Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation, jcm@btobioinnovation.com

Mergers, Acquisitions and Joint Ventures

Johnson & Johnson acquires Actelion (Allschwil, Switzerland) for $30 billion.After weeks of exclusive talks, both companies have entered into a definitive transaction agreement under which the J&J will launch an all-cash tender offer to acquire all of the outstanding shares of Actelion for $280 per share. Under the terms of the deal Actelion will spin out its drug discovery operations and early-stage clinical development assets into a newly created Swiss biopharmaceutical company, headed by former CEO, Jean-Pierre Clozel, which will be listed on the SIX Swiss Exchange. J&J will initially hold a 16% equity in the NewCo and rights to an additional 16 %, through a convertible note, as well as a license option on ACT-132577, currently in a Phase II for resistant hypertension. "The price is quite high at around 30 times price to estimated 2018 earnings. J&J is paying a lot and R&D is not even included, just a substantial minority stake," one Zurich-based trader was quoted by Reuters as commenting on the transaction. "But it represents only 10 % of J&J's market capitalisation and they are finally investing the cash they hold in Europe".

Celgene acquires Delinia (Cambridge, MA, USA) in a deal worth $775 million and gets access to DEL106, a preclinical candidate as well as related programs. DEL106 is an IL-2 mutein Fc fusion protein designed to upregulate regulatory T cells (Tregs) in order to avoid autoimmune diseases. Under the terms of the deal, Celgene will make an upfront payment of $300 million and up to $475 million in various milestones.

Ethypharm (Saint Cloud, France) acquires Martindale Pharma (Wooburn, UK) a specialty pharmaceutical company and increases its presence in the UK. Financial terms of the deal were not disclosed.

Altimmune (Gaithersburg, MD, USA), merges with PharmAthens (Athens, Greece) a biodefense company, in an all-stock deal to form a company with immunotherapy and vaccine candidates for influenza, anthrax and chronic hepatitis B. The new company will retain the Altimmune name and will be headquartered in Gaithersburg, MD.

Intrexon (Germantown, MD, USA) acquires GenVec (Gaithersburg, MD, USA) in an all stock deal which values GenVec at $7/share.

Novartis’ CEO Joe Jimenez indicated that his company might divest Alcon, its ophthalmology unit, which it acquired progressively from Nestlé for $52 million back in 2008. The company said that it will look at all options for Alcon, “ranging from retaining the business to separation via a capital markets transaction” like an IPO or a spinoff. A decision is expected by the end of the year.

Business

Incyte (Wilmington, DL) cashes $112 million from Jakavi or ruxolitinib royalties based on $581 million sales made by partner Novartis.

Merck KGaA enters a collaboration with Domain Therapeutics (Strasbourg, France) to develop adenosine receptor antagonists as immune-oncology drugs. Adenosine receptor antagonists are small molecules that have the potential to slow tumor progression and improve the response to combination immunotherapies by inhibiting adenosine, a compound generated by cancer cells that inhibits antitumor responses by binding to T cells. Financial terms of the deal were not disclosed.

Enteris Biopharma (Booton, NJ, USA) secures two deal to use its excipient-based platform to enhance delivery of preclinical peptide candidates. A first one with Sanofi to help develop an oral formulation of a preclinical peptide for the treatment of type 2 diabetes.  A second one with Nordic Bioscience (Herlev, Denmark) to advance the development of a metabolic peptide.  The Peptelligence technology aims at improving the bioavailability of APIs, allowing the oral delivery of small molecules and peptides which could only be delivered by a subcutaneous our intravenous route.

GlaxoSmithKline, Merck, Johnson & Johnson, Pfizer, Sanofi and Takeda shave joined the Bill & Melinda Gates Foundation, Wellcome Trust and the governments of Germany, Japan and Norway to form the Coalition for Epidemic Preparedness Innovations (CEPI).  The group has netted $460 million in funding with the aim to initially focus on the MERS-CoV, Lassa and Nipah viruses.

Pfizer enters the Milner Therapeutics Consortium (Cambridge, UK), a global therapeutic alliance that aims to enable the transfer of materials between industry and academia. The Consortium is essentially a 'match-making' service between pharmaceutical companies and researchers at Cambridge University, providing access to novel therapeutic agents across the entire portfolio of drugs being developed by each member firm.

Adocia (Lyon France) announces the termination by Eli Lilly of the collaboration on BioChaperone Lispro for the treatment of type 1 and Type 2 diabetes.  This is the second time Lilly opts out of its deals with Adocia. « We are extremely disappointed and surprised by Lilly’s decision to terminate the collaboration on our product which has demonstrated significant improvement in terms of performance vs Humalog® across 6 clinical studies. Based upon this stage of development, we are convinced that BC Lispro can improve the lives of people with diabetes and Adocia will continue to prepare launch of phase 3 clinical trials while looking for a new partner. » said Gérard Soula, Chairman and CEO

Merck, Bristol-Myers Squibb and Ono settle a long-standing dispute over their checkpoint inhibitors, whereas Merck will pay $625 million in cash and a 6.5% royalty on Keytruda sales for the next six years, which will be split 75/25 between BMS and Ono.

Op2Lysis (Boulogne-Billancourt, France) a start-up which develops an innovative therapeutic approach to reduce the most severe outcomes of hemorrhagic stroke (1.5 million new events per year). In order to perform preclinical studies Op2Lysis has initiated a first-round funding with a crowdfunding platform, Wiseed, together with co-investment funds. Voting and promise of investment is now ongoing. (https://www.wiseed.com/fr/startups/op2lysis?)

Approval of drugs and vaccines

No major reported approval this week

Drugs at clinical stage

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is recommending approval of Pfizer's XELJANZ (tofacitinib citrate) 5 mg twice daily for the treatment of patients with moderate-to-severe active rheumatoid arthritis (RA). If approved, XELJANZ, in combination with methotrexate (MTX), will be indicated for adults with RA who have failed to respond adequately to or are intolerant of one or more disease-modifying antirheumatic drugs (DMARDs). CHMP rejected the original filing in July 2013 over safety concerns, specifically the risk and type of serious infections observed with tofacitinib.

US FDA grants orphan status to:

TG Therapeutics (New York, USA) combination of TG-1101/TG 1202 for the treatment of diffuse large B-cell lymphoma. TG-1101 is a glycoengineered anti-CD20 monoclonal antibody. TG-1202 is a PI3K delta inhibitor.

…and to Concert Pharmaceutical’s (Lexington, MA, USA) CTP-656, or deuterated ivacaftor, as a treatment for cystic fibrosis in patients with gating mutation. CTP-656, a novel, next generation CFTR potentiator, is a once-daily deuterated modified form of ivacaftor, which has shown to demonstrate superior pharmacokinetic profile compared to Kalydeco with a reduced rate of clearance, longer half-life, substantially increased exposure and greater plasma levels at 24 hours.

Eisai’s Lenvima or lenvatinib, met its primary endpoints in phase 3 for first-line use against for hepatocellular carcinoma (HCC) a liver cancer in proving non-inferiority to Nexavar. The drug is already approved for kidney cancer in combination with Afinitor.

Actelion (Allschwil, Switzerland) announces the failure of Opsumit, or macitentan, to meet its primary endpoint fortreating pulmonary for treat­ing pul­monary ar­te­r­ial hy­per­ten­sion (PAH) due to Eisen­menger Syn­drome. Eisenmenger's syndrome is a form of congenital heart disease in which the pressure in the pulmonary arteries is high, causing an increased resistance to blood flow in the lungs. Op­sumit is al­ready ap­proved to treat PAH.

Medical Devices and Diagnosis News.

Exosome Sciences (Houston, TX, USA) a diagnostic subsidiary of Aethlon Medical’s (San Diego, CA, USA) is working on a study to validate a biomarker candidate as a way to detect and monitor Chronic Traumatic Encephalopathy (CTE) in living individuals. CTE, a neurodegenerative disease often found in people who have sustained repetitive head trauma, is currently only diagnosable after death.  While the study will mainly look at former football players, CTE is also commonly found in boxers, in professional wrestler and in ice hockey players.

Science & Technology

Shark antibodies, because they are smaller than human antibodies and bind to the transferrin receptor in a unique way, are an attractive way to deliver biologics to the brain according to Ossianix (Stevenage, UK) which uses this technique with Lundbeck (Copenhagen, Denmark) to allow the transfer of agents through the blood brain barrier.

Cost, Pricing and Market Access

The UK National Institute for Health and Care Excellence has recommended the use of Gilead Sciences’ Epclusa, or sofosbuvir and velpatasvir as a treatment for chronic hepatitis C genotypes 1-6 infection in adults.

Miscellaneous

Novartis Elzeri a biosimilar version of Enbrel will not reach the US market prior to 2019, although the drug has been approved by the US FDA nearly five months ago. In addition to the ongoing patent litigation, another legal battle between Novartis and Amgen is now before the US Supreme Court that will affect how quickly biosimilars get to market. The Supreme Court earlier this month agreed to consider arguments over when a required six-month waiting period begins to run after a biosimilar company notifies the original developer about its would-be rival drug.

Regeneron Pharmaceutical acquires its Mount Pleasant and Greenburgh-based Landmark Headquarters at Eastview campus (New York State, USA) for $720 million.

US FDA has introduced a new designation to allow drugs to be eligible for approval under a regenerative advanced therapy status. Drugmakers can apply for the designation if their treatment is a human cell and tissue product, therapeutic tissue engineering product, cell therapy or combination product intended to treat, reverse, modify or cure a serious or life-threatening condition or disease, with clinical evidence indicating that it can address unmet medical needs for the condition.

People on the move:

Ingmar Hoerr, CEO of CureVac, has been appointed as one of 15 members of a new group that will advise the European Commission on strengthening the environment for research and innovation in the European Union.

Bioevents

3^rdAnnual Biotech and Money London on February 7-8, in London (UK)

BIO CEO & Investor Conference on February 13-17, in New York City (USA)

European Life Sciences CEO Forum & Exhibition on March 6-7, Zurich (Switzerland)

BIO Asia on March 14-15, in Tokyo (Japan)

BIO-Europe Spring on March 20-22, in Barcelona (Spain)

BIOTrinity on May 8-10, in London (UK)

9^th Annual China BIO Partnering Forum on May 10-11 in Shunde (China)

BIO International Convention on June 19-22 in San Diego (USA)

BIOPharm America on September 26-27 in Boston (USA)

BIO Latin America on October 26-28 in Sao Paulo (Brazil)

BIO Europe on Novmber 6-8 in Berlin (Germany)

BIOFIT on November 28-29 in Strasbourg (France)

http://btobioinnovation.com/events/pharma-biotech-events/

http://btobioinnovation.com/events/in-vitro-diagnostic-events/

This document has been prepared by btobioinnovation and is provided to you for information purposes only.  The information contained in this document has been obtained from sources that btobioinnovation believes are reliable but btobioinnovation does not warrant that it is accurate or complete. The views presented in this document are those of btobioinnovation’s editor at the time of writing and are subject to change.  btobioinnovation has no obligation to update its opinions or the information in this document.