On September 20, 2016 Oncology Venture Sweden AB (OV:ST) and Cadila Pharmaceuticals Ltd., Ahmedabad, State of Gujarat, India reported the entering of a co-development agreement to develop the anticancer product LiPlaCis in combination with its Drug Response Predictor – DRP (Press release, Oncology Venture, SEP 20, 2016, View Source;and-its-drug-respo,c2082912 [SID1234561591]). The aim is to evaluate the LiPlaCis efficacy in several different indications and perform a randomized phase 3 trial as corner stone and part of the data package study for marketing approval by the FDA, EMA, CDSCO (Central Drugs Standard Control Organization of India). The mutual goal is to sell or out license the product in combination with its Companion Diagnostic (DRP) when the clinical benefit has been documented. Cadila will perform four (4) phase 2 and one pivotal, randomized phase 3 trial over a period of three years. Initiation of individual studies will be announced separately. Cadila will invest in kind in research and drug development activities in 310 cancer patients and DRP screening of more than 1400 patients. In the consortium of owners now including Cadila Pharmaceuticals, LiPlasome, MPI and Oncology Venture – Oncology Venture owns 29% of the total value of the LiPlaCis project after Phase 3. Cadila has commercialization rights in India, Russia, Africa and South East Asia (ASEAN countries only). Oncology Venture has the commercialization rights in America, Europe and China and RoW. Oncology Venture is responsible for the manufacturing and will provide the product. Estimated costs for product in 2017-2018 is 0,6 MUSD. Cadila will in collaboration with an expert team in Oncology Venture set up a laboratory for the tissue handling in India. The DRP analysis will be paid by Cadila and Oncology Venture will provide the DRP evaluations. When developed, the parties may choose to market themselves in their own territories or out-license or sell to a third party. The potential of LiPlaCis sales in the two major indications alone in breast cancer in USA and EU is in excess of 700 MUSD annually and if successful LiPlaCis would compete in a market which currently has a value in excess of 5 billion USD in lung cancer in Europe and USA.

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Around 310 cancer patients will according to the deal partake in clinical trials at a FDA and EMA quality level.
The agreement is entered between Cadila Pharmaceuticals Ltd. and Oncology Venture ApS which is 100% owned by Oncology Venture Sweden AB. Cadila Pharmaceuticals Ltd. is one of the largest privately held pharmaceutical companies in India.

"Cadila is one of the largest privately held pharma companies in India. The transformational partnership with Cadila places Oncology Venture in another league. Together with Cadila we aim to take LiPlaCis and its Drug Response Predictor – DRP – through a strong and focused development program with the goal of receiving marketing approval. We will together with Cadila who invests heavily as an ‘in kind’ investment test LiPlaCis in four promising indications: breast, head & neck, skin and esophageal cancer which gives the drug a really good chance to benefit patients who are likely to respond," says Peter Buhl Jensen, M.D., CEO of Oncology Venture. "In this partnership OV has the opportunity to build a much larger value instead of selling it outright. Cisplatin is one of the most used drugs in cancer treatment and the potential sales with the improved LiPlaCis formulation is huge," Buhl Jensen further comments.

On this occasion, Dr. Rajiv Modi, Chairman and Managing Director, Cadila Pharmaceuticals Ltd., said, "Cadila Pharmaceuticals believes in providing world-class healthcare products to improve quality of life of patients. This agreement with Oncology Venture is an affirmation of our commitment to develop novel treatment for those diseases in the realm of unmet medical needs. Cancer affects millions of people around the globe. We look forward to developing the product to benefit millions of patients who are affected by the deadly disease."
 
The Partnership deal
The deal with Cadila Pharmaceuticals will finance and perform studies in a total of 310 cancer patients with highest likelihood of sensitivity to LiPlaCis. The deal covers the following:
1. Screening by the use of the LiPlaCis-DRP of 1 250 metastatic breast cancer patients to identify 250 patients with high likelihood to respond to LiPlaCis treatment and perform a randomized phase 3 trial in these 250 patients comparing standard therapy with LiPlaCis.
2. Through Cadilas strong network and Cadilas CRO run four (4) clinical Phase 2 trials in 20 patients (out of 100 screened) with Head & Neck cancer, 20 prostate cancer patients (out of 100 screened), and 10 skin cancer patients and 10 esophagus cancer patients – the two latter indications are in a high frequency sensitive to cisplatin – of which LiPlaCis is an improved formulation – why the patients will not be screened.

Cadila has commercialization rights in India, Russia, Africa and South East Asia (ASEAN countries only), Oncology Venture has the commercialization rights to America, Europe and China and RoW. Oncology Venture will be responsible for the manufacturing and pay for manufacturing of the product. Estimated costs for product in 2017-2018 is 0,6 MUSD. In the consortium of owners now including Cadila Pharmaceuticals, LiPlasome, MPI and Oncology Venture – Oncology Venture owns 29% of the total value of the LiPlaCis project after Phase 3. When developed parties may choose to market themselves in their own territories or out license or sell to a third party.

About the LiPlaCis license from LiPlasome Pharma and the DRP license from MPI
Oncology Venture has in-licensed LiPlaCis from LiPlasome Pharma and the LiPlaCis DRP from MPI and has now entered a development partnership with Cadila Pharma. The financial impact is as follows: In the consortium of owners now including Cadila Pharmaceuticals, LiPlasome, MPI and Oncology Venture – Oncology Venture owns 29% of the total value of the LiPlaCis project after Phase 3.OV pays for the manufacturing of the product. Oncology Venture did not pay any upfront payment to LiPlasome but pays 2×9 MUSD in sales milestones to LiPlasome once LiPlaCis is commercialized either via a partner or sold on the market. (please see latest company prospectus).Cost of clinical trials in oncology all phases per patient 59.500 USD (PhRMA 2013).
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On September 20, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for its lead product candidate PB272 (neratinib) for the extended adjuvant treatment of patients with early stage HER2-overexpressed/amplified breast cancer who have received prior adjuvant trastuzumab (Herceptin)-based therapy (Press release, Puma Biotechnology, SEP 20, 2016, View Source [SID:SID1234515515]).

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"The FDA acceptance of our NDA is an important regulatory milestone," said Alan H. Auerbach, Chief Executive Officer and President of Puma. "Although the use of trastuzumab in the adjuvant setting has led to a reduction in disease recurrence in patients with early stage HER2-positive breast cancer, there remains an unmet clinical need to further reduce the risk of recurrence and improve outcome following trastuzumab therapy. We believe that neratinib may be able to provide this type of improvement to further help patients with this disease. We look forward to working with the FDA during their review of this submission."

The submission is supported by the results of the ExteNET Phase III study, in which treatment with neratinib resulted in a 33% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.67, p = 0.009). The 2-year invasive disease free survival (DFS) rate for the neratinib arm was 93.9% and the 2-year invasive DFS rate for the placebo arm was 91.6%. For the pre-defined subgroup of patients with hormone receptor positive disease, the results of the trial demonstrated that treatment with neratinib resulted in a 49% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.51, p = 0.001). For the patients with hormone receptor positive disease, the 2-year invasive DFS rate for the neratinib arm was 95.4% and the 2-year invasive DFS rate for the placebo arm was 91.2%.

Results of the study were published online in The Lancet Oncology on February 10, 2016.

The most frequently observed adverse event for the neratinib-treated patients was diarrhea, with approximately 39.9% of the neratinib-treated patients experiencing grade 3 or higher diarrhea (1 patient (0.1%) had grade 4 diarrhea). Patients who received neratinib in the ExteNET trial did not receive any prophylaxis with antidiarrheal agents to prevent the neratinib-related diarrhea. In patients with HER2-positive early stage breast cancer who have previously been treated with adjuvant trastuzumab and received anti-diarrheal prophylaxis with loperamide, interim results of a Phase II study of neratinib monotherapy demonstrated that treatment with prophylactic loperamide reduced the rate of grade 3 or higher diarrhea to between 13.0% and 18.5%.

About ExteNET

The ExteNET trial is a double-blind, placebo-controlled, Phase III trial of neratinib versus placebo after adjuvant treatment with trastuzumab (Herceptin) in women with early stage HER2-positive breast cancer. The trial randomized 2,840 patients in 41 countries with early-stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomized to receive extended adjuvant treatment with either neratinib or placebo for a period of one year. Patients were then followed for recurrent disease, ductal carcinoma in situ (DCIS), or death for a period of two years after randomization in the trial. The primary endpoint of the trial was invasive DFS.

On September 21, 2016 BioNTech AG, a fully integrated private biotechnology company developing personalized cancer immunotherapies, reported that it will enter into a worldwide strategic collaboration with Genentech, a member of the Roche Group, to develop, manufacture and commercialize novel messenger RNA (mRNA)-based, individualized cancer vaccines (Press release, BioNTech, SEP 20, 2016, View Source [SID:SID1234515277]). The collaboration will combine Genentech’s leading cancer immunotherapy portfolio and research program with BioNTech’s proprietary mRNA cancer vaccine technology platform, and personalized medicine expertise. Together, the two companies will develop individually tailored cancer immunotherapies against a broad range of cancers to potentially provide a new treatment paradigm for cancer patients.

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The collaboration will focus on the development of mRNA cancer vaccines targeting neoantigens, based upon BioNTech’s Individualized Vaccines Against Cancer (IVAC) MUTANOME clinical platform for the potential treatment of multiple cancers. A patient’s cancer genome can be rapidly sequenced with next generation technology to define a spectrum of unique mutations known as "neoantigens" or "neoepitopes" present in a particular patient’s tumor (the "mutanome"). An mRNA vaccine encoding selected neoepitopes can be manufactured for each individual tumor’s mutanome signature, which may trigger an immune response highly specific to the tumor resulting in precisely targeted cancer cell death.

Initial clinical development will focus on combination studies using IVAC MUTANOME in a variety of cancer types.

Under the terms of the agreement Genentech will pay BioNTech $310 million in upfront and near-term milestone payments. The two companies will equally share all development costs and any potential profits for certain programs under the agreement. BioNTech has the right to co-promote certain products that arise from the agreement in the United States and certain countries, including Germany and other major European markets. Under certain circumstances, BioNTech may have sole commercialization rights for other products that Genentech elects not to commercialize. BioNTech will manufacture mRNA cancer vaccines for clinical studies. Genentech will manufacture mRNA cancer vaccines for commercial supply and BioNTech will have the right to manufacture commercial product as part of the global supply network.

Professor Dr. Ugur Sahin, CEO of BioNTech AG commented: "We are delighted to collaborate with a leading cancer immunotherapy company such as Genentech. Supported by its extensive tumor immunology understanding, BioNTech has been building clinical experience with its proprietary mRNA vaccines in a number of cancer types over several years. Combining BioNTech’s broad proprietary capabilities in the design, formulation, manufacturing and clinical testing of individualized neoantigen-based mRNA vaccines with Genentech’s eminent cancer immunotherapy, diagnostic, manufacturing and commercial expertise, will allow us, on a global scale, to drive forward the development of individualized vaccines to the market to treat a broad range of cancers. "

Sean Marett, COO of BioNTech added: "This alliance underpins BioNTech’s strategy of collaborating with companies that are committed to developing truly disruptive immunotherapies and its long term ambitions of bringing its own products to market ."

"Unlike any medicine we have ever developed, virtually all cancer patients may potentially benefit from a custom built cancer vaccine," said James Sabry, M.D., Ph.D., Senior Vice President and Global Head of Genentech Partnering. "By collaborating with BioNTech on this cutting edge approach, we hope to truly advance cancer treatments by using a common molecular backbone – mRNA – that is uniquely tailored to an individual patient."

BioNTech will continue to develop its non-neoepitope mRNA cancer vaccines outside of the collaboration.

The completion of the agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and is expected to occur in the fourth quarter of 2016.

On September 20, 2016 Allergan plc (NYSE: AGN), a leading global pharmaceutical company, and Tobira Therapeutics, Inc. (NASDAQ: TBRA), a clinical-stage biopharmaceutical company focused on developing and commercializing therapies for non-alcoholic steatohepatitis (NASH) and other liver diseases, reported that they have entered into a definitive agreement under which Allergan will acquire Tobira for an upfront payment of $28.35 per share, in cash, and up to $49.84 per share in Contingent Value Rights (CVRs) that may be payable based on the successful completion of certain development, regulatory and commercial milestones, for a total potential consideration of up to $1.695 billion (Press release, Allergan, SEP 20, 2016, View Source [SID:SID1234515266]). The Boards of Directors of both companies have unanimously approved the transaction.

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NASH is a severe type of non-alcoholic fatty liver disease (NAFLD), which is characterized by the accumulation of fat in the liver with no other apparent causes.ii NASH occurs when the accumulation of liver fat is accompanied by inflammation and cellular damage.ii The inflammation can lead to fibrosis (scarring) of the liver and eventually progress to cirrhosis, portal hypertension, liver cancer and eventual liver failure.ii

The acquisition adds Cenicriviroc (CVC) and Evogliptin, two differentiated, complementary development programs for the treatment of the multi-factorial elements of NASH, including inflammation, metabolic syndromes and fibrosis, to Allergan’s global Gastroenterology R&D pipeline.

"The acquisition of Tobira is a strategic R&D investment within a white space area of our global Gastroenterology franchise and an opportunity to advance the development of novel treatments for NASH," said Brent Saunders, CEO and President of Allergan. "With the increasing rates of diabetes, obesity and other metabolic conditions in the U.S. and in developed nations globally, NASH is set to become one of the next epidemic-level chronic diseases we face as a society. It is important that we invest in new treatments today so that healthcare systems, providers and patients have treatment options to face this challenge in the coming years."

"With this acquisition, Allergan will now have one of the strongest portfolios of development stage programs for the treatment of NASH, with Cenicriviroc as the cornerstone. We will continue to look for differentiated development-stage assets that can bolster this position and enhance our commitment to innovation in this disease," added Saunders.

Cenicriviroc (CVC) is a first-in-class, once-daily, oral Phase 3 ready potent immunomodulator that blocks two chemokine receptors, CCR2 and CCR5, which are involved in the inflammatory and fibrogenic pathways in NASH that cause liver damage and often lead to cirrhosis, liver cancer or liver failure. In the Phase 2b CENTAUR study, CVC demonstrated a clinically and statistically significant improvement in fibrosis of at least one stage without worsening of NASH, one of two key secondary endpoints, after one year of treatment.

The acquisition also adds Evogliptin, an oral DPP-4 (Dipeptidyl peptidase-4) inhibitor for the potential treatment of NASH. Evogliptin is being studied in a Phase 1 trial assessing the safety, tolerability and steady-state pharmacokinetic parameters of the compound when administered with and without CVC. In NASH, increased DPP-4 serum levels and hepatic DPP-4 expression is correlated with disease severity.

"Both the CVC and Evogliptin programs provide highly differentiated compounds that can make a significant impact in the treatment of NASH, where today there are no approved therapies available for patients," said David Nicholson, Chief Research & Development Officer, Allergan. "Importantly, NASH treatment may well require a multi-therapeutic approach to address the multiple factors of the disease. CVC has been shown in clinical trials to provide significant improvement in liver fibrosis, the hallmark of NASH. Liver fibrosis is associated with key long-term outcomes, including overall mortality, liver transplantation and liver-related events. Evogliptin, in preclinical models, has been shown to decrease hepatic glucose production, improve hepatic triglyceride content and steatosis, and reduce histologic markers of inflammation of the liver. Together, these programs provide a highly complementary potential therapeutic approach to address the inflammatory, metabolic and fibrotic elements of NASH that the medical community will need to treat this condition."

"I am extremely excited to see Tobira and Allergan come together," said Laurent Fischer, M.D., Chief Executive Officer, Tobira Therapeutics. "The combination of our team’s innovation in the NASH space and the infrastructure, development expertise and world-class ability of Allergan to market medicines will enable us to more rapidly develop and commercialize needed medications for patients suffering from NASH and other serious fibrotic diseases around the world."

"We are delighted that cenicriviroc will be rapidly advancing into Phase 3 studies under the stewardship of Allergan, an industry leader with world class capabilities in advancing novel treatment options to patients across the globe, and I look forward to the future success of this partnership," added Dennis Podlesak, Chairman of the Board of Tobira.

Under the terms of the merger agreement, a subsidiary of Allergan will commence a cash tender offer to purchase all of the outstanding shares of Tobira common stock for $28.35 per share, plus one Contingent Value Right to receive up to $49.84 per share in future payments based on the successful completion of certain development, regulatory and commercial milestones. The closing of the tender offer is subject to customary closing conditions, including U.S. antitrust clearance and the tender of a majority of the outstanding shares of Tobira common stock. Holders of approximately 36 percent of the outstanding shares of Tobira common stock have entered into an agreement to tender their shares into the tender offer. The merger agreement contemplates that Allergan will acquire any shares of Tobira that are not tendered into the offer through a second-step merger, which will be completed as soon as practicable following the closing of the tender offer. Pending approvals, Allergan anticipates closing the transaction by the end of 2016.

Covington & Burling LLP is serving as Allergan’s lead legal counsel. Centerview Partners and Citi are serving as financial advisors to Tobira and Skadden, Arps, Slate, Meagher & Flom LLP and Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP are serving as Tobira’s legal counsel.