Amendment_1_to_RFP_CSOF_75N94023R00008rev2_0002.pdf

AMENDMENT TO NICHD SOLICITATION

CHEMICAL SCREENING OPTIMIZATION FACILITY

Solicitation Number: RFP 75N94023R00008 Amendment Number: 1 Amendment Issue Date: May 31, 2023 Proposal Due Date: June 8, 2023

DATE, TIME, Local Time CHANGED

Issued By: Lola St John Contracting Officer

NICHD

Office of Acquisitions

Point of Contact:

Lola St John, Contracting Officer E-Mail: lk202p@nih.gov

This amendment is issued to all potential Offerors.

The above numbered solicitation is amended as set forth below. The hour and date specified for receipt of proposals (HAS NOT) been extended. Offerors must acknowledge receipt of this amendment by identifying this amendment number and date on each copy of the offer submitted. Failure to receive your acknowledgement may result in the rejection of your offer.

If by virtue of this amendment you desire to change an offer already submitted, such a change may be made by e-mail, provided each e-mail makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

Except as provided herein, all terms and conditions of the RFP remain unchanged and in full force and effect. THE PURPOSE OF THIS AMENDMENT is to issue clarification questions received and to address updates to the RFP.

1. Question: The RFP mentions “Listed below are mandatory qualification criteria.”, however no actual criteria is listed. Can the government specify the mandatory qualification criteria?

Answer: There is no mandatory criteria

2. Question: Will the government please provide Statements of Work for the base contract and the task orders (#1-7). The link provided does not seem to be working (Attachment 3 (CSOFSOWsCombined.pdf)).

Answer: We have emailed Statements of Work and proposal packaging instructions to all potential offerors. Due to a systems error, attachments were not able to be downloaded on SAM.gov

3. Question: Will a library of compounds be provided?

Answer: Library of compounds for screening may either be procured (in this case, it would be tailored to the target - e.g., allosteric kinase inhibitors, provided by a service requestor, or conducted via an in-house chemical library.

mailto:lk202p@nih.gov

4. Question: Is an HTS system required for screening?

Answer: No, but an offeror should have staff on hand that can conduct an HTS screening campaign (including knowledge of how to reproduce an identified screen provided by a service requestor). Alternatively, the offeror could identify a subcontractor to conduct a HTS campaign.

5. Question: Approximately how many compounds are expected to be synthesized for each tier of screening?

Answer: If there are expected to be 2 tiers of synthesis, one could expect there to be up to 10 to 15 compounds per tier and quantifiable go/no-go metrics to justify advancement to the next tier.

6. Question: Will the incumbent be expected to generate crystal structures of the kinase with bound and unbound inhibitors?

Answer: Yes, the offeror should have the ability to conduct X-Ray crystallization efforts or subcontract the effort out.

7. Question: Where can we find the specific sample tasks that are described on pages 89-99? There was no attachment that we could find for the sample tasks. Are we to assume that we should describe our expertise with those tasks in general?

Answer: Due to a glitch in the system, attachments were not immediately available and were emailed to offerors who contacted us. These documents are being re-uploaded with this amendment. Concerning describing their expertise for identified task orders – the offeror should address the sample task order(s) as precisely as possible. As an example, if an offeror has experience developing a 5HT1F antagonist, they should outline how they developed the lead molecule and the metrics and go/no-go criteria used to achieve that outcome.

END OF AMENDMENT #1 To RFP (75N94023R00008)

CHEMICAL SCREENING AND OPTIMIZATION FACILITY (CSOF) BASE

CONTRACT AWARD STATEMENT OF WORK (SOW)

I. BACKGROUND AND INTRODUCTION

As nearly half of the pregnancies in the United States are unintended, there is a critical need for fertility regulation methods that fit the needs of women and men throughout their reproductive lives. There is also a need to develop (or improve upon) new reproductive health related therapies in the areas of: infertility, gynecologic health, obstetrics, pediatrics, pregnancy and perinatology. The objective of this contract is to support the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in its mission to develop novel contraceptive methods and reproductive health related therapies (e.g., infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism) by providing a Chemical Screening and Optimization Facility (CSOF) to identify safe and effective contraceptive and reproductive health related agents for development. The CSOF also has an important role in the production of optimized compounds for early stage in vitro and in vivo testing.

The Contraception Research Branch (CRB) at the NICHD supports research on the development of new and innovative male and female contraceptives and is looking to expand into efforts for reproductive health related indications.

The required research at the CSOF will encompass discovery and optimization of small molecule antagonists and/or agonists of validated targets using state-of-the art scientific disciplines to support that goal. It also includes, but is not limited to, the production of active recombinant protein, assay development, high throughput screening, x-ray crystallography, computational chemistry, medicinal chemistry, and pharmacology. The Contractor must have the capability to produce and/or purify active protein, screen tens of thousands of compounds, identify one or more lead chemical series, perform chemical optimization, and produce sufficient amounts of novel optimized compounds for required in vitro and in vivo testing. As such, the Contractor must be knowledgeable about early-stage drug discovery and development.

The Contractor will be required to identify potential subcontractors with required capabilities to achieve goals and to issue and administer subcontracts for the development of products as assigned by the Contracting Officer’s Representative (COR). The Contractor will communicate and collaborate with External Project Leaders as specified by the COR.

II. SCOPE

The objective of this contract is to serve as the Chemical Screening and Optimization Facility (CSOF) with the capability to carry out the production of active recombinant protein, assay development, chemical screening, identification and optimization of chemical lead series and production of milligram to kilogram quantities of materials for in vitro and in vivo testing for contraception and/or reproductive health-related therapeutic indications.

III. TECHNICAL REQUIREMENTS

Independently, and not as an agent of the Government, the Contractor shall furnish as specified by task orders all required services, including but not limited to qualified personnel, material(s), instrumentation and facilities not otherwise provided by the Government as needed to maintain and operate a Chemical Screening and Optimization Facility and perform the Statement of Work below.

A. CHEMICAL SCREENING AND OPTIMIZATION SERVICES

1) Target Screening and Identification of Active Molecules

a) Biological/biochemical assay development

b) High throughput screening performance

c) Confirmation of active molecules identified from high throughput screens

d) Evaluation and selection of confirmed active molecules for further development

e) Medicinal chemistry services for the development and identification of lead series

2) Chemical Lead Series Optimization

a) Medicinal chemistry activities (e.g., structure activity relationships)

b) Chemical and protein structural analysis

c) Computational molecular modeling services

d) Intellectual property analysis (e.g., evaluation of distinction from prior art)

e) Pharmacokinetic analysis

The required activities at the CSOF will encompass research to enable the discovery and optimization of small molecule antagonists and/or agonists of defined targets as specified in Task Orders issued by the Contracting Officer (CO) in accordance with the procedures described in Article G of the Contract.

The Contractor shall provide the following expertise, as specified in task orders for all activities related to:

• Protein production and/or purification

• Demonstration of activity of purified protein

• Biological/biochemical assay development for high throughput screening, including cell culture facilities

• High throughput compound screening

• Assay hit verification

• Intellectual property evaluation summary by qualified legal expert(s)

• Medicinal chemistry activities including, but not limited to; o Compound synthesis on the milligram to kilogram scale o Purification and characterization including but not limited to:

■ Compound purification, as required, using:

• Chromatography (e.g., HPLC)

■ Structural confirmation, as required, using:

• Infrared spectroscopy (IR)

• 1H and 13C nuclear magnetic resonance (NMR)

• Ultraviolet and/or mass spectroscopy data (i.e., LC-MS)

• Optical rotation and enantiomeric excess (where necessary)

• Elemental analysis and/or X-ray structure confirmation

■ Computational molecular modeling

■ X-ray crystallography

• In vitro biological characterization (e.g., cellular permeability)

• Absorption, distribution, metabolism, excretion studies

• One or more reproductive scientists skilled in the science of male and/or female gametogenesis/fertilization for consultation

• Radiochemical synthesis

• Peptide synthesis

The Contractor shall provide the following services, as specified in task orders for all activities related to:

• Label, catalogue, and store synthesized compounds under proper laboratory storage conditions

• Maintain current records of compound identification, quantity, purity, and all associated analytical data

• Provide access to the Government for all information directly related to the contract including, but not limited to, all bound laboratory notebooks or e-notebooks (which must be used to record all data), spectral, analytical and chromatographic data

All work shall be performed in accordance with all local, state, and federal laws and regulations.

B. GENERAL SERVICES:

1) Project planning (Initial Project Plan), implementation and management (Quarterly Reporting, Annual Reporting, Final Reporting)

2) Database, data, document, product, specimen/reagent and inventory management (Weekly Progress Summaries)

3) Information and physical access security (IPAS)

4) Receive, format, store, ship and record compounds/products and biological agents (Technology Transfer Reporting)

5) Transition plans (Initial and Final)

1) Project Planning (Initial Project Plan), Implementation and Management (Quarterly Reporting, Annual Reporting, Final Reporting)

The Contractor shall provide services for chemical screening and optimization as specified in task orders.

The specific services required will depend on the status of the individual programs.

The Contractor shall be responsible for project planning, initiation, implementation, management and communication, including evaluation, selection, and management of subcontractors, as well as all deliverables as specified in task orders. All reports and deliverables required herein and any additional reporting requirements that may be specified in individual Task Orders shall be produced and submitted under Administrative Task Order #1. The list of deliverables includes:

• An Initial Transition Plan Draft

• An Initial Transition Plan Final

• An Initial Project Plan

• A Weekly Progress Summary with Meeting Minutes to be discussed via teleconference

• A Quarterly Progress Report

• A Quarterly Summary of Intellectual Property Assessment

• A Quarterly Subcontractor Performance Assessment

• An Annual Technical Report

• A Final Study Report

• A Final Report

• A Final Transition Plan Draft

• A Final Transition Plan Final

• Technology Transfer Reports

The Contractor shall perform work only as directed in Task Orders issued by the CO in accordance with the procedures described in Article G of the Contract (TASK ORDER PROCEDURES).

The Contractor shall provide services for, but is not limited to:

a) Chemical Screening and Optimization

As specified in task orders, develop and implement plans for the chemical identification and optimization of small molecule antagonists and/or agonists against therapeutic target(s) and produce specified compounds in amounts requested by the COR and approved by the CO. b) Overall Project Management

As specified in task orders, provide technical and administrative infrastructure to ensure efficient planning, initiation, implementation, and management of all projects carried out under this contract as well as effective communication with the COR and the CO. This communication includes providing a written weekly progress summary to be discussed via teleconference with the COR and CO and a quarterly summary of intellectual property assessment. The infrastructure shall include a Principal Investigator (PI) with responsibilities specific but not limited to overall project management and communications, tracking, monitoring and reporting on project status and progress, and recommending modifications to project requirements and timelines, including projects undertaken by subcontractors. This infrastructure shall also include a Project Manager (PM) to coordinate and integrate all facility activities conducted under this contract. Additional PM responsibilities should include, but are not limited to, financial management and financial reporting on all activities conducted by the Contractor and subcontractors. The PM role is not required to be a full-time position, but the PM or delegate must be responsive to NICHD inquiries within 24 hours during normal business hours. The PM position does not require project management certification.

c) Project Plan and Project Initiation

As specified in task orders the Contractor shall provide a written Initial Project Plan within 30 days that includes the following:

i) A determination regarding whether the work can be performed in-house by the Contractor or if subcontracting is required;

ii) Specification of the resources and services to be provided; iii) A description of the key development objectives; iv) Delineation of project milestones and timelines for the accomplishment of milestone objectives;

v) A description of the technical approach to carrying out the project and the physical facilities and other necessary resources to be made available;

vi) A description of the project deliverables and a timeline for completion; vii) A list of proposed scientific and technical personnel and a description of their qualifications and relevant experience;

viii) A detailed budget of all project costs.

d) Site visits

As specified in task orders each site visit will be held on a date designated by the COR in consultation with the PI. The PI shall be responsible for meeting arrangements/logistics. The PI, the PM, the Contractor’s Project Leaders, the key subcontractor personnel and the NICHD staff will attend these meetings. The agenda will be prepared by the COR and CO in consultation with the Principal Investigator. Meetings shall be closed to the public and shall involve oral and electronic presentations including:

i) Updates to include results of studies completed since the prior meeting;

ii) Interim reports on active task orders; iii) A description of any problem that may have arisen; iv) A discussion of potential future work.

Subcontractors may not be allowed to attend portions of the meeting in which potentially proprietary/confidential information will be presented/discussed.

e) Subcontract Execution, Management and Reporting

The Contractor shall manage the subcontracting activity and shall ensure that the award and management of subcontracts is in accordance with FAR Clause 52.244-2. Specifically, the Contractor shall carry out the following for each project to be initiated under a subcontract:

i) Execute and manage subcontracts, oversee the technical, administrative and operational activities of subcontractors daily, including auditing subcontractor facilities, monitoring services and financial expenditures, tracking deliverables and reporting requirements;

ii) Include with the submission of each quarterly technical report, an assessment of subcontractor performance and progress toward achievement of defined milestones; identify and resolve problems with subcontractor performance; iii) Ensure that subcontractor personnel, equipment and facilities are compliant with regulatory requirements in effect throughout the contract period;

iv) Ensure the complete and effective transfer of technology by the subcontractors to the Contractor, the United States Government, or a third party as requested by the COR and approved by the CO.

v) Perform all necessary transition and closeout functions on each subcontract.

f) Biocontainment, Safety and Training The

Contractor shall:

i) Provide safe facilities and resources and conduct work in accordance with the Biosafety in Microbiological and Biomedical Laboratories guidelines, Centers for Disease Control and Prevention and the National Institutes of Health, third edition, HHS Pub. No. (CDC) 93-8395 published by the U.S. Government Printing Office, May 1993, stock number 17- 0400-00523-7; ii) Provide adequate biocontainment facilities and staff with the required training, experience and expertise to operate the facilities and conduct the services, when appropriate, in accordance with Biosafety Level (BSL) 2 guidelines (http://bmbl.od.nih.gov/index.htm).

2) Databases, Data, Document, Product and Specimen/Reagent and Inventory Management (Weekly

Progress Summaries)

The Contractor shall provide as specified in task orders services for, but not limited to:

a) Provide, implement, and maintain data management systems to support all contract activities described in the Statement of Work

b) Provide, implement, and maintain secure in-house data management capabilities and equipment to submit, compile, store, collate, analyze, track, and retrieve data, structures, results, specimens, reagents, biological agents, product produced and released, documents generated in product development, and data received from other compound screening activities performed by third parties. This database will contain confidential proprietary information that cannot be used for data-mining purposes by the Contractor or subcontractors.

c) Ensure secure electronic communications, including email, word processing and transmission of data files, between the Contractor, NICHD staff, subcontractors, and consultants. Organize, maintain, and transfer information on protocols and test results and provide electronic copies of all reports to the COR and CO.

d) Provide an annual report summarizing the compounds synthesized, and all studies, tests, and procedures performed during the year and provide a final study report after the completion of each study.

e) Provide all equipment and operational systems to maintain the confidentiality of data received from the NICHD or third parties and data generated within the scope of the contract.

3) Information and Physical Access Security (IPAS)

IPAS is applicable to this contract and this information should be provided by the Contractor.

The Homeland Security Presidential Directive (HSPD)-12 and the Federal Information Security Management Act of 2002 (P.L. 107-347) (FISMA) requires each agency to develop, document, and implement an agency-wide information security program to safeguard information and information systems that support the operations and assets of the agency, including those provided or managed by another agency, contractor (including subcontractor), or other source.

4) Receive, Format, Store, Ship and Record Compounds/Products (Technology Transfer Reporting)

The Contractor shall develop and maintain efficient and effective procedures sufficient to support contract activities for receiving, storing, shipping and recording compounds/products.

The Contractor shall provide as specified in task order services for, but not limited to:

http://bmbl.od.nih.gov/index.htm) http://bmbl.od.nih.gov/index.htm)

a) Transfer assays, processes, methods, standard operating procedures, reagents, products or other materials, data and documentation developed under the contract to a third party as specified in the task orders. The Technical Transfer packages shall include information (Technology Transfer Report), material reagents and in-place training of others at the Contractor's or subcontractor's site or the site of a third party sufficient to completely and effectively transfer the technology.

b) Obtain the appropriate licenses and permits required by International, Federal, State and local authorities for the safe transport, storage, and distribution of compounds/products and biological agents;

c) Provide for safe packing, labeling, and shipping of compounds/products and biological agents to sites specified in the task orders so that shipments are coordinated for timely receipt;

d) Pay costs for shipping from suppliers to the contract/subcontract site or to third parties, and from third parties to contract/subcontract site;

e) Maintain stability of all shipments received by providing the appropriate temperature control in transit from the airport or other site to the Contractor/subcontractor facility;

f) Provide shipping containers for compounds/products and biological agents that comply with domestic and international postal regulations and pertinent International Air Transport Association (www.iata.org) and the International Civil Aviation Organization (www.icao.int) regulations. The shipping containers shall provide a sufficient margin of safety for maintaining appropriate environmental safeguards and desired refrigeration levels for specific products in transit, depending on the mode of transportation employed;

g) Provide secure, safe and stable storage of reagents, products and biological agents under the required conditions (e.g., Biosafety Level, GMP, aseptic);

h) Maintain a secure electronic record of any therapeutic and biological agents received, such as in an Excel spreadsheet or database compatible with Microsoft Office XP or software currently used and approved by NICHD, that includes searchable information such as compound identifiers, amounts available, storage locations, shipping data and other biological and chemical characteristics of the compounds (e.g., dose profile, IC50, cLogP,1H-NMR, etc.).

5) Transition Plans (Initial and Final)

As specified in task orders the Contractor shall provide an orderly transition to a successor contractor or to the Government at the end of the contract. Thus, the Contractor shall provide:

a) Initial Transition Plan

Within 15 days of contract award the Contractor shall provide an Initial Transition Plan and timetable for the receipt storage and study (as necessary) of all items potentially being transferred from the outgoing Contractor. This may include equipment, test agents, etc.

b) Final Transition Plan Ninety days before the expiration date of the contract, the Contractor shall provide a Final Transition Plan to the COR for the orderly transition of contract-related materials to a successor contractor or to the Government. Materials may include equipment, reagents and data not already transferred to the Government. The Final Transition plan shall include an estimated cost of shipping materials to a successor contractor or to the Government.

CHEMICAL SCREENING AND OPTIMIZATION FACILITY (CSOF)

SAMPLE TASKS 2 – 7 SOW & TEC DOCUMENTS

INTRODUCTION TO SAMPLE TASK ORDER PROPOSALS

The Chemical Screening and Optimization Facility has been tasked with the support of developing multiple:contraceptive targets, infertility targets, gynecologic health related targets, obstetric and pediatric targets, and pregnancy and perinatology related targets. Screening and chemical optimization must be performed to identify new chemical series that interact with the target proteins. For some targets, the generation of crystals and analysis of those crystals are needed to support molecular modeling and medicinal chemistry. Six sample task orders have been assigned to the Offeror’s facility to carry out the sample tasks described in Sample Task 2, Sample Task 3, Sample Task 4, Sample Task 5, Sample Task 6 and Sample Task 7.

SUMMARY OF SAMPLE TASK ORDERS

Sample Task 2 – Kinase Inhibitor Identification via High Throughput Screening for contraception, or treatment for: infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism.

Following the SOW as described in the Base SOW, propose a general strategy and specific approach in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out to identify novel allosteric inhibitors for up to 3 serine/threonine kinases starting from the performance of a high throughput screen and develop a plan for chemical optimization while ensuring that the optimized chemical entities allow freedom to operate. The cost differences among the different kinases are expected to be minimal and the offeror should provide a budget on a per-kinase cost basis. The government may, or may not, award on all 3 kinases and reserves the right to award based on what is in the government’s best interest or most feasible.

Sample Task 3 – Kinase Inhibitor Identification through Chemical Optimization for contraception, or treatment for: infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism.

Following the SOW as described in the Base SOW, propose a general strategy and specific approach in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out to identify novel allosteric inhibitors for up to 3 serine/threonine kinases starting from identified hits from a screen already performed, and develop a plan for chemical optimization while ensuring that the optimized chemical entities allow freedom to operate. The cost differences among the different kinases are expected to be minimal and the offeror should provide a budget on a per- kinase cost basis. The government may or may not award on all 3 kinases and reserves the right to award based on what is in the government’s best interest or most feasible.

Sample Task 4 – Potassium Ion Channel Inhibitor Identification for contraception, or treatment for: infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism.

Following the SOW as described in the Base SOW, propose a general strategy and specific approach in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out to identify novel inhibitors for a monomeric potassium ion channel, and develop a plan for chemical optimization while ensuring that the optimized chemical entities allow freedom to operate.

Sample Task 5 – Inhibitors of Protein-Protein Interaction Identification for contraception, or treatment for: infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism.

Following the SOW as described in the Base SOW, propose a general strategy and specific approach in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out to identify novel inhibitors for a protein-protein interaction target, and develop a plan for chemical optimization while ensuring that the optimized chemical entities allow freedom to operate.

Sample Task 6 – Protein Expression and/or X-ray Crystallography for contraception, or treatment for: infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism.

Following the SOW as described in the Base SOW, propose a general strategy and specific approach in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out to generate an active protein or peptide, develop crystals leading to a resolved structure of less than or equal to 2.2 Angstrom resolution.

Sample Task 7 – Scalable amount of an identified lead compound for contraception, or treatment for: infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism.

Following the SOW as described in the Base SOW, propose a general strategy and specific approach in detail, including the experiments, studies, processes, evaluation and steps, that the Offeror would carry out to generate a scalable amount, meaning 20 grams or more, of an identified lead compound.

STATEMENTS OF WORK (SOWs) FOR SAMPLE TASK ORDERS

1) SOW – SAMPLE TASK 2 – Kinase Inhibitor Identification via High Throughput Screening

Many kinases have been identified with expression primarily or exclusively in the male or female reproductive tract with functions/activities critical to produce functional male or female gametes or play a critical role in reproductive health or related indication topics (e.g., infertility, gynecologic health, obstetrics and pediatrics, perinatology and pregnancy). The research contained within this sample task order will encompass discovery and optimization of allosteric small molecule antagonists for up to 3 defined kinase targets using scientific disciplines to support that goal, including, but not limited to, assay development, high throughput screening, computational chemistry, intellectual property evaluation, medicinal chemistry and pharmacology.

The scope of this sample task order is to generate active recombinant kinase protein, develop a high throughput assay to identify novel allosteric kinase inhibitors using commercially sourced materials (e.g., small molecules) for screening. It includes performing a high throughput screen and counter screens to ultimately identify two distinct lead chemical series which may then be optimized to lead chemicals that have characteristics permitting the establishment of intellectual property and freedom to operate. The sample tasks described in this SOW may be requested for up to 3 distinct kinases. The cost differences among the different kinases are expected to be minimal and the offeror should provide a budget on a per-kinase cost basis. The government may or may not award on all 3 kinases and reserves the right to award based on what is in the government’s best interest or most feasible.

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material(s), instrumentation, facilities and capabilities to discover, design, synthesize and optimize novel chemical entities to identify two chemical allosteric inhibitor series against a validated reproductive tract-specific kinase or reproductive health, or related as discussed above, indication where the validated kinase plays a causative role in the indication’s progression. Both identified chemical series must be distinct from established intellectual property and amenable to the establishment of new intellectual property. The required research will encompass production and purification of active target protein, development of screening assays, implementation of screens to identify two distinct chemical series with freedom to operate that interact specifically with the target and development of a plan for their optimization as entities for clinical development. The Contractor must have continuous ability to perform intellectual property analysis by qualified individuals or legal representatives.

Technical Approach

• Develop and perform assays of target protein activity.

• Design, optimize and validate a high throughput screen to identify allosteric inhibitors of the target kinase protein, 96 well format, minimum.

• Propose and screen chemical libraries. The number of compounds screened must be sufficient to ultimately result in the identification of two novel chemical series of allosteric inhibitors

• Propose and perform secondary and tertiary screens to eliminate potential false positive and false negative hits against actives identified in the high throughput screen.

• Describe and perform the studies needed to generate and characterize compounds for selection of two distinct lead chemical series, including freedom to operate.

• Provide an estimate and justification of the number of compounds that are expected to be synthesized to identify two distinct lead chemical series.

• Describe the criteria to be used to select two novel, distinct lead chemical series, including freedom to operate and the ability to establish intellectual property.

• Propose a strategy for structure based chemical optimization of both series using state-of- the-art methodologies.

• The use of medicinal chemistry and computational chemistry are required.

• Other technologies may be included.

• Provide a timeline for all activities.

IV. PERIOD OF PERFORMANCE AND DELIVERABLES

Period of Performance: 12 months

The Contractor shall be required to prepare and submit the following reports electronically to the Contracting Officer’s Representative (COR) and the Contracting Officer (CO):

1) Assay development, screening results with structures, intellectual property evaluation of identified leads, development of two lead series and a strategy for optimization will be delivered to the COR. Other milestones are dependent on the experimental design for each task order.

2) An Initial Project Plan will be due within the first 30 days of task order award and shall consist of the following:

i) A determination regarding whether the work can be performed in-house by the Contractor or if subcontracting is required;

ii) Specification of the resources and services to be provided;

iii) A description of the key development objectives;

iv) Delineation of project milestones and timelines for the accomplishment of milestone objectives;

v) A description of the technical approach to carrying out the project and the physical facilities and other necessary resources to be made available;

vi) A description of the project deliverables and a timeline for completion;

vii) A list of proposed scientific and technical personnel and a description of their qualifications and relevant experience;

viii) A detailed budget of all project costs.

3) Weekly Progress Summary with Meeting Minutes to be discussed via teleconference with the COR and CO. This will provide real-time updates with a summary of status on any problems that may have arisen. This will ensure effective communication between the contractor, the COR, and CO.

4) A Quarterly Technical Report (3 per year) to provide an update on all progress being made, any issues that have occurred as well as the resolutions to those issues.

5) A Quarterly Summary of Intellectual Property Assessment is to be completed and submitted by a qualified legal expert.

6) A Quarterly Subcontractor Performance Assessment detailing of progress toward achievement of defined milestones; identity and resolution of any problems with subcontractor performance.

7) An Annual Technical Report summarizing the compounds synthesized and all studies, tests, and procedures performed during the year.

8) A Final Study Report is to be completed and submitted upon completion of each study.

9) A Technology Transfer Report shall be submitted for each Technical Transfer Package and shall include information on material reagents and in-place training of others at the Contractor’s or subcontractor’s site or a third-party site sufficient to completely and effectively transfer the technology.

V. TECHNICAL REPORTS AND DELIVERY SCHEDULE

Satisfactory performance of the contract is defined as satisfactorily performing the statement of work and delivering the following items as specified in task orders:

Item Type of Deliverable Recipients & Number of

Copies Due Date

1. Initial Project Plan 1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

Within 30 days of task order award

2. Weekly Progress Summary with Meeting Minutes

1 Copy to COR 1 Original to CO/CS Teleconference and Electronic (via e-mail)

Weekly date and time to be determined upon task order award.

3. Quarterly Progress Report 1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

First quarterly report due on/before Dec 31, 2023; thereafter, all are due on or before March 31, June 30, and September 30.

4. Quarterly Summary of Intellectual Property Assessment

1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

First quarterly report due on/before Dec 31, 2023; thereafter, all are due on or before March 31, June 30, and September 30.

5. Quarterly Subcontractor Performance Assessment

1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

First quarterly report due on/before Dec 31, 2023; thereafter, all are due on or before March 31, June 30, and September 30.

6. Annual Technical Report

1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

An annual report is due December 31st of each year beginning in 2024.

7. Technology Transfer Report

1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

Due each time a compound/product transfer occurs

8 A Final Study Report 1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

Due at the end of each task order study

2) SOW – SAMPLE TASK 3 – Kinase Inhibitor Identification through Chemical Optimization

Many kinases have been identified with expression primarily or exclusively in the male or female reproductive tract with functions/activities critical to produce functional male or female gametes. Many kinases have also been implicated in the progression of reproductive health, or related, indications (e.g., infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism). The research contained within this sample task order will encompass discovery and optimization of allosteric small molecule antagonists for defined kinase targets using scientific disciplines to support that goal, including but not limited to, assay development, high throughput screening, computational chemistry, intellectual property evaluation, medicinal chemistry and pharmacology.

The scope of this sample task order is to identify novel allosteric inhibitors of the kinase starting from identified hits following high throughput screening as outlined in sample Task 2. The sample tasks described in this SOW may be requested for up to 3 distinct kinases. The cost differences among the different kinases are expected to be minimal and the offeror should provide a budget on a per-kinase cost basis. The government may or may not award on all 3 kinases and reserves the right to award based on what is in the government’s best interest or most feasible.

Independently, and not as an agent of the Government, the contractor shall furnish all the necessary services, qualified personnel, material, instrumentation, facilities and capabilities to discover, design, synthesize and optimize novel chemical entities to identify two chemical series of allosteric inhibitors against a validated reproductive tract-specific or reproductive health related kinase. Both identified chemical series must be distinct from established intellectual property and amenable to the establishment of new intellectual property. The required research requires evaluation of active hits to identify two distinct chemical series with freedom to operate that interact specifically with the target and development of a plan for their optimization as entities for clinical development. The Contractor must have continuous ability to perform intellectual property analysis by qualified individuals or legal personnel.

Technical Approach

• Propose and perform secondary and tertiary screens to eliminate potential false positive and false negative hits against provided active hits.

• Describe and perform the studies needed to generate and characterize compounds for selection of two distinct lead chemical series, including freedom to operate investigations.

• Provide an estimate and justification of the number of compounds that are expected to be synthesized to identify two distinct lead chemical series.

• Describe the criteria to be used to select two novel, distinct lead chemical series, including freedom to operate and the ability to establish intellectual property.

• Propose a strategy for structure based chemical optimization of both series using state-of- the-art methodologies.

• The use of medicinal chemistry and computational chemistry are required.

Period of Performance: 24 months

The Contractor shall be required to prepare and submit the following reports electronically to the Contracting Officer’s Representative (COR) and the Contracting Officer (CO):

1) Counter screen results with structures, intellectual property evaluation of identified leads, identification of two lead series and a strategy for optimization will be delivered to the COR.

2) An Initial Project Plan will be due within the first 30 days of task order award and shall consist of the following:

i) A determination regarding whether the work can be performed in-house by the Contractor or if subcontracting is required;

ii) Specification of the resources and services to be provided;

iii) A description of the key development objectives;

iv) Delineation of project milestones and timelines for the accomplishment of milestone objectives;

v) A description of the technical approach to carrying out the project and the physical facilities and other necessary resources to be made available;

vi) A description of the project deliverables and a timeline for completion;

vii) A list of proposed scientific and technical personnel and a description of their qualifications and relevant experience;

viii) A detailed budget of all project costs.

3) Weekly Progress Summary with Meeting Minutes to be discussed via teleconference with the COR and CO. This will provide real-time updates with a summary of status on any problems that may have arisen. This will ensure effective communication between the contractor, the COR, and CO.

4) A Quarterly Technical Report (3 per year) to provide an update on all progress being made, any issues that have occurred as well as the resolutions to those issues.

5) A Quarterly Summary of Intellectual Property Assessment is to be completed and submitted by a qualified legal expert.

6) A Quarterly Subcontractor Performance Assessment detailing of progress toward achievement of defined milestones; identity and resolution of any problems with subcontractor performance.

7) An Annual Technical Report summarizing the compounds synthesized and all studies, tests, and procedures performed during the year.

8) A Final Study Report is to be completed and submitted upon completion of each study.

9) A Technology Transfer Report shall be submitted for each Technical Transfer Package and shall include information on material reagents and in-place training of others at the

Satisfactory performance of the contract is defined as satisfactorily performing the statement of work

Due Date

1. Initial Project Plan 1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

Within 30 days of task order award

2. Weekly Progress Summary with Meeting Minutes

1 Copy to COR 1 Original to CO/CS Teleconference and Electronic (via e-mail)

Weekly date and time to be determined upon task order award.

3. Quarterly Progress Report 1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

First quarterly report due on/before Dec 31, 2023; thereafter, all are due on or before March 31, June 30, and September 30.

4. Quarterly Summary of Intellectual Property Assessment

1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

First quarterly report due on/before Dec 31, 2023; thereafter, all are due on or before March 31, June 30, and September 30.

5. Quarterly Subcontractor Performance Assessment

1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

First quarterly report due on/before Dec 31, 2023; thereafter, all are due on or before March 31, June 30, and September 30.

6. Annual Technical Report 1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

An annual report is due December 31st of each year beginning in 2024.

7. Technology Transfer Report 1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

Due each time a compound/product transfer occurs

8 A Final Study Report 1 Copy to COR 1 Original to CO/CS Electronic (via e-mail)

3) SOW – SAMPLE TASK 4 –Potassium Ion Channel Inhibitor Identification

Several ion channels have been identified with expression primarily or exclusively in the male reproductive tract with functions/activities critical to produce functional male gametes. Ion channels have also demonstrated roles in reproductive health related indications (e.g., infertility, polycystic ovarian syndrome, fibroids, endometriosis, dysmenorrhea, adenomyosis, gynecologic and/or pelvic pain, and vulvodynia, premature birth, placenta health, improving lactation quality and quantity, preeclampsia, perinatal microbiome, gestational diabetes, inflammation, bacterial infections, viral infections, necrotizing enterocolitis, bronchopulmonary dyplasia, pre-term birth, fetal growth restriction, mastitis, Cushing's disease, Down Syndrome, Ricketts, Muscular Dystrophy, Rett syndrome, sepsis, or Autism). The research contained within this sample task order will encompass discovery and optimization of small molecule inhibitors for a defined monomeric potassium ion channel using scientific disciplines to support that goal, including but not limited to, assay development, high throughput screening, computational chemistry, intellectual property evaluation, medicinal chemistry, and pharmacology.

The scope of this sample task order is to use an existing and available cellular based system to develop a high throughput assay to identify novel inhibitors of a monomeric potassium ion channel. In addition, using a high throughput screen and appropriate counter screens, the contractor shall begin with commercially source chemical libraries to identify two distinct chemical lead series and provide a plan to optimize those chemical lead series for subsequent development including, a plan for establishing freedom to operate and characteristics permitting the establishment of intellectual property.

services, qualified personnel, material(s), instrumentation, facilities and capabilities to discover, design, synthesize and optimize novel chemical entities to identify two chemical series of inhibitors…