Atriva announces closing of € 8.6 million ($ 10.2 million) oversubscribed convertible loan

- Round led by existing investors Meneldor and High-Tech Gründerfonds

- Proceeds to be used to start Phase II study with ATR-002 in moderate to severe COVID-19 and clinical development in influenza and other respiratory viral infections

- ATR-002 mode of action inhibits viral propagation of respiratory RNA viruses and prevents the cytokine storm, as demonstrated in preclinical studies

Tübingen (Germany), August 11, 2020 - Atriva Therapeutics GmbH, a biopharmaceutical company pioneering the development of host-targeting antiviral therapies, today announced the closing of a € 8.6 million ($ 10.2 million) convertible loan led by Meneldor B.V. and High-Tech Gründerfonds (HTGF), and joined by existing shareholders and new German and international investors.

The proceeds of the transaction will enable Atriva to start a multinational, double-blind, randomized clinical Phase II study in patients with moderate to severe COVID-19 infections, once authorization is granted by the German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM). It will further be used to prepare a Phase II trial in influenza and to continue building a therapy platform to treat respiratory diseases induced by RNA viruses, such as Hantavirus. ATR-002 has been 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.

Preclinical studies demonstrated that MEK inhibition by ATR-002 inhibits SARS-CoV-2 replication and significantly decreases pro-inflammatory cytokine and chemokine expression in human cells and in an animal model of acute lung injury (ALI). These preclinical studies show that ATR-002 could prevent a cytokine storm and the associated disease progression to a life-threatening condition, such as observed in patients with COVID-19.

"The strong belief in the science on which Atriva was built, combined with drive and endurance of Atriva's management team made Meneldor decide to continue investing in this vital technology. Congratulations to the team. With confidence we look forward to the further development of the company and especially now of the clinical development of Atriva's programs," said Paul Lelieveld, Founding Partner, Meneldor, The Netherlands. "In scientific and medical terms, this therapy approach holds great promise for COVID-19 patients and doctors, until there is broad access to vaccines that can work for everyone worldwide. ATR-002, according to our analysis, has great potential in this approach and potentially also for other RNA virus-related diseases," noted Frans van Dalen, Founding Partner, Meneldor, The Netherlands.

"The recent preclinical studies as well as the Phase I study completed in 2019 give us great faith that ATR-002 will be able to fulfill the urgent need for an effective COVID-19 therapy," said Dr. Frank Hensel, Principal of High-Tech Gründerfonds (HTGF, Germany). "The mode of action of this oral therapy approach certainly differentiates it from other therapies, currently in development. We believe this technology has a high potential for success and could still address other rapidly spreading viral infections of the respiratory tract. Furthermore, it will be a pleasure to continue working alongside the Atriva team through these urgently needed Phase II trials and potentially see the regulatory approval for this orally available small molecule MEK inhibitor."

"With such highly committed investors continuing to support our plans we will now focus on ramping-up this important pivotal Phase II trial to treat patients with moderate to severe COVID-19," said Dr. Rainer Lichtenberger, co-founder and CEO of Atriva. "This transaction is connected to additional ongoing financing activities which will support Atriva all the way through completion of two Phase II programs in COVID-19 and influenza."

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

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.

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. Atriva's 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. A Phase II study to evaluate efficacy in hospitalized COVID-19 patients is in preparation; a Phase II study in influenza is planned to start in early 2021. The Company owns eleven patent families with broad international coverage related to the use of MEK inhibitors and other kinase inhibitors for anti-viral therapies. The patent life runs through 2041. Atriva Therapeutics is located in Tübingen and Frankfurt, Germany.

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About Meneldor
Meneldor is an investment fund, focused on early stage biotech and pharma companies that (re)develop (New) Biological or Chemical Molecular Entities, that have outstanding technology with strong IP, address significant unmet medical needs and attractive markets. Meneldor scouts especially for companies that work on relatively low risk and high growth opportunities, and mainly invests in projects which are in preclinical, Phase I or Phase II and in indications with preferably clear well-defined clinical endpoints. Meneldor's geographic focus is Western Europe.

Contact:
Ir. Paul Lelieveld
Van Heemstraweg 123d
6651 KH Druten, The Netherlands
phone: 57

About High-Tech Gründerfonds
High-Tech Gründerfonds (HTGF) is a seed investor that finances high-potential, tech-driven start-ups. With around EUR 900 million in total investment volume across three funds and an international network of partners, HTGF has already helped forge almost 600 start-ups since 2005. Driven by their expertise, entrepreneurial spirit and passion, its team of experienced investment managers and startup experts help guide the development of young companies. HTGF's focus is on high-tech start-ups in the fields of digital tech, industrial technology, life sciences, chemistry and related business areas. To date, external investors have injected over EUR 2.5 billion into the HTGF portfolio via more than 1,600 follow-on financing rounds. HTGF has also successfully sold interests in more than 100 companies.

Investors in this public-private partnership include the Federal Ministry For Economic Affairs and Energy, KfW Capital, and Fraunhofer-Gesellschaft e.V., as well as the companies ALTANA, BASF, BAYER, B.Braun, Boehringer Ingelheim, Robert Bosch, BÜFA, CEWE, Deutsche Post DHL, Dräger, Drillisch AG, EVONIK, EWE AG, FOND OF, Haniel, Hettich, Knauf, Körber, LANXESS, media + more venture Beteiligungs GmbH & Co. KG, PHOENIX CONTACT, Postbank, QIAGEN, RWE Generation SE, SAP, Schufa, Schwarz Gruppe, STIHL, Thüga, Vector Informatik, WACKER and Wilh. Werhahn KG.

Contact:
High-Tech Gründerfonds Management GmbH
Dr. Frank Hensel
Schlegelstr. 2
53113 Bonn, Germany
phone: 00

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^[3] 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.