Tiziana Life Sciences Announces New Data With Foralumab, a Fully Human Anti-CD3 Antibody

Tiziana Life Sciences plc, the clinical-stage biotechnology company developing targeted drugs for cancer and autoimmune diseases, recently announced new data from animal studies demonstrating the potential of its novel oral therapy with foralumab (NI-0401) for NASH, diabetes, and other life-threatening inflammatory diseases. Tiziana’s foralumab is the only fully human engineered anti-CD3 monoclonal antibody (mAb) in clinical development to date.

“Until recently, it has been generally accepted that despite the convenience and appeal of oral therapies, immunotherapies could not be administered orally because they would be degraded and inactivated by the harsh conditions in the gastrointestinal tract,” commented Gabriele Cerrone, Chairman of Tiziana Life Sciences. “New data demonstrating oral efficacy in animals with foralumab is a major milestone and potential game-changer for the treatment of NASH and autoimmune diseases.”

Foralumab, a long half-life therapeutic mAb candidate, with high affinity and potency for CD3 epsilon, has shown consistent efficacy via oral administration in preclinical studies conducted by Prof. Kevan Herold, a member of Tiziana’s Scientific Advisory Board, at Yale University. “This study demonstrates that oral administration works consistently in our preclinical models with human immune cells. This suggests that oral CD3-specific mAb has the potential for treating NASH, diabetes, and other autoimmune diseases in humans – an entirely novel approach for the treatment of currently unmet needs,” commented Prof. Kevan Herold.

Further animal studies conducted by a member of Tiziana’s Scientific Advisory Board, Prof. Howard Weiner, in his laboratory at Harvard University supports the potential of oral treatment with foralumab for the treatment of autoimmune and inflammatory diseases in humans. A recent publication in J. Autoimmunity (https://www.ncbi.nlm.nih.gov/pubmed/27745778) by Prof. Weiner provides additional support to this novel approach utilizing a murine anti-CD3 mAb (OKT3) in mouse models.

“Our data suggest that oral treatment with anti-CD3 mAb induces an anti-inflammatory response through induction of regulatory T cells (Tregs),” noted Prof. Weiner, “This proof-of-concept of foralumab in humanized mice demonstrates that this approach could be used successfully in humans as well.”

In prior published studies, oral therapy with anti-CD3 mAb (OKT3) to patients with NASH was safe and well tolerated, and the therapy produced positive clinical effects in several hepatic, metabolic and immunologic parameters. These recently published findings in J. Clin Immunol. (https://www.ncbi.nlm.nih.gov/pubmed/25876706), provide further support for future clinical trials to investigate the effect of oral treatment with foralumab in patients with NASH and autoimmune diseases.

“We are very excited with these recent findings and are now moving forward to conduct a proof-of-concept clinical trial in NASH patients with foralumab, said Dr. Ilan Yaron, Director of the Department of Medicine at Hebrew University Hadassah Medical Center, Israel. “Oral immunotherapy using anti CD3 holds promise as an effective anti-inflammatory treatment with high safety profile enabling chronic use of the drug.”

Non-alcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver, which occurs when fat is deposited (steatosis) in the liver due not related to alcohol use. It affects 30% of the western world population. Non-alcoholic steatohepatitis (NASH) is a severe type of NAFLD. NASH occurs when the accumulation of liver fat is accompanied by inflammation and cellular damage. The inflammation can lead to fibrosis (scarring) of the liver and eventually progress to cirrhosis, portal hypertension, liver cancer and liver failure. According to a market research report Nonalcoholic Steatohepatitis Treatment Market 2015-2025 published by iHealthcareAnalyst, Inc., the global nonalcoholic steatohepatitis treatment market is estimated to reach USD 19.5 Billion in 2025, expanding at a current annual growth rate of 10.0% from 2016 to 2025. Currently there is no approved therapy for NASH.

Tiziana Life Sciences plc is a UK biotechnology company that focuses on the discovery and development of novel molecules that treat human disease in oncology and immunology. The company is focused on its lead compound, milciclib, a molecule which blocks the action of specific enzymes called cyclin-dependent kinases (CDK) involved in cell division as well as a number of other protein kinases. Milciclib is currently completing Phase II clinical trials for epithelial thymic carcinoma and/or thymoma in patients previously treated with chemotherapy and has filed an IND to enroll patients in an exploratory trial in Hepatic Cellular Carcinoma (HCC).

The company is also in clinical development of foralumab. Foralumab is the only fully human engineered anti-human CD3 antibody in clinical development. This Phase II compound has potential application in a wide range of autoimmune and inflammatory diseases, such as ulcerative colitis, multiple sclerosis, type-1 diabetes (T1D), inflammatory bowel disease (IBD), psoriasis, and rheumatoid arthritis, where modulation of a T-cell response is desirable.

Tiziana Life Sciences’ clinical development teams are working on its Bcl-3 candidate; which has a prominent role in the metastasis of mammary cancers, and has elucidated the mechanism of Bcl-3 action to be a regulator of cancer cell motility and has also determined that Bcl-3 inhibition suppresses cell motility in triple-negative, HER-2-positive PR- and ER-positive breast cancer sub-types, suggesting that Bcl-3 may be a master regulator of this metastatic property not only in aggressive breast cancers, but across the clinical spectrum of breast disease. The Company is preparing the IND package with the intention of progressing to clinical trials early 2017. For more information, visit www.tizianalifesciences.com.