TART_Peptides_Pre-Sol_N02CO62603-57.pdf

General Information

Short Title: Production of cGMP TARP Peptides.

Document Type: Pre-solicitation Notice

Solicitation Number: N02CO62603-57

Posted Date: 06/10/2016

Response Date: 06/20/2016

Classification Code: 68 – Chemicals & Chemical Products

NAICS Code: 325414

Contracting Office Address

Department of Health and Human Services, National Institutes of Health, National Cancer

Institute, Office of Acquisitions, 9609 Medical Center Drive, Room 1E128, Bethesda, MD

20892, UNITED STATES.

Description

The National Cancer Institute (NCI), Vaccine Branch, plans to procure on a sole source basis clinical grade TARP (TCR Alternative Reading Frame Protein) peptides under cGMP conditions that shall cover the entire 58 amino acid sequence of the TARP protein as well as include the original two 9 amino acid proteins TARP 27-35 and 29-37-9V from PolyPeptide

Laboratories 9395 Cabot Drive, San Diego, CA 92126.

This acquisition will be processed under FAR Part 12 – Acquisition for Commercial Items and will be made pursuant to the authority in FAR 13.106-1 (b)(2) and 13.501-(a)(1) using simplified acquisition procedures for commercial acquisitions. The North American Industry

Classification System code is 325414 and the employee size standard is 500.

Only one award will be made as a result of this solicitation. This will be awarded as a firm fixed price type contract.

The delivery date is six (6) months after award of order.

It has been determined there are no opportunities to acquire green products or services for this procurement.

The NCI protocols 15-C-0075 and 15-C-0076 were approved by the NCI IRB in

January 2015; with enrollment of the first study subjects in each protocol occurring in May

2015 after Department of Transfusion Medicine personnel had been hired and trained in the manufacture of the multi-eptiope (ME) TARP peptide vaccines. As previously noted, the investigational supply of ME TARP peptides was depleted as a result of additional sterility testing associated with the PDS quarantine that began in June 2015. Consequently, enrollment in both studies has been on hold since September 2015 until a new source of vialed, cGMP TARP peptides could be identified. Completion of these studies is contingent upon manufacturing completion and delivery of the cGMP TARP peptides to the NCI

Vaccine Branch.

A. CONTRACTOR RESPONSIBILITIES

The Contractor shall produce clinical grade TARP (TCR Alternative Reading Frame Protein) peptides under cGMP conditions that shall cover the entire 58 amino acid sequence of the TARP protein as well as include the original two 9 amino acid proteins TARP 27-35 and 29-37-9V.

TARP is a novel protein that is expressed in ~90-95% of prostate and ~50% of breast cancers and is being developed as a therapeutic vaccine to treat these and possibly other cancers. The amino acid sequence of the TARP protein is below:

The use of two 9 amino acid TARP peptides (TARP 27-35 and TARP 29-37-9V) in a therapeutic vaccine platform was investigated in a pilot/phase I clinical trial conducted by the NCI (09-C-

0139/ NCT00972309) in men with stage D0 prostate cancer. The amino acid sequences of the peptides used in this first generation TARP vaccine platform are below:

The study documented that the TARP peptide vaccine was safe, very well tolerated, immunogenic and resulted in a slowing in the rate of PSA rise in the majority of subjects at 24 and 48 weeks. As a result of this success, investigators within the NCI Vaccine Branch have moved forward with the development of a second-generation multi-epitope (ME) TARP peptide vaccine platform comprised of multiple, longer, overlapping TARP peptides that they hypothesize will induce better immune responses and clinical outcomes in a broader patient population.

The overlapping cGMP peptides to be manufactured by the Contractor are 20 amino acids in length (except for the fifth peptide that is 18 amino acids in length), overlap by 10 amino acid residues and cover the entire 58 amino acid TARP protein sequence as specified below.

Specifically, the Contract shall manufacture the following seven cGMP TARP peptides using protected amino acids of non-animal origin in the quantities outlined below:

1. Peptide 1: TARP 27-35 (MPS-326) Length: 9 amino acids Amount: 1.2 gram

Sequence: H- Phe-Val-Phe-Leu-Arg-Asp-Phe-Ser-Leu-OH

Acetate

2. Peptide 2: TARP 29-37-9V (MPS 327) Length: 9 amino acids Amount: 1.2 gram

Sequence: H-Phe-Leu-Arg-Asp-Phe-Ser-Leu-Met-Val-OH

Acetate

3. Peptide 3: TARP 1-20 (MPS-479) Length: 20 amino acids Amount: 1.5 gram*

Sequence: H-Met-Gln-Met-Phe-Pro-Pro-Ser-Pro-Leu-Phe-

Phe-Phe-Leu-Gln-Leu-Leu-Lys-Glyn-Ser-Ser-OH

Acetate

*A higher quantity of this peptide needs to be manufactured due to previously identified solubility issues.

4. Peptide 4: TARP 11-30 (MPS-480) Length: 20 amino acids Amount: 1.2 gram

Sequence: H-Phe-Phe-Leu-Gln-Leu-Leu-Lys-Gln-Ser-Ser-

Arg-Arg-Leu-Glu-His-Thr-Phe-Val-Phe-Leu-OH

5. Peptide 5: TARP 21-40 (MPS-481) Length: 20 amino acids Amount: 1.2

Sequence: H-Arg-Arg-Leu-Glu-His-Thr-Phe-Val-Phe-Leu-

Arg-Asn-Phe-Ser-Leu-Met-Leu-Leu-Arg-Gly-OH

6. Peptide 6: TARP 31-50 (MPS-482) Length: 20 amino acids Amount: 1.2

Sequence: H-Arg-Asn-Phe-Ser-Leu-Met-Leu-Leu-Arg-Gly-

Ile-Gly-Lys-Lys-Arg-Arg-Ala-Thr-Arg-Phe-OH

7. Peptide 7: TARP 41-58 (MPS-483) Length: 18 amino acids Amount: 1.2

Sequence: H-Ile-Gly-Lys-Lys-Arg-Arg-Ala-Thr-Arg-Phe-

Trp-Asp-Pro-Arg-Arg-Gly-Thr-Pro-OH

Each manufactured cGMP peptide shall be verified with the following testing specifications:

TEST SPECIFICATION

Appearance White to off white powder

Identity by MS/MS Correct Sequence

Identity by LC/MS Correct MW + 1 amu.

Identity by Amino Acid Analysis (AAA) Correct amino acid ratios with total recovery within 10% and individual recoveries within

15% of theory, except for Cys, Trp, Ile, Val and Pro whose recovery may be low.

Peptide Purity by RP-HPLC > 95% by area integration (excluding spontaneous methionine oxidation)

Related Substances by RP-HPLC < 5% total

Net Peptide Content (NPC)* > 75%

Counter Ion Content < 15%

Water Content by Karl Fischer < 10%

Residual Trifluoroacetate < 0.25%

Residual Solvents Report Results

Bacterial Endotoxin, LAL test (EU/mg) Report Results

Bioburden (cfu/g) Report Results

Mass Balance 90-105% [ (NPC, Counter ion, H2O)]

*NPC may be determined by Quantitative AAA or Nitrogen Analysis

Each manufactured bulk cGMP TARP peptide shall be delivered following the Contractor’s manufacture, testing and release by arrangement with the NCI, approximately 4-6 months after the order is placed. The bulk cGMP TARP peptides shall be shipped in appropriately packaged, temperature-controlled, regulatory compliant shipping containers and delivered by FedEx to the

Pharmaceutical Development Service of the NIH Clinical Center Pharmacy with all appropriate

CMC, Certificate of Analysis and IND regulatory documentation. FedEx shipping costs and insurance shall be paid for by the NCI Vaccine Branch separate from this contract award.

The cGMP TARP peptides should be shipped to:

TBA

Bethesda, MD 20892-1196

Once received, bulk cGMP TARP peptide shall be formulated and vialed by an independent contractor identified by the Vaccine Branch and confirmed with the FDA and PDS staff into single unit-dose vials for investigational use in the preparation of autologous multi-epitope

TARP dendritic cell vaccines. The branch will also oversee the performance of sterility, stability, storage and other quality control testing and generate finished product specification for each ME TARP peptide.

B. DELIVERY DATE

The NCI estimates the delivery time to be between 4-6 months from the receipt of the award.

Timeline for Product Provision: The cGMP TARP peptides shall be provided to the NCI following manufacture and testing and release. This is generally approximately 3-6 months from placing the official order for the cGMP peptide products.

The Contractor shall provide all supplies and labor necessary to provide the cGMP TARP peptides described in this SOW. Peptide production must occur within 3 months and no later than six months (180 days) from the awarding of the contract.

Peptide Product: The cGMP includes the original 9 amino acid peptides used in the Phase I

NCI protocol 09-C-0139 (TARP 27-35 and TARP 29-37-9V) plus five overlapping multi-epitope

TARP Peptides (detailed above) for a total of 7 peptides in the cancer vaccine.

Proposed Product Use: The original TARP WT27-35 and TARP 29-37-9V and ME TARP peptides will be used in combination to generate a 7 peptide, multi-epitope TARP peptide autologous dendritic cell vaccine. This second generation vaccine shall be studied in patients with prostate and potentially other cancers as a therapeutic treatment for disease.

Guidelines for Manufacture, Testing and Documentation of the TARP Peptide Products:

The Contractor shall follow current Good Manufacturing Practice (cGMP) guidelines in accordance with the CGMP Regulations outlined in 21CFR Parts 210 and 211, in the manufacture and testing of the final, clinical, bulk TARP peptide products. The Contractor shall prepare and complete documentation as tasks are performed. This documentation shall subsequently be reviewed by the QA division of the Contractor and shall include for each peptide all appropriate documentation regarding the peptide amino acid sequence verification, the manufacturing batch records, the testing and specifications previously outlined in this SOW, certificate of analysis and any other manufacturing related information for CMC documentation required for IND filing.

In summary, the Contractor shall provide:

1. 1.2g bulk cGMP Peptide 1 TARP 27-35: H-FVFLRNFSL-OH, acetate, > 95% pure.

2. 1.2g bulk cGMP Peptide 2 TARP 29-37-9V: H-FLRNFSLMV-OH, acetate, > 95% pure.

3. 1.5g bulk cGMP Peptide 3 TARP 1-20: H-MQMFPPSPLFFFLQLLKQSS-OH, acetate, > 95% pure

4. 1.2g bulk cGMP Peptide 4 TARP 11-30: H-FFLQLLKQSSRRLEHTFVFL-OH, acetate, > 95% pure

5. 1.2g bulk cGMP Peptide 5 TARP 21-40: H-RRLEHTFVFLRNFSLMLLRG-OH, acetate, > 95% pure

6. 1.2g bulk cGMP Peptide 6 TARP 31-50: H-RNFSLMLLRGIGKKRRATRF-OH, acetate, > 95% pure

7. 1.2g bulk cGMP Peptide 7 TARP 41-58: H-IGKKRRATRFWDPRRGTP-OH, acetate, >

95% pure

C. PAYMENT

The Contractor shall receive payment after submission and acceptance of all peptides. Payment authorization requires submission and approval of invoice to the NIH NCI Contracting Officer’s

Representative (COR) and to NIH Commercial Accounts per the attached Invoice & Payment

Provisions.

D. CONTRACT TYPE

This will be awarded as a Firm Fixed Price type contract.

These new peptides are replacements for ones consumed in mandatory sterility testing after the

2015 NIH pharmacy quarantine. To maintain continuity of the clinical trial, it is essential that the replacement peptides come from the same source, PolyPeptide Laboratories since the lab cannot change products in the middle of the clinical trial. These are urgently needed to treat prostate cancer patients who are waiting to be treated.

This notice is not a request for competitive quotation. However, if any interested party, especially small business believes it can meet the above requirement, it may submit a proposal or quote for the Government to consider. The response and any other information furnished must be in writing and must contain material in sufficient detail to allow NCI to determine if the party can perform the requirement. Responses must be received in the contracting office by 1 PM

EST, on June 20, 2016. All responses and questions must be in writing and faxed to

240-276-5399 or emailed to Reyes Rodriguez, Contracting Officer via electronic mail at reyes.rodriguez@nih.gov. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the

Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. No collect calls will be accepted. In order to receive an award, contractors must be registered and have valid certification in the Central

Contractor Registration (CCR) and the Online Representations and Certifications Applications

(ORCA) through sam.gov. Reference: N02RC62603-57 on all correspondence.

mailto:rodriguezra@mail.nih.gov