PTC Therapeutics, Inc. announced that the U.S. FDA has authorized the initiation of a Phase 2/3 trial to investigate PTC299, a dihydroorotate dehydrogenase (DHODH) inhibitor, as a potential treatment for COVID-19. PTC299 is an oral investigational drug with a novel dual mechanism of action that has the potential to address the two critical elements of COVID-19: 1) the high viral replication and 2) the uncontrolled inflammatory response that ensues after infection. PTC will initiate an integrated Phase 2/3 study in the U.S. in the coming days with additional sites planned globally.

“We are excited about the potential of PTC299 to be part of the solution to this unprecedented global public health crisis and have made it a high priority within our organization,” said Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics, Inc. “The fact that PTC299 inhibits DHODH uniquely addresses the two key issues of COVID-19, namely reducing the high viral replication and also selectively attenuating the immune response caused by the uncontrolled cytokine storm resulting from the SARS-CoV-2 infection.”

PTC299 is an oral, small molecule tablet that inhibits the cellular enzyme DHODH which is used to produce the RNA building blocks for the production of SARS-CoV-2. PTC299 has demonstrated potent inhibition of viral replication in SARS-CoV-2 cell-based assays, which has led to PTC moving rapidly into the clinic. A number of RNA viruses require the same building blocks, which explains why in preclinical tests PTC299 has shown broad-spectrum antiviral activity.

“Infection with SARS-CoV-2 has caused COVID-19 in millions of people around the world and the death of hundreds of thousands. In the year ahead, SARS-CoV-2 could infect and kill even greater numbers of people. As a global community, we are working together with unprecedented speed to find treatments that block the virus and the deadly consequences of COVID-19,” said Dr. Jeremy Luban, Professor, University of Massachusetts Medical School. “PTC299 is among the most promising potential treatments on the immediate horizon because it potently inhibits SARS-CoV-2 in the lab, it has already been used in people, it is already formulated as a tablet, and it may attenuate the deadly inflammation observed in the most severe cases of COVID-19. Additionally, PTC299 targets a cellular enzyme, as opposed to a viral one, and is, therefore, less likely to elicit drug-resistant SARS-CoV-2.”

The integrated Phase 2/3 study will evaluate the efficacy and safety of PTC299 in two stages, the first stage consisting of 40 patients, followed by a larger cohort of approximately 340 patients. The primary objective is to evaluate the clinical efficacy of PTC299 compared with placebo assessed by time to respiratory improvement in adult individuals hospitalized with COVID-19.

PTC299 is also being developed for treatment in oncological indications and has been extensively studied in nine clinical trials in over 300 individuals, including both oncology patients and healthy volunteers. In addition, PTC299 is currently being studied in a clinical trial in acute myeloid leukemia (AML) patients. In a PTC299 clinical study, results showed that PTC299 inhibited DHODH, confirming the mechanism of action in patients.

About PTC299

PTC299 is an investigational oral small molecule that inhibits the cellular enzyme dihydroorotate dehydrogenase (DHODH). Recently, DHODH has been independently identified as one of the top three most promising targets for intervention in COVID-191. PTC299 is being evaluated for the potential treatment of patients with COVID-19. With a novel dual mechanism of action, PTC299 inhibits DHODH activity which leads to a reduction of pyrimidine biosynthesis and SARS-CoV-2 viral replication and selectively modulates the immune response by attenuating the stress-induced inflammatory cytokine storm. PTC299 has broad-spectrum antiviral activity and potent inhibition of numerous RNA viruses with low nanomolar potency. PTC299 is also currently being evaluated in an ongoing clinical study in acute myeloid leukemia (AML). For more information regarding PTC299 clinical trials, visit clinicaltrials.ptcbio.com or www.clinicaltrials.gov and search PTC299