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Sosei Acquires Heptares Therapeutics for up to USD 400 million

On February 23, 2015 Sosei reported that it has acquired Heptares Therapeutics (Press release, Heptares, FEB 23, 2015, View Source [SID:1234507116]).

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The combination will create a leading global biopharmaceutical group with:

sustainable, proven and highly successful drug discovery and clinical development capabilities for generating innovative medicines;
a broad and balanced pipeline with strong growth prospects, including products with blockbuster potential;
access to global pharmaceutical markets;
regulatory expertise across the EU, US and Japan; and
a significant cash balance.

These strengths will enable the Group to sustain its pipeline and revenue stream on a long-term basis. Heptares will become a wholly owned subsidiary of the Group, with its existing R&D operations continuing in the UK.

Shinichi Tamura, Chairman and CEO of Sosei Group Corporation, said: "Today is an historic day for Sosei. Heptares is based on truly world-class science and its drug discovery and development capabilities will contribute to a sustainable stream of new products for the Group. While core to our future, an independent subsidiary structure will ensure Heptares is able to maintain the culture and business model that has been the foundation of its success so far."

Dr Malcolm Weir, CEO of Heptares, added: "This is an excellent next step for Heptares which maintains our integrity and purpose within a Group that has a clear and coherent vision. It is a great example of the translation of ground-breaking UK academic science into economic and potential therapeutic value and secures significant investment into our technology platform and clinical pipeline well into the future. We look forward to working within the Group to advance our programmes, both partnered and in-house, and, over time, to providing much needed new treatment options for patients."

1. Strategic rationale
The Group has been exploring strategic opportunities that can both build on and go beyond the secured revenue stream in milestones and royalties derived from the two COPD products (Ultibro Breezhaler and Seebri Breezhaler*) marketed by its partner Novartis.

The acquisition of Heptares, with its exciting clinical and preclinical pipeline of potentially transformative new medicines targeting serious diseases with major unmet need (e.g. Alzheimer’s disease, ADHD, metabolic disease, schizophrenia, migraine, and others), and its unique, differentiated and high potential StaR drug discovery platform, significantly fulfils this goal and further represents a major step towards the Group’s strategic vision of becoming a significant global biopharmaceutical company arising from Japan.

In addition to its pipeline and platform, Heptares has established collaborative partnerships with a number of the world’s leading pharmaceutical companies that provide the company with a prospective stream of revenue through milestones and royalties. Consolidation of these revenues will make a significant contribution to the Group’s financial position. The combined entity expects continued strong growth driven by revenues from new clinical-stage alliances and platform partnerships.

Heptares overview
Heptares was founded in 2007 based on the pioneering work of its founding scientists Richard Henderson and Christopher Tate at the MRC Laboratory of Molecular Biology (Cambridge, UK), with investment from MVM Life Science Partners and led by co-founders Malcolm Weir and Fiona Marshall. From these origins, and with additional venture funding from MVM, Clarus Ventures, Novartis Venture Fund, Takeda Ventures and the Stanley Family Foundation, Heptares has moved on to develop its unique StaR technology platform that enables it to design drugs precisely based on a detailed understanding of the structure of the drug target – an approach known as structure-based drug design (SBDD). By this method, Heptares aims to design and develop superior medicines that are more effective, with better selectivity and fewer side effects.

Heptares applies this approach primarily to GPCRs – a superfamily of membrane proteins found in every cell in the body that are crucial to communication between cells. Their central role in many biological processes means that they are important targets for drugs: GPCRs are the site of action of about 40% of currently marketed drugs. The potential of the Heptares platform for both discovery of novel, differentiated small molecules and biologics, is therefore very high.

Heptares brings to the Group

An enhanced product pipeline
Heptares’ StaR platform has been used to generate an exciting, wholly owned pipeline of new medicines with potential to transform the treatment of a wide range of human diseases. The pipeline is focused on highly validated targets and is diversified across the neuroscience, metabolic and orphan disease areas, creating multiple future opportunities for both internal development and partnering, and thereby poised to generate revenue in the near future and over a long-term period.

Heptares’ pipeline of first-in-class or superior next-generation therapeutics includes:

Development programme Indication Development Stage
M1 agonist Cognitive impairment in Alzheimer’s disease/ Schizophrenia/others) Phase Ib
A2A antagonist ADHD IND open
M4 agonist Psychosis (Schizophrenia/ Alzheimer’s disease/others) Pre-clinical
M1M4 dual agonist Cognitive impairment and psychosis in Schizophrenia/ Alzheimer’s disease/others) Pre-clinical
CGRP antagonist Migraine Pre-clinical
GLP-1 agonist peptide Diabetes Pre-clinical
GLP-1 antagonist Congenital hyperinsulinism Pre-clinical
Orexin OX1 antagonist Addiction Pre-clinical

Besides the above-mentioned programmes, the enlarged product portfolio of the Group will also include two COPD products, Seebri Breezhaler and Ultibro Breezhaler, developed and marketed in the EU, Japan, etc. (NDA submitted in the US) by licensing partner Novartis, SO-1105, a Phase III product indicated for oropharyngeal candidiasis, and four early stage products

A proprietary drug discovery technology platform that is expected to generate revenue through and beyond the expiration of the Group’s COPD patents in 2026
In addition to in-house development, Heptares has leveraged the capabilities of its proprietary StaR technology to sign partnership agreements with a number of the world’s leading pharmaceutical and biologics companies, including AstraZeneca, Cubist (Merck), Takeda Pharmaceutical, MorphoSys, MedImmune and Novartis. These existing partnerships have provided more than USD 30 million in upfront and milestone payments to-date and are expected to continue generating revenues through milestone payments and royalties over the coming years and beyond the expiration of the Group’s COPD products patents in 2026. New pipeline products and alliance deals will likewise generate income for many years to come.

The Heptares platform will complement the existing technologies of the Group subsidiaries: Activus’ nanoparticle technology (APNT), and Jitsubo’s novel peptide manufacturing technology (Molecular Hiving) and peptide modification technology (Peptune). Together, these technologies are expected to generate synergies in the effort to identify new compounds, and to further strengthen the pipeline and enhance corporate value.

Experienced leadership team with enhanced development and regulatory potential
Heptares is founded on world-class UK science and has built an outstanding team of scientists with expertise in GPCRs, SBDD, drug discovery and development, and neuroscience. These capabilities of Heptares in the EU and US will complement those of the Group in Japan, and will be supported by the management team that has extensive expertise in EU/US drug development and commercialization.

2. Management Structure
The Group will continue to be led by Shinichi Tamura as Chairman and CEO. Dr Malcolm Weir, Heptares co-founder and CEO, will remain as CEO of Heptares, which will be managed as an autonomous subsidiary of the Group. Dr Weir will also join the enlarged Group as Chief R&D Officer and will be responsible for worldwide research and development outside Japan. Dr Declan Doogan and Peter Bains, currently serving as non-executive directors on the Group’s main Board, will join the Heptares Board representing the Group’s interest. Dr Fiona Marshall, co-founder of Heptares and CSO, will also join the Heptares Board

3. Transaction details
Sosei has acquired 100% of Heptares’ share capital for USD 180 million in cash consideration and up to USD 220 million contingent upon the successful progression of the company’s pipeline and platform.

Sosei was advised by Moelis & Company and Clifford Chance LLP. Heptares was advised by Goldman Sachs International and Covington & Burling LLP.

A webcast to present the agreement can be accessed at View Source

Taiho Pharmaceutical Announces TAS-102 (brand name in Japan: "Lonsurf®") New Drug Application for Refractory Metastatic Colorectal Cancer Accepted for Review by FDA

On February 23, 2015 Taiho Pharmaceutical reported that the U.S. Food and Drug Administration (FDA) has accepted the Company’s submission of a New Drug Application (NDA) for TAS-102 (nonproprietary names: trifluridine and tipiracil hydrochloride, brand name in Japan: "Lonsurf combination tablet T15, T20"). TAS-102 is an oral combination investigational anticancer drug for the treatment of refractory metastatic colorectal cancer (mCRC). The PDUFA goal date is December 19, 2015 (Press release, Taiho, FEB 23, 2015, View Source [SID:1234502140]).

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Results from the Phase III RECOURSE trial of TAS-102 in 800 mCRC patients, whose disease had progressed after or who were intolerant to standard therapies, form the foundation for the NDA. The TAS-102 RECOURSE trial met the primary efficacy endpoint of statistically significant improvement in overall survival versus placebo (HR = 0.68, p < 0.0001) and demonstrated a safety profile consistent with that observed in earlier clinical trials.

About TAS-102
TAS-102 is an oral combination investigational anticancer drug of trifluridine (FTD) and tipiracil hydrochloride (TPI). FTD is an antineoplastic nucleoside analog, which is incorporated directly into DNA, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase. TAS-102 was approved initially in Japan in March 2014 for the indications of "unresectable advanced or recurrent colorectal cancer (only if refractory to standard therapies)," based on the results of the Phase II clinical trial conducted in Japan, and launched in Japan in May 2014 under the brand name "Lonsurf combination tablet T15, T20".

Novartis receives FDA approval of Farydak®, the first HDAC inhibitor for patients with multiple myeloma

On February 23, 2015 Novartis reported that the US Food and Drug Administration (FDA) has approved Farydak (panobinostat, previously known as LBH589) capsules in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior regimens, including bortezomib and an immunomodulatory (IMiD) agent (Press release Novartis, FEB 23, 2015, View Source [SID:1234501839]).

“Farydak represents an exciting agent with a new mechanism of action that is part of a promising class of drugs in this setting,” said study investigator Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. “Importantly, Farydak has been shown to improve progression-free survival in relapsed multiple myeloma patients who have received at least two prior regimens, including bortezomib and an IMiD, which is an area of particular unmet medical need.”

Farydak has been shown to extend the progression-free survival (PFS) benefit of the standard-of-care therapy in this patient population. Farydak is approved under accelerated approval based on PFS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The FDA’s accelerated approval program gives patients access to treatments for serious or life-threatening illnesses that provide meaningful therapeutic benefit over existing treatments. The FDA has approved a risk evaluation and mitigation strategy (REMS) for Farydak. The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Farydak treatment.

This FDA approval is based on efficacy and safety data in a pre-specified subgroup analysis of 193 patients who had received prior treatment with both bortezomib and an IMiD during the Phase III, randomized, double-blind, placebo-controlled, multicenter global registration trial, called PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA). The trial found that the median PFS benefit increased in Farydak patients who had received prior treatment with both bortezomib and an IMiD (10.6 months; n=94), as compared to the placebo arm (5.8 months; n=99) (hazard ratio=0.52 [95% confidence interval (CI): 0.36, 0.76]).

The most common adverse reactions (incidence >= 20%) in clinical studies are diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia and vomiting. The most common non-hematologic laboratory abnormalities (incidence >= 40%) are hypophosphatemia, hypokalemia, hyponatremia and increased creatinine. The most common hematologic laboratory abnormalities (incidence >= 60%) are thrombocytopenia, lymphopenia, leukopenia, neutropenia and anemia. Farydak can cause fatal and serious toxicities including severe diarrhea and cardiac toxicities. Severe diarrhea occurred in 25% of Farydak-treated patients. Severe and fatal cardiac ischemic events, including severe arrhythmias and ECG changes have occurred in patients receiving Farydak. Serious adverse events (SAEs) occurred in 60% of patients treated with Farydak, bortezomib and dexamethasone compared to 42% of patients in the control arm. The most frequent (>= 5%) treatment-emergent SAEs reported for patients treated with Farydak were pneumonia (18%), diarrhea (11%), thrombocytopenia (7%), fatigue (6%) and sepsis (6%). Additional serious adverse reactions included hemorrhage, myelosuppression, infections, hepatotoxicity and embryo-fetal toxicity.

“Novartis is committed to developing innovative first-in-class therapies for patients who need treatment options,” said Bruno Strigini, President, Novartis Oncology. “Farydak represents a new drug class in multiple myeloma, providing these patients with an important treatment approach for this difficult-to-treat cancer.”

Farydak is the first histone deacetylase (HDAC) inhibitor available to patients with multiple myeloma. As an HDAC inhibitor, its epigenetic activity may help to restore cell function in multiple myeloma.

Additional regulatory submissions for Farydak are being reviewed by health authorities worldwide.

NGM and Merck Announce Broad Strategic Collaboration to Discover, Develop and Commercialize Novel Biologic Therapeutics

On February 23, 2015 NGM Biopharmaceuticals and Merck reported that they have entered into a multi-year collaboration to research, discover, develop and commercialize novel biologic therapies across a wide range of therapeutic areas (Press release Merck & Co, FEB 23, 2015, View Source [SID:1234501835]). This agreement will become effective upon the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

“We are very pleased to establish this alliance with Merck, which will be transformational for NGM, providing us with the resources and flexibility to pursue our ambitious research and development goals while preserving our unique drug discovery culture,” said William J. Rieflin, Chief Executive Officer of NGM. “We look forward to working with Merck to generate a robust pipeline of therapies with the potential to make a significant difference in the lives of patients.”

“NGM has developed a uniquely powerful research program that has permitted identification of novel, and quite consequential, pathways for metabolic regulation,” said Dr. Roger M. Perlmutter, President of Merck Research Laboratories. “Through this new collaboration, we hope to apply Merck’s well-established translational capabilities to advance innovative biologics that address the needs of patients suffering from diabetes, metabolic dysregulation, and malignancy.”

The collaboration includes multiple drug candidates currently in preclinical development at NGM, including NP201, which is being evaluated for the treatment of diabetes, obesity and nonalcoholic steatohepatitis (NASH). NGM will lead the research and development of the existing preclinical candidates and have the autonomy to identify and pursue other discovery stage programs at its discretion. Merck will have the option to license all resulting NGM programs following human proof of concept trials. If Merck exercises this option, Merck will lead global product development and commercialization for the resulting products, if approved.

Under the terms of the agreement, Merck will make an upfront payment to NGM of $94 million and will purchase a 15 percent equity stake in NGM for $106 million at a price per share that represents a 20 percent premium to NGM’s most recent financing. Merck will commit up to $250 million to fund all of NGM’s efforts under the initial five-year term of the collaboration, with the potential for additional funding if certain conditions are met.

Prior to Merck initiating a Phase 3 study for a licensed program, NGM may elect to either receive milestone and royalty payments or, in certain cases, to co-fund development and participate in a global cost and revenue share arrangement of up to 50 percent. The agreement also provides NGM with the option to participate in the co-promotion of any co-funded program in the United States. Merck will have the option to extend the research agreement for two additional two-year terms.

“This collaboration brings together our biology-driven research and development product platform with Merck’s late-stage development and commercialization expertise, while also enabling NGM to explore exciting new drug targets,” commented Dr. Jin-Long Chen, Founder and Chief Scientific Officer of NGM. “Both companies’ commitment to scientific excellence and willingness to creatively combine our strengths was key to establishing this relationship.”

NGM’s lead program, NGM282, currently in clinical development for primary biliary cirrhosis (PBC) and NASH, as well as programs that are the focus of NGM’s pre-existing collaboration agreements, are not subject to the option under the Merck collaboration.

Foundation Medicine and H3 Biomedicine Announce Collaboration to Develop Precision Therapies for Cancer

On February 23, 2015 Foundation Medicine and H3 Biomedicine reported a multi-year collaboration for the discovery and development of precision medicines in oncology (Press release Foundation Medicine, FEB 23, 2015, View Source [SID:1234501833]). The collaboration marries Foundation Medicine’s comprehensive genomic knowledgebase of more than 35,000 genomic profiles, FoundationCORE, with H3 Biomedicine’s drug discovery engine and computational biology platform. The approach aims to identify potential drug targets based on the unique genomic dependencies of individual cancers, rapidly accelerate clinical development, and lead to the commercialization of new, safe and effective precision medicines for individuals living with cancer.

“Large-scale genomic data sets are the key to identifying actionable targets and addressing the multitude of difficult-to-treat cancers,” said Markus Warmuth, M.D., president and chief executive officer of H3 Biomedicine. “More than ever before, we in cancer drug development have the benefit of an ever-growing arsenal of genomic information including publicly available data sets that inform validation of targets, development of therapies and translation from bench to bedside. In this regard, we believe Foundation Medicine offers one of the most comprehensive cancer genomics knowledgebases available. This collaborative effort will further empower our state-of-the-art discovery engines to deliver novel first-in-class medicines and improve our clinical development strategies by accessing a wealth of clinically annotated, genomic information at least in part derived from later-stage and metastatic cancers.”

“This collaboration with H3 Biomedicine shows how Foundation Medicine is creating value through FoundationCORE,” said Michael J. Pellini, M.D., president and chief executive officer of Foundation Medicine. “Recent scientific advances identifying the unique molecular drivers of cancer are elucidating new approaches to targeted drug development. FoundationCORE, our unique and rapidly growing genomic knowledgebase, can provide valuable insights for our life sciences partners and help them accelerate and increase the probability of success for clinical development of new targeted therapies for patients with cancer.”

Under the terms of the agreement, H3 Biomedicine will pay Foundation Medicine a technology access fee for identification of target concepts arising from FoundationCORE and success milestones for selection, validation, clinical progression, and commercialization of products developed from the program. In addition, Foundation Medicine is eligible to receive royalties on sales of any products resulting from the collaboration.