Therapeutic product candidates
Multiple sclerosis (MS) is a chronic, unpredictable and incurable disease of the central nervous system, which is made up of the brain, spinal cord and optic nerves. Most people are diagnosed with MS between the ages of 20 and 50, although it can develop in individuals as young as 2 and as old as 75 with most patients developing the disease between the ages of 20 and 40.8
The World Health Organization estimates that more than 2.5 million people suffer from MS worldwide.9 As with many autoimmune diseases, MS is far more common in women than men. MS can cause many debilitating symptoms that over time may come and go, or persist and worsen, including blurred vision, loss of balance, poor coordination, slurred speech, tremors, numbness, extreme fatigue, problems with memory and concentration, paralysis, blindness and more. MS develops as a result of the immune system attacking healthy tissue in the central nervous system causing inflammation and damaging the myelin sheath (the protective insulation surrounding nerve fibres), oligodendrocytes (cells that make central nervous system myelin) and subsequently damaging the underlying nerve fibre. MS can either be progressive or be characterised by periods of relapse and remission; the unpredictable nature of the disease makes life very hard for patients. Relapsing-remitting MS is the most common form of MS with 85% of new diagnoses.10
ATX-MS-1467 – a potential game changer for multiple sclerosis
Apitope's lead product candidate ATX-MS-1467 is in development for the treatment of MS. It is a potential first in class treatment for MS that combines high efficacy with an excellent, and thereby differentiating, safety profile.
ATX-MS-1467 is a peptide mixture of 4 different, highly soluble apitopes derived from myelin basic protein (MBP). A study using the experimental model EAE confirms the ATX-MS-1467 tolerogenic mechanism to be induction of antigen-specific Tr1 regulatory T cells producing IL-1011 as has been demonstrated for other apitopes in experimental studies12.
Phase IIa study results demonstrated a significant reduction in total new and persisting brain lesions as well as the volume of brain lesions and has showed a highly favourable and differentiating safety profile with zero treatment-related serious or severe adverse events across the 68 patients treated in clinical studies to date.13,14
Importantly, ATX-MS-1467 halted progression of the disease and demonstrated a strong trend towards overall reduction in disability during the Phase IIa study, underpinned by a significant improvement in cognition after six months of treatment. Apitope believes this constitutes one of the first reports of an improvement in cognition following immunotherapy in patients with MS based on their assessment of the market.14
Most current treatments for MS globally suppress the immune system (thereby increasing the risk of life-threatening infections, cancers and other immune complications) and only reduce relapse frequency and slow the progression of MS, resulting in a poor pay-off between efficacy and safety. ATX-MS-1467 addresses the significant medical need for a high relapse reduction in combination with high tolerability, with the additional potential to improve cognitive disability in MS patients.
8 Mansour A.M., Arevalo J.F., Al Kahtani E, et al. (2014) “Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma”, Journal of Ophthalmology, vol. 2014
9 Haussleite, I, Brüne, M & Juckel, G. (2009). Psychopathology in Multiple Sclerosis: Diagnosis, Prevalence and Treatment. Therapeutic Advances in Neurological Disorders, 2(1), 13-29.
10 National Multiple Sclerosis Society NMSS
11 De Souza A.L.S, Rudin S, Chang R et al. (2018). ATX-MS-1467 Induces Long-Term Tolerance to Myelin Basic Protein in (DR2 × Ob1)F1 Mice by Induction of IL-10-Secreting iTregs. Neurol Ther. Vol 7(1):103-128.
12 Burton, B.R., Britton, G.J., Fang, H. et.al. (2014) Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy. Nature Communications Vol 3; 5: 474
13 Streeter, H.B., Rigden, R., Martin, K.F. et.al. (2015) Pre-clinical development and first in man study of ATX-MS-1467 for immunotherapy of MS. Neurology, Neuroimmunology, Neuroinflammation vol. 2 no. 3 e93
14 Chataway J, Martin K, Barrell K, et.al. (2018) Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis. Neurology Vol 90(11):e955-e962.