ExeVir Bio Announces New Publication from VIB Scientists Showing Potent and Broad Neutralizing Activity and Infection Protection Against SARS-COV, its Variants of Concern and Related Coronaviruses

- XVR011 antibody expected to be effective against SARS-Cov-2 and importantly its rapidly spreading variants and other Sarbecoviruses to emerge in future

- Unique Llama-derived VHH72-Fc antibody (XVR011) for potential treatment and prevention of Covid-19, ready to start human trials

GHENT, Belgium, March 9, 2021 /PRNewswire/ -- ExeVir, which is developing single domain antibody therapies providing broad protection against viral infections, announces the preprint communication on BioRxiv of research by VIB scientists on the XVR011 antibody, demonstrating highly potent viral neutralizing activity, protection against infection by SARS-COV-2 and therapeutic efficacy in in vivo mouse and hamster models and minimized development of alveolar [lung] damage.  See link to paper: https://www.biorxiv.org/content/10.1101/2021.03.08.433449v1

As global vaccination progresses with SARS-CoV-2 likely staying endemic in the human population for the foreseeable future, antibody immunity escape variants are likely to become the causative agent for a large proportion of Covid-19 disease, and antibody therapeutics that work against those variants remain an urgent need.

Torsten Mummenbrauer, CEO of ExeVir Bio, said: "Covid-19 vaccines will unquestionably be a cornerstone of controlling the pandemic, yet a significant population segment will also need treatments. Immunity may be short-lived and vaccine efficacy may be lower in the elderly and immunosuppressed who are most at risk of developing severe Covid-19, as well as potentially in patients with Covid-19 infection caused by new variants. Limited vaccine availability in many countries, vaccine hesitancy and viral evolution to escape human immunity, of which we are now acutely aware as we are seeing rapidly spreading new variants, are other factors of uncertain impact. Hence, passive antibody immunotherapy with potent and broadly neutralizing molecules like our XVR011, to prevent or suppress viral replication in the lower airways, should find an important place in rescuing Covid-19 patients."

Professor Xavier Saelens, Molecular Virology Group Leader, VIB-UGent Center for Medical Biotechnology, said: "The study demonstrates that the mutations in the viral spike protein of the recently observed SARS-CoV-2 'Variants of Concern' (VoCs) do not hamper neutralisation by XVR011. This includes the variants first observed in South Africa (B.1.351) and the UK (B.1.17), which are neutralized by XVR011 with equal potency as earlier SARS-CoV-2 pandemic strains. This contrasts with reported loss of activity due to these mutations for several of the neutralizing antibodies that have received an emergency use approval in the USA for non-hospitalized patients, and for several more that are still in clinical trials."

As the world is gearing up to be better prepared against future outbreaks of other Sarbecoviruses, the family to which SARS and SARS-CoV-2 belong, the scientists have determined that XVR011's VHH72 epitope is uniquely highly conserved across Sarbecoviruses and hence XVR011 binds to a broad variety of spike proteins of these viruses. XVR011 is therefore expected to be effective against most circulating SARS-CoV-2 and-1 viral variants as well as a broad range of other related coronaviruses (sarbecoviruses) known to be circulating in animal (bat) populations.

Professor Nico Callewaert, Scientific Director, VIB-UGent Center for Medical Biotechnology, commented: "The cross-disciplinary work at the VIB, ExeVir, UCB and our many collaborators have enabled rapid progress and firmly established the ground for clinical development of XVR011 for potential treatment and prevention of Covid-19. With manufacturing and formulation support from UCB, a highly regarded leading pharmaceutical development organization, we are excited to be ready to start clinical testing of XVR011 imminently. XVR011 is the first European broadly neutralizing antibody based Covid-19 therapeutic approach with best-in-class potential to meet the current and future challenges posed by the spillover of coronaviruses into humans".

About XVR011 (VHH72-Fc)

Exevir's lead asset XVR011 is a single domain-based anti- Covid-19 antibody (VHH-Fc) optimized for stability, safety, broad neutralizing capability and excellent manufacturability. It demonstrates best-in-class potential offering breadth and potency against a range of Coronaviruses and is significantly differentiated from other antibody treatments

• The single domain antibody (VHH) anti-coronavirus platform was developed by VIB-UGent scientists, Professors Xavier Saelens and Nico Callewaert
• The lama-derived single-domain antibodies are smaller than human antibodies and can attach to parts of a virus that are difficult to access for the human immune system
• XVR011 inactivates spike proteins and sterically blocks spike binding to ACE2, preventing virus from entering a human cell, stopping viral replication; this supplements the patient's own immune response in a critical time window during which many patient's immune system reacts too slowly, giving it more time to do its job and eliminate the virus.
• Epitope is much less susceptible to human antibody immunity pressure that can lead to "viral escape", resulting in retained potency against such escape variants – No impact of any variants of concern on potency as of today
• XVR011: Targets unique epitope in conserved region, leading to broad spectrum of binding to spike RBDs across numerous sarbecoviruses

XVR011 fits across the coronavirus treatment paradigm from hospitalised to recently diagnosed patients as both a therapeutic and prophylactic

• Number of Covid-19 cases remains high, with the virus expected to become endemic for the foreseeable future, and with the virus mutating incl. under human antibody immune pressure. Chronic implications in those who survive COVID-19disease, such as lung damage, impact on heart, neurological signs and symptoms; to date unclear durability of protection from vaccines.
• Therapeutic use could help slow viral replication in the lungs, reduce inflammation, and give patients valuable time to raise their own productive immune response.
• XVR011 Covid-19 IV (intra venous) – for hospitalized patients with mild to moderate symptoms. IV formulation allows systemic exposure to penetrate lung tissue.
• XVR011 Covid-19 SC (sub cutaneous) – earlier, prevention of progression for patients who have tested positive and are at medical or professional high risk, asymptomatic or with mild symptoms but not hospitalised. SC formulation facilitates accessibility for earlier stage patients.
• Prophylactic use could protect particularly susceptible individuals in which vaccination is contra-indicated or less effective, and deployment from a stockpile could support the ringfencing of a SARS-like virus outbreak in the future.

About ExeVir Bio

ExeVir Bio is harnessing its VHH technology platform to generate robust antiviral therapies providing broad protection against viral infections, including coronaviruses. It is a spin out from VIB, the world class Belgium-based life sciences research institute, based on the work of Professor Drs Xavier Saelens and Nico Callewaert from VIB in collaboration. ExeVir Bio is led by a team of experts that combines international biotech and pharma experience with a successful track record of developing and bringing products to market. It has raised over €23M from blue chip investors led by Fund+, VIB, UCB Ventures, FPIM, V-Bio and several Belgian Family Offices.

About bioRxiv

BioRxiv (pronounced "bio-archive") is a free online archive and distribution service for unpublished preprints in the life sciences. It is operated by Cold Spring Harbor Laboratory, a not-for-profit research and educational institution. By posting preprints on bioRxiv, authors are able to make their findings immediately available to the scientific community and receive feedback on draft manuscripts before they are submitted to journals.