AIMSPRO
Technically, AIMSPRO is hyperimmune caprine serum raised against an inactivated HIV IIIB viral lysate. The serum is extracted from a closed herd of goats bred and raised in Tasmania. Following a complex GMP purification process the product is frozen and remains in that state until being thawed immediately prior to administration. AIMSPRO is a subcutaneously delivered peptide/polyclonal “large biologic” that is under investigation to evaluate if it can provide a treatment for a variety of neuro-degenerative, inflammatory and autoimmune diseases. AIMSPRO exhibits tri-partite functionality by targeting the HPA axis and other pathways and by regulating several key intracellular protein kinases via a highly coordinated mechanism that gives the drug considerable biodiversity and possible application. AIMSPRO has been administered to patients with a range of conditions including; Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Parkinson’s Disease, Myasthenia Gravis, Motor Neuron Disease, Inflammatory Bowel Diseases (Crohn’s and Ulcerative Colitis), Psoriatic Arthritis, Multiple Sclerosis, Scleroderma, HIV and Hepatitis C.
The demonstration that an injection with AIMSPRO leads, via a modification of the HPA axis, to a substantial Th-1 to Th-2 cytokine shift (with suppression of TNF-alpha generation) led to AIMSPRO’s use in several rheumatological disorders. Positive “low dose” and “fatal dose” LPS studies in various animal species have underpinned the clinical observations. In addition, studies demonstrating the ability of AIMSPRO to augment the neuroendocrine response and inhibit the mixed lymphocyte response, together with the generation of anti-HLA antibodies, point towards a dampening down of the pro-inflammatory response, which is readily seen as being instrumental in the cause and propagation of pathological processes in many disease states. Because AIMSPRO appears to function through these several mechanisms of action, one of which includes significant anti-inflammatory properties, this is what allows the medication to be considered for use in the treatment of various severe forms of acute and chronic neuro-degenerative, rheumatologic and cutaneous diseases. Daval’s scientists are working to secure further mechanisms of action in the anti-inflammatory and protein kinase regulatory realm.
For a more detailed history and account of AIMSPRO please see the Research & Development.
Ceremben
Ceremben, the veterinary equivalent of AIMSPRO, has shown a powerful protective effect in two high dose murine LPS experiments. This data has been further expanded upon in different animal models, as exemplified by a pyrogen study in rabbits, as well as looking at the effects of Ceremben on the cytokine-response to pyrogen exposure in sheep.
Comprehensive Phase I trials have been successfully completed (without adverse events) in horses and sheep. In the Phase II trials Ceremben had shown itself to be a potentially effective treatment for equine endotoxaemia in a low dose LPS model. In a field study of young thoroughbred horses afflicted by chronic lower respiratory tract disease, results showed that Ceremben trended towards statistical benefit over placebo with respect to coughing, auscultatory findings, mucus production (on double-blinded bronchoscopic assessment) and mucus viscosity. There was also a statistically significant reduction of mucus polymorph counts in Ceremben-treated horses. This evidence suggests that the medication may have a clinical indication in the treatment of chronic obstructive pulmonary disease (COPD) in humans. The success of the equine respiratory disease field trial has led to the scoping of a fully powered study in Australia.
In May 2009 the APMVA awarded a Research Certificate for the carrying out of an equine field study in Australia. A Minor Use permit, which enables the sale of Ceremben to Veterinary Surgeons in Australia (for equine endotoxaemia) was then awarded in September 2010 (Permit Number PER12341). A fully powered Phase II study of Ceremben in a respiratory indication in thoroughbreds has been approved.
Ceremben has been shown to have activity in companion animals and certain other species, as well as horses. The positive Phase II efficacy findings are supported by the excellent safety and tolerability profiles in earlier Phase I studies.
AIMSPRO and Ceremben are both fully developed and biologically effective products. They have demonstrated they have been effective in various pathologies and appear to be disease modifying and well-tolerated.