Tiziana Life Sciences plc ("Tiziana", "the Company", AIM: TILS), the clinical stage biotechnology company focused on targeted drugs to treat diseases in oncology and immunology, is pleased to announce that it has exclusively licensed milciclib from Nerviano Medical Sciences Group ("Nerviano"), an Italian company dedicated to the discovery and development of breakthrough treatments for cancer.
Milciclib blocks the action of specific enzymes called cyclin-dependent kinases ("CDKs"), which are involved in cell division as well as a number of other protein kinases. Milciclib is currently in phase II clinical trials for thymic carcinoma in patients previously treated with chemotherapy. Milciclib has demonstrated that it is well tolerated in over 263 patients in phase I and II clinical trials and has been granted orphan designation by the European Commission and by the U.S. Food and Drug Administration ("FDA") for the treatment of malignant thymoma/thymic epithelial tumours. Subject to successful completion of the ongoing phase II trials, Tiziana is committed to initiate a phase III study in this indication in 2016.
Nerviano has shown in preclinical studies that milciclib has potential in other cancer indications, in particular liver cancer and breast cancer, for which potential biomarkers of response have been identified and which will support the clinical development in these indications planned to start in 2015. Tiziana plans to immediately enrol patients into a new phase II trial in hepatocellular carcinoma using a protocol already prepared by Nerviano, and will explore the potential for an additional phase II trial in breast cancer.
Commenting on the licensing agreement, Gabriele Cerrone, Chairman and Founder of Tiziana, said: "Nerviano is a high value partner for Tiziana with immense scientific heritage in oncology that started with the success of the anthracyclines and is now continuing with innovative targeted therapies. The addition of milciclib, with its robust safety profile, significantly strengthens Tiziana's pipeline and offers us the potential to provide a new treatment for liver cancer, an additional approach for treating breast cancer and continuing phase II trials in thymic carcinoma. Milciclib broadens our breast cancer franchise and, together with foralumab, which we licensed in late 2014, we now have two clinical assets with three different clinical indications."
Under the terms of the licensing agreement with Nerviano, Tiziana will make an upfront cash payment of US$3.5 million for the license to Nerviano. Tiziana will also pay to Nerviano specified milestone payments of up to US$35 million and a royalty on net sales of any products containing milciclib.
In addition, Tiziana will pay £2.14 million to be satisfied by the issue of 4,233,616 new ordinary shares (the "Shares") in the Company to Nerviano (at a price of 50.5p per share which is the closing price of the Company's ordinary shares on 16 January 2015, the last business day prior to execution of the licensing agreement). The Shares are subject to restrictions dependent on the success of the clinical development programmes. In the event that there is an unsuccessful phase II trial in liver cancer or breast cancer, or a phase II trial has not been completed by 19 January 2020, the Company has the right to buy back the Shares for a consideration of £1. Nerviano has agreed that the Shares will be subject to a lock-in arrangement until successfu completion of a phase II trial and for a period of 12 months thereafter. Nerviano will be able to exercise voting rights relating to the Shares whilst they are locked in.
Application has been made to the London Stock Exchange for the Shares to be admitted to trading on AIM which is expected to occur on or around 26 January 2015. Following the issue of the Shares, the Company will have 88,905,928 ordinary shares in issue. The Shares will rank pari passu with the existing ordinary shares of the Company. Exercise of the Company's buy back rights is subject to shareholder approval under the UK Companies Act and is expected to be obtained at the Company's annual general meeting in 2015.
Under the licensing agreement, Tiziana will be responsible for future development costs for milciclib in thymoma / thymic epithelial tumours and in any additional indications, including hepatocellular carcinoma and breast cancer. Tiziana will entrust the manufacturing and the performance of clinical studies for milciclib up to completion of phase II to Nerviano.
"We are delighted to enter into this agreement with Tiziana Life Sciences, as a further recognition of our research approach and the value of our pipeline," said Luciano Baielli, CEO of Nerviano. "As a group, Nerviano is, in fact, actively building alliances to strengthen the development of our projects and offer new therapeutic options for physicians and patients' unmet needs. Our goal is to lead innovation in oncology and I am confident that our recognised expertise as a provider of integrated R&D capabilities will lead to a further significant new hope for cancer patients."
Milciclib is a spectrum selective multi-kinase inhibitor of cyclin-dependent kinases initially identified in a CDK2 inhibitor project, as a potent inhibitor of the CDK2/Cyclin A complex. It possesses an unusual kinase inhibitory profile, being active also against other selected members of receptors tyrosine kinases, src family and splicing kinases.
Milciclib is currently in phase II as single agent in thymic carcinoma ("Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma Previously Treated With Chemotherapy". NCT01011439, http://clinicaltrials.gov). Orphan designation was granted by the European Commission and by the FDA to milciclib for the treatment of malignant thymoma / thymic epithelial tumours.
About Tiziana Life Sciences
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 has a phase II asset, foralumab, the only fully human engineered anti-human CD3 antibody in clinical development. Foralumab has potential application in a wide range of autoimmune and inflammatory diseases, such as 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' research team has discovered that Bcl-3 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. Tiziana 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.