Candidate: OT-101

Category: ANTIVIRAL

Type: First-in-class, TGF-beta antisense drug designed to inhibit SAR-CoV-2 replication

Status: Mateon said November 4 that it received approval from Instituto Nacional de Salud (INS), the regulatory agency of Peru, to begin the C001- Phase II clinical trial of OT-101 for the treatment of patients with mild to severe COVID-19 infection.

C001 is a multi-center, double blind, randomized, placebo-control study designed to evaluate safety and efficacy of OT-101 in combination with standard of care on two patient cohorts: 1) mild or moderate disease, and 2) severe disease requiring mechanical ventilation or intubation. The study will enroll approximately 48 patients in Peru, part of the total 72 patients studywide.

The primary efficacy endpoint is the proportion of subjects with clinical improvement score (measured by an 8‑point World Health Organization [WHO] COVID‑19 Clinical Improvement Ordinal Scale) as assessed by the Odds Ratio (OR) at Day 14.

On October 19, Mateon received approval from Argentina regulator Poder Ejecutivo Nacional to begin the company’s Phase II clinical trial assessing OT-101 in patients with mild to severe COVID-19 infection.

The multi-center, double blind, randomized, placebo-control study is designed to evaluate the safety and efficacy of OT-101 in combination with standard of care on two patient cohorts: Mild or moderate disease, and severe disease requiring mechanical ventilation or intubation. The trial is set to enroll 72 patients, of which approximately 24 patients will be recruited in Argentina. The trial’s primary efficacy endpoint will be the proportion of subjects with clinical improvement score (measured by the eight‑point World Health Organization COVID‑19 Clinical Improvement Ordinal Scale) as assessed by the Odds Ratio (OR) at Day 14.

Mateon CEO Vuong Trieu, PhD, presented data at Pharma Forum 2020/ Pharmacology and Toxicology, held September 21, showing that six pancreatic cancer patients showed significant reduction in IL-6 following first-cycle of dosing with OT-101, with two of the six exhibiting a rebound following treatment stop on cycle 1 which decreased again on subsequent cycle 2 of dosing: “The data are supportive of OT-101 against COVID-19.”

In April, Mateon submitted an IND application to the FDA to study OT-101 in a randomized, double-blind, placebo-controlled Phase I study intended to evaluate the safety and efficacy of OT-101 in adults hospitalized with COVID-19 and pneumonia in the U.S.

Three days earlier, a special report in Annals of Pulmonary and Critical Care Medicine detailed Mateon’s medical-scientific rationale for its planned randomized, placebo-controlled, Phase II Study of OT-101 in COVID-19 patients with hypoxemic respiratory failure. The company reasoned that that COVID-19 is a TGF-beta driven disease treatable with TGF-beta inhibitor such as Mateon’s OT-101.

OT-101 targets not only viral replication but often-lethal clinical sequelae of COVID-19, including pneumonia and fibrosis—which according to Mateon gives its treatment an efficacy and safety index on par or superior to Gilead Sciences’ remdesivir. OT-101 has also shown broad efficacy against solid tumors across multiple Phase II oncology trials, including pancreatic cancer, glioblastoma, and melanoma (Study P001) and in high-grade gliomas (Study G004), the company said.


COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA