D. Attachment 1 - Statement of Work_Final.docx

STATEMENT OF WORK (SOW)

GENERAL INFORMATION

Title of Project:

Biological Therapeutics Product Development Subject Matter Expert Consulting Services to Support the Development of Therapeutic Biotechnology Products (Biologics)

Background Information and Objective:

General

The National Institutes of Health (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 National Institute of Neurological Disorders and Stroke (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.

The NINDS has a need for biological therapeutics development subject matter expert (SME) consultants to provide technical recommendations and advice that will support the translational development of novel therapeutics (Biologics) for NIH drug discovery and development programs. The support included in this contract will cover chemistry, manufacturing, and controls (CMC) expertise.

NIH Drug Development Programs Involving Biologics

This requirement supports the NIH Biologics development projects under the NIH Blueprint Neurotherapeutics Network Biologics (BPN-Biologics) program, the NINDS Ultra-Rare Gene Therapy (URGenT) program, the Helping to End Addiction Long-term Pain Therapeutics Development Program (HEAL-PTDP), and other extramural or intramural NIH drug discovery and development programs.

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 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

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs development of biological therapeutics for neurological diseases (BPN-Biologics). (https://neuroscienceblueprint.nih.gov/neurotherapeutics/bpn-biologics).

The URGenT program (https://www.ninds.nih.gov/Current-Research/Research-Funded- NINDS/Translational-Research/urgent-network) has been established by the NINDS to support the development and clinical evaluation of therapeutics to address ultra-rare genetically based neurological disorders. The network 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 HEAL-PTDP program (https://heal.nih.gov/) is a multi-IC initiative that has been established by the NIH to support preclinical optimization and development of safe, effective, and non- addictive biologic therapeutics to treat pain. The goal of the program is to accelerate the optimization and development of promising small molecule and biologic hits/leads to Phase I clinical trials and readiness for the Early Phase Pain Investigation Clinical Network (EPPIC-Net) or other Phase II clinical studies. Applicants must have a promising biologic hit/lead, robust biological rationale for the intended approach, and identified assays for optimization of the agent. The scope of this program includes optimization and early development activities, IND- enabling studies, development of a PD/ target engagement biomarker, assembly and filing of an IND application and Phase I clinical testing. This is a milestone-driven phased cooperative agreement program involving participation of NIH program staff in the development of the project plan and monitoring of research progress.

The NIH anticipates needing a single consultant during this timePeriod of Performance:

The total period of performance (PoP) includes a one-year base period and one (1) subsequent one year option period. The anticipated PoP dates are as follows:

Base Period: November 17, 2023 – November 16, 2024 – Qty 20 hours Option Line 00001 – Qty 385 hours Option Line 00002 – Travel NTE $1,200.00

Option Period One: November 17, 2024 – November 16, 2025 – Qty 20 Hours Option Line 00001 – Qty 385 hours Option Line 00002 – Travel NTE $1,200.00

Place of Performance:

The primary place of performance will be the Contractor site. Conference calls and email will be the primary mode of communication; however, the Contractor may be required to work at Government facilities or the facilities of selected principal investigators on an as needed basis.

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 that are needed to support NIH biologics programs, including NIH BPN-Biologics, URGenT, and HEAL PTDP.

The Contractor shall provide this support on an ad hoc basis or while serving on NIH Biologics Lead Development Teams (LDTs), which include both SME consultants and NIH staff. These teams will map out a product development and clinical evaluation research strategy, including milestones, and oversee manufacturing and nonclinical study services by Contract Manufacturing Organizations (CMOs) and Contract Research Organizations (CROs).

SME consultants will be expected to provide feedback and guidance on project milestones, development strategy, study design, and data interpretation through in-person meetings, conference calls, and email. Specific consulting responsibilities will depend on the expertise of the individual consultant and the needs of individual biologics projects and programs.

Consultants may be involved in multiple projects.

SMEs will be required on a part-time basis; hours will vary depending on the needs of the projects they are assigned to. The NIH estimates 20-405 hours per year.

Specific Requirements:

The contractor shall provide consulting services in the following Performance Area(s). Please note that the Government will consider SME consultants with expertise in one or more performance areas.

Performance Area 1: Biologics Chemistry, Manufacturing and Controls (CMC) SME(s) Subject matter experts in manufacturing of the various biological therapeutics platforms, including but not limited to, modalities such as therapeutic oligonucleotides (e.g., antisense oligonucleotide -ASOs, small interfering RNAs -siRNAs, etc.), AAV, lentivirus or other viral vector therapeutics, purified proteins, recombinant proteins, peptides, antibody-based and cell-based therapeutics, and ex vivo cellular therapies are required. Biologics CMC consultants will be expected to provide senior-level chemistry, manufacturing and controls expertise and contribute feedback and guidance on projects to the NIH and to LDT members through conference calls and by email.

Please note that, for Performance Area 1, the Government will consider SME consultants with expertise in one or more manufacturing modalities.

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 development and validation of potency assays required for characterization of quality attributes and release testing.

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

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

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

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

g) Provide feedback on proposed biologics formulations.

h) Provide feedback on critical quality attributes, release testing, etc.

i) Evaluate CMC data on a weekly or biweekly basis.

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

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

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

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

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

o) 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.

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

q) 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.

j) Must have experience with replication-defective HSV containing CA8 gene.

Education and Specific Work Experience Requirements:

a) A MS, PhD, or MD in a relevant scientific discipline is preferred. If a BS or MS, must have PhD-level experience in biopharmaceutical industry.

b) Must have at least 10 years of relevant professional experience.

c) Must have at least 10 years demonstrated experience in biologics product development.

d) Must have at least 10 years of experience in managing or being a senior leader in biologics development projects in the biopharmaceutical industry.

e) SME consultants supporting the URGenT program must also have at least 5 years of experience in supporting rare and/or ultra-rare biologics product development programs.

f) SME consultants supporting BPN-Biologics must have at least 10 years of experience across broad biological therapeutics product development programs, including cellular therapy, gene therapy and immunotherapy.

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

h) Experience interacting with the FDA or other regulatory authorities preferred.

i) Extensive understanding of FDA or other regulatory agency requirements for IND submissions and clinical trial execution (and when applicable for 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.

Deliverables and Reporting Requirements:

SME consultants 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.

Consultants 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:

The Contractor may be required to travel within the contiguous United States to provide the services described in this SOW. The Contractor shall make its own travel arrangements; the Government shall reimburse all reasonable travel costs up to the Government approved limits.

All travel arrangements must be made in accordance with Federal Travel Regulations in effect at the time of travel and must be approved by the Contracting Officer’s Representative and authorized by the Contracting Officer prior to being finalized or invoiced.

Information System Security Plan:

The Contractor must ensure that any computer system used in the course of this contract shall include the following features:

1. Any computer used in relation to this contract must be patched with most updated IT Security Patches.

2. Any Contractor computer used in relation this contract must have virus protection loaded and running with definition files that are updated on at least a daily basis.

3. Hard drives and portable media used for this contract must be encrypted using the FIPS 140-2 standard.

4. Contractors are required to take NIH Security and Privacy Training annually http://irtsectraining.nih.gov/

5. Contractor are required to sign the NIH non-disclosure agreement http://irtsectraining.nih.gov/NIH_Non-Disclosure_Agreement.pdf

6. Contractors are required to report any lost or stolen NIH data to the NINDS ISSO within one hour of knowing of the lost or theft even if the data is on a Contractor furnished computer.

7. Contractors are required to adhere to the NIH IT rules of behavior which can be found at https://ocio.nih.gov/InfoSecurity/training/Pages/nihitrob.aspx

8. Any computers used in reference to this contract must be assessed for vulnerabilities.

9. Any computers used in reference to this contract must be backed up on an external hard drive which is password protected.

10. Any computers used in reference to this contract must have auditing enabled such that if an incident occurred then that event could be reconstructed.

11. Any computers that are used in reference to this contract must employ at a minimum username and password authentication or if possible two factor authentication.

12. Any computer used in relation to this contract must be password protected. All Password must meet the NIH standard such that users must choose passwords that have at least eight characters and at least three of the following types of characters:

a. capital letters

b. lower case letters

c. numeric characters

d. special characters (!@#$%^&*()_+|~-=\`{}[]:";'<>?,./)

Data Rights:

The NIH shall have unlimited rights to, and ownership of, all deliverables provided under this contract, including reports, analyses, recommendations and all other deliverables. This also includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights General,” shall be incorporated by reference into any resulting award.

Project related data 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.

Section 508—Electronic and Information Technology Standards:

Section 508 of the Rehabilitation Act of 1973 requires that Federal agencies’ electronic and information technology (EIT) is accessible to people with disabilities. The Federal Acquisition Regulations (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 state that they will comply with the requirements of Section 508 or cite a justifiable reason for an exception.

Confidentiality of Information:

Consultant(s) shall guarantee strict confidentiality of the information/data that is provided by the NINDS or by any other participant on a project to which the consultant is assigned. The NINDS has determined that the information/data that the consultant will be provided during the performance of the consulting contract is of a sensitive nature.

Consultant(s) may only disclose the information/data generated for a particular project to other participants on that same project. These specific individuals will be identified when the consultant is assigned to a project.

Disclosure of the information/data, in whole or in part, by the consultant to anyone else can only be made after the consultant receives prior written approval from the Contracting Officer.

Whenever the consultant is uncertain with regard to the proper handling of information/data under the contract, the consultant shall obtain a written determination from the Contracting Officer.

Contractor agrees that it will not use the Confidential Information for any purpose except as set forth within this SOW, unless such time as such Confidential Information becomes public information.

Publications and Publicity:

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

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 Regulations (FAR).