On January 20, 2015 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 reported 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 (Press release, Tiziana Life Sciences, JAN 20, 2015, View Source [SID:1234513954]).

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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 successful 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."

On January 20, 2015 Celator Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for CPX-351 (cytarabine:daunorubicin) for the treatment of elderly patients with secondary Acute Myeloid Leukemia (AML) (Press release Celator Pharmaceuticals, JAN 20, 2015, View Source [SID:1234501354]).

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The FDA established the Fast Track designation process to facilitate the development and expedite the review of drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Fast Track designation facilitates meetings with FDA to discuss all aspects of development to support approval. It also provides the opportunity to submit sections of a New Drug Application (NDA) on a rolling basis, where FDA may review portions of the NDA as they are received instead of waiting for the entire NDA submission. In addition, a Fast Track designated product could be eligible for priority review if supported by clinical data at the time of NDA submission.

"We are pleased that FDA has granted Fast Track status for CPX-351 for the treatment of elderly patients with secondary AML," said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals. "Our ongoing Phase 3 study in these patients has completed enrollment, and we expect induction response rate data to be available in the second quarter of this year, and to have overall survival data, the primary endpoint of the study, in the first quarter of 2016. If our Phase 3 study, comparing CPX-351 to the current standard of care, is successful, the Fast Track designation may provide an added benefit of facilitating the NDA review process."

On January 20, 2015 Verastem reported on dosing of the first patient in a new clinical trial evaluating the combination of VS-5584, its dual mTORC1/2 and PI3K inhibitor, in combination with VS-6063, the Company’s lead focal adhesion kinase (FAK) inhibitor, in patients with relapsed mesothelioma (Press release Verastem, JAN 20, 2015, View Source;p=RssLanding&cat=news&id=2008677 [SID:1234501359]).

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The Phase 1 open-label, dose escalation and schedule finding study is designed to assess safety, pharmacokinetics, pharmacodynamics and initial observations of clinical activity. The study is expected to enroll up to 56 patients at clinical sites in the UK and US.

"We are very pleased to initiate the first ever Phase 1 trial combining a dual mTORC1/2 and PI3K inhibitor (VS-5584) with a FAK inhibitor (VS-6063)," said Udai Banerji, MD, PhD, FRCP, Reader in Molecular Cancer Pharmacology and Honorary Consultant in Medical Oncology at The Royal Marsden Hospital and The Institute of Cancer Research London. "This study builds on robust synergy data from pre-clinical mesothelioma models presented by Verastem at the recent iMiG meeting. The trial is enrolling patients with relapsed mesothelioma: a patient population in dire need of new treatment options."

"Mesothelioma is a devastating disease and Verastem is committed to the development of new treatment options," said Dr. Joanna Horobin, Chief Medical Officer of Verastem. "This is the third study we have initiated with VS-6063 in patients with mesothelioma. We are very pleased with the progress of the multinational COMMAND study evaluating VS-6063 as a switch maintenance therapy following frontline chemotherapy in patients with malignant pleural mesothelioma. As reported in October at the 2014 iMIG, we are encouraged by the biomarker response and intriguing tumor shrinkage observed after 12 days of single agent VS-6063 administration in patients with untreated mesothelioma, prior to planned surgery. In this new study of VS-6063 in combination with VS-5584, building on the synergy seen in pre-clinical models, we hope to extend the potential benefit to patients with mesothelioma that has relapsed following initial therapy."

VS-5584 is currently in a Phase 1 study in advanced solid tumors where the compound has been generally well tolerated and preliminary activity has been observed, including in mesothelioma. Some patients have been on study for over 6 months and the maximum tolerated dose of VS-5584 has not been reached.

The combination clinical trial is supported by preclinical work demonstrating the synergistic activity of VS‐6063 and VS‐5584 in mesothelioma models in vitro and in vivo. In this preclinical research, the combination of VS‐6063 and VS‐5584 displayed synergistic reduction in cell viability based on multiple combination analysis models. When tested in vivo for reduction of mesothelioma tumor growth, VS‐6063 and VS‐5584 were each active as single agents and demonstrated synergistic antitumor efficacy when used in combination.

On January 20, 2015 European biotechnology company Valneva SE ("Valneva") and UK company BliNK Therapeutics Ltd ("BliNK Therapeutics") reported the closing of the transaction creating BliNK Biomedical SAS, a private company specialised in the discovery of innovative monoclonal antibodies as announced on December 11th, 2014 (Press release, Cancer Research Technology, JAN 20, 2015, View Source [SID1234523212]).

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The new company is owned by Valneva, Kurma Biofund I (founding investor of BliNK Therapeutics), funds managed by Idinvest Partners, Cancer Research Technology (CRT) and BliNK Therapeutics’ founders.

BliNK Therapeutics’ technology has been developed by Facundo Batista, Head of the Lymphocyte Interaction Laboratory at Cancer Research UK’s London Research Institute.

On January 20, 2015 BioInvent International (OMXS: BINV) reported an agreement with Cancer Research UK, Cancer Research Technology (CRT), the charity’s development and commercialisation arm, and Leukaemia & Lymphoma Research (LLR) to take its investigational drug, BI-1206, into a collaborative phase I/II trial for patients with chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) (Press release, Cancer Research Technology, JAN 20, 2015, View Source [SID1234523213]).

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The first in man study will be funded and conducted by Cancer Research UK, CRT and LLR. BioInvent has been granted the option to take up an exclusive license to the study data, subject to payment of milestones and royalties to Cancer Research Technology.

BI-1206 is a fully-human anti-CD32b antagonistic antibody that in addition to directly killing tumour cells is thought to work by maintaining CD20 antibodies on the cell membrane of cancer cells, preventing them from becoming resistant to the current state-of-the-art treatment, rituximab.

The antibody has shown promise both in combination with CD20 antibodies and as a single agent in chronic lymphocytic lymphoma (CLL) and other types of NHL, in an extensive package of preclinical studies carried out by Leukaemia & Lymphoma Research-funded scientists at the University of Southampton. The potential development opportunity for BI-1206 may extend well beyond NHL.

The open label Phase I/ll study will enroll between 50 and 60 patients who will receive either BI-1206 alone or BI-1206 in combination with rituximab. The study will primarily enroll CLL patients but smaller cohorts of patients with other types of NHL, such as mantle cell lymphoma, follicular lymphoma and diffuse large B-cell lymphoma, may also be recruited. The study is expected to commence in the second half of 2015.

Each year in the UK approximately 12,800 people are diagnosed with NHL and 3,200 people are diagnosed with CLL. In Europe and North America around 157,000 people are diagnosed with NHL yearly and approximately 35,000 people are diagnosed with CLL.*

Michael Oredsson, CEO of BioInvent, said: "We are very pleased that Cancer Research UK and Leukaemia & Lymphoma Research have chosen to conduct and fund the BI-1206 Phase I/ll trial. Cancer Research UK is one of the world’s leading cancer research charities with in-house clinical, regulatory and medical capabilities and an established network of clinical cancer centres and leading clinicians in the UK. This agreement provides BioInvent with an ideal resource to execute the first-in-man study for BI-1206 whilst preserving the commercial value in the project."

Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said "Monoclonal antibodies have boosted survival rates for many types of lymphoma and leukaemia in recent years, but patient responses remain varied. BI-1206 has shown great promise in reducing treatment resistance in the laboratory. Leukaemia & Lymphoma Research has funded research into this treatment at the University of Southampton since 2008 and we’re very excited that through this partnership patients could benefit from it soon."

Dr Nigel Blackburn, Cancer Research UK’s Director of Drug Development, said "BI-1206 has performed well in preclinical studies making it an ideal candidate for our Clinical Development Partnerships program, which helps industry run trials of potential new cancer treatments that would otherwise never progress beyond the lab. There is a real need for new blood cancer drugs that help boost the effectiveness of conventional chemotherapy drugs, as many patients cannot tolerate or become resistant to these treatments over time. Consequently, we look forward to seeing the results of this trial."

BI-1206 will be developed under Cancer Research UK’s Clinical Development Partnerships (CDP) program, a joint initiative between Cancer Research UK’s Centre For Drug Development (CDD) and CRT, to develop promising anti-cancer agents, which pharmaceutical companies do not have the resources to progress through early phase clinical trials.

It is the first drug to be entered into a new partnership through which Cancer Research UK and Leukaemia & Lymphoma Research will be jointly funding early phase clinical trials for patients with blood cancers.

Cancer Research UK’s CDD will manage and sponsor the study through the Experimental Cancer Medicine Centre (ECMC) network, with Leukaemia & Lymphoma Research providing the majority of the funding.