Attachment 1_SOW.pdf

STATEMENT OF WORK (SOW)

GENERAL INFORMATION

Title of Project:

Therapeutic Oligonucleotide Platform Biologics Chemistry, Manufacturing and Controls (CMC) Subject Matter Expert Consultant

Statement of Need and Purpose:

The National Institutes of Health (NIH) is seeking a highly experienced, senior-level, biological therapeutics development consultant with expertise in Therapeutic Oligonucleotide Platform Biologics Chemistry, Manufacturing and Controls (CMC). This individual would be expected to provide guidance and advice on biologics development processes for the National Institute of Neurological Disorders and Stroke (NINDS) Ultra-Rare Gene Therapy (URGenT) program, the NIH Blueprint Neurotherapeutics (BPN) Biologics program, and other NINDS and trans-NIH programs where therapeutic oligonucleotide CMC expertise is required.

Background Information and Objective:

The NIH is the nation’s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and apply that knowledge to enhance health, lengthen life, reduce illness and disability, and conduct, support, and make medical discoveries that improve people’s health and save lives. The NINDS is an institute within the NIH that conducts research into the causes, treatment, and prevention of neurological disorders and stroke. The NINDS mission is to seek fundamental knowledge about the brain and nervous system and use that knowledge to reduce the burden of neurological disease. Consequently, the NINDS seeks to support translational development of novel therapeutics, including biologics, that can provide health benefits to patients.

The NINDS has established the URGenT program to support the development and clinical evaluation of therapeutics to address ultra-rare genetically based neurological disorders (https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational- Research/urgent-network). The program will provide neuroscience researchers with funding and access to a full range of industry-style biologics development services and expertise and in the future may expand to include other NIH institutes. The program is intended to rapidly advance patient-customized therapeutics through manufacturing, preclinical toxicology testing, and evaluation in Phase 1 clinical studies.

The NIH Blueprint Neurotherapeutics (BPN) network (https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-neurotherapeutics-bpn-network) is a consortium comprised of the NIH Office of the Director and 14 NIH Institutes and https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/urgent-network https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/urgent-network

Centers (ICs) that support neuroscience research. BPN provides neuroscience researchers with funding and access to a full range of industry-style drug development services and expertise.

The program, originally focused on small molecules, was launched for projects requiring medicinal chemistry optimization, pharmacokinetics (PK), pharmacodynamics (PD), drug manufacturing and formulation, investigational new drug (IND)-enabling toxicological studies support through Phase I clinical testing and it is now being expanded to include the development of biological therapeutics for neurological diseases (BPN-Biologics).

(https://neuroscienceblueprint.nih.gov/neurotherapeutics/bpn-biologics).

The NINDS anticipates needing 1-3 consultants to cover all projects.

Period of Performance:

The total period of performance (PoP) for this requirement includes a one-year base and two one-year option periods. The anticipated PoP is:

Base Period: September 15, 2023 – September 14, 2024 Option Period One: September 15, 2024 – September 14, 2025 Option Period Two: September 15, 2025 – September 14, 2026 Place of Performance:

The primary place of performance shall be the Contractor site. Conference calls and email shall be the primary mode of communication.

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities not otherwise provided by the Government as needed to perform this Statement of Work (SOW).

Any resultant contract will be specific to, and reflect the NIH’s time commitment needs for, the areas of expertise outlined in this SOW. The consultant will provide information and input that will allow the NINDS to design and implement new programs to address external research needs and objectives.

The consultant will be expected to provide feedback and guidance on scientific processes and gap areas/needs assessments through in-person meetings, conference calls, and email. It is preferred that the consultant be able to provide information on the neurological ultra-rare disease space. This will assist the NIH with better understanding the requirements for product developers to move their therapeutics through the research and development stage into clinical evaluation studies as well as development strategies and alternatives. Specific consulting responsibilities will depend on the expertise of the consultant and the needs of the program.

Specific Requirements:

The Contractor shall provide consulting support services to the NIH as follows:

1. Biologics Chemistry, Manufacturing and Controls (CMC) Oligonucleotide therapeutics

SMEs

Subject matter expert in manufacturing of oligonucleotide therapeutics platforms, including but not limited to modalities such as antisense oligonucleotides (ASOs), small interfering RNAs -siRNAs, etc. is required. Biologics CMC consultant will be expected to provide senior-level chemistry, manufacturing and controls expertise and contribute feedback and guidance to programmatic staff through conference calls and by email.

The role of the CMC SME consultant may include, but is not limited to, the following responsibilities and tasks:

a. Review and comment on the adequacy of biologic manufacturing, including scale-up, analytical method development, and process development (upstream and downstream processing) approaches proposed by Principal Investigators (PIs) and CMOs

b. Provide guidance on delivery methods, which may include complex formulations such as polymer, liposomes, and other nanoparticle constructs

c. Provide expert advice on master and working cell and viral bank development and testing

d. Provide strategy and feedback on biologics process development and manufacturing plans proposed by the team

e. Provide feedback on therapeutic oligonucleotide sequences and synthesis processes proposed by the team

f. Provide feedback on proposed biologics formulations

g. Provide feedback on critical quality attributes, release testing, etc.

h. Evaluate CMC data on a weekly or biweekly basis

i. Serve as the CMC expert in order to identify potential product manufacturing challenges and suggest strategies to address these challenges

j. Accompany NIH staff or visit, at NIH staff request, CROs and CMOs under contract to the NIH.

k. Inspect facilities and discuss appropriateness of CRO/CMO proposed methodology

l. CMC consultant may be asked to evaluate the potential tractability (including surrounding IP space) of a proposed biological therapeutic

m. Collaborate on design of investigative studies in support of therapeutics development projects

n. In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage CMC to facilitate preclinical evaluation and safety testing, Investigational New Drug (IND) submissions, and clinical studies

o. Facilitate LDT discussions via telephone and email regarding assigned CMC efforts

p. Provide strategic guidance for the continued development and improvement of the BPN-

Biologics, HEAL PTDP, and URGenT biologics programs

Key Personnel:

The Contractor employee working under this award shall be considered key personnel. Key Personnel requirements are as follows:

General Requirements:

a) Demonstrated senior-level oversight of research and development efforts for biological therapeutics products

b) A track-record of successfully building and leading biologics development teams

c) A significant track-record of scientific accomplishment as evidenced by publications and/or contributions to the development of marketed products

d) Experiences in team leadership, consulting, or service on strategic and advisory boards are desired

e) Must be able to work in a virtual, cross-functional team environment and manage competing priorities

f) Must participate actively in project team discussions

g) Must have strong interpersonal skills, an attention to detail, excellent organizational, writing, communication, presentation, and documentation skills as well as computer and software literacy

h) Broad experience across the entire biologics discovery and development process is especially desired

i) Must have experience working with multi-disciplinary teams at a senior level preferably in the biopharmaceutical industry, especially teams with members from outside organizations and members at various management levels

Education and work experience requirements:

1) A MS, PhD, or MD in a relevant scientific discipline is preferred

2) Preferred to have at least 10 years of demonstrated experience in biologics product development

3) Preferred to have at least 10 years of experience in managing or being a senior leader in biologics development projects in the biopharmaceutical industry

4) Preferred to have at least 10 years of experience across broad biological therapeutics product development programs

5) It is preferred that consultants also have at least 5 years of experience in supporting rare and/or ultra-rare biologics product development programs

6) Experience with biologics for nervous system conditions is preferred but not required.

7) Experience interacting with the FDA or other regulatory authorities preferred

8) Extensive understanding of FDA or other regulatory requirements for IND submissions and clinical trial execution (and when applicable for rare/ultra-rare diseases) is preferred

The proposed Key Personnel will become subject to the provisions of Health and Human Services Acquisition Regulation (HHSAR) Clause HHSAR 352.237-75 Key Personnel as follows:

The key personnel specified in this contract are essential to work performance. At least 30 days prior to the contractor voluntarily diverting any of the specified individuals to other programs or contracts the Contractor shall notify the Contracting Officer and shall submit a justification for the diversion or replacement and a request to replace the individual. The request must identify the proposed replacement and provide an explanation of how the replacement's skills, experience, and credentials meet or exceed the requirements of the contract. If the employee of the contractor is terminated for cause or separates from the contractor voluntarily with less than thirty days’ notice, the Contractor shall provide the maximum notice practicable under the circumstances. The Contractor shall not divert, replace, or announce any such change to key personnel without the written consent of the Contracting Officer. The contract will be modified to add or delete key personnel as necessary to reflect the agreement of the parties.

Level of Effort:

The required level of effort to support NINDS programs may vary depending on the quantity and complexity and the number of projects at any given time.

The NINDS anticipates a Labor Hour contract type and that a minimum of 20 hours of support will be required annually. A Not to Exceed (NTE) amount of 580 Optional Hours may also be exercised, if needed, using FAR Clause 52.217-7 Option for Increased Quantity-Separately Priced Line Item.

Deliverables and Reporting Requirements:

The consultant shall be responsible for providing subject matter expertise in the following areas:

1) Needs and/or gap assessment of ultra-rare gene-based therapeutic development processes

2) Advice on technical flow of various stages of the development process

3) Estimation of time, cost, and effort involved in each stage of the development process

The consultant shall also be responsible for submitting ad hoc summary reports of their analyses as needed.

OTHER CONSIDERATIONS

Government Responsibilities:

The Government does not anticipate providing Government-furnished property. Project related data (i.e., Government furnished information) will be provided to the Contractor for performance of work efforts. All data provided to the Contractor must be treated as confidential and shall not be disclosed to any third party.

Project data will be collected and stored by the NIH. NIH will provide data as needed to the Contractor each time it requests service. The Contractor may store data up to 12 months after initially receiving it, after which time the Contractor should either delete the data files and sanitize the computer using National Institute of Standards and Technology (NIST) SP 800-88 (current revision), or if information is still needed, contact the COR for permission to store the data for a longer period of time.

Travel:

Not Applicable. Travel is not required for this effort and the NINDS shall not reimburse the Contractor for travel expenses incurred in performance of any resultant contract.

Information System Security Plan:

Not Applicable. The statement of work does not require the contractor to (1) develop, (2) have the ability to access, or (3) host and/or maintain a federal information system(s). Therefore, the NIH information security policies and procedures are not applicable to the requirement.

Data Rights:

Not Applicable. Data will not be produced, furnished, acquired, or used in meeting the SOW requirements. Therefore, there are no data rights considerations under FAR Part 27.

Confidentiality of Information:

The NINDS does not anticipate providing information to the Contractor under any resultant contract, however, the Contractor must guarantee strict confidentiality of any Government-furnished information it receives.

Disclosure of information, in whole or in part, by the Contractor to anyone else shall only be made after the Contractor receives prior written approval from the CO. If the Contractor is ever uncertain with regard to the proper handling of information under the contract, it shall first obtain a written CO determination.

Publications and Publicity:

Not applicable. The Contractor will not write or publish articles of data produced as a result of the SOW requirements.

Section 508—Electronic and Information Technology Standards:

Section 508 of the Rehabilitation Act of 1973 requires that Federal agencies’ electronic and information technology (EIT) be accessible to people with disabilities. The FAR Final Rule for Section 508 (EIT Accessibility) can be found at www.section508.gov and at the Access Board’s Web site at https://www.access-board.gov/508.htm. The Contractor must comply with the requirements of Section 508 or cite a justifiable reason for an exception.

Non-Personal Service Statement:

Contract employee performing services will be controlled, directed and supervised at all times by management personnel of the Contractor. Actions of contractor employees may not be interpreted or implemented in any manner that results in any contractor employee creating or modifying Federal policy, obligating the appropriated funds of the U.S. Government, overseeing the work of Federal employees, providing direct personal services to any Federal employee, or otherwise violating the prohibitions set forth in Parts 7.5 and 37.1 of the Federal Acquisition Regulation

(FAR).

file://nidawfsprd01.nida.nih.gov/SHARED/OM/CMB/RED/NINDS_Section/Contracts/EvanFeely/21-004452%20AAV%20Micropurchase%20Consultant/www.section508.gov https://www.access-board.gov/508.htm