< PreviousM&A ROUND-UP10Pharma Business International www.pbiforum.net© Shutterstock /Milena.photos08-11.qxp_Layout 1 04/12/2018 15:07 Page 3Pharma Business International 11www.pbiforum.netM&A ROUND-UPAlphabet-backed cancer analytics start-up Flatiron Health for $1.9 billion. Rochesaid of its intentions that it aims to createan industry-wide development anddelivery of breakthrough medicine forcancer patients. GlaxoSmithKline, meanwhile, paid £9.2billion for a 36.5 per cent stake inNovartis’ Consumer Health Joint Venture.From a financial point of view, it seemedlike a no brainer, with the businessreporting sales in excess of £7.8 billion.As well as selling, Novartis was also onthe buying end with its $8.7 billionacquisition of Nasdaq-listed clinical stagegene therapy company AveXiscompleting in May. April saw US-basedmulti-nationalconsumer goods giantProctor & Gamblestrengthen itshealthcare portfolio withthe addition of Merck’s Consumer Healthbusiness. The company said at the timethat the €3.4 billion deal expands itsexisting consumer health competencesby adding a flourishing portfolio ofdifferentiated, physician-supportedbrands across a broad geographicfootprint. Although Shire has this year beenpreoccupied with another deal (more onthat later), it also offloaded its oncologybusiness to French pharma outfit Servierfor $2.4 billion. For Servier, the dealprovided a foothold in the US with animmediate presence to capitalise on andscale up. For Shire, meanwhile, the dealwas motivated by its oncology positionno longer aligning with its longer-termstrategy, despite the businesses’ high-growth and profitability. With that,though, Servier can make a name foritself as a global oncology player. Spring was rounded off with Eli Lillypaying $1.6 billion for later-stageimmune-oncology company ARMOBioSciences. The deal included thelatter’s lead immune-oncology asset –pegilodecakin – which is being studied inmultiple tumour types. Summer saw the completion ofSanofi’s acquisition of Ablynx, but alsosaw the company sell its Europeangenerics business, Zentiva, to US privateinvestment firm Advent International for€1.9 billion.Roche has been busy this year with theSwiss multi-national snapping up theoutstanding shares of FoundationMedicine’s common stock that wasn’talready owned by itself or affiliates for$2.4 billion. Roche CEO Daniel O’Dayhailed the deal as an important part ofthe company’s personalised healthcarestrategy. Although Johnson and Johnson hasthese last few years been mired in thetalcum powder controversy, summer sawthe company refocus its efforts andoffload its LifeScan business. Thebusiness, which specialises in bloodglucose monitoring and produces theOneTouch brand of products, was sold toprivate equity firm Platinum Equity for$2.1 billion. As summer gave way to autumn, USpharma business Alexion swooped forSyntimmune, a Boston, MA biotech firmdeveloping antibody therapeuticstargeting the neonatal Fc receptor. Thedeal was worth up to $1.2 billion,comprising the initial upfront payment of$400 million, with the potential foradditional payments of up to $800 milliondependent on milestones. Throughout this round-up, Takeda’sambitious purchase of Shire has beenabsent, but rest assured we’ve saved thebiggest for last. In what has been hailedas the biggest acquisition of a drugcompany since 2000, Japan’s Takeda ispaying £46 billion for the Irish company.The deal has been a mainstay in our bi-monthly columns and, as of publishing,has gained the backing of the EuropeanCommission, on top of regulatoryapproval in both the US and Japan. Allthe stars are aligning, and the signs aregood for the deal to finally pass andmake pharmaceutical history. There are many geopolitical issues atplay in the global marketplace, but herein the UK the pharmaceutical industry isnot only pressing ahead with M&Aactivity but on safer ground to weatherany Brexit disruption. Indeed, the 19th‘Capital Confidence Barometer’ from EYfound that sixty-seven per cent of UK lifesciences executives have a stable orpositive outlook on the impact of Brexiton investment and acquisition. Certaintythere’ll be more confidence in the M&Amarket as we move into the New Yearthan the picture we were seeing twelvemonths before.08-11.qxp_Layout 1 04/12/2018 15:07 Page 4MULTIPLE SCLEROSIS EXPOSE12Pharma Business International www.pbiforum.netMultiple sclerosis (MS) is an autoimmunecondition where the immune system attacksthe myelin sheath – the protective layer thatsurrounds nerves. Damage and scarringaccrued to this outer layer – and potentially tothe underlying nerves themselves – mean thatmessages travelling along the nerves becomeslowed or disrupted. This can result in a widerange of symptoms including problems withvision, motor function, sensation and balance.Although much is already known about MS,what causes the immune system to act in sucha way remains a mystery. Current thinkingindicates that a combination of genetic andenvironmental factors are the primarycontributors. However, research is ongoing andthere have been new discoveries unveiling theorigin of MS and mapping its progression. There’s been decades worth of studiesexploring the origins, precursors and, indeed,the contributing factors behind MS, but onecompelling study has shown that gut flora hasa role to play. These new findings, from aresearch group spearheaded by MireiaSospedra and Roland Martin from theUniversity of Zurich’s Clinical Research PriorityProgram Multiple Sclerosis, indicate the needto widen research perspectives in order to gaina better understanding of the condition’spathological processes. As our understandingof the role the gut and microbiome play inautoimmune and other conditions, scientistscan create better treatments and work towardscures. Writing in the journal Science TranslationalMedicine, the scientists report that T cells reactto a protein called GDP-L-fucose synthase – anenzyme formed in human cells as well as inbacteria commonly found in the gastroenteritisflora of patients suffering from MS. “We believe that the immune cells areactivated in the intestine and then migrate tothe brain, where they cause an inflammatorycascade when they come across the humanvariant of their target antigen,” says MsSospedra.Results show that gut microbiota could playa far greater role in the pathogenesis of thedisease than had been previously assumed.Hoping these findings can soon be translatedinto therapy, Ms Sospedra is planning to testthe immunoactive components of GDP-L-fucose synthase using an approach that theresearchers have been pursuing for a numberof years already. As this innovative new approach inchescloser towards meaningful results, other clinicalWorkingtowards a cure Currently, there’s no cure for multiple sclerosis, but the research space for the condition is full ofinnovation and breakthroughs as Pharma Business International explores. 14 Á12-15.qxp_Layout 1 04/12/2018 15:08 Page 1© Shutterstock / martin_stuard12-15.qxp_Layout 1 04/12/2018 15:08 Page 2MULTIPLE SCLEROSIS EXPOSE14Pharma Business International www.pbiforum.nettrials are yielding impressive findings. Arecent clinical trial of more than 250 MSpatients found that thephosphodiesterase inhibitor ibudilast wasbetter than a placebo in slowing downbrain shrinkage. Though hardly a cure, itdoes offer a sliver of hope for peoplesuffering with MS where treatmentoptions are limited at best. “The trial’s results are very encouragingand point towards a potential newtherapy to help people with progressiveMS,” said Robert J. Fox, a neurologist atCleveland Clinic in Ohio, who led the trial.“It also increased our understanding ofadvanced imaging techniques, so thatfuture studies may require a smallernumber of patients followed over ashorter period of time. This leads toincreased efficiency of clinical research.These imaging methods may also berelevant to a host of other neurologicaldisorders.”Although there are many promisingnew treatment options entering and,indeed, flourishing in human clinical trials,some of the most innovative work istaking place in animal models. Whenexamining human brain tissues,researchers from the University of Albertaand McGill University found that thetissue from MS sufferers contained anextremely high level of the proteincalnexin compared to those without MS.Using a mouse model of human MS, theresearchers tested the susceptibility ofmice lacking calnexin and found thatthose lacking the protein were completelyresistant to condition. This exciting12-15.qxp_Layout 1 04/12/2018 15:08 Page 3breakthrough could pave the way forthe development of a treatment forMS. “We think this exciting findingidentifies calnexin as an importanttarget for developing therapies forMS,” said Luis Agellon, aprofessor at the McGill School ofHuman Nutrition. “Our challengenow is to tease out exactly how thisprotein works in the cells involved inmaking up the blood-brain barrier. Ifwe knew exactly what calnexin doesPharma Business International 15www.pbiforum.netMULTIPLE SCLEROSIS EXPOSE© Shutterstock / Billion Photosin this process, then we could find away to manipulate its function topromote resistance for developingMS.”Multiple sclerosis remains acomplex and difficult condition, withpatients lacking a robust pipeline oftreatment options. However, theresearch space is fertile with newbreakthroughs working towards waysto better manage the condition aswell as laying the groundworkstowards a potential cure.The next World MS Daytakes place on30 May 2019 12-15.qxp_Layout 1 04/12/2018 15:08 Page 4GENE THERAPY16Pharma Business International www.pbiforum.netAlthough there’s still asignificant risk attachedwith gene and celltherapies, the sector isemerging as one of themost vital and innovativeacross the pharmaceuticalspectrum.Despite many innovative and high-profile successes, gene therapy remainsvery much in its infancy. In its simplestform, this experimental technique usesgenes to treat or prevent disease.Success has certainly been seen in thepresent, but it’s to the future thatresearchers and many of gene therapy’smost fervent supporters look. They claimthat the technique may someday allowdoctors to treat a disorder by inserting agene into a patient’s cells in place ofdrugs or surgery. According to the National Institutes ofHealth, researchers are testing severalapproaches to gene therapy. Theseinclude replacing a mutated gene thatcauses disease with a healthy copy;inactivation a mutated gene that isfunctioning improperly; and introducing anew gene into the body to help fight adisease. Despite these innovative stepsforward, the technique remains risky andis still being scrutinised under study todetermine it can be both safe andeffective. At present, gene therapy isbeing tested solely for diseases thatHardcell 16-19.qxp_Layout 1 04/12/2018 15:09 Page 1Pharma Business International 17www.pbiforum.netGENE THERAPYcurrently have no cures, with researchfinding it is a promising treatment optionfor inherited diseases, some types ofcancer and certain viral infections. It isn’t academic organisations andscientists alone, however, with majorpharmaceutical players, including GileadSciences, Novartis and Celgene, leadingthe charge. Among these products, it’sNovartis’ Kymriah, a ground-breakingCART-cell therapy aimed at patients agedunder twenty-five suffering from B-cellprecursor acute lymphoblastic leukaemia(ALL), which has been dominatingheadlines and making waves of late. Theone-time treatment uses a patient’s ownT cells to fight cancer. It was originallyapproved the United States Food andDrug Administration back August 2017and, since then, has cleared a number ofother regulatory hurdles on both sides ofthe Atlantic. Most recently, the treatmentwas recommended by the UK’s NationalInstitute for Health and Care Excellence(NICE) for young ALL patients for use onthe NHS. “CART-cell therapy is expensive andcomplex. We have worked in partnershipwith our stakeholders, NHS England andthe company to make the therapyavailable to patients quickly,” saysMeindert Boysen, Director of the Centrefor Health Technology Evaluation atNICE. “Novartis have agreed to offertisagenlecleucel at a lower price so thatpeople using the NHS can be among thefirst in the world to access this excitingnew treatment.”This recommendation is the latestmilestone for the UK’s flourishing cell and© Shutterstock /HQuality19 Á16-19.qxp_Layout 1 04/12/2018 15:09 Page 2© Shutterstock /Mopic16-19.qxp_Layout 1 04/12/2018 15:09 Page 3Pharma Business International 19www.pbiforum.netGENE THERAPYgene therapy industry. Indeed, newresearch from the nation’s own Cell andGene Therapy (CGT) catapult found thatthe industry is going from strength-to-strength with investment boosting bothmanufacturing space and jobs over thelast year. Since November 2017, the UK hasexperienced a sixty per cent uptick inmanufacturing space specifically for celland gene therapies licenced by theMedicines and Healthcare productsRegulatory Agency (MHRA) and meetingGood Manufacturing Practice standards.Part of this increase is owed to theopening of the CGT Catapult’s own GoodManufacturing Practice manufacturingcentre back in April, alongside theexpansion of facilities of Cobra Biologicsand Scottish National Blood TransfusionService. There’s also been a marked increase inthe utilisation of capacity, which is nowrunning at eighty-one per cent comparedwith last year’s seventy-seven per cent.As well as indicating the overall upsurgein research and development, it alsodemonstrates the continuously increasingdemand for cell and gene therapyservices and infrastructure driven by therapidly evolving pipeline of advancedtherapies. Although other areas of the UK’sdiverse healthcare and pharmaceuticalsectors are experiencing uncertainty, thecell and gene therapy industry has ahugely positive outlook. Indeed, some1,500 square metres of cleanroom spaceis scheduled to come online before theend of 2019. This impressive increasebrings the nation’s total cleanroomfootprint to 8,000 square metres. However, it isn’t just infrastructure andfacilities that have increased this lastyear, with the research finding a thirty percent growth in employment. Currently inthe UK, more than five hundred peopleare employed in manufacturing bytwenty-one organisations operationacross multiple sites. This number isforecast to growth significantly in linewith the growth of the industry and thenumber of therapies currently reachingcommercialisation.“This year’s sixty per cent increase inmanufacturing space and thirty per centgrowth in jobs is a sign of a burgeoningUK industry that is investing in scaling upto become a global destination for ATMPmanufacturing and development,” saysKeith Thompson, CEO of the CGT. “With the continuing investment by UKResearch an Innovation in initiatives suchas the Advanced Therapy TreatmentCentres Network, and the newapprenticeship programme alongside theinvestment made by industry, the UK hasbuilt and Advanced Therapy Ecosystemsecond to none becoming the first placeoutside of the US where a CAR-Ttherapy could be approved and adoptedby the National Health Service.”This year alone has seen a dramaticupsurge in manufacturing space and jobsin the cell and gene therapy space, notto mention therapies themselves clearingimportant regulatory milestones andhelping to transform the lives of patients.© Novartis16-19.qxp_Layout 1 04/12/2018 15:09 Page 4Next >