any discoveries/ideas that come to fruition? And is everything shared with you confidential?

ANSWER: Please refer to FAR 52.227-20 Rights in Data-SBIR Program (May 2014). Inventions and patents remain with the small business even after contract award. The SOW will be attached to the award document; however, the technical proposal application states under the Proposed Statement of Work section, “Please limit the proposed Statement of Work to no more than 5 pages. The Statement of Work will be attached to the award document. Please do not include confidential or propriety information.”

12. QUESTION: With regards to ARPA-H’s “Research and development (R&D) that will contribute toward Advanced Research Projects Agency for Health (ARPA- H) mission needs and Small Business Innovation Research (SBIR) program objectives”, we have a fundamental question / clarification to ensure we submit we comply with the solicitation:

We were considering applying under the proposal ARPA-H 04 “Personalized medicine platform for predicting response to immunotherapy”. From reading the entire solicitation and this ARPA-H 04 Topic in particular, it is angled more towards oncology and cancer research (in addition to the separate Cancer Moonshot solicitation). Would our solution comply with this Topic, as presented above, and be weighted equal with regards to topic and importance to cancer / oncology submissions? We fully understand you are not providing us with any guidance, or indication on whether our application

Solicita�on 75N91024R00006 Amendment 4 10 would be accepted, our question is merely to confirm if our solution and application would comply with this sub topic ARPA-H 04 and not be weighted differently as it is a substance use disorder where individuals develop or have developed resistance or tolerance to opioid and therefore susceptible to addiction which has led to the current US opioid epidemic.

ANSWER: This funding call is mostly targeted to solid cancer applications, and specifically to those which have a relatively small percentage of patients who respond, yet many more patients are given a costly, and ultimately ineffective therapy.

13. QUESTION: On page 71 it states: “Prior, Current, or Pending Support of Similar Proposals or Awards.

1) Name and address of the Federal Agency(s) or HHS Component, to which a proposal was submitted, will be submitted, or from which an award is expected or has been received.

2) Date of proposal submission or date of award.

3) Title of proposal.

4) Name and title of principal investigator for each proposal submitted or award received.

If a proposal submitted in response to this solicitation is for essentially equivalent work (as defined in this solicitation) as another proposal that was funded, is now being funded, or is pending with a federal agency, you must make the appropriate certification in Appendix A, as well as provide the following information in Appendix C:”

Is it only if we have similar work we are working on or do you want to see something like the attached?

ANSWER: Per the solicitation, please detail prior, current, or pending support of similar proposals or awards – and if this is applicable, please complete #s 1-4 as listed above.

Solicita�on 75N91024R00006 Amendment 4 11

14. QUESTION: I have three specific questions for ARPA-H-04 as a Phase II project:

• Will applying for the Phase II observational clinical study be viewed as too aggressive and that we should first apply for the Phase I?

ANSWER: No.

• Would the inclusion of patients treated with chemo + ICI in our proposal be supported by this ARPA-H program? In the clinical setting, patients are often treated with chemo + ICI. We believe that we can breakdown the contributions of each component in our platform by treating the PDOTS in our platform with a negative control, the ICI, the chemo and the chemo combination.

ANSWER: As per the solicitation: “Alternative solutions could be proposed that would disentangle the effect of chemotherapy and immunotherapy, if the two are given concomitantly.“

• Does this proposal require two cancer types? We are planning on focusing on NSCLC or CRC to better power the study but will include both if two cancer types are required.

ANSWER: No, focusing on one cancer type is acceptable.

15. QUESTION: Our company has experience writing to DoD and NIH SBIR topics.

Because the review process appears similar to NIH SBIR review panels, are we to assume that a similar audience such as a combination of academic and industry experts will review the proposals? Or will reviews be solely completed by ARPA-H officers such as is the practice within other DoD agencies?

ANSWER: ARPA-H is exempt from the NIH peer review process. An ARPA-H Program Manager will provide a technical evaluation for each proposal submitted under their topic.

16. QUESTION: What technology readiness level (TRL) does ARPA-H define as the deciding point between a Fast-Track and a Direct-to-Phase II submission? Will Fast-Track proposals be seen as less responsive than a Direct-to-Phase II submission due to the higher price point?

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ANSWER: Each topic will specify the type of SBIR mechanism that will be accepted. Which mechanism you choose depends on the amount of preliminary research and technology development you have done in advance of applying to ARPA-H.

• Fast-Track: The Fast-Track process allows you to submit both the Phase I and Phase II in one application for review. The Fast-Track mechanism can minimize the funding gap between phases but requires a fully developed Phase II application at the time of submission.

• Direct to Phase II: If your project has already demonstrated feasibility and you have significant amounts of preliminary data but you have not received a Phase I SBIR or STTR, you can apply for a Direct to Phase II award.

17. QUESTION: With regard to the RFP for ARPA-H 06 - Improving Identity and Access Management with Clinical Context, we were hoping to ask a few questions:

• The RFP stipulates that “custom agents” are out of scope for this topic.

However, in the Q&A of the first amendment, it says that a smartphone app is within scope. Can software be installed on endpoints (PCs/workstations/mobile devices/…) as part of a solution that streamlines access for clinicians and administrators? Could you please clarify?

• In the requirements, it mentions automation that can sense insecure IAM configurations -- is that a requirement that must be included in a solution and/or is a solution that reduces the chances/opportunities for insecure configurations also within scope?

ANSWER: The approach a researcher takes to this challenge is open but installing agents on medical devices has historically been fraught with problems. In addition, ARPA-H would prefer to see an open-source solution that can have the largest impact, rather than a commercial solution with less impact. Submissions that both sense AND suggest a solution to an insecure IAM configuration are ideal but a submission that only identifies but does not suggest solution for insecure IAM configurations will also be considered.

Solicita�on 75N91024R00006 Amendment 4 13

18. QUESTION: For ARPA-H 06, the last activity in the solicitation is: “Present this model to small, rural hospitals for feedback, approval and support.” Is this to be done and completed during Phase I? Also, what is "rural” defined as?

ANSWER: This is a Phase I activity. In this context, “rural” is referring to rural, critical access hospitals as previously mentioned in the topic.

19. QUESTION: Language p. 21 under subsection Business Proposal: "The award will result in a Firm-Fixed Price (FFP) contract type.". Language p. 26 under subsection 6.10 Phase II Award Information, "Phase II contracts may be either firm fixed price or cost-reimbursement type." Can you confirm which language applies to ARPA-H 05 Saving Baby Hearts?

ANSWER: Phase II SBIR awards made under this solicitation will be completion-type research and development contracts. The NCI Office of Acquisitions will typically make SBIR contract awards on a Fixed-Price basis, with payment tied to delivery of technical reports that reflect best efforts towards completing the research and development tasks set forth in the award document. That said, all awards made as a result of this solicitation, including ARPA-H 05, will be Firm Fixed Price.

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