RFP_Amendment_No_01_(N01TR-17-2004).pdf

“CRO Support for NCATS Bioanalytical Method Development for Biologics”

Amendment of Solicitation No.: RFP N01TR-17-2004

Amendment No.: 01

Amendment date: March 13, 2017

Due Date for Proposals: Tuesday, March 28, 2018 at 5:00 PM EDT

Issued By:

National Center for Advancing Translational Sciences NINDS R&D Contracts Management Branch NIDA Office of Acquisition National Institutes of Health Neuroscience Center 6001 Executive Boulevard Suite 3287, MSC 9531 Bethesda, Maryland 20892-9531

* For FedEx/UPS/Courier/Hand-Delivery, use Rockville, MD 20852

Primary Point of Contact: Secondary Point of Contact:

Jeffrey Schmidt, Contracting Officer Lisa Bielen, Contracting Officer Phone: (301) 402-1488 Phone: (301) 451-7167 E-Mail: schmidtjr@mail.nih.gov E-Mail: lisa.bielen@nih.gov

NAME AND ADDRESS OF CONTRACTOR: To All Offerors

The above numbered solicitation is amended as set forth below. Offerors must acknowledge receipt of this amendment on each copy of the offer submitted. FAILURE OF YOUR

ACKNOWLEDGMENT 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, provided each letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

PURPOSE: to respond to formal questions submitted in response to the solicitation.

All other terms and conditions of the RFP remain unchanged.

RFP No. N01TR-17-2004 RFP Amendment No. 01

RESPONSES TO QUESTIONS

QUESTION 1: Could you please provide further details regarding Biologic A for a better tailored response?

ANSWER 1: The example of Biologic A is a pegylated peptide. At this moment, we couldn’t provide more details on the molecule since it is under an active contract. We use it as an example to illustrate the bioanalytical assay needs for future TRND projects.

QUESTION 2: Are there shared epitopes between Biologic A and PTH?

ANSWER 2: Yes, there are shared epitopes between Biologic A and PTH. As explained in Question 1, this molecule is under an active contract, and it is used as an example to illustrate the bioanalytical assay needs for future TRND projects.

QUESTION 3: Are there unique epitopes on Biologic A not present on PTH?

ANSWER 3: The pegylated peptide has a couple of mutant amino acids which link to the PEG tail. The binding affinity is expected to be different between the pegylated peptide and PTH.

QUESTION 4: Could you please provide details surrounding the problems encountered developing antibodies against Biologic A in the past?

ANSWER 4: As explained, the assay development is under an active contract. We won’t be able to provide more details on the progress of the assay development at this moment.

QUESTION 5: Is there an established neutralization assay that will be transferred to the contractor upon award?

ANSWER 5: TRND Biology will transfer the assays needed for the neutralization assay development.

QUESTION 6: Is Biologic A bispecific?

ANSWER 6: Biologic A is not bispecific.

QUESTION 7: Does Biologic A induce PTH?

ANSWER 7: It is not expected that Biologic A will induce PTH.

QUESTION 8: Is there interaction between Biologic A and endogenous PTH?

ANSWER 8: The interference of endogenous PTH on the bioanalytical assay for Biologic A needs to be assessed in the assay development.

QUESTION 9: Does Biologic A induce or modify related molecules like Calcitonin?

ANSWER 9: Biologic A doesn't directly regulate calcitonin. Indirectly, increased serum calcium level up regulates calcitonin to counter the effect of Biologic A.

QUESTION 10: What is the nature of the therapeutic? (ie, peptide, protein, monoclonal antibody?)

ANSWER 10: The nature of therapeutics for TRND Project varies depending on the final awards to application packages from a solicitation. The current pipeline contains molecules from peptides, pegylated peptides, and engineered human proteins.

The Biologic A listed in the sample task is a pegylated peptide.

QUESTION 11: In Attachment 1: Packaging and Delivery of the Proposal, it is not clear if Offerors should deliver 1 original and 10 copies (Technical Proposal) and 1 original and 5 copies (Business Proposal) to NIDA in paper format and CD-ROM or if the Offeror can deliver in either paper or CD-ROM format. Please advise.

ANSWER 11: Offerors must submit one original hardcopy and ten additional hardcopies of the Technical Proposal; and one original hardcopy and five additional hardcopies of the Business Proposal. In addition to the required hardcopies, Offerors have the option to submit electronic copies of their Technical Proposal and Business Proposal via CD-ROM. Though not required, electronic copies of the Technical Proposal and Business Proposal expedite the review.

QUESTION 12: 2. Is this an analog of an endogenous substance? If yes, does the native form circulate in significant concentrations?

ANSWER 12: Biologic A is a pegylated analog of an endogenous substrate. There is the presence of a native form in the circulation, and its level is expected to be low in patients compared to the healthy subjects. The interference of the native form on the assay for Biologic A needs to be assessed in the assay development.

QUESTION 13: 3. Should the selectivity (PK) and cut point (ADA) be established in disease-state matrix? If yes, what disease-states should be studied?

ANSWER 13: Healthy animals will be used in PK and tox studies. In the efficacy study, a rat surgical model of hypoparathyroidism will be used. It is appropriate to take disease-state conditions into the consideration in the establishment of the assay selectivity and ADA cut point.

QUESTION 14: A target sensitivity of pg/mL range is highly dependent on the quality of antibody generated. QPS plans to bid on tasks #2, 3, 4 but not task #1. The outcome of the task #1 will impact the sensitivity achievable in task #2. Will the sponsor readjust the target LLOQ based on the outcome of task #1?

ANSWER 14: We understand that the sensitivity of an assay will depend on the quality of the antibody. While we are looking for a sensitive and specific assay, we do take the considerations of other factors, such as quality of the antibody and interference of endogenous levels, in the LLOQ establishment.

QUESTION 15: As noted, this bid is related to the PTH active form. QPS has previously supported PTH programs and has validated a PK assay (from a kit) and a cell-based NAb assay fitting the RFP description. At this time, our Translational Medicine department is aware of one kit globally and can imagine that antibody production for this assay will be very challenging.

ANSWER 15: TRND will provide the antibody needed for the assay development if only Tasks 2, 3 and 4 are bided.