2_BARDAs Responses to Questions Regarding AOI 9.7.pdf

BARDA BAA Amendment 38 Q&A Attachment

BARDA’s Responses to Questions Regarding AOI 9.7 March 3, 2023

Note: The number of pages and attachments in the responses are referenced to the BARDA BAA Amendment 37.

Question 1: In the Transfer of Obligation Table of the Draft Protocol Synopsis (page 20), there is mention of preparing and translating diaries. There is no specific diary mentioned in the Schedule of Assessments (SOA). Please clarify if a patient diary is expected.

Response 1: This was an error in the Transfer of Obligation Table. We do not require the preparation and translation of diaries in the trial. Therefore, this information is removed in the updated Transfer of Obligation Table under Amendment 38.

Question 2: Please clarify if there are any comparator agents to be included in the trial as mentioned in the Transfer of Obligation Table of the Draft Protocol Synopsis (pages 15 and 21). What are the potential sponsors sourcing the comparator agents?

Response 2: This was an error in the Transfer of Obligation Table. We do not have any comparator agents in the trial. In each cohort, the active drug will be compared to the matched placebo on top of the standard of care. Please see the updated Transfer of Obligation Table under Amendment 38.

Question 3: In the Transfer of Obligation Table of the Draft Protocol Synopsis (page 13), the offeror is asked to "plan, conduct and attend investigators’ meeting(s)." We assume this is one Investigator Meeting per sponsor and IP cohort - i.e., 3 planned with potential adaptive design to include others.

From a budget perspective, we will budget for at least 3 Investigator Meetings; each of these meetings would include a general session to cover the master protocol with separate break-out sessions per meeting to cover each of the cohort's specific protocol appendices. Please confirm if this is an appropriate interpretation of the number of investigator meetings to budget for.

Response 3: Three investigator meetings (one per company/product/cohort) are expected.

Question 4: In the Transfer of Obligation Table of the Draft Protocol Synopsis (pages 20 and 21), this section discusses the management of an ECG vendor; however, there is no ECG assessment listed on the Schedule of Assessments (SOA). Please confirm the time points when ECGs will be collected and if these will be triplicate ECGs so we can obtain an appropriate quote from a central ECG vendor.

Response 4: Please provide the budget with the assumption that all three therapeutic candidates will need a baseline ECG assessment locally. However, no ECG assessment from a central vendor is required.

The ECG assessment may need to repeat on treatment and/or at a follow-up visit for a specific product.

It will be determined after the therapeutic candidates are identified for inclusion in the trial.

Question 5 (The Draft Protocol Synopsis - Specimen Collection and Processing and Schedule of Assessments, pages 9 - 12): As a general question pertaining to all the laboratory samples - can you please define which labs are tested locally versus centrally or is this left to the offeror's discretion to define? For example, for the safety labs specifically, the SOA table indicates a central lab; for the other laboratory samples particularly those which may be done as part of Standard of Care, such as blood cultures, microbiological diagnostic testing, and biomarker testing - where is it expected that the testing will be performed?

Response 5: Sample storage and testing for safety laboratory assessments and biomarkers will be in a central lab. Microbiological diagnostic tests will be performed locally.

Question 6 (The Draft Protocol Synopsis - Specimen Collection and Processing and Schedule of Assessments, pages 9 - 12): Please confirm whether we should include PBMC isolation within our laboratory quote, or will this be performed locally and only the isolates will be sent for sample storage?

Response 6: Please provide the budget with the assumption that PBMC isolation will be performed locally (e.g., < 8 hours after the blood collection) using one of the methods (density-gradient centrifugation, fluorescence-activated cell sorting/FACS, or magnetic-activated cell sorting/MACS). The PBMC isolation and cryopreservation protocol and/or references should be included in Appendix in the full proposal. In addition, please note all the blood samples (serum, plasma, whole blood, and cryopreserved PBMCs) will be stored at -80°C in a central lab for biomarker assays and future research use.

Question 7 (The Draft Protocol Synopsis - Specimen Collection and Processing and Schedule of Assessments, pages 9 - 12): Please confirm for the 2.5mL PAXgene RNA sample collection – should we assume any RNA isolation services on these samples or storage only?

Response 7: Please provide the budget with the assumption that frozen PAXgene Blood RNA tubes will be shipped to a central lab for RNA purification using a commercial nucleic acid purification kit (e.g., PAXgene Blood RNA Kit). The PAXgene Blood RNA tube collection/processing/shipping protocol and RNA isolation protocol should be included in Appendix in the full proposal. In addition, please note all the RNA samples will be stored at -80°C in a central lab for biomarker assays and future research use.

Question 8 (The Draft Protocol Synopsis - Specimen Collection and Processing and Schedule of Assessments, pages 9 - 12): Please confirm for the chest radiography (x-ray or CT) required at screening if this will need to be read by a central reader.

Response 8: Radiography is required at baseline locally. No central reading is needed.

Question 9 (The Draft Protocol Synopsis - Specimen Collection and Processing and Schedule of Assessments, pages 9 - 12):

In the Schedule of Assessments (SOA), Footnote 10 states, "Patients are expected to come back for in-person visits or use home health care services."

In the SOA, Footnote 11 states, "Home health care services may be considered at Days 22, 60, and 90 if the subject is discharged to assess clinical status (ordinal scale), hospital readmission, and mortality only."

Page 2 of the protocol synopsis, study design section states, "Subjects discharged from the hospital will be asked to attend study visits on Days 15, 22, 30, 60, and 90. Home health care services may be considered for patient follow-up visits post-discharge from the primary facility."

Page 9, under Participant Duration, states, "Home health care services may be considered for patient follow-up visits as needed post discharge from the primary facility."

Please confirm whether home health care services should be considered for all possible post-discharge visits, including Days 15, 22, 30, 60, and 90.

Response 9: Please provide the budget with the below assumption for post-discharge visits:

• 30% of the patients will die

• 55% of the patients will have in-person visits on Days 15, 22, 30, 60, and 90

• 15% of the patients will have home health care services on Days 15, 22, 30, 60, and 90

Question 10: Due to the nature of the 3+ therapeutic agent platform trial and current unknown investigational products/agents, please confirm that AOI 9.7 CRO offerors are exempt from submitting the following attachments (page 85; Table 2 of the BARDA BAA Amendment 37):

- Animal Welfare

- Intellectual Property

- Use of Select Agents

- Target Product Profile (TPP)

- Supporting Data

- FDA Communication

Response 10: The therapeutic candidates for the phase 2 ARDS trial have not been determined at this time; therefore, please provide a short statement “BARDA has not determined the therapeutic candidates for the phase 2 ARDS screening trial; therefore, the information regarding XXX (the required attachment from the mentioned list in your question) is not available at this time” in the full proposal if applicable.

Question 11: Please confirm that the offerors for AOI 9.7 are not required to submit a new or updated Quad Chart (page 56 of the BARDA BAA Amendment 37, Section 2.1).

Response 11: A white paper with an initial Quad Chart is not required for AOI 9.7. However, a Quad Chart in the required template (in Attachment 5) is needed according to Table 2 Technical Proposal Attachments (page 85) in Part VI: Full Proposal Instructions (Stage 2).

Question 12: Are the offerors for AOI 9.7 required to submit biographical sketches in the NIH bio-sketch format for Key Personnel (page 85, Table 2 of the BARDA BAA Amendment 37) or can we utilize our company-specific CV/resume format?

Response 12: A biographical sketch in the NIH bio-sketch format (in Attachment 9) that documents key personnel's qualifications and experience for a specific role in related projects is required based on Table 2 Technical Proposal Attachments (page 85) and the description of a biographical sketch (page 88).

Question 13: On page 94 of the BAA, in Table 3 “Cost Proposal Attachments”, the link for “Small Business Subcontracting Plan” results in “Page Not Found”. Could you please provide a valid link.

Response 13: Please use the attached Small Business Subcontracting Plan, if applicable.

Question 14: Other than the FAR requirements listed throughout the RFP document, will a list of required FAR/HHSAR clauses be provided?

Response 14: The required FAR/HHSAR clauses will be provided to organization(s) that are selected for award.

Question 15: Does Attachment 8 – Cost Certification need to be provided with the offeror’s proposal or once a final cost has been negotiated?

Response 15: If applicable, cost certification should be provided with the offeror’s proposal and with any subsequent revisions to the proposal.

Question 16: Would it be sufficient to provide an estimate for the options as a ROM in the business narrative and not fully priced within the price proposal as the template does not include options.

Response 16: Options must be fully priced. Offerors may adjust the template to fit the scenario of their cost proposal.