On September 21, 2016 Eleven Biotherapeutics, Inc. (NASDAQ: EBIO) and Viventia Bio Inc., reported that the two companies and the shareholders of Viventia entered into a definitive share purchase agreement under which Eleven Biotherapeutics agreed to, and simultaneously completed, the acquisition of Viventia (Press release, Eleven Biotherapeutics, SEP 21, 2016, View Source [SID:SID1234515276]). Under the agreement, Eleven purchased all of the outstanding capital stock of Viventia in exchange for the issuance of 4,013,431 newly issued shares of Eleven common stock, which represented approximately 19.9% of the voting power of Eleven as of immediately prior to the issuance of such shares, and the agreement by Eleven to pay to the selling shareholders certain post-closing contingent cash payments upon the achievement of specified milestones and based upon net sales related to Viventia’s lead product candidate, Vicinium. Schedule your 30 min Free 1stOncology Demo! The acquisition creates a NASDAQ-listed company focused on the development of novel therapies based upon antibody fragments genetically fused to cytotoxic proteins, or targeted protein therapeutics (TPTs), as new treatments in areas of oncology with significant unmet need. The combined company will continue to be named Eleven Biotherapeutics, and Stephen Hurly, formerly Viventia’s chief executive officer, was appointed President and Chief Executive Officer of Eleven in connection with the acquisition. Abbie C. Celniker, Eleven’s former President and Chief Executive Officer, will remain a director of Eleven Biotherapeutics.
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Eleven’s pipeline now includes Viventia’s lead product candidates Vicinium and Proxinium. Vicinium is in a Phase 3 clinical trial for high grade non-muscle invasive bladder cancer (NMIBC), with topline data expected in the first half of 2018. To date, Vicinium has been evaluated in more than 100 patients. In a Phase 2 clinical trial, Vicinium demonstrated a complete response rate of 40% at three months with no drug-related serious adverse events observed in the trial.
Proxinium is expected to enter Phase 2 development in early 2017 for the treatment of late-stage squamous cell carcinoma of the head and neck. In previous clinical trials, Proxinium was generally safe and well-tolerated and showed signs of anti-tumor activity. Proxinium has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and Fast Track designation from the FDA. Both product candidates are anti-EpCAM (epithelial cell adhesion molecule) fusion proteins that have been optimized for local tumor administration.
Eleven’s pipeline now also includes Viventia’s earlier stage pipeline of next generation TPT candidates that are designed and optimized for systemic administration for the potential treatment of a broader spectrum of cancer types.
"We are excited to join with Eleven to create a company with extensive experience in engineering and developing novel protein therapeutics for local delivery that we believe may maximize efficacy and reduce toxicity. Our TPTs combine specific tumor targeting with a protein based tumor killing payload, and will be developed to serve cancer patients in areas of high unmet need. Together we have a strong Board of Directors, management team, product pipeline and technology platform, and the capital needed to support the Company’s development plans into 2018," said Stephen Hurly, Chief Executive Officer of Eleven Biotherapeutics.
"As previously announced, Eleven performed an extensive review of our strategic alternatives, and our Board of Directors believes that the acquisition of Viventia offers Eleven shareholders a compelling opportunity for enhancing long-term value," said Abbie Celniker, Ph.D., former President and Chief Executive Officer of Eleven Biotherapeutics and current member of Eleven’s Board of Directors. "Our combined company will continue to support Roche as they develop EBI-031, and will benefit from the capital contributed by this partnership, which provides the necessary funding to enable further development of Vicinium and Proxinium."
About Targeted Protein Therapeutics (TPTs)
Viventia’s drug development is currently focused on locally administered targeted protein therapeutics (TPTs) for the treatment of cancer. Viventia’s TPTs are expressed as a single fusion protein with a differentiated payload mechanism, eliminating the need for payload conjugation and multi-step manufacturing. We believe TPTs have a dual action of both directly killing the cancer cell and enhancing the local immune response.
License Agreement with Roche
On August 16, 2016, Eleven announced the effectiveness of its exclusive license agreement with F. Hoffman-La Roche Ltd. and Hoffman-La Roche Inc. (Roche) for Eleven’s IL-6 antagonist antibody technology, including EBI-031. Eleven granted Roche an exclusive, worldwide license to develop and commercialize EBI-031 and all other IL-6 antagonist antibody technology owned by Eleven. Eleven has received $30 million in payments from Roche, including a $7.5 million upfront payment in connection with the effectiveness of the license agreement, and a $22.5 million milestone payment based on the Investigational New Drug (IND) application for EBI-031 becoming effective. Under the terms of the agreement, Eleven could receive up to an additional $240 million upon the achievement of certain future regulatory, development and commercialization milestones. In addition, Eleven could be entitled to receive royalties based on net sales of potential future products containing EBI-031 or any other potential future products containing other Eleven IL-6 compounds.
Viventia Acquisition Details
Under the share purchase agreement, Eleven purchased all of the outstanding capital stock of Viventia in exchange for the issuance of 4,031,431 newly issued shares of Eleven common stock, which represented approximately 19.9% of the voting power of Eleven as of immediately prior to the issuance of such shares, and the agreement by Eleven to pay to the selling shareholders certain post-closing contingent cash payments upon the achievement of specified milestones and based upon net sales related to Viventia’s lead product candidate, Vicinium.
The acquisition was approved by the boards of directors of both companies.
Stifel, Nicolaus & Company, Incorporated acted as financial advisor and Wilmer Cutler Pickering Hale and Dorr LLP is acting as legal advisor to Eleven. Hogan Lovells US LLP acted as legal counsel to Viventia.
Management and Organization
In connection with the acquisition, Eleven’s Board of Directors elected Stephen Hurly and Leslie L. Dan, Viventia’s former Executive Chairman and largest beneficial owner prior to the acquisition, to serve as members of Eleven’s Board of Directors, and Cary G. Pfeffer, M.D., resigned from the Eleven’s Board of Directors. Stephen Hurly will serve as President and Chief Executive Officer of Eleven. Also in connection with the acquisition, Arthur P. DeCillis, M.D., Viventia’s Chief Medical Officer, was appointed as Chief Medical Officer of Eleven, and Karen L. Turbidy, Eleven’s Chief Development Officer, resigned from Eleven. In addition, Gregory Adams Ph.D., Chief Development Officer and Glen MacDonald, Ph.D., Chief Scientific Officer, will join Eleven’s management team from Viventia. John McCabe, will continue to serve as Chief Financial Officer of Eleven. Abbie C. Celniker, former President and Chief Executive Officer of Eleven, will remain a member of Eleven’s Board of Directors. Following the acquisition, an entity affiliated with Leslie L. Dan became the second largest shareholder of Eleven.
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AstraZeneca provides update on cediranib EU marketing authorisation application
On September 21, 2016 AstraZeneca reported its decision to withdraw the Marketing Authorisation Application (MAA) submitted to the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) in June 2015 for cediranib in combination with platinum-based chemotherapy followed by maintenance monotherapy for the treatment of adult patients with platinum-sensitive relapsed ovarian cancer (including fallopian tube or primary peritoneal sub types) (Press release, AstraZeneca, SEP 21, 2016, View Source [SID:SID1234515263]). Schedule your 30 min Free 1stOncology Demo! Cediranib remains an important part of AstraZeneca’s ovarian cancer medicine pipeline and this decision does not affect the ongoing primary development programme testing cediranib as a combination treatment alongside the Company’s existing and potential medicines.
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The decision to withdraw the MAA was based on outstanding questions raised by the European Medicines Agency (EMA) at this late stage of the review process. The MAA for cediranib was supported by data from ICON6, a Phase III trial led by investigators from University College London (UCL) and the Medical Research Council (MRC). AstraZeneca has not made additional regulatory submissions for cediranib in this indication in any other markets.
AstraZeneca is committed to enhancing treatment options for patients with ovarian cancer, including developing chemotherapy-free alternatives to help delay or avoid the use of platinum-based chemotherapies.
Oncology Venture enters development deal with Cadila Pharmaceuticals on LiPlaCis® and its Drug Response Predictor
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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Puma Biotechnology Announces U.S. FDA Acceptance of New Drug Application for PB272 (Neratinib) for Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer
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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.
BioNTech to enter into worldwide strategic collaboration with Genentech to develop individualized mRNA cancer therapies
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.