Solicitation HHS-NIH-NIDA

ATTACHMENT 1

PACKAGING AND DELIVERY OF THE PROPOSAL

Your proposal shall be organized as specified in Section L.2., General Instructions. An official authorized to contractually bind your organization must sign your proposal.

Shipping and marking shall be as follows:

EXTERNAL PACKAGE MARKING

In addition to the address cited below, mark each package as follows:

RFP: "HHS-NIH-NIDA (MH)-12-029"

"TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY"

NUMBER OF COPIES AND SHIPPING

• TECHNICAL PROPOSAL: One (1) unbound original, ten (10) paper copies, and one (1) copy on CD.

• BUSINESS PROPOSAL: One (1) unbound original, five (5) paper copies, and one (1) copy on CD

PROPOSALS must be received by the Contracting officer NO LATER THAN 4:30 PM local prevailing time, on May 11,2012, at the following address:

If using overnight delivery service: If using U.S. Postal Service:

Attn: Craig D. Sager Contracting Officer NIDA Neuroscience COAC R&D Contracts Management Branch Supporting: National Institute of Mental Health 6001 Executive Blvd., Room 8154 (MSC 9661) Rockville, M D 20852

Attn: Craig D. Sager Contracting Officer NIDA Neuroscience COAC R&D Contracts Management Branch Supporting: National Institute of Mental Health 6001 Executive Blvd., Room 8154 (MSC 9661) Bethesda, MD 20892-9661

NOTE: Please be aware that the U.S. Postal Service's "Express Mail" DOES NOT deliver to the Rockville, Maryland address and delivery to the Bethesda, Maryland address will result in a delayed delivery to our office here in Rockville, Maryland (up to 3-5 days). If a proposal is not received at the place, date and time specified herein, it will be considered a "late proposal".

PLEASE HAVE THE ORIGINALS READILY ACCESSIBLE FOR DATE STAMPING PURPOSES.

For questions please contact Craig D. Sager. Contracting Officer Telephone: 301-443-1193; Main: 443-443-2696 fax: 301-442-0601 e-mail: csager@mail.nih.gov

Collect calls will not be acce ted

RFP#: HHS-NIH-NIDA (MH)-12-029 Page 1 of 1 March 26, 2012

I mailto:csager@mail.nih.gov

ATTACHMENT 2

PROPOSAL INTENT RESPONSE SHEET

RFP#: HHS-NIH-NIDA (MH)-12-029

RFP TITLE: "NIH Small Molecule Repository"

Please review the attached Request for Proposal and furnish the information requested below by April 10, 2012. Your expression of intent is not binding but will greatly assist us in planning for proposal evaluation.

D DO INTEND TO SlJBMIT A PROPOSAL D DO NOT INTEND TO SlJBMIT A PROPOSAL FOR THE FOLLOWING

REASONS:

Companyllnstitution Name (print): ________________ Address (print): ______________________

Project Director's Name (print): _____~__________ Title (print): ______________________ SignaturelDate: ____________________ Telephone Number and E-mail Address (print clearly):

Business Representative Name: _______________ Title:

E-Mail Address: ________________ Telephone Number: _______________

Names of Collaborating Institutions and Investigators (include Subcontractors and Consultants) (print):

on a separate page ifnecessary)

RETURN VIA MAIL, FAX OR E-MAIL TO:

NIDA Neuroscience COAC

R&D Contracts Management Branch

Supporting: National Institute of Mental Health (NIMH)

6001 Executive Blvd., Rm. 8154 (MSC 9661)

Bethesda, MD 20892

[For commercial overnight services use: Rockville, MD 20852]

Attention: Craig Sager

Voice: 301-443-2696; Direct 301-443-1193

E-mail: csager@mail.nih.gov

PROPOSAL INTENT RESPONSE SHEET ATTACHMENT 2

mailto:csager@mail.nih.gov

STATEMENT OF WORK (SOW)

Title: NIH SMALL MOLECULE REPOSITORY (SMR)

I. Background

The NIH Small Molecule Repository (SMR), initiated in 2004, was developed as part of the Molecular Libraries Program, an NIH Common Fund Initiative. The goals of the SMR are to identify, acquire, maintain, and distribute a collection of chemically diverse compounds with known and unknown biological activities for use in high-throughput screening (HTS). These compounds are intended to serve as starting material for the development of chemical probes to explore basic biology, as well as leads for therapeutics development.

The SMR currently contains approximately 380,000 compounds. This compound collection is comprised of known bioactives, targeted libraries, natural products, and a large set of diverse compounds with unknown activity. The collection includes both commercial compounds and novel compounds developed by academic chemists. This library has been used by the Centers that form the ML Probe Production Centers Network (MLPCN) to generate a large volume of publicaUy available screening data on a wide variety of biological targets and to develop hundreds of chemical probes. Data on all compounds in the current library can be found in the NIH database, PubChem, using the search term "MLSMR" at:

http://pubchem.ncbi.nlm.nih.gov/search/search.cgi.

Through this acquisition, the SMR will continue to store, maintain, and distribute the collection, supporting the MLPCN Centers. In addition, as part of NIH's continuing efforts to support translational science, components of the SMR compound library will be made available more broadly, to support other NIH screening and translational efforts, as well as selected extramural groups conducting HTS for probe and drug discovery. Library enhancement efforts will continue to shape, improve, and expand the collection.

The current contract was awarded in 2004 to Discovery Partners International, Inc., (now Compound Focus, Inc., and owned by Evotec) under contract N01MH41001. The repository is located in San Francisco, CA.

Libraries Program (MLP))

III. Specific Technical Requirements

Page 1 of 13 Attachment 3 Solicitation HHS-NIH-NIDA (MH)-12-029 Statement of Work 3/26/2012 http://pubchem.ncbi.nlm.nih.gov/search/search.cgi

Independently, and not as an agent of the federal government, the Contractor shall furnish, as needed to perform the work set forth below in the Task Areas below, all necessary labor (qualified and experienced personnel), services, equipment, materials, supplies, and facilities, in accordance with approved task orders, and except as otherwise specified herein. The Contracting Officer's Representative (COR) whose position is defined in Section G of this contract shall monitor all work under this contract.

A. Special Conditions

The following special terms and conditions involving the SMR operations are applicable to performance under this contract:

1. Confidentiality The Contractor shall protect the confidentiality of any compound synthesized or received under the contract. The Contractor shall not release information regarding a proprietary compound without the express written consent of the NIH. The Contractor shall not use compounds in the NIH Small Molecule Repository, or compounds received from other sources under this contract for non-contract related research. If necessary, the Contractor may be given access to proprietary data associated with compounds submitted to the SIVIR and/or data generated from use of the compounds. The Contractor shall be prohibited from publishing or patenting any uses, product designs, or inventions resulting from such proprietary data.

2. Agreements The Contractor may be asked to sign agreements such as Confidentiality and Nondisclosure Agreements or Material Transfer Agreements, etc. (see http://ott.od.nih.gov for examples) and the Contractor agrees to do so; compound recipients may also be asked to sign such agreements, and the Contractor agrees to ensure this is accomplished.

3. Special Licenses It is expected that the Contractor will acquire special licenses for specific classes of compounds if and when required (e.g. HHS/COC select agents and toxins). As controlled substances are included in the SMR, the Contractor shall have in place or in process at the time of proposal submission, all necessary OEA licenses for the storage and distribution of Schedule 2-4 substances.

B. Contract Type and Task Areas

This is an Indefinite Oelivery, Indefinite Quantity (IOIQ) contract. The ultimate compound collection size and any expansion of the repository function beyond the current operation cannot be determined at this time. The types of compounds to be acquired, stored, plated and shipped are unknown, and will vary based on the needs of the NIH and individual investigators.

This contract will be administered and funded via Task Orders (T.O.) and approved Tasks.

Task order numbers will be assigned to each approved task under this 10lQ contract. The Contractor shall track and report progress and costs under each specific task order.

Page 2 of 13 Attachment 3 Solicitation HHS-NIH-NIDA (MH)-12-029 http:http://ott.od.nih.gov

The SOW is organized into Task Areas. The Task areas in this SOW are summarized as follows (details are provided below):

1. Task Area 1 is the yearly operation and maintenance of the current facility, including possible increases in the current activities to accommodate library enhancement, replenishment, and increased use of this resource by a broader scientific community.

An annual task order will be issued, after agreement is reached between the Government and the Contractor on a cost estimate and the technical approach.

2. Task Area 2 is the expansion of the compound collection (acquisition of new compounds which increase the collection size).

3. Task Area 3 is the Government-funded purchase of any repository equipment to replace existing failed equipment or acquire new equipment necessary to accommodate an expanded library collection (e.g., more storage space is necessary due to NIH approved additional compounds).

4. Task Area 4 is the effort needed to potentially transition/relocate the SMR at the end of the contract to a third party site or to the Government.

C. TASK AREA 1 (CLIN 0001)- YEARLY OPERATION AND MAINTENANCE OF THE

REPOSITORY

1. Store and maintain the NIH Small Molecule Repository Collection

a. Storage

(1) The Contractor shall provide all the necessary expertise, equipment, and facilities to store, maintain, and track the Small Molecule Repository inventory ..

(2) The Contractor shall provide a compound tracking and retrieval system suitable for long-term storage of a collection of small molecule compounds, both neat and in solution. The Contractor shall store samples and plates under temperature and atmospheric conditions shown to maintain compound integrity (e.g., at subambient temperatures and under dry inert gas).

(3) Storage space must be sufficient to accommodate the current SMR collection of -380,000 compounds, with each compound stored in both neat form and as a DMSO solution, as well as storage capacity for compound plates to maintain a sufficient inventory of pre-plated sets for distribution and provide short-term storage of custom orders. In addition, the Contractor shall have the capacity or the expansion capability to provide storage for newly acquired compounds. It is anticipated that the SMR may ultimately contain up to 650,000 compounds.

(4) The Contractor shall provide dry storage of compounds in vials (typically less than 30mg of each compound). From these dry stores, compounds shall be weighed, solubilized, and stored in solution in DMSO. Stored compounds shall be organized in a manner to optimally support the screening needs of the user community (e.g., by chemical class or target, by date of acceptance into the collection, etc.). The preferred storage method for solubilized samples is in microtubes, with a storage and retrieval system allowing for rapid and efficient cherry picking of compounds for the creation of plates. Alternative systems

Page 30f13 Attachment 3 Solicitation HHS-NIH-NIDA (MH)-12-029 allowing comparable speed and efficiency of compound selection are also acceptable. The SMR collection currently contains -380,000 compounds, which are being stored in the following format:

(5) Storage and handling shall comply with all applicable local, state and Federal regulations.

b. Quality Control and Assurance

(1) Quality Control(QC)

i. The Contractor shall have the ability to perform rapid analyses of weight, solubility (including filtration or centrifugation), and chemical identity and purity (e.g., LC/MS, HPLC, and/or NMR) in order to monitor the stability of compounds in the repository. The Contractor shall assess the quality of all new and re-supply compounds acquired for inclusion in the collection. In addition, the Contractor shall conduct regular monitoring of the identity and purity of compounds in the collection, through quality control analysis of a subset of collection at set intervals, as well as samples accessed for distribution.

ii. Quality control capacity should be sufficient to accommodate analysis of all incoming compounds (up to 50,000 compounds per year), at least 10% of the stored collection, and all samples accessed for cherry picking.

(2) Quality Assurance

The Contractor shall provide adequate quality assurance to regularly monitor the fidelity of the proposed compound plating and handling processes, as well as the functioning of all equipment used to store and process the SMR

c. Inventory Monitoring and Re-supply

(1) Inventory Monitoring The Contractor shall monitor the compound inventory regularly to ensure that sufficient threshold quantities, as specified by the COR, of all compounds are available to support screening needs. The Contractor shall provide a plan for efficient assessment and replenishment of the library to minimize unavailable samples.

(2) Replenishment of solubilized samples As solubilized samples become depleted, the Contractor shall undertake all activities necessary to replenish the sample from the neat sample inventory. The Contractor shall provide a plan for minimizing the number of samples unavailable for plating at any given time.

(3) Resupply As compounds become depleted from the neat inventory, the Contractor shall

Page 4 of 13 Attachment 3 Solicitation HHS-NIH-NIDA {MH)-12-029 undertake all activities necessary to maintain sufficient quantities of the compound inventory.

d. Disaster Recovery The Contractor shall have in place a sufficient disaster recovery plan for maintaining and distributing the collection after a catastrophic event. This should include plans for off-site storage of a complete copy of the SMR compound collection, in sufficient quantities to maintain "minimal operations" for up to one year after any catastrophic event, as well as a plan for quickly restoring operational capabilities to a level sufficient to support minimal operations, and a longer-term plan for restoring the SMR to fully operational status.

In the unlikely event of a catastrophic loss of compounds, not due to the fault or negligence of the Contractor, a separate task order may be issued to restore the collection. Compound loss due to fault or negligence of the Contractor shall be the responsibility of the Contractor and any replacement shall not be funded by the Government.

2. Compound Plating and Distribution The Contractor shall provide all the necessary expertise and equipment to meet the ongoing plating requirements detailed below. The Contractor shall have the capability of plating compounds in multiple plate types, well-arrangements, volumes, and concentrations, depending upon the requirements of the requesting screening center.

Specific formats to be offered will be determined after award (see Appendix for list of formats currently in use by the SMR).

a. NIH The Contractor shall provide regular and ongoing plating and distribution services for 4 high-throughput screening centers supported by the NIH through initiatives such as the MLP (see www.mli.nih.gov). Plating requirements include:

(1) Full Set The Contractor shall provide automated plating of the full set of compounds contained in the SMR (including collection increases), dissolved in DMSO, in 384 and 1536 well format, to produce arrays suitable for use as mother-plates to support screening of multiple assays or as single use/assay-ready plates. It is anticipated that full set plating and distribution will be done on an annual basis, with quarterly shipments of newly acquired compounds.

(2) Standard Subsets The Contractor shall have the capability of plating pre-selected subsets of the library, which will be created in collaboration with NIH and external consultants selected by NIH (see3b 'Creation of Subsets' below). It is anticipated that subset plating will be done on an annual basis and each center will be provided a copy of each subset.

(3) Custom Subsets The Contractor shall have the capability of creating and plating custom subsets of the library. The Contractor may receive compound lists from the Centers, Page 5 of13 Attachment 3 Solicitation HHS-NIH-NIDA {MH)-12-029 http:www.mli.nih.gov specifying the members of a custom subset, or may be given general parameters and asked to select compounds for inclusion in the subset.

(4) Hit Follow-Up Cherry- Picks The Contractor shall provide rapid cherry picking to support hit verification and follow-up. Cherry pick requirements will typically range from 250-4,000 compounds per request, and limits on formats and compound number and quantity will be set by the NIH, and may be requested in single concentration or dose-response format. Turn-around times of 3-5 business days are expected.

b. Fee-for-service Users In addition to providing plating and distribution of the SMR to NIH screening initiatives as described above, the Contractor shall conduct plating and distribution of the collection, on a fee-for-service basis, for NIH approved investigators. Credits will be provided on subsequent invoices which will offset contract costs.

The Contractor's price for the services provided will be based on the actual costs of plating to include compound acquisition costs, labor, consumables, and indirect costs. The price may not include profit. Costs shall be monitored periodically and the prices adjusted as necessary.

Plating requirements for fee-for-service users include:

(1) Full Set The Contractor shall conduct automated plating of the full set of compounds contained in the SMR, suspended in DMSO, in 96, 384, and 1536 well format, to provide arrays in a format suitable for use as mother-plates to support screening of multiple assays or single use/assay-ready plates.

(2) Standard Subsets The Contractor shall provide plating of pre-selected subsets of the library, typically in single-use format. These subsets will be provided in collaboration with NIH and external consultants selected by NIH (see 3b, 'Subsets' below), and may include the NIH Clinical Collection, a known bioactive set, a natural product set, diversity sets, and targeted libraries. It is antiCipated that the user group for these subsets of the SMR will be substantial; therefore the Contractor shall propose a plan to provide for efficient, rapid, and cost-effective pre-selected subsets of the collection in a limited number of formats and arrangements, without significant negative impact on the plating and distribution activities to support the NIH/ Centers.

(3) Custom Subsets The Contractor shall provide for custom subsets of the library. Fee-for-service custom requests will be required to specify the compounds for inclusion in the set.

(4) Hit Follow-Up Cherry Picks The Contractor shall provide fee-for-service cherry picking to support hit verification. Cherry pick requests will typically range from 250-4000 compounds, Page 6 of 13 Attachment 3 and limits on formats and compound number and quantity will be set by the NIH.

A standard turn-around time of 5-10 business days is considered optimal;

however, this may be modified to limit impact on turn-around times for NIH/MLP orders.

Prices for the fee-for-service work shall be based on actual cost of cherry picking to support hit verification .. No profit or fee can be included in the approved price(s). Costs associated with additional project management, informatics, or infrastructure required to conduct this work will not be included in the fee-for service price(s) and should be included in the proposed Task 1 budget.

c. Plating Formats

The Contractor shall have the ability to provide compound arrays in multiple formats.

This will include multi-use plates (suitable for use as mother plates to support screening of multiple assays), single-use plates (low volume, intended for a single transfer to the assay plate), and dose-response plates (containing multiple concentrations of each compound). The Contractor shall have the ability to add new plate types and formats, as needed, at the direction of the COR.

The Contractor shall have the ability to provide accurate dispensation and distribution of dry samples, in quantities and formats to be determined by the NIH (typically milligram quantities in pre-tared vials).

d. Shipping The Contractor shall provide compound arrays to NIH approved requestors, as needed. It is anticipated that this will involve regular shipments with the capability to ship on a daily basis. The Contractor shall have the capability of 'next business day' shipment or mix of 'same day' and 'next business day' for domestic shipments. The Contractor should also have the capability to ship internationally. Compound shipments shall be made in such a way as to ensure the integrity of the arrays and shall comply with all applicable federal, state, and local regulations and international shipping and custom regulations.

3. Library Enhancement

a. Library Assessment (with NIH and external consultants) The Contractor shall provide the necessary equipment and expertise to assess the SMR collection in order to provide recommendations for library enhancement, including, but not limited to, identifying compounds to be discarded or removed from the standard screening deck (due to promiscuous activity, problematic substructures, etc.) and areas of the library to target for expansion. The Contractor will be an active participant in library assessment activities, which will be conducted in collaboration with the NIH and external consultants identified by the NIH.

b. Subsets The Contractor shall be an active participant in the recommendation of subsets of the SMR collection, in collaboration with the NIH and external consultants. Using publicly available screening data generated on the current collection, as well as their internal cheminformatic resources, the Contractor shall assist in the identification of

Page 7 of 13 Attachment 3 compounds for inclusion in target and diversity-based subsets, as well as the identification of compounds for acquisition to optimize a subset. Subsets of interest may include, but are not limited to, diversity sets of varying size, a drug-like set, known bioactives, and targeted libraries for common screening targets (e.g., GPCRs, kinases, nuclear hormone receptors, and protein-protein interactions).

4. Data Management

a. Compound Registration Compound structure database - The Contractor shall maintain and update an electronic database containing each chemical structure and associated chemical data, and assign a unique identifier to each unique structure. This unique identifier will provide a mechanism that may be used to map all subsequently collected data (in vitro, in vivo, in silico, etc) back to the structure. The Contractor will eliminate redundant and ambiguous chemical structures in the compound structure database.

Specifically:

i. Salts: each salt of a given structure will be treated as a unique structure

ii. Hydrates: each hydrate of a given structure will be treated as a unique structure

iii. Geometrical: each geometrical (e.g. double bond) isomer will be treated as a unique structure

iv. Diastereomers: each diastereomer of a given structure will be treated as a unique structure

v. Optical isomers; each enantiomer of a given structure will be treated as a unique structure

vi. Isomeric ambiguity: Identical structures of unknown stereochemistry will be treated as a single unique structure.

vii. Mixtures: different compositions will be treated as a unique mixture

The Contractor will also maintain a list of alternative IDs associated with each structure (e.g. PubChem CID and SID, compound supplier 10, CAS number, etc.). In addition to structural information, the database should include related chemistry data including molecular weight, molecular formula, SMILES strings, IUPAC name, common names, phYSical properties, physical appearance, solubility, optimal storage conditions, QC data and any available material data safety information.

b. Inventory and Distribution Database The Contractor shall maintain and update a compound inventory database that will record information about all samples that are, or have been, stored in the repository.

Each sample will be given a unique sample identifier. The source, including supplier and lot 10, will be recorded for each physical sample that is processed through the repository. The Contractor will also maintain all information relevant to that sample such as sample specific physical properties, date of purchase or synthesis, date of quality control analysis and results, amount in stock, physical appearance, and physical constants. The database shall contain all details of each compound's plating and shipping history. These details will include such items as the structure and sample identifier, shipping date, destination, and purpose for each shipment.

c. Web-based ordering and reporting System

Page 8 of 13 Attachment 3

(1) The Contractor shall make available a web-based ordering system, allowing NIH-approved users to select compounds and compound sets and acceptable format and plate-type options, and in addition enable web-based reporting functionality for NIH and approved users to generate standard reports.

Reports shall include, but are not limited to:

received, shipment date)

• Non-commercial supplier reports, including automated emails notifying suppliers of key results

• Turn-around time for plating, distribution, compound-inprocessing, etc.

(2) At the direction of the NIH, additional report types may be added, based on user feedback.

(3) The Contractor must comply with the "Electronic and Information Technology Accessibility Provisions" set forth by the Architectural and Transportation Barriers Compliance Board (also referred to as the "Access Board") in 36 CFR part 1194 for all electronic and information technology (EIT) products and services acquired, maintained, or used under this contract/order, including EIT deliverables such as electronic documents and reports.

d. Distribution of Data Files For all shipments from the SMR, the Contractor will provide SO format data 'files containing, at minimum, the following information for each compound in the shipment:

Page 9 of 13 Attachment 3

Statement of Work ·3/26/2012

• Physicochemical Properties (calculated)

Additional data elements may be added based on user feedback.

e. Data Deposition It is expected that the Small Molecule Repository will deposit data on the majority of the compounds held in the collection to one or more publicly accessible databases (e.g., PubChem) designated by the NIH. Potential data exchange requirements would include, but are not limited to the following:

i. For new samples, promptly submit chemical structure and descriptive information to PubChem or other NIH specified database.

ii. Coordinate with NCBI or other NIH-specified database operator as necessary to validate bulk deposition procedures using one or more formats supported by

. that database(s).

iii. As part of the data submission, provide a link to the repository web site indicating availability of that compound. This will be displayed by the .database(s) as a "link-out" to the Repository.

iv. Maintain links to PubChem and/or other NIH-specified database. If chemical structure or descriptions are revised, submit a revised entry using the previously assigned accession code. If repository web sites change, submit revised link-out data.

1. Anonymized Samples It is anticipated that a subset of compounds acquired by or submitted to the SMR may be proprietary. The Contractor shall have the capability of accepting and handling anonymized samples, submitted with identifiers, but without structural information.

g. Informatics Support The Contractor shall provide all informatics infrastructure and expertise to conduct aI/ required contract activities.

h. Disaster Recovery The Contractor shall have a suitable data disaster recovery plan in place, to ensure minimal loss of data and operational downtime after a catastrophic event.

i. Website

(1) The Contractor shall provideand maintain a Molecular Libraries Repository website, describing the SMR program, includinga description of available services and how those services can be accessed. All databases provided with contract funds shall be the property of the Federal Government. All IT systems and procedures must conform to the NIH IT Security policies and procedures.

(2) The Contractor must comply with the "Electronic and Information Technology Accessibility Provisions" set forth by the Architectural and Transportation Barriers Compliance Board (also referred to as the "Access Board") in 36 CFR part 1194 for all electronic and information technology (EIT) products and

Page 10 of 13 Attachment 3 services acquired, maintained, or used under this contract/order, including EIT deliverables such as electronic documents and reports.

j. Travel The Contractor will be expected to participate in meetings of the NIH Molecular Libraries Probe Production Network Steering Committee, held 3 times per year.

Additional travel to advertise the program, present SMR-related data at scientific meetings, or interact with the NIH or SMR customers may be required. If required, specifics will be included in the TORFP.

k. Reporting The technical reports listed below will be required as documentation of progress under Task Orders issued under this contract.

All technical reports shall be submitted to the Contracting Officer's Representative (COR) electronically, in Microsoft Excel or Microsoft Word format for PCs (the most recent versions released or that have been released within the 18 months prior to the period for which the report is submitted) or comparable programs that are compatible with NIH systems.

As specified in Task Orders, the Contracting Officer shall also receive electronic copies of all monthly and final technical reports, in addition to signed hard copies of each final report.

In addition to any reports that may be required by the other terms of this contract, the Contractor shall prepare and submit the following reports, in the manner stated below and in accordance with ARTICLE F.2. DELIVERIES of this contract:

Monthly Task Order Reports Monthly reports shall be discussed via teleconference with the COTR, and followed up with written report submitted within 7 calendar days of the teleconference. The report shall consist of a summary of activity conducted under the contract, including, but not limited to, samples acquired, results of QC conducted, requests received, shipments, problems or delays encountered. If determined necessary by the COTR, teleconferences may be held more frequently (e.g., weekly, biweekly).

Final Task Order Reports The final task order reports shall be submitted to the COR electronically on or before the completion of each contract year (under Task Area 1) and shall include a summary of all activities conducted under the contract (in all Task Areas), including compounds acquired, shipments made, summary results of quality control analyses, and copies of the Compound Registration and Inventory and Distribution databases.

Final Contract Report

The contract final report shall be submitted to the COTR electronically on or before the effective expiration date and shall include a summary of all activities conducted under the contract, including compounds acquired, shipments made, summary

Page 11 of 13 Attachment 3 results of quality control analyses, and copies of the Compound Registration and Inventory and Distribution databases.

D. TASK AREA 2 (CLIN 0002)- EXPANSION OF THE COMPOUND COLLECTION

(ACQUISITION OF NEW COMPOUNDS)

This Task Area involves all activities necessary to acquire sufficient quantities of new compounds approved by NIH for inclusion in the Small Molecule Repository collection, and the processing SOPs for inclusion (e.g., transfer to standard containers, solubilization, and quality control).

1. The Contractor shall undertake all activities necessary to acquire sufficient quantities (typically 5-30 mg) of compounds approved by NIH for inclusion in the Small Molecule Repository collection, and process them for inclusion in the collection (e.g., transfer to standard containers, solubilization, quality control).

2. It is anticipated the collection will expand on a continuing basis and evolve over time based on the results of ongoing library assessment. The ultimate collection size is unknown, but it is estimated that the collection will grow at a rate of approximately 7,500-15,000 compound per year. Of this annual increase one-half are anticipated to be acquired through direct purchase from commercial sources with the remainder being submitted from academic and non-profit sources. Larger compound purchases are possible, with an upper limit of -50,000 compounds in a given year.

3. Purchases of new compounds shall be approved and funded by the NIH by individual task orders after receipt and approval of the Contractor's proposal.

E. TASK AREA 3 (CUN 0003)- GOVERNMENT- FUNDED PURCHASE OF

REPOSITORY EQUIPMENT

1. The Government will consider equipment purchase for this contract, in accordance with NIH property regulations. This task area would provide funds to replace existing failed equipment during the contract, or acquire new equipment necessary to accommodate an expanded library collection (e.g., more storage space is necessary due to NIH approved additional compounds).

2. Purchase of any new, planned storage and retrieval equipment cannot be proposed for start-up of the repository operation, upon contract award. While the Government may provide funds for equipment necessary for expansion of the repository or repair/replacement of current equipment, all sources must provide their own resources/equipment at start-up to continue the current repOSitory operation.

3. Purchases of any new Government-owned equipment shall be approved and funded by the NIH by individual task orders after receipt and approval of the Contractor's proposal.

Page 12 of 13 Attachment 3

F. TASK AREA 4 (CLIN 0004)- TRANSITION TO SUBSEQUENT CONTRACTOR OR

THIRD PARTY

1. Prior to completion of this contract, and at the direction of the COTR, the Contractor will undertake all activities necessary to complete a transition/relocation of the MLSMR contents including all compounds, data, and government owned property, to a subsequent Contractor or third party designated by the NIH. The Contractor shall fully cooperate with any successor Contractor and the NIH to ensure the efficient transfer of all data, materials, and equipment.

A funded task order will be issued to do so.

2. At least 120 days prior to the contract expiration date, and if requested by the COTR, the Contractor shall provide the COTR with an updated version of the original Transition Plan approved with award of this contract, and shall prepare a budget to accomplish a transition.

3. This activity shall be approved and funded by the NIH by an individual task order after receipt and approval of the Contractor's proposal.

Page 13 of 13 Attachment 3

ATTACHMENT 4

ACTUAL/SAMPLE TASKS - STATEMENTS OF WORK

TITLE: NIH SMALL MOLECULE REPOSITORY (SMR)

Notes: Proposals are required for each actual/sample task described below, based upon the assumptions and instructions provided. See also the Additional Technical Proposal Instructions (Attachment 5, and Additional Business Proposal Instructions (Attachment 6).

The "Notes to Offerors" are provided to assist in the submission of technical and cost proposals for these tasks. The Notes are labeled as to whether they provide instructions related to preparing the technical proposal or the business proposal. These notes will not be included in the final Task Order SOW.

TASK AREA 1 (CLIN 0001)- YEARLY OPERATION AND MAINTENANCE OF THE REPOSITORY

Task Area 1 is the yearly operation and maintenance of the current facility, including possible increases in the current activities to accommodate library enhancement, replenishment, and increased use of this resource by a broader scientific community.

The work described below is anticipated to be the Actual Task Order to be assigned first under this contract.

Your technical proposal for this Actual Task will be evaluated in accordance with Section M of this RFP.

It is important to develop a detailed technical proposal for this sample task.

A cost proposal is required based upon the assumptions provided in the Notes to Offerors below;

subsequent Task Orders for this service will be negotiated and on a yearly basis (however, while this is anticipated it is not guaranteed).

ACTUAL TASK 1- STATEMENT OF WORK

I. Title: Year one (1) Operation and Maintenance of the NIH Small Molecule Repository

II. Period of Performance: September 4, 2012 - September 3, 2013

III. Description (with Notes to Offerors for preparing a technical and cost proposal)

As described below and in the contract Statement of Work, Section III. Specific Technical Requirements, provide for:

Storage, maintenance and operation of the current NIH Small Molecule Repository Collection of -380,000 compounds, including:

A. Storage B. Quality control and assurance C. Inventory monitoring and resupply D. Disaster recovery capabilities E. Compound plating and Distribution

Page lof16 Attachment 4

Actual/Sample Tasks 3/26/2012

F. Library Enhancement G. Data Management and Reporting

1. Store and maintain the NIH Small Molecule Repository Collection

a. Storage

(1) The Contractor shall provide all the necessary expertise, equipment, and facilities to store, maintain, and track the Small Molecule Repository inventory.

(2) The Contractor shall provide a compound tracking and retrieval system suitable for long term storage of a collection of small molecule compounds, both neat and in solution. The Contractor shall store samples and plates under temperature and atmospheric conditions shown to maintain compound integrity (e.g., at subambient temperatures and under dry inert gas).

(3) Storage space must be sufficient to accommodate the current SMR collection of -380,000 compounds, with each compound stored in both neat form and as a DMSO solution, as well as storage capacity for compound plates to maintain a sufficient inventory of pre-plated sets for distribution and provide short-term storage of custom orders. In addition, the Contractor shall have the capacity or the expansion capability to provide storage for newly acquired compounds. It is anticipated that the SMR may ultimately contain up to 650,000 compounds.

(4) The Contractor shall provide dry storage of compounds in vials (typically less than 30mg of each compound). From these dry stores, compounds shall be weighed, solubilized, and stored in solution in DMSO. Stored compounds shall be organized in a manner to optimally support the screening needs of the user community (e.g., by chemical class or target, by date of acceptance into the collection, etc.). The preferred storage method for solubilized samples is in microtubes, with a storage and retrieval system allowing for rapid and efficient cherry picking of compounds for the creation of plates. Alternative systems allowing comparable speed and efficiency of compound selection are also acceptable. The SMR collection currently contains -380,000 compounds, which are being stored in the following format:

[NOTE 1 TO OFFERORS (Business Proposal): An Offeror proposing an alternative format should include costs associated with reformatting the current collection of -380,000 compounds.]

(5) Storage and handling shall comply with all applicable local, state and Federal regulations.

[NOTE 2 TO OFFERORS (Technical Proposal): Offerors should propose a plan for compound storage, organization, and retrieval. The plan should indicate the equipment to be used and its capacity, storage temperature and conditions, and the proposed organization of the collection.]

b. Quality Control and Assurance

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(1) Quality Control(QC)

i. The Contractor shall have the ability to perform rapid analyses of weight, solubility

(including filtration or centrifugation), and chemical identity and purity (e.g., LC/MS, HPLC, and/or NMR) in order to monitor the stability of compounds in the repository.

The Contractor shall assess the quality of all new and re-supply compounds acquired for inclusion in the collection. In addition, the Contractor shall conduct regular monitoring of the identity and purity of compounds in the collection, through quality control analysis of a subset of collection at set intervals, as well as samples accessed for distribution.

ii. Quality control capacity should be sufficient to accommodate analysis of all incoming compounds (up to 50,000 compounds per year), at least 10% of the stored collection, and all samples accessed for cherry picking.

[NOTE 3 TO OFFERORS (Technical Proposal): Offerors should propose a plan for quality control, detailing a recommended method of analysis and frequency of assessment, acceptance cut-offs, a plan for analysis of the resulting data, and an action plan for remediation in the event of quality control failures.]

(2) Quality Assurance

The Contractor shall provide adequate quality assurance to regularly monitor the fidelity of the proposed compound plating and handling processes, as well as the functioning of all equipment used to store and process the SMR.

[NOTE 4 TO OFFERORS (Technical Proposal): Offerors should propose a full quality assurance plan including all relevant SOPs for the proposed processes and equipment, including a staff training plan. The proposal should include a plan for routine maintenance and repair of equipment. Replacement of equipment is included under Task Area 3, belOW.]

c. Inventory Monitoring and Re-supply

(1) Inventory Monitoring The Contractor shall monitor the compound inventory regularly to ensure that sufficient threshold quantities, as specified by the COR, of all compounds are available to support screening needs. The Contractor shall provide a plan for efficient assessment and replenishment of the library to minimize unavailable samples.

(2) Replenishment of solubilized samples As solubilized samples become depleted, the Contractor shall undertake all activities necessary to replenish the sample from the neat sample inventory. The Contractor shall provide a plan for minimizing the number of samples unavailable for plating at any given time.

[NOTE 5 TO OFFERORS (Business Proposal): For the purposes of preparing a budget, assume that 25% of the collection will require solubilization during year 1.]

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(3) Resupply As compounds become depleted from the neat inventory, the Contractor shall undertake all activities necessary to maintain sufficient quantities of the compound inventory.

[NOTE 6 TO OFFERORS (Business Proposal): For budget purposes, assume that 2% of the total collection will be replaced in year 1, at a cost of $30/compound for resupply.]

d. Disaster Recovery The Contractor shall have in place a sufficient disaster recovery plan for maintaining and distributing the collection after a catastrophic event. This should include plans for off-site storage of a complete copy of the SMR compound collection, in sufficient quantities to maintain "minimal operations" for up to one year after any catastrophic event, as well as a plan for quickly restoring operational capabilities to a level sufficient to support minimal operations, and a longer-term plan for restoring the SMR to fully operational status.

In the unlikely event of a catastrophic loss of compounds, not due to the fault or negligence of the Contractor, a separate task order may be issued to restore the collection. Compound loss due to fault or negligence of the Contractor shall be the responsibility of the Contractor and any replacement shall not be funded by the Government.

[NOTE 7 TO OFFERORS (Technical Proposal): Offerors should propose a technical approach to implement:

Note: "minimal operations" will be defined as full set, standard subsets, and cherry picking plating and distribution in support of the NIH (see 2a).]

[NOTE 8 TO OFFERORS (Business Proposal):

• If offsite storage in not currently implemented include those costs in the Actual

Task 1 budget, with timelines.

• For restoration of minimal operations and full operations, provide separate cost estimates with timelines, not to be included in the Actual Task 1 budget.

2. Compound Plating and Distribution The Contractor shall provide all the necessary expertise and equipment to meet the ongoing plating requirements detailed below. The Contractor shall have the capability of plating compounds in multiple plate types, well-arrangements, volumes, and concentrations, depending upon the requirements of the requesting screening center. Specific formats to be offered will be determined after award (see Appendix for list of formats currently in use by the SMR).

a. NIH

The Contractor shall provide regular and ongoing plating and distribution services for 4 high throughput screening centers supported by the NIH through initiatives such as the MLP (see www.mILnih.gov). Plating requirements include:

(1) Full Set

Page 4ofI6 Attachment 4 Solicitation HHS-NIH-NIDA (MH)-12-029 http:www.mILnih.gov

The Contractor shall provide automated plating of the full set of compounds contained in the SMR (including collection increases), dissolved in DMSO, in 384 and 1536 well format, to produce arrays suitable for use as mother-plates to support screening of multiple assays or as single use/assay-ready plates. It is anticipated that full set plating and distribution will be done on an annual basis, with quarterly shipments of newly acquired compounds.

(2) Standard Subsets The Contractor shall have the capability of plating pre-selected subsets of the library, which will be created in collaboration with NIH and external consultants selected by NIH (see3b 'Creation of Subsets' below). It is anticipated that subset plating will be done on an annual basis and each center will be provided a copy of each subset.

(3) Custom Subsets The Contractor shall have the capability of creating and plating custom subsets of the library. The Contractor may receive compound lists from the Centers, specifying the members of a custom subset, or may be given general parameters and asked to select compounds for inclusion in the subset.

[NOTE 9 TO OFFERORS (Business Proposal): It is antiCipated that both custom and standard subsets will typically include 5,000 to 15,000 compounds. For the purposes of preparing a cost proposal, assume a subset size of 10,000 compounds per set.]

(4) Hit Follow-Up Cherry- Picks The Contractor shall provide rapid cherry picking to support hit verification and follow-up.

Cherry pick requirements will typically range from 250-4,000 compounds per request, and limits on formats and compound number and quantity will be set by the NIH, and may be requested in single concentration or dose-response format. Turn-around times of 3-5 business days are expected.

[NOTE 10 TO OFFERORS (Business Proposal): For the purposes of preparing a cost proposal, assume the following year 1 workload for plating to support NIH screening initiatives:

quarter

orders.]

b. Fee-for-service Users In addition to providing plating and distribution of the SMR to NIH screening initiatives as described above, the Contractor shall conduct plating and distribution of the collection, on a fee-for-service basis, for NIH approved investigators. Credits will be provided on subsequent invoices which will offset contract costs.

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The Contractor's price for the services provided will be based on the actual costs of plating to include compound acquisition costs, labor, consumables, and indirect costs. The price may not include profit. Costs shall be monitored periodically and the prices adjusted as necessary.

Plating requirements for fee-for-service users include:

(1) Full Set The Contractor shall conduct automated plating of the full set of compounds contained in the SMR, suspended in DMSO, in 96, 384, and 1536 well format, to provide arrays in a format suitable for use as mother-plates to support screening of multiple assays or single use/assay-ready plates.

(2) Standard Subsets The Contractor shall provide plating of pre-selected subsets of the library, typically in single-use…