Indications

Indications

The Atriva Projects

Atriva Therapeutics researches first-in-class host-targeting therapies to treat respiratory viral infections, including COVID-19 and influenza.

Rationale: COVID-19

The COVID-19 death toll is driven by the viral infection, the overwhelming cytokine storm in the infected organs, and pre-existing comorbidities.

Based on its mode of action, its broad-spectrum antiviral activity against many RNA viruses, and its safety profile, zapnometinib (pINN) was evaluated by the Company’s scientists as a drug candidate that might be effective against the coronavirus SARS-CoV-2 – the cause of the COVID-19 pandemic.

Given the urgent need for a therapeutic approach, the company decided to investigate zapnometinib (pINN)’s efficacy against this new virus and conducted preclinical studies with SARS-CoV-2.

The results clearly demonstrated the dual benefit of zapnometinib (pINN)’s mode of action: The host cell factor blocks RNA-virus replication and in parallel it generates immuno-modulating-effects:

  • Benefit 1: Inhibition of the viral propagation by interference with host cell kinase
  • Benefit 2: Inhibition of cytokine response

These observations established the rationale to clinically investigate zapnometinib (pINN) in COVID-19. In December 29th, 2020, Atriva Therapeutics obtained RESPIRE trial approval in COVID-19 patients from German authorities. In April 2021, the Company announced the dosing of the first patient at Charité, Universitätsmedizin Berlin, Germany.

Clinical phase II in COVID-19

RESPIRE [Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial to Evaluate the Safety and Efficacy of zapnometinib (pINN) in Adult Hospitalized Patients with COVID-19] 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 zapnometinib (pINN) 900 mg, administered as tablets once daily on day 1, followed by zapnometinib (pINN) 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 objective of the study is to prove the efficacy of zapnometinib (pINN) 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. All patients will be followed-up for 90 days. The study will also evaluate the pharmacokinetics of zapnometinib (pINN).

Prof. Gernot Rohde, M.D., Head of Pneumology and Professor for Respiratory Medicine and Allergology at the Goethe University Hospital, Frankfurt am Main, Germany, will act as Global Coordinating Investigator. The study will be run at the Goethe University Hospital and additional German and international clinical centers.

Figure: RESPIRE clinical trial design.