XVR011, ExeVir's clinical lead candidate has emerged from scientific research from labs of highly regarded virologist Xavier Saelens and biochemist Nico Callewaert. Nonclinical data has recently been published in Cell and a preprint on BiorxIV. XVR011 is a nanobody-Fc fusion, has best-in-class potential, neutralizes SARS-CoV-2 and minimizes the development of lung damage in hamsters. 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 COVID-19 patient's immune system reacts too slowly, giving it more time to do its job and eliminate the virus. It binds to a unique highly conserved epitope in the viral receptor-binding domain. Its epitope is much less susceptible to human antibody immunity pressure that can lead to viral escape, resulting in retained potency against such escape variants. It thus neutralises the rapidly spreading SARS-CoV-2 variants, and exhibits a unique, wide scope binding across the Sarbecovirus clades. Furthermore, XVR011 has been optimized for stability, safety and manufacturability. XVR011 received approval from the Belgium regulators to move into its Phase 1b. Seven IP patents were filed early on during the pandemic. ExeVir has surrounded itself with both a team of experienced entrepreneurs and is backed by a mix of private and public experienced partners and has a strong board of directors bringing with expertise across the whole value chain. The objectives of this proposal is to demonstrate XVR011 safety and efficacy in a global Phase 2; to strengthen its nonclinical package including neutralising variants data, set-up its manufacturing process and progress its regulatory pathway.

Cervical cancer (CxCa) is caused by high risk types of the human papillomavirus (a.o. HPV16). Prophylactic HPV vaccination is not the standard of care in all European countries, and where approved it is not sufficiently adopted. Once infected, these vaccines no longer prevent premalignant lesions and CxCa, which can only be treated with surgery or radio-chemotherapy. However, this is not effective in recurrent/advanced CxCa. In underdeveloped countries, CxCa is often detected when it is too late for curative treatment. With an estimated global incidence of 500.000 new cases of CxCa and 274.000 deaths per year, the need for an effective therapy is extremely high. Targeted immunotherapy is an effective approach to induce a tumour-directed immune response. Previously, members of the IMMUNISA consortium have formulated ISA101, a cancer vaccine consisting of overlapping synthetic long peptides covering all epitopes of the HPV16 oncogenic proteins. ISA101 has shown promising Phase 1 clinical trial results in patients with advanced CxCa where it works synergistically with chemotherapy. IMMUNISA now proposes the multi-centre randomised Phase 2 CervISA-2 trial; a careful assessment of the efficacy of the proprietary ISA101b therapeutic vaccine in combination with chemotherapy for the treatment of CxCa, measured by a prolonged progression free survival. A multidisciplinary collaboration between leading clinical EU sites specialised in CxCa, a partner providing strategic and operational regulatory service and a cutting-edge biotech SME will enable the optimal implementation of the CervISA-2 trial, exploitation activities and overall project dissemination. This is pivotal to catapult further development of ISA101b as a commercial vaccine and push it towards clinical implementation as fast as possible. For ISA101b, IMMUNISA will provide, 1) clinical data on the efficacy, 2) a solid exploitation strategy and 3) the regulatory framework for efficient translation to clinical use.

Parkinson’s Disease (PD) is a major neurodegenerative disorder with no established treatment modalities capable of modifying disease pathology, and no means of early diagnosis. Vaccines targeting aSyn aggregates are a promising route to disease-modifying therapy for PD, but the current generation of PD vaccines utilise conventional formulations, which are limited in their immunogenicity and require substantial quantities of adjuvant to achieve efficacy. NEXGEN’s proprietary WISIT vaccine platform is the first of the novel class of gluconeoconjugate vaccines (GNCVs), which are administered intradermally and specifically formulated to leverage skin dendritic cells (DCs) to generate substantially stronger and more specific immune responses than conventional vaccines. These stronger immune responses allow substantial reduction in adjuvants, while simultaneously increasing therapy efficacy. NEXGEN will identify and characterise candidate WISIT constructs targeting aSyn (PD-WISITs) and develop a novel extracellular vesicle (EV)-based biomarker assay that enables early diagnosis of PD using liquid biopsies, suitable for point of care use. Safety and efficacy of PD-WISITs will be demonstrated preclinically, before being translated to first-in-human Phase I/Ib clinical trials, along with the novel EV-based biomarker assay. The results of NEXGEN will be the extraordinary accomplishments of cheap and effective disease-modifying treatment of early PD and a novel biomarker assay to diagnose and guide prodromal/early PD treatment. Further still, GNCV technology will be clinically demonstrated, which has the potential to be transformative to the treatment of a wide range of additional diseases, resulting in far-reaching impacts to the health of millions.