GHDDI Announces Advancement of a Novel Oral Antiviral Candidate for COVID-19 in Its Investigational New Drug Studies

Jan 25, 2022

Beijing, January 25, 2022 – Global Health Drug Discovery Institute (GHDDI) announces that it is accelerating Investigational New Drug-enabling studies and the manufacturing of GDI-4405, a pre-clinical candidate molecule targeting the novel coronavirus 3CL protease. GHDDI is expecting GDI-4405 to enter clinic trials in the second half of 2022. GDI-4405 has shown in multiple experiments potent inhibition of SARS-CoV-2 replication with good bioavailability and safety profile, which positions it to be a potential better specific drug for the treatment and prevention of the continuously evolving COVID-19.

"As the global pandemic continues to evolve, there is an urgent need for more effective and convenient oral treatments to better serve global drug access. To this end, I am proud of our team's hard work and significant breakthroughs, and I am grateful to our founding partners——Tsinghua University, the Bill & Melinda Gates Foundation and Beijing Municipal Government as well as various partners such as the Tencent Foundation, who have supported us. Toward the end of last year, we selected our pre-clinical candidate molecule, GDI-4405, which demonstrated much greater inhibition potency than Pfizer's Nirmatrelvir (the active compound in the approved Paxlovid against SARS-CoV-2 3CL) in multiple assays. The multiple assays included using primary human-derived airway epithelial cells infected with live SARS-CoV-2 viruses, and the Delta variant. GDI-4405 also demonstrated superior bioavailability and exposure in rats and cynomolgus monkeys. In animal toxicology assessments, GDI-4405 demonstrated an excellent safety profile. Its manufacturing cost is also significantly lower than that of Pfizer's Paxlovid," said Dr. DING Sheng, Institute Director of GHDDI and Dean of School of Pharmaceutical Sciences at Tsinghua University.

In response to the global pandemic, GHDDI began targeting SARS-CoV-2 3CL in early 2020. The team successfully designed, synthesized, and tested a series of potent compounds based on 3CL’s structure and function via joint efforts of medicinal chemistry, virology, structural biology, and data science teams, among which GDI-3549 and GDI-4405 demonstrated high potential for development as drug candidates. In May 2021, Pfizer announced that it had selected and advanced PF-07321332 (Nirmatrelvir) into human trials. Given that PF-07321332 is structurally identical to GDI-3549, independently designed and discovered by GHDDI also in 2020, GHDDI decided to select a superior compound, GDI-4405, as a pre-clinical candidate molecule.

3CL protease, as the main protease of COVID-19, is necessary for the replication of the SARS-CoV-2 virus. Therefore, it is an excellent antiviral drug target. Multiple antiviral drugs (e.g., drugs for HIV, HCV) in the market in fact target/inhibit 3CL protease. Among them, Lopinavir and Ritonavir, inhibitors of HIV 3CL protease, have only weak inhibitory activity against SARS-CoV-2 3CL protease in vitro. They have been proved to be ineffective in clinical trials for COVID-19 patients. Thus, discovery and development of potent and specific SARS-CoV-2 3CL protease inhibitors is particularly important. Recently, the U.S. Food and Drug Administration (FDA) approved Pfizer’s Paxlovid (in which Nirmatrelvir is the 3CL protease inhibitor) for treatment of COVID-19.

Currently Pfizer’s Paxlovid is the only highly effective and approved COVID-19 novel oral small molecular drug discovered and developed specifically targeting SARS-CoV-2. It is unprecedented in pharmaceutical development to conduct R&D from identifying the target to clinical trials and eventually receiving approval in less than two years. “It certainly relies on its R&D experience targeting SARS and its incomparable investment,” Dr. DING commented. “Meanwhile, GHDDI also demonstrated its strengths and capabilities in innovative drug discovery. We independently designed and discovered GDI-3549 which was later shown to be the same compound as Nirmatrelvir in Paxlovid. By advancing GDI-4405, a superior candidate, into further studies, we hope to contribute to the global fight of COVID-19 pandemic.”

About GHDDI

The Global Health Drug Discovery Institute (GHDDI) was jointly founded by Tsinghua University, the Bill & Melinda Gates Foundation and Beijing Municipal Government in 2016 through an innovative Public-Private Partnership (PPP). It is an independent and not-for-profit research organization, first-of-its-kind in China. GHDDI is committed to improving global health and saving lives through accelerated development of new drugs and innovative technologies.

GHDDI focuses on translational research – from the bench to the bedside. Its research areas include COVID-19 and antivirals, tuberculosis, malaria, helminth infections, and EED (Environmental Enteric Dysfunction) etc.

For more information, please visit www.ghddi.org.