Safe and effective anti CD antibodies for therapeutic intervention

Abstract CD CD L is a key target for immunomodulation due to its central role in controlling the activation of the immune system This well studied immune switch has been the focus of extensive drug development for over two decades The validation of this drug target consists of reproducible and robust data using rodent and NHP models of chronic inflammation autoimmune disease and organ transplant In fact this is one of the few undeveloped drug targets where antibodies have shown promising therapeutic efficacy in treating human autoimmune disease in several clinical trials Therefore the choice of CD as a drug target for commercial development is clear The limitation on commercializing this clinical success was based on the thromboembolic toxicity of the drugs used in early trials and the limited knowledge on the cause of these adverse events AEs Consequent to these early trials the mechanism of toxicity was shown to be related to the FcR binding capacity of those former antibody drugs Aggressive approaches to fix the AEandapos s have proven successful in early human trials however these molecules show reduced potency in inhibiting the CD pathway likely owing to the use of non conventional drug design ImmuNextandapos s engineering and development of a high affinity anti CD antibody INX shows that silencing the platelet Fc binding and ablating the complement fixation properties of the molecule eliminates the risk of thromoboembolic toxicity as demonstrated in vitro and an in vivo non GLP NHP tox study INX is a high affinity drug with a long half life and likely low immunogenicity Together these features place INX as a best in class drug for several disease indications Systemic lupus erythematosus is the first indication of choice The mechanisms of action of CD also suggest that treating idiopathic thrombocytopena IBD and TNF resistant RA are plausible alternative indications to be considered following the completion of human safety studies The Specific Aims of this proposal are Process Development Formulation Development andamp Manufacture of GLP Tox Material Design of Phase A and B Clinical Trials and Supporting GLP Tox Study When these Aims are complete ImmuNext can perform the IND enabling GLP tox study that will enable partnering of this asset Induction of tolerance the `holy grailandapos of immunology will be one step closer to commercial reality Treatment of human autoimmune disease with antibody based drugs Rituxan Infliiximab Stellara etc has revolutionized the management of rheumatoid arthritis inflammatory bowel disease psoriasis and many others This application is to support the development of a new antibody based therapeutic that we believe will surpass all of these other drugs in the treatment of autoimmunity We propose that this new drug anti CD INX will induce long term remission of disease with intermittent treatment