20-09-COVID-19_Treatment_MIDRP

Development of Treatments for COVID-19

The pandemic COVID-19, a disease caused by a novel coronavirus, continues to spread worldwide. As of March 23, 334,981 confirmed cases of COVID-19 have been reported worldwide, with 14,652 deaths from the disease (www.who.int), the total number of COVID-19 cases in the United States is 33,404 and total number of deaths is 400 (www.cdc.gov). Currently, there are currently no FDA-approved vaccines or treatments for COVID-19.

 

The goal of this RPP is to develop prototype countermeasures for the treatment of COVID-19.

 

  • The expected technology readiness level (TRL) at start of the period of performance (POP) is 3/4 and at the end of the POP is TRL 6 [TRL definitions: https://mtec-sc.org/wp-content/uploads/2016/12/TRL-definitions.pdf]
  • The Offeror is expected to have at the onset a candidate therapeutic with non-clinical data (in vitro, tox, pre-clinical data, etc.) suggesting safety and/or efficacy
  • The Offeror should have demonstrated manufacturing feasibility of the candidate therapeutic
  • Offerors who have had at least one meeting with the FDA to discuss the regulatory strategy for their candidate(s) are preferred
  • Repurposing commercially available, approved products or products in clinical development for related indications with demonstrated safety in humans are preferred
  • Partnering with DoD investigators on pre-clinical testing in animal models is encouraged, where appropriate.

 

The expected deliverable at the end of the POP is a final technical report to support a Go/No go decision for the product to enter Phase II clinical trials for the treatment of COVID-19. The research project award recipients were selected from the Offerors who responded to MTEC’s Request for Project Proposals (20-09-COVID-19_Treatment_MIDRP).

 

 

 

Favipiravir for the Treatment of COVID19

Project Team: FUJIFILM Pharmaceuticals USA

Award Amount: $1.38M (additional cost share = $800K)

Project Duration: 18 months

Project Objective: The goals of this project are to conduct an open label randomized Phase 2 clinical trial in hospitalized patients (FAVI-COV-US201) to demonstrate the anti-SARS-CoV-2 activity of favipiravir. A total of 50 subjects will be randomized based on age group and disease severity to receive either favipiravir + standard of care (SOC) or SOC alone.

 

 

 

Ultra-Rapid, Low-Cost Neutralizing Antibody Therapeutic for COVID-19

Project Team: Lumen Bioscience

Award Amount: $9.88M (additional cost share = $459K)

Project Duration: 31 months

Project Objective: A therapeutic to directly prevent and treat infection of the gastrointestinal (GI) tract by SARS-CoV-2 could substantially improve the U.S. response to the COVID-19 epidemic. A GI-targeted therapy to eliminate this viral reservoir could not only reduce overall viral burden, inhibit disease progression, and accelerate viral clearance, but also prevent this common route of infection and block the potentially significant fecal-oral transmission route. Lumen Bioscience (Seattle, WA) has developed an integrated drug development and cGMP manufacturing system uniquely suited to fill this gap. Using Lumen’s unique development and cGMP manufacturing system we will develop an oral SARS-CoV-2 passive immune-prophylaxis product targeting the GI viral reservoir, ready for initiation of a Phase 2 study.

 

 

 

Rapid Development of an Optimized Antibody Therapeutic for Clinical Treatment of Pandemic COVID 19

Project Team: Centivax

Award Amount: $1.21M

Project Duration: 8 months

Project Objective: Centivax is developing a SARS-CoV-2 antibody therapeutic for use in hospital and non-hospital environments engineered for limited single-use dosing with IV and/or subcutaneous injection. Our therapeutic will be useful prophylactically (providing 8-10 weeks of protection for at risk populations typically unable to tolerate a vaccine) as well as therapeutically to treat acute infections. Further, effectiveness in the acute setting allows for rapid therapeutic studies in hospitalized patients. This enables our therapeutic to advance into the clinical setting and into broader field use through compassionate use/expanded access protocols.

 

 

 

Rapid Development of Transmissible, Self-deploying Therapeutic Interfering Particles (TIPs) to Reduce Population-Level COVID-19 Transmission

Project Team: Vx Biosciences

Award Amount: $11.02M

Project Duration: 17 months

Project Objective: he project goals are to: (i) engineer a TIP optimized for SARS-CoV-2, (ii) test safety and efficacy in animal models, and (iii) conduct a Phase-I clinical trial to test safety, tolerability, and immunogenicity of a TIP against SARS-Cov-2. The hypothesis is that an engineered TIP against SARS-Cov-2 will conditionally replicate with SARS-CoV-2, effectively interfere with SARS-CoV-2 replication, lower viral loads, and confer transmissive protection (i.e., TIP R0 > 1). The study design is to rapidly repurpose Gladstone|UCSF technology to engineer TIPs for SARS-CoV-2. VxBiociences will use modern machine learning algorithms to dramatically accelerate candidate selection and test TIP in cell culture and animal models with USAMRIID (see attached letter) and a non-blinded, single-arm Phase-I clinical trial will be conducted in healthy volunteers at UC San Diego. The deliverables are: (i) A validated platform for rapid engineering of libraries of TIP candidates for a previously unknown virus; (ii) demonstration of efficacy and safety of TIPs against SARS-CoV-2 in animal models; and (iii) A TIP candidate with demonstrated safety profile in humans.

 

 

 

Treatment and Prevention of ARDS in Patients with COVID-19 using AKB-9778

Project Team: Aerpio Pharmaceuticals

Award Amount: $3.52M (additional cost share = $2.79M)

Project Duration: 13 months

Project Objective: AKB-9778, a best-in-class Tie2 activator, will treat the devastating, life-threatening complications of COVID-19 by stabilizing the pulmonary vasculature and reducing the inflammatory response in the lungs that leads to Acute Respiratory Distress Syndrome (ARDS). The proposed study seeks to (1) assess the safety of SQ AKB-9778 in COVID-19 patients with ARDS; (2) assess the efficacy of SQ AKB-9778 in COVID-19 patients with ARDS; (3) extend the results of the treatment study to support prevention of ARDS in COVID- 19 patients; (4) expand manufacturing capacity for emergent use in early 2021 (5) receive FDA CTAP approval. The long-term strategy is to scale up manufacturing of a sterile pre-filled syringe on a high capacity line capable of producing 100,000 – 300,000 syringes per batch within 18-24 months.

 

 

 

 

RD-Ad5 in the Treatment of Ambulatory Patients with Early Onset COVID-19

Project Team: Altimmune

Award Amount: $4.73M

Project Duration: 16 months

Project Objective: The aim of the project is to evaluate a novel immunotherapeutic intervention strategy for COVID-19 in a Phase 1/2 clinical trial of ambulatory patients with early onset infection. The therapy is an intranasally administered replication-deficient adenovirus 5 vector (RD-Ad5) that promotes rapid innate immune responses, prevents pulmonary inflammation and multiple organ failure and alters the course of the disease. RD-Ad5 development is supported by a full GLP toxicology program, and 187 subjects have been exposed to RD-Ad5 vectors across 5 clinical studies with a safety experience similar to placebo. The proposed Phase 1/2 study is anticipated to commence in mid-May 2020. Altimmune has been in active discussions the Office of Vaccines Research and Review (OVRR) at the Center of Biologics Evaluation and Research (CBER) at FDA to expedite an IND for the treatment of COVID-19.

 

 

 

Production and Phase 1/2a Trial of Inhaled Immunotherapy for COVID‐19

Project Team: Inhalon Biopharma

Award Amount: $6.91M

Project Duration: 23 months

Project Objective: Inhalon is advancing IN-005, an inhaled monoclonal antibody therapy that can block SARS-2 from spreading in the airways and actively clears the virus from the lung, based on its proprietary muco-trapping technology. IN-005 can be used as both treatment and prophylaxis for military personnel and the general population. When given after diagnosis, we believe our treatment would be highly effective in preventing hospitalization and associated pulmonary morbidities. The proposed project will provide initial safety and efficacy results from a Phase 1/2a in patients diagnosed with COVID-19.