Pipeline

VBX-1000 - First-in-Class Cathepsin-K Inhibitor (Oral Small Molecule)

• VBX-1000 Program is a potent, selective and reversible cathepsin K inhibitor

• GLP/GCP package up and including human phase I

• In vitro and in vivo efficacy in several animal models and humans.

• Cathepsin K is a key player of bone resorption produced by osteoclasts and tooth resorption by odontoclasts.

• Inhibition of cathepsin K by selective inhibitors decreased bone resorption.

• Inhibition of cathepsin K by selective inhibitors does not impair bone formation (decoupling of boneresorption and bone formation)

• Inhibition of cathepsisn K by selective inhibitors improves bone quality.

• Strong proof of efficacy of selective Cathepsin K inhibitors in clinical trials in human; 50% reduction of fracture risk in post-menauposal women (Phase 3). Significant reduction in bone and cartilage degradation in human patients with knee osteoarthritis (phase 2a - 2020).

• No selective Cathepsin K inhibitor yet approved to date for treating human bone and resorptive tooth diseases

VBX-1000 - Potential future Game Changer for the treatment of Periodontitis

• 80% of dogs and cats over 3 years are suffering from periodontal disease (PD)

• Periodontal disease (PD) is one of the most common inflammatory diseases in dogs. It affects the periodontium, leadingto gingivitis and/or several degrees of periodontitis.

• No therapeutic treatment available to treat bone resorption in Dogs and Cats: only antibiotics to limit microbialsystemic infection risk and NSAIDs to manage inflammation/pain. VETBIOLIX with the VBX-1000 program targets periodontitis and aims to control the bone resorption physiopathological process.

• Only the first stage of the disease is reversible. Inflammation of the gums can be reduced with proper care. Afterthat stage, bone loss becomes a factor, and it can't be returned to its previous state. But, stopping the bone lossas early as possible will prevent the disease from advancing to its latter stages and more permanent damage.

• Complete/partial tooth removal (dental surgery) is the only option available when the Periodontitis reach advanceddiseased stage (traumatic for both Pets and Pet’ parents, only managed by a limited numbers of Vetenarian and costly / not appropriate for Cats)

• VBX-1000 Program might be a first-in-class  veterinary medicine for Periodontal disease, Osteoarthritis and Osteoporosis

VBX-1000 - Potential veterinary blockbuster product for canine & feline Periodontitis

VBX-2000 - First-in-Class Adenosine A3 Agonist (Oral Small Molecule)

• VBX-2000 is a structure modifying osteoarthritis Drugs

• Activation of A3R inhibits the NFKb pathway and reduces release of major inflammatory mediators: TNFa, IL1b, IL6, IL8…

• Activation of receptor A3R have anti-inflammatory effects in animal models of inflammatory diseases.

• VBX-2000 improves histopathological lesions and pain in a recognized animal model of osteoarthritis (ACLT induced arthritis in rat; Bai et al. 2022;26:4230-4243)

VBX-2000 - Potential future 1st structure modifying Osteoarthritis Drugs for the treatment of Canine & Feline Osteoarthritis.

• 30% of dogs and cats over 1 year are suffering from Osteoarthritis (long list of publications supporting this number)

• Osteoarthritis is a significant cause of pain, lameness and morbidity in dogs and many otherspecies, including humans

• It is a multi-factorial, progressive, degenerative disease of synovial joints, affecting not only the articular cartilage but also other structures within the specific synovial joint (Loeser et al. 2012). Degradation of articular cartilage, subchondral bone sclerosis, osteophytosis, varying degrees of synovitis, meniscal and ligament degeneration are all characteristics of the disease process

• VBX-2000 : first-in-class disease modifier therapeutic agent for the treatment of Canine / Feline Osteoarthritis by (i) preventing cartilage degradation and (ii) reducing inflammation

VBX-2000 - Potential veterinary blockbuster product for canine & feline Osteoarthritis

• Pet OA market Worldwide reached 2,875 Bn€ in 2021

• Forecast Pet OA market (World): 5,520 Bn$ by 2031

VBX-3000 - First-in-Class 5-hT4 Agonist (Oral Small Molecule)

• 5-HT 4 receptors are expressed in the enteric nervous system of GI tract, and are well-known to beassociated with the modulation of GI motility.

• Activation of 5-HT 4 receptors evokes release of neurotransmitters. In this process, acetylcholine(ACh) release is also promoted at the myenteric plexus.

• Increased release of ACh is attributed to increased motor activity in GI tract.

• VBX-3000 (RQ-10) offers a therapeutic potential for the treatment of hypomotility disorders of the upper and lower GI tract.

• VBX-3000 Program is a new generation, highly selective and safe 5-HT 4 receptor partial agonist

• Superior selectivity profile vs others 5-HT4 agonists

• First in human Study in healthy volunteers completed: (i) well tolerated at doses up to 2mg p.o., (ii) enhanced gastric emptying at 3 μg or above and (iii) no densensitization in an accelerated gastric emptying following 8 days treatment was observed

• No safety issues identified in the Human Study : especially no QTc prolongation and other cardiac abnormal changes were seen in VBX-3000 (RQ-10) phase 1 Study,following single and multiple oral administration

• Strong preclinical data generated in Beagle Dog (Tox package for Human Drug Development) confirming (i) VBX-3000 successfully enhanced GI contraction and (ii) VBX-3000 reduce hypomotility induced by Clonidine in Beagle Dogs

VBX-3000 - Potential future 1st new generation prokinetic agent  for the treatment of Canine gastroparesis & Feline coprostasis.

• Prokinetic drugs to restore GI motility are ideal drugs for treating the primary cause of GI dysmotility disorders.

• Today, there is no prokinetic drugs approved for use in companion animals:

• Low doses of erythromycine or prucalopride may be empirically  used off-label

• Agonists of 5HT4 are a prototypical class of prokinetics acting at all levels of GI tract.

• 5-HT4 agonists were human medicines initially approved for treatment of upper GI motility disorders and lower GI motility disorders

• Certain 5-HT4 agonists has been successfully used off-label in dogs and cats suffering from various GI-dysmotility disorders.

• All 5-HT4 agonists initially approved for Human are no longer available after removal  from the Human health market.

• GI-dysmotility disorders in dogs and cats remain important unmet medical needs: VBX 3O00 could become the 1st new prokinetic (5HT4 agonist) for both Gastroparesis in dog and for Chronic Constipation (coprostase) in cat

VBX-3000 - Potential veterinary blockbuster product for canine & feline Gut Motility Disorders

• Pet Gut Motility Disorders market Worldwide reached 0,775 Bn€ in 2021

• Forecast Pet Gut Motility Disorders market (World): 1,520 Bn$ by 2031