ABX464 is the only drug candidate with a potential triple action for COVID-19 treatment: antiviral, anti-inflammatory and tissue repair

• ABX464, as assessed by RTqPCR, inhibits in vitro viral replication of SARS-CoV-2 (COVID-19)
• Simultaneously, Abivax receives ANSM and CPP clearance^[1] to test ABX464 as promising COVID-19 therapeutic candidate in Phase 2b/3, randomized, 1,034 patient, miR-AGE clinical trial
• COVID-19 patients die from acute respiratory failure resulting from viral replication inducing pulmonary hyper-inflammation or longer-term fibrosis
• ABX464 is the sole drug candidate with such promising triple activity, inhibition of SARS-CoV-2 replication shown in vitro, inflammation reduction and tissue repair shown in ulcerative colitis patients
• ABX464 would meet U.S. NIH/NIAID COVID-19 strategic priorities for novel drugs: antiviral, anti-inflammatory, tissue repair, oral administration, convenient once-daily administration

PARIS, FRANCE - EQS Newswire - May 14, 2020 - Abivax SA (Euronext Paris: FR0012333284 - ABVX), a clinical-stage biotechnology company harnessing the immune system to develop novel treatments for inflammatory diseases, viral diseases and cancer, announces today that ABX464 inhibits replication of SARS-CoV-2 in an in vitro reconstituted human respiratory epithelium model, as assessed by Transepithelial electrical resistance and RTqPCR. ABX464 has already been shown to be an effective drug candidate in a severe inflammatory disease, ulcerative colitis. miR-124 specific upregulation by ABX464 can explain the triple effect of the drug candidate on inhibiting viral replication, down-regulation of cytokines that induce inflammation and tissue repair.

The breakthrough scientific data Abivax is reporting today make ABX464 a unique potential treatment for COVID-19 patients. Given the current pandemic and patient's excessive inflammatory response to viral replication as the primary cause of acute respiratory distress syndrome (ARDS) and death of COVID-19 patients, ABX464 with its convenient oral administration and its potential unique triple mode of action, will be urgently tested in a European clinical trial as a potential new treatment to:

• Prevent and reduce inflammation, as already demonstrated in another severe inflammatory disease, ulcerative colitis. Indeed, ABX464 has been shown to upregulate miR-124^[2], a "natural brake" of inflammation. miR-124 down-regulates the multiple chemo- and cytokines involved in the COVID-19 cytokine storm, including TNF alpha, IL-1 beta, G-CSF, IL-6, MCP-1 and IL-17
• Reduce viral replication, mediated by RNA quality control and miR-124 induced inhibition of dynamin 2, a key component necessary for viral replication.
• Promote tissue repair and decrease pulmonary fibrosis.

By binding to the Cap Binding Complex (CBC), ABX464 allows the splicing of a non-coding RNA, LncRNA 205, to produce miR-124, a potent anti-inflammatory microRNA that prevents the translation of multiple chemo- and cytokines as mentioned above. Furthermore, the replication of SARS-CoV-2 requires dynamin 2, a GTPase responsible for vesicle scission and cell penetration of the virus. Dynamin 2 is a target gene of miR-124 and downregulated by miR-124 upregulation.

Antiviral experiments were performed at the International Research Center specialized in infectiology at Claude-Bernard-Lyon-1 University, VirPath laboratory.

Manuel Rosa-Calatrava, Ph.D., VirPath Co-director at the International Center for Infectiology Research in Lyon, France said: "Although in vitro results cannot predict clinical benefits in patients, this antiviral effect against SARS-CoV-2 with ABX464 obtained in our laboratory is very promising, in addition to the known anti-inflammatory properties. ABX464's antiviral effect and protection of tissue integrity are significant as they are based on a physiologic in vitro reconstituted human pulmonary epithelium model and not on the more basic monkey kidney Vero E6 cells model".

Philippe Pouletty, M.D., Chairman of Abivax and CEO of Truffle Capital said: "When we patented the anti-SARS-CoV-2 effect of ABX464, based on our research on its mechanism of action and coronavirus physiopathology, we were very cautious about the ability to demonstrate an antiviral effect in such a stringent human pulmonary epithelium model. We wish to thank the VirPath team that was able to do this rapidly and rigorously."

Prof. Hartmut Ehrlich, M.D., CEO of Abivax added: "Our demonstration of the antiviral effect of ABX464 against SARS-CoV-2 further strengthens the rationale for initiating the miR-AGE clinical study, making ABX464 a promising drug candidate to be investigated clinically. With the recent approval of the miR-AGE clinical trial by ANSM (the French regulatory authorities) and the ethics committee, we will soon start patient recruitment to find out whether this triple activity of ABX464 can be translated into clinical benefits for patients diagnosed with COVID-19."

This potential triple role of ABX464 is extremely promising, and it is the only drug candidate in the world today to show such a complementarity. In addition, convenient ABX464 daily oral dosing allows early treatment of patients in or out of hospital, to potentially act on viral replication, cytokine production, pulmonary tissue repair, before severe complications occur.