Statement of Work

Proposal Number: MTEC-20-09-COVID-19-065


Title: Treatment and Prevention of Acute Respiratory Distress Syndrome (ARDS) in Patients with COVID-19 3 a

ACURO approval needed: No

HRPO approval needed: Yes

EGS#: MT20009.065

Die i! provide all FDA communications and documents related

to this award for review if requested by SOTR, HRPO and ORP.


Providing a pharmacologic therapeutic to accelerate recovery in patients with COVID-19 and prevent progression to moderate-to-severe ARDS would overcome many of the challenges facing lack of hospital beds, ventilators and trained personnel including in the military setting. Preclinical models, large human observational studies, and human genetic studies from leading groups worldwide have converged on the concept that a vascular endothelial receptor, Tie2, may play a pivotal role in the defense against microvascular breach in ARDS. Ree il) exhibit an acceptable safety profile and show efficacy for treatment and prevention of COVID-19 associated ARDS and be a life- saving therapeutic for service members in the field suffering from the devasting respiratory effects of COVID-19.

Scope: will exhibit an acceptable safety profile and show efficacy

for treatment of COVID-19 by promoting earlier recovery and preventing progression to moderate to severe ARDS via pleiotropic actions to (a) restore vascular barriers; (b) blunt inflammation; (c) enhance endothelial cell viability; (d) reduce pulmonary vascular resistance; (e) attenuate in situ thrombosis; and (f) promote lymphatic function for the clearance of lung edema.

in patients with moderate to severe not yet requiring mechanical ventilation.

Project Objectives: 1. Safe and efficacious dose for treatment of warfighters with moderate to severe COVID- 19 to prevent progression to ARDS and promote earlier recovery 2. Submit to FDA emergency use authorization

3 a for emergent use

Major milestones (deliverables): 1. Demonstrate safe and efficacious dose of patients with ARDS due to COVID-19 2. Receive FDA authorization for emergent use or advance to Phase 3


Task 1: Study Development (100% complete)

Request for Project Proposals MTEC-20-09-COVID-19_Treatment_MIDRP

Number W81XWH-15-9-0001

Time: Approximately 14 days Deliverable: Research Protocol

Task 2: IRB submission and approval (using central IRB)

Time: approximately 14 days Deliverable: IRB approval

Task 1 and Task 2 Requirements:

To develop research protocol, submit IND and receive IRB approval, internationally

renowned ARDS researcher i

will serve as advisors to the program.

All work will be completed in the United States, with no international sites. Bg ill lead communication

with the US Food and Drug Administration (FDA). will serve as the lead scientific advisor. The program’s steering committee, consisting of an internationally renowned team of ARDS researchers, cardiologists, immunologists and experts in vascular biology as it relates to Tie2 will provide clinical and scientific support for the to treat patients suffermg from ARDS due to COVID-19. This team includes

case report forms (eCRFs).

All sites will use a common protocol and eCRFs maintained by jg in conjunction with the selected CRO and approved by a central IRB. Coordinators and investigators at all enrolling sites will be given access to these electronic CRF’s for data entry. After data entry into the CRF, blinded data will be immediately available to key study personnel for monitoring and ongoing safety analysis. [jg and the selected CRO will be charged with maintaining the protocol and case report form, training all sites on execution of the protocol, monitoring and cleaning the data, maintaining IRB approval, reporting adverse events, and analyzing the final data. Investigators and coordinators at each site will be charged with executing the trial locally.

A qualified medical monitor and [§jggjgj/CRO clinical operations personnel will be on call at all times when the Phase 2 trial is active for site personnel to contact with questions. Collection kits for biological specimens will be provided by a central laboratory to each of the enrolling sites. Specimens will be collected by research personnel at each enrolling site, temporarily stored locally, and then shipped to the program’s central. Specimens will be analyzed in the central laboratory and results entered into the CRF.

Request for Project Proposals MTEC-20-09-COVID-19_Treatment_MIDRP

Number W81XWH-15-9-0001

Task #3: To conduct a Phase 2 clinical trial of jg for the treatment of ARDS in patients with COVID-19. Phase 2 trials will be conducted at 10 clinical sites

D) (4

Time: 6 months Deliverable: Safety and Efficacy in Treatment of ARDS in COVID-19 patients

Task #4: Data Readout

Time: 4 weeks Deliverables: Date readout and analysis Task #5: Request to the FDA for approval of yyy under the Coronavirus Treatment

Acceleration Program (CTAP) or development of Phase 3 protocol for registration study starting January 2021.

Time: 4 weeks Deliverables: Request to FDA

Task #6: Prepare for Phase III

Time: 4 weeks Deliverable: Type C meeting with the FDA

Task #7:

Time: 4 weeks to develop plan Deliverable: Plans for large scale manufacturing

Request for Project Proposals MTEC-20-09-COVID-19_Treatment_MIDRP

Number W81XWH-15-9-0001

Period of Performance Summary:

ee eee a a |

Task #1 Study Development Task #1 Task #2_|1RB Approval ____ AERERERERSRRRERERRR RE ee

Task#a |DataReadout |] R FDAE nt Use Approval

Task #6 Prepare for Phase Ill Task #6 PY

f rose ames LUT Emergent Use

Preferred Payment Method: Cost Reimbursement Milestones (with ceiling).

Payment Schedule: Cost reimbursement requests will be made at the end of each month with an invoice. We anticipate a relatively even distribution of patients but our clinical sites might have the capacity and opportunity to enroll and complete more patients than expected whereby our initial invoices might be higher (or lower).

hicacaatl Milestone Event MTEC Amount Aerpio Cost Share

Execution of Work Order end = of [2 | Ast nvestigstor/ Ste Pass Through | 7715/2020 _ "ll bl A and Business Reports) [a ___[ €RO First Patient Enroled | 8715/2020 _ io a (6 YP ERO 25% Patients Enrolled ———«(9/15/2000 | |e | 3rd Investigator / Site Pass Through 9/15/2020 ee [o___[Athinvestigator Ste Pass Through [0s | i— |i a ne Technical and Business Reports) it [CRO 100% Patients Enrolled | 14/18/2020_| a ESS EC ——— | —— on ——

CRO Final Database Lock oe _ ____ =m

Request for Project Proposals MTEC-20-09-COVID-19_Treatment_MIDRP

Number W81XWH-15-9-0001

15 7th Investigator / Site Pass Through 1/15/2021 OG 16 CRO Clinical Study Report 1/31/2021 OG 17 8th Investigator / Site Pass Through 2/15/2021 OG 18 Final Reports (Technical and Business | 2/25/2021 0 Reports) Total Ola $7,903,574 Data Rights:

The Offeror shall comply with the terms and conditions defined in the Base Agreement regarding Data Rights. It is anticipated that anything delivered under this proposed effort would be delivered to the Government with Government purpose data rights or unlimited data rights. If this is not the intent, then the proposal should discuss data rights associated with each item, and possible approaches for the Government to gain Government purpose data rights or unlimited data rights as referenced in the Base Agreement. Rights in technical data in each Research Project Award shall be determined in accordance with the provisions of MTEC Base Agreement. If applicable, complete the below table for any items to be furnished to the Government with restrictions.

Please indicate your assertion: Unlimited Data Rights.