On January 21, 2015 Curis and Aurigene reported that they have entered into an exclusive collaboration agreement focused on immuno-oncology and selected precision oncology targets (Press release Curis, JAN 21, 2015, View Source [SID:1234501360]). The collaboration provides for inclusion of multiple programs, with Curis having the option to exclusively license compounds once a development candidate is nominated within each respective program. The partnership draws from each company’s respective areas of expertise, with Aurigene having the responsibility for conducting all discovery and preclinical activities, including IND-enabling studies and providing Phase 1 clinical trial supply, and Curis having responsibility for all clinical development, regulatory and commercialization efforts worldwide, excluding India and Russia, for each program for which it exercises an option to obtain a license.

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The first two programs under the collaboration are an orally-available small molecule antagonist of programmed death ligand-1 (PD-L1) in the immuno-oncology field and an orally-available small molecule inhibitor of Interleukin-1 receptor-associated kinase 4 (IRAK4) in the precision oncology field. Curis expects to exercise its option to obtain exclusive licenses to both programs and file IND applications for a development candidate from each in 2015.

"We are thrilled to partner with Aurigene in seeking to discover, develop and commercialize small molecule drug candidates generated from Aurigene’s novel technology and we believe that this collaboration represents a true transformation for Curis that positions the company for continued growth in the development and eventual commercialization of cancer drugs," said Ali Fattaey, Ph.D., President and Chief Executive Officer of Curis. "The multi-year nature of our collaboration means that the parties have the potential to generate a steady pipeline of novel drug candidates in the coming years. Addressing immune checkpoint pathways is now a well validated strategy to treat human cancers and the ability to target PD-1/PD-L1 and other immune checkpoints with orally available small molecule drugs has the potential to be a distinct and major advancement for patients. Recent studies have also shown that alterations of the MYD88 gene lead to dysregulation of its downstream target IRAK4 in a number of hematologic malignancies, including Waldenström’s Macroglobulinemia and a subset of diffuse large B-cell lymphomas, making IRAK4 an attractive target for the treatment of these cancers. We look forward to advancing these programs into clinical development later this year."

Dr. Fattaey continued, "Aurigene has a long and well-established track record of generating targeted small molecule drug candidates with bio-pharmaceutical collaborators and we have significantly expanded our drug development capabilities as we advance our proprietary drug candidates in currently ongoing clinical studies. We believe that we are well-positioned to advance compounds from this collaboration into clinical development."

CSN Murthy, Chief Executive Officer of Aurigene, said, "We are excited to enter into this exclusive collaboration with Curis under which we intend to discover and develop a number of drug candidates from our chemistry innovations in the most exciting fields of cancer therapy. This unique collaboration is an opportunity for Aurigene to participate in advancing our discoveries into clinical development and beyond, and mutually align interests as provided for in our agreement. Our scientists at Aurigene have established a novel strategy to address immune checkpoint targets using small molecule chemical approaches, and have discovered a number of candidates that modulate these checkpoint pathways, including PD-1/PD-L1. We have established a large panel of preclinical tumor models in immunocompetent mice and can show significant in vivo anti-tumor activity using our small molecule PD-L1 antagonists. We are also in the late stages of selecting a candidate that is a potent and selective inhibitor of the IRAK4 kinase, demonstrating excellent in vivo activity in preclinical tumor models."

In connection with the transaction, Curis has issued to Aurigene approximately 17.1 million shares of its common stock, or 19.9% of its outstanding common stock immediately prior to the transaction, in partial consideration for the rights granted to Curis under the collaboration agreement. The shares issued to Aurigene are subject to a lock-up agreement until January 18, 2017, with a portion of the shares being released from the lock-up in four equal bi-annual installments between now and that date.

The agreement provides that the parties will collaborate exclusively in immuno-oncology for an initial period of approximately two years, with the option for Curis to extend the broad immuno-oncology exclusivity.

In addition Curis has agreed to make payments to Aurigene as follows:

for the first two programs: up to $52.5 million per program, including $42.5 million per program for approval and commercial milestones, plus specified approval milestone payments for additional indications, if any;
for the third and fourth programs: up to $50 million per program, including $42.5 million per program for approval and commercial milestones, plus specified approval milestone payments for additional indications, if any; and
for any program thereafter: up to $140.5 million per program, including $87.5 million per program in approval and commercial milestones, plus specified approval milestone payments for additional indications, if any.

Curis has agreed to pay Aurigene royalties on any net sales ranging from high single digits to 10% in territories where it successfully commercializes products and will also share in amounts that it receives from sublicensees depending upon the stage of development of the respective molecule.

For more information, please refer to the Current Report on Form 8-K filed by Curis with the U.S. Securities & Exchange Commission on January 21, 2015.

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 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 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."