NasVax develops improved immunotherapeutics.
Anti-CD3 oral immunotherapy: Oral anti-CD3 monoclonal antibody (aCD3 MAb) immunotherapy is directed toward the treatment of inflammatory and autoimmune diseases. Intravenous aCD3 MAb immunotherapy was approved for >20 years for the treatment of graft rejection after transplantation; however, its use for chronic inflammatory and autoimmune disease indications has been hampered due to its profile of significant AEs following injection. Preclinical studies have shown that oral aCD3 MAb does not induce side effects and confers efficacy in preventing induction or progression of disease in a range of animal models of inflammatory and autoimmune diseases. These studies also showed that oral aCD3 MAb induces regulatory T cells (Treg) and anti-inflammatory immune responses that convey efficacy. A Phase 2a clinical trial in 36 subjects with NASH (Nonalcoholic steatohepatitis) or “fatty liver” and the metabolic syndrome showed that oral aCD3 immunotherapy was safe and well-tolerated, and induced positive trends in clinical biomarkers and in immunological markers in groups receiving oral aCD3 MAb but not in the placebo group – some of these trends were statistically significant in spite of the very small group sizes. These favorable effects were reduced blood levels of two enzymes that are biomarkers for liver inflammation which is a favorable outcome for subjects with NASH, and reduced blood levels of glucose and triglycerides and improved performance in glucose tolerance testing which is a favorable outcome for subjects with type-2 diabetes or altered glucose metabolism. Another Phase 2a clinical trial in 36 subjects with chronic hepatitis C also showed that oral aCD3 immunotherapy was safe and well-tolerated, and induced favorable trends in clinical biomarkers and in immunological markers in groups receiving oral CD3 MAb but not in the placebo group – some of these trends also were statistically significant. These favorable effects were reduced blood levels of two enzymes that are biomarkers for liver inflammation and reduced blood levels of hepatitis C virus, both of which are favorable outcomes for subjects with chronic hepatitis C. The oral application for aCD3 MAb immunotherapy was discovered by Dr. Howard Weiner of Brigham & Women’s Hospital, Harvard Medical School in Boston, USA. A Phase 2a clinical trial as an Investigator IND study in the US is ongoing for subjects with ulcerative colitis.
Alzheimer’s Disease Immunotherapy: BBS technology is focused on developing an immunotherapeutic MAb for Alzheimer’s disease (AD). Unlike other AD immunotherapies that have been shown to be unsuccessful in advanced clinical trials, the BBS MAb approach has a novel and distinctive mechanism of action in its binding to its target molecule for inhibiting the production of multiple molecules that contribute to AD and that could offer certain safety and efficacy advantages over other immunotherapeutic and related approaches for AD therapy. The BBS MAb has shown efficacy in improving behavior and inhibiting the production of key pathogenic molecules as well as an improved safety profile in diverse animal models of AD. Recent genetic data show that a mutation in the target molecule for BBS MAb and that causes the same inhibition as that from BBS MAb results in a lowered incidence of AD and improved cognition, which supports the potential clinical benefit of BBS MAb immunotherapy. A new MAb was developed with much higher affinity than the first-generation MAb. The BBS technology is protected by a family of several registered patents and patent applications. The technology was developed by Professor Beka Solomon of Tel-Aviv University in Israel, a recognized international expert in the field of AD research and immunotherapeutic.
The following project has a patent portfolio covering extensive innovative work. Adjuvant-Delivery system: The VaxiSome® technology platform serves as a potent adjuvant for stimulating enhanced immune responses via the Th1 and Th2 pathways and as an efficient delivery system. Preclinical studies showed that VaxiSome-Influenza vaccine is significantly more protective than conventional commercial influenza vaccine and significantly more immunogenic than two commercial adjuvanted influenza vaccines. Studies with adjuvanted hepatitis B, anthrax, and swine and avian flu vaccine antigens have demonstrated increased potency. The adjuvant effect of VaxiSome for increasing antibody titers was apparent in two of four Phase 1/2a clinical trials of intramuscular commercial influenza vaccine (VaxiSome-Influenza) and all clinical studies showed the adjuvant effect of longer duration of HI titers between 1 and 3 months of follow-up post-vaccination. Since immunotherapeutic vaccines generally use adjuvants to amplify immune modulation and since dual Th1/Th2 activities are useful for augmenting both antibody and cell-mediated responses, VaxiSome may be a useful adjunct to immunotherapeutic applications such as cancer and Alzheimer’s disease. VaxiSome® was co-developed at Hebrew University in Jerusalem by Professors Eli Kedar and Yechezkel Barenholz, who is a co-inventor of the anticancer drug marketed in the USA by Johnson & Johnson (as Doxil®) and in Europe by Merck (as Caelyx). We have been working with Novartis on applying VaxiSome® non-exclusively to Novartis’ influenza and one other vaccine target under a Research and Option-for-License Agreement.