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

Editor’s Note

During a press conference on Wednesday, US President Elect Donald Trump promised to control drug prices in pledging aggressive federal bidding process. Some of the ex­cerpt: “We have to get our drug in­dus­try com­ing back. Our drug in­dus­try has been dis­as­trous. They are leav­ing left and right. They sup­ply our drugs but they don’t make them here, to a large ex­tent. And the other thing we have to do is cre­ate new bid­ding pro­ce­dures for the drug in­dus­try. They are get­ting away with mur­der. Pharma has a lot of…lob­by­ists and a lot of power and there iss very lit­tle bid­ding on drugs.    We arere the largest buyer of drugs in the world, and yet we don’t bid prop­erly. We are going to start bid­ding. We’re going to save bil­lions of dol­lars over a pe­riod of time.”

During the JP Morgan Healthcare Conference an important number of deals are often announced. This was again the case in 2017 and we just highlight the most significant ones in this newsletter.

Mergers, Acquisitions and Joint Ventures

Takeda Pharmaceuticals (Osaka, Japan) acquires Ariad Pharmaceuticals (Cambridge, MA, USA) for $5.2 billion, at a 74% premium, and expands its oncology franchise. The deal will give Takeda access to Iclusig, or ponatinib, a pan-kinase inhibitor already approved for the treatment of leukemia and brigatinib, an ALK inhibitor for the treatment of non-small cell lung (NSCL) cancer patients who no longer respond to Xalkori.  The US rolling submission of brigatinib has been completed and drug approval is expected in the coming months.

Allergan has negotiated an option to acquire Lysosomal Therapeutics (Cambridge, MA, USA) in a mean to enter into the field of Parkinson’s disease. LTI-291, Lysosomal Therapeutics’ lead product, stimulates the activity of glucocerebrosidase (GCase) in the brain, which is reduced because of mutations in the GBA1 gene. Around five to 10 percent of patients with Parkinson's disease (PD) have such mutations. Activation of GCase by LTI-291 will help to slow down the disease Allergan has acquired the right to purchase the company after a Phase Ib trial for LTI-291 has been completed. Details on the deal structure were not disclosed, except that Allergan will provide an upfront and research and development payment.

Kite Pharma (Santa Monica, CA, USA) and Fosun Pharmaceutical (Shanghai, China) are forming a joint-venture to develop Kite’s axicabtagen ciloleucel, a chimeric antigen receptor T-cell immunotherapy in China. Fosun will make a $40 million upfront payment, $35 million in milestone payments and up to $20 million in funding to support the clinical and manufacturing development as well as mid-single digit royalties on sales. Both parties will share the profits of the JV.

China’s Sanpower Group acquires Valeant Pharmaceuticals’ (Laval, Canada) equity interest in cancer drugmaker company Dendreon for $819.9 million in cash. This is the first time a Chinese company takes over a US drugmaker that develops innovative medications, and is the most expensive pharma purchase by a Chinese company in the US. The deal will transfer ownership of Provenge, the only FDA-approved immunotherapy for prostate cancer and the only commercialized product of Dendreon, approved for the first time by the US FDA in 2010, to the Chinese conglomerate.

Business

Ipsen (Boulogne-Billancourt, France) acquires the oncology assets from Merrimack Pharmaceuticals (Cambridge, MA, USA) for $1.1 billion and increases its presence in the US. Under the terms of the agreement, Ipsen will gain exclusive commercialization rights for the current and potential future ONIVYDE indications in the U.S., as well as the current licensing agreements with Shire for commercialization rights ex-U.S. and PharmaEngine for Taiwan. The transaction also includes Merrimack’s commercial and manufacturing infrastructure, and generic doxorubicin HCl liposome injection. Under the terms of the agreement, Ipsen will make a $575 million payment in cash and up to $450 million upon the approval of first-line pancreatic cancer indication, a small cell lung cancer as well as a third indication for ONIVYDE in the U.S.

Amgen has entered a collaboration with Immatics Biologics (Tübingen, Germany) to develop next-generation T-cell engaging bispecific immunotherapies targeting multiple cancers in a deal worth up to $1.3 billion. Both companies are planning to utilise Immatics' XPRESIDENT target discovery and T-cell receptor (TCR) capabilities and Amgen's Bispecific T-cell Engager (BiTE) technology to create novel oncology drugs. Bispecific antibodies have gained attention in the immuno-oncology field for their ability bind to two different sites which can improve binding specificity and efficacy in inactivating disease targets. Under the terms of the deal, Amgen will be responsible for the clinical development, manufacturing and commercialisation worldwide of any successful candidates.

Sanofi and Immunext (Lebanon, NH, USA) enter into an agreement, focused on the development of novel antibodies to treat autoimmune diseases, with the exclusive license to develop and commercialize INX, a CD40L monoclonal antibody as well as a discovery collaboration. Potential milestones could reach up to $500 million and Sanofi will pay sales tiered double-digit royalties.

Kite Pharmaceuticals (Santa Monica, CA, USA) enters a strategic partnership with Daiichi Sankyo (Tokyo, Japan) to develop and commercialize Axicabtagene Ciloleucel (KTE-C19) a CAR-T cell therapy for the treatment of lymphomas and leukemias in Japan. Under the terms of the deal, Daiichi Sankyo will make a $50 million upfront payment and up to $250 million and development milestones plus double-digit royalties on sales. In addition, Daiichi Sankyo has an option to license additional Kite product candidates for Japan including KITE-718, Kite's T cell receptor product candidate targeting MAGE-A3/A6 and other product candidates over the next three years. Kite earlier announced the establishment of a JV with Fosun to develop Axicabtagene Ciloleucel in China (see above).

Celgene enters a global research and strategic collaboration with Anokion (Lausanne, Switzerland) to develop tolerance-inducing therapeutics for autoimmune diseases and potentially to reduce the immunogenicity of therapeutic proteins. Under the terms of the deal, Celgene will make an undisclosed equity investment and $45 million upfront in return for exclusive access to Anokion’s platform and the right to acquire Anokion at specific option points.

Merck KGaA (Darmstadt, Germany) in-licenses Vertex’s (Boston, MA, USA) pro­grams on an ataxia telang­iec­ta­sia and Rad3 re­lated (ATR) pro­tein ki­nase in­hibitor pro­gram — cov­er­ing VX-970 and VX-803 – as well as a DNA-de­pen­dent pro­tein ki­nase (DNA-PK) in­hibitor pro­gram for VX-984 for the treatment of various tumors. Under the terms of the deal, Merck KGaA will make a $230 million upfront payment to license rights to two clinical candidates and two preclinical programs.

Two days after announcing the acquisition of Ariad, Takeda Pharmaceuticals (Osaka, Japan) announces an investment of $125 million into Maverick Therapeutics (Brisbane, CA, USA) with an option to acquire the company and de­velop unique, small and cus­tomiz­able T-cell en­gage­ment ther­a­peu­tics.

Pierre Fabre (Castres, France) and PIQUR Therapeutics (Basel, Switzerland) enter a collaboration agreement for the development of PIQUR’s lead compound PQR309 in dermato-oncology. The exclusive deal will see PIQUR and Pierre Fabre’s R&D teams work together on the evaluation and development of dermatological formulations of PI3K/mTOR inhibitors across multiple therapeutic indication. Financial terms were not disclosed

Abivax (Paris, France) announces a funding of €8.4 million from the competitive funding call “Projets de R&D Structurants Pour la Compétitivité” (PSPC) of the “Invest in the Future Program” (PIA) operated by BpiFrance to accelerate the identification and optimization of novel antiviral therapeutics.

Approval of drugs and vaccines

European regulators have approved:

Novo Nordisk's Fiasp for the treatment of diabetes in adults. Fiasp is an ultra-fast rapid-acting insulin that improves control of postprandial glucose excursions which has been developed for the treatment of people with both type I and type II diabetes.

Gilead’s Vemlidy or tenofovir alafenamide (TAF) a novel produg of tenofovir with high antiviral efficacy similar to Gilead's Viread (tenofovir disoproxil fumarate; TDF) at one-tenth of the dose. Because TAF enters cells more efficiently than TDF it can be given at a lower dose, massively reducing the amount of tenofovir present in the bloodstream.

US FDA rejects Tesaro’s (Waltham, MA, USA) Varubi, a new intravenous formulation of ralapitant, a selective NK1 receptor antagonist, on manufacturing issues.

Drugs at clinical stage

The European Medecine Agency (EMA) has granted orphan designation to FG2’s (Manchester, UK) F901318, a systemic antifungal of the orotomide class, for the treatment of invasive Aspergilosis as well as rare mold infection caused by Scedosporium species.

Merck has filed an early and stunning US FDA application to market a combination of Keytruda, its checkpoint inhibitor, and chemotherapy for first-line lung cancer. The US FDA has ac­cepted the sup­ple­men­tal ap­pli­ca­tion and agreed to give the ap­pli­ca­tion a speedy re­view, of­fer­ing a PDUFA date of May 10. “Keytruda in com­bi­na­tion with chemother­apy has shown promise ver­sus chemother­apy alone in the first-line treat­ment of non-squa­mous metasta­tic non-small cell lung can­cer, re­gard­less of PD-L1 lev­els. If ap­proved, this could be the first reg­i­men com­bin­ing chemother­apy with an im­muno-on­col­ogy agent for pa­tients with ad­vanced non-small cell lung can­cer” said  Dr. Roger Dansey, se­nior vice pres­i­dent and ther­a­peu­tic area head, on­col­ogy late-stage de­vel­op­ment, Merck Re­search Lab­o­ra­to­ries.

Cure­Vac’s (Tübingen, Germany) lead­ing mRNA pro­gram CV9104, a prostate can­cer vac­cine, has failed to meet the primary end-points on improving overall survival and on improvement on progression-free survival over a placebo in a crit­i­cal Phase 2 trial. This fail­ure fol­lows a wave of clin­i­cal flops for can­cer vac­cines in gen­eral, which proved far too weak to di­rect a sig­nif­i­cant im­mune sys­tem at­tack on can­cer.

Medical Devices and Diagnosis News.

Johnson & Johnson’s DePuy Synthes Products collaborates with Orthocell (Perth, Australia) on development of a stem cell-based approach to the regeneration of tendons. Ortho-ATI, an acronym of autologous tenocyte implantation, is made up of a patient’s own tendon cells, known as tenocytes. Orthocell makes each personalized cell therapy by harvesting a small piece of healthy tendon and then isolating and growing the tenocytes it contains. After four to five weeks of growth, the tenocytes are injected into the damaged tendons. Ultrasound is used to show the site of the injury, making the process less invasive than surgical alternatives. Australian Football League players were among the early adopters of the treatment.

Cost, Pricing and Market Access

The UK National Institute for Health and Care Excellence (NICE) is now recommending Novartis’ Afinitor (everolimus) as an option for treating advanced renal cell carcinoma that has progressed during or after treatment with vascular endothelial growth factor targeted therapy. The Institute had originally rejected the drug back in April 2011.

Miscellaneous

Novo Nordisk has hired Flour Corporation (Irving, Texas, USA) to design and build its US diabetes drug Active Product Ingredient (API) 830,000 sqft facility in Clayton (North Carolina).  Novo expects to employ 700 people at the site when it is operational in 2020.

US Supreme Court has agreed to hear two related lawsuits over provisions governing biosimilar approval process. The specific date of the hearing has not been set.

Bioevents

9^th Biotech Showcase Investor Conference on January 9-11, in San Francisco (USA)

JP Morgan 35th Annual HealthCare Conference on January 9-12, in San Francisco (USA)

BIO CEO & Investor Conference on February 13-17, 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)

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/pharma-biotech-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.