Atriva Therapeutics obtains approval from German authorities for Phase II trial in COVID-19 patients, led by Charité Clinic in Berlin

Atriva Therapeutics obtains approval from German authorities for Phase II trial in COVID-19 patients, led by Charité Clinic in Berlin

- RESPIRE is a placebo-controlled, international, multi-center trial treating hospitalized patients with moderate to severe COVID-19

- The Phase II clinical trial will evaluate efficacy, safety and pharmacokinetics of ATR-002, an orally available small molecule with a beneficial dual antiviral and immunomodulatory effect

- Charité - Universitätsmedizin Berlin, and further German and international clinical trial sites to start enrollment of 220 patients

Tübingen and Frankfurt (Germany), January 5th, 2021 - Atriva Therapeutics GmbH, a biopharmaceutical company pioneering the development of host-targeting antiviral therapies, announced today approval from the German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) to initiate a pivotal Phase II clinical study with ATR-002 to treat hospitalized patients with moderate to severe COVID-19.

RESPIRE^[1] is a randomized, double-blind, placebo-controlled, international, multi-center Phase II clinical trial in 220 adult patients with moderate to severe COVID-19, requiring hospitalization, but not requiring ICU admission or ventilator support at the time of screening or randomization. On top of standard of care, half the patients will receive ATR-002 900 mg, administered as tablets once daily on day 1, followed by ATR-002 600 mg once daily on days 2 to 6. Patients in the control group will receive placebo in a matching scheme, on top of standard of care.

Primary endpoint of the study is to prove the efficacy of ATR-002 versus placebo in addition to standard of care; secondary endpoints include the measurement of changes in clinical signs and symptoms and other relevant clinical parameters, scores, and study events. Outcomes will be assessed based on the clinical severity status on day 15, using a 7-point ordinal scale as suggested by the WHO COVID-19 Therapeutic Trial Synopsis.^[2] All patients will be followed-up for 90 days. The study will also evaluate the pharmacokinetics of ATR-002.

The Atriva lead candidate ATR-002 is a small molecule developed specifically to treat respiratory viral infections by inhibiting MEK, a host cell factor required for the replication of various RNA viruses, including influenza virus and SARS-CoV-2. MEK also modulates cytokine and chemokine release. Due to this mode of action with a dual benefit, ATR-002 not only inhibits viral replication but could also prevent a cytokine storm and the associated disease progression to a life-threatening condition and, thus, reduce the resulting burden on hospitals and healthcare systems.^[3]

"We are delighted to receive this approval from the German authorities and are grateful for their positive feedback and encouragement. At the same time, we are preparing for additional approvals to involve clinical centers in other European and Non-European countries," said Dr. Rainer Lichtenberger, co-founder and CEO of Atriva. "After the recent financing and commitment from our investors, this authorization further enhances the clinical development program of ATR-002, the only host-targeted antiviral specifically developed to treat respiratory RNA virus infections."

Prof. Martin Witzenrath, M.D., Vice Director Department of Infectious Diseases and Respiratory Medicine at Charité - Universitätsmedizin Berlin, Germany, will act as Global Coordinating Investigator. The study will be run at Charité and additional German and international clinical centers.

Explaining the significance of the study, Prof. Martin Witzenrath said: "There is an urgent need for an effective treatment to stop COVID-19 patients from progressing to critical conditions requiring intensive care and causing potentially permanent health issues and even death. ATR-002's capability to both fight the virus and combat the excessive immune response that we see in patients with moderate or severe COVID-19 makes it a very promising therapeutic candidate for this patient population. We are confident that this pivotal study will quickly lead to an effective treatment for the patients most severely affected by this disease."

"Starting a Phase II clinical trial with ATR-002 in patients suffering from COVID-19 is an important step for Atriva and we have every confidence in the expertise and support of the Charité medical team to lead this study. With this trial, we intend to rapidly advance our drug candidate so patients in need for therapeutic options can potentially benefit from it. Ultimately, our goal is to provide a safe antiviral that can help treat not only infections with SARS-CoV-2, but also influenza and future emerging RNA virus outbreaks," concluded Dr. Martin Bauer, M.D., FNWC, Atriva's Chief Medical Officer.

About ATR-002's mode of action with dual benefit

The Atriva lead product ATR-002 is developed specifically to treat diseases such as influenza and COVID-19, caused by RNA viruses. ATR-002 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 virus, hantavirus or respiratory syncytial virus (RSV) and also SARS-CoV-2, the virus that causes COVID-19. In influenza virus infected cells, the interaction of ATR-002 with MEK (MAPK/ERK kinase) prevents export of the viral genome protein complexes (ribonucleoprotein, RNP) from the nucleus to the cytoplasm, thus blocking the formation of functional new viral particles. This ultimately reduces the viral load in the body.^[4]

In addition, ATR-002 has the potential to modulate the pro-inflammatory cytokine response of the body, avoiding overshooting cytokine response that can be caused by such viral infections. MEK inhibition can reduce the gene expression of some of the cytokines involved, like TNF-α, IL-1ß, IP-10, IL-8, MCP-1 and MIP-1a, and thus mitigate the overactive inflammatory response in the lungs of patients who are severely ill with influenza or COVID-19.^[5]

About Atriva Therapeutics GmbH

Atriva Therapeutics, founded in 2015, is a biopharmaceutical company pioneering the development of host-targeting antiviral therapies set up by a team of leading scientists in viral research and seasoned 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 ATR-002 is a first-in-class host-targeting agent which inhibits viral replication in influenza and favorably modulates the body's immune response. ATR-002 is under clinical development and has successfully completed a Phase I trial to demonstrate safety and tolerability in healthy subjects. The Company has obtained regulatory approval for a Phase II study to evaluate efficacy in hospitalized COVID-19 patients; a Phase II study in influenza is planned to start later in 2021. The Company owns eleven 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 located 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.

^[1] 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
^[2] https://www.who.int/publications/i/item/covid-19-therapeutic-trial-synopsis.
^[3] https://doi.org/10.1016/j.healun.2020.03.012.
^[4] Pleschka S et al. Nat Cell Biol 2001 Feb 3:301-5; Planz O Antiviral Res 2013 Jun 98(3):457-68; Haasbach E et al. Antiviral Res 2017 Jun 142:178-4; Laure M et al. Antiviral Res 2020 Jun 178:104806.
^[5] Pinto R et al. Antiviral Res 2011 Oct 92(1):45-56; Planz O Antiviral Res 2013 Jun 98(3):457-68; Schräder T et al. Antiviral Res 2018 Sep 157:80-92.