Atriva Therapeutics’ lead candidate Zapnometinib shows substantial efficacy against SARS-CoV-2

  • 5 min read
  • New results support the potential of zapnometinib for the treatment of COVID‑19
  • Significant reduction of viral load and pathological signs in vivo
  • Broad antiviral efficacy of zapnometinib against different Coronavirus variants in vitro

Tübingen and Frankfurt, Germany, November 09, 2021 – Atriva Therapeutics GmbH, a biopharmaceutical company pioneering the development of host-targeting antiviral therapies, today announced new results on the efficacy of Atriva’s lead candidate zapnometinib against coronaviruses. The study was conducted in collaboration with Viroclinics-DDL, a leading Dutch contract research organization (CRO) for preclinical antiviral studies.

The preclinical study investigated the antiviral efficacy of zapnometinib against SARS-CoV-2 compared to drug-free controls in a well-established preclinical infection model based on Syrian hamsters. The treated groups showed a reduction of viral load in the respiratory tract and considerable attenuation of pulmonary inflammation and lung injury.

Furthermore, the effect of zapnometinib on different coronaviruses was evaluated in vitro, namely the wildtype, alpha and beta variants of SARS-CoV-2, as well as SARS-CoV-1 and MERS-CoV. The cell culture-based assays demonstrated that zapnometinib successfully inhibited viral replication by more than 90 % in all viruses tested.

“We are happy to see such strong results further corroborating the potential of zapnometinib, especially with regards to improving the lung symptoms. From the mode of action, we expected our lead candidate to be effective also against Coronavirus variants and are very satisfied to see this confirmed,“ said Prof. Dr. Oliver Planz, CSO of Atriva Therapeutics, who initiated and supervised the study with his scientific team. “We are now looking forward to the results of our ongoing Phase II clinical trial even more, which will take us an important step towards our goal of providing a safe and effective treatment for COVID-19 patients.”

The manuscript containing the complete results of the studies is currently in preparation and will be submitted to a well-renowned peer-reviewed journal accordingly.

About zapnometinib’s mode of action with dual benefit

The Atriva lead product zapnometinib (pINN, currently known as ATR-002) is developed specifically to treat diseases such as influenza and COVID-19, caused by RNA viruses. Zapnometinib is a clinical stage MEK inhibitor drug candidate targeting the intracellular Raf/MEK/ERK signaling pathway. This pathway is central for replication of many RNA viruses, such as the influenza virus1, hantavirus2 or respiratory syncytial virus (RSV)2 and also coronaviruses2, thereof SARS-CoV-2. Zapnometinib inhibits the cellular MEK (MAPK/ERK kinase), blocking the formation of functional virus particles in the host cell, ultimately reducing the viral load in the body.3,4 The specific mode of action varies depending on the actual virus type. E.g., in influenza virus infected cells, MEK inhibition blocks the export of the viral genome protein complexes (ribonucleoprotein, RNP) from the nucleus to the cytoplasm.1

In addition, zapnometinib has the potential to modulate the immune response of the body, among others avoiding overshooting cytokine/chemokine response that can be caused by such viral infections. MEK inhibition can reduce the gene expression of some of the cytokines/chemokines involved, like TNF-α, IL-1ß, IP-10, IL-8, MCP-1 and MIP-1a,5,6 and thus mitigate the overactive inflammatory response in the lungs of patients who are severely ill with influenza or COVID‑19.7

About Atriva Therapeutics GmbH 

Atriva Therapeutics, founded in 2015, is a biopharmaceutical company that is pioneering the development of host-targeting antiviral therapies. It was set up by a team of leading scientists in viral research as well as proven industry experts. The company aims to develop a therapy platform to treat severe respiratory diseases induced by RNA viruses with a high unmet medical need, such as influenza and COVID-19. The Atriva lead product zapnometinib (pINN, currently known as ATR-002) is a first-in-class, host-targeting agent that aims to inhibit viral replication and to favorably modulate the body’s immune response in such RNA viruses. Zapnometinib is under clinical development and has successfully completed a Phase I trial to demonstrate safety and tolerability in healthy subjects. The Company is actively enrolling patients in a Phase II study to evaluate efficacy in hospitalized COVID-19 patients.8 A Phase II study in influenza is currently planned, as are further Phase II and III studies in COVID-19. The Company owns 11 patent families with broad international coverage related to the use of MEK inhibitors and other kinase inhibitors for antiviral therapies. The patent life runs through 2041. Atriva Therapeutics is based in Tübingen and Frankfurt, Germany.

Atriva is a founding member of the BEAT-COV initiative. www.beat-cov.de

For further information, please visit www.atriva-therapeutics.com and follow us on LinkedIn and Twitter.

About Viroclinics-DDL

Viroclinics-DDL is a leading specialty contract research organization, serving the biopharmaceutical community with a broad range of preclinical research, clinical diagnostic, assay development, laboratory and clinical trial logistic services. It offers its clients a global reach through a network of 35 processing laboratories. Viroclinics-DDL extensive experience in clinical and preclinical studies for viruses, including its specialty in respiratory and blood-borne viruses, puts the company at the forefront in supporting the development of vaccines, antibodies and antiviral compounds targeting viral infectious diseases. Its in-house state-of-the-art preclinical and clinical BSL-2 and BSL-3 laboratories facilitate complex experiments with highly pathogenic organisms. Viroclinics-DDL is based in Rotterdam, Rijswijk and Schaijk in the Netherlands, and employs more than 350 highly-trained, dedicated scientists and technical experts.

For more information, visit www.viroclinics.com and www.ddl.nl


Contact:
Atriva Therapeutics GmbH

Dr. Rainer Lichtenberger, CEO
+49 69 667781 5180
+49 151 7443 3175
lichtenberger@atriva-therapeutics.com


Media and Investor Relations:
MC Services AG
Eva Bauer / Raimund Gabriel
+49 89 210 228 80
atriva-therapeutics@mc-services.eu

References:

1      Pleschka S et al. Nat Cell Biol 2001; 3:301-5

2    Pleschka S, Biol. Chem. 2008; 389:1273-1282

3   Haasbach E et al. Antiviral Res 2017; 142:178-4

4    Laure M et al. Antiviral Res 2020; 178:104806

5     Planz O Antiviral Res 2013; 98:457-68

6   Pinto R et al. Antiviral Res 2011; 92:45-56

7    Ragab D et al., Front Immunol 2020; 11: 1446

8   RESPIRE – A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients with COVID-19.