XVR011, ExeVir’s lead candidate in 2021, emerged from the scientific research from the labs of highly regarded virologist Xavier Saelens and biochemist Nico Callewaert. Nonclinical data on the discovery and nonclinical development had been published in Cell and, as a preprint on BiorxIV. XVR011 consists of an antigen-binding domain derived from a lama fused to a Fc and had best-in-class potential, neutralizing SARS-CoV-2 and minimizing the development of lung damage in SARS-CoV-2 challenged hamsters. The Lama derived VHH’s Fc fused heavy-chain only antibodies are smaller than human antibodies and therefore are very suited to bind to small clefts of target antigen and attach to parts of a virus that are difficult to access for conventional antibodies. XVR011 neutralizes SARS-CoV-2, prevents ACE2 binding and destabilizes the spike protein, preventing the virus from entering human cells and therefore stopping viral replication. XVR011 binds to a highly conserved epitope that is poorly recognized by vaccine- or infection-induced antibodies and thus complements the patient’s response in a critical time window during which the patient’s immune system mostly reacts too slowly. This made XVR011 very effective against the SARS-CoV-2 variants that escaped immunity of the human host and were rapidly spreading in the population back in 2021. In May 2021, ExeVir had indeed demonstrated that XVR011 could neutralize all major variants of concern (VOC) and exhibited a unique, wide scope binding broadly across the Sarbecovirus clades. Furthermore, XVR011 had been optimized for stability, safety and manufacturability. A strong intellectual property rights (IPR) portfolio was filed very early on during the pandemic.
Early on in the development of XVR011, UCB, a European mid-size Biopharmaceutical company, assisted ExeVir with the formulation of XVR011 and production of the GMP clinical material for the clinical development in their 2000 liters BioPlant. In March 2021, the technology was transferred from UCB’s BioPlant to the large commercial contract development and manufacturer (CDMO), Millipore/Merck, to establish the process to produce first three consistency lots required for registration and commercial manufacturing thereafter. A clinical trial application was submitted to the Belgian regulators offices (FAHMP). At the end of February 2021, XVR011 received approval from the FAHMP to move into the Phase 1b/2. Approval from the Ethics Committee was obtained in April 2021. The first patient in was therefore expected early May 2021, at the time of the submission of this project application.
ExeVir had successfully raised 42M€ from both private and public entities since its creation to support the company through the clinical trial. It had also raised in May 2021, 2.9M€ from the Flemish government and 3,6M form the Walloon Region. However, to leverage the current global market demand, ExeVir had to accelerate its efforts.
The overall objective of the Horizon project was to demonstrate clinically that XVR011 is an efficacious therapeutic COVID-19 treatment with broad neutralizing activity across SARS-CoV-2 isolates and its rapid evolving variants. Indeed, with a Phase 1b clinical study underway, ExeVir needed to quickly progress to Phase 2, further strengthen its nonclinical data, together with VIB, and prepare the EMA and FDA regulatory packages, with Granzer. In order to ensure availability of product at launch, consistency lots had to be produced and commercial manufacturing had to be set-up, with the help of Millipore/Merck. Finally, ExeVir intended to ensure a successful communication and dissemination of the results. The expertise and knowledge acquired in the scope of this SARS-CoV-2 project would also be important in the development of other antiviral biologics directed against other viruses and pandemic threat candidates, e.g. as listed on the WHO Blueprint list of severe emerging diseases.
