Your guide to the pharmaceutical world Volume 9 Issue 1 Digital therapeutics Depending on digital Collaboration Coming together RNAi therapies The growth of gene silencing PharmaBUSINESS INTERN ATION AL The total package From development to dispensing The total package From development to dispensing Digital therapeutics Depending on digital Collaboration Coming together RNAi therapies The growth of gene silencing www .pbiforum.net 01.qxp_Layout 1 08/02/2021 13:41 Page 1 INTER N Food Food &&& Food Food & N ATI O N &&Drin Drin Drin &&Drin AL nk nk nkk app A r f h hi ts a ews Ingredient spotlight End offline packkaaging For businesses that are serious about reducing their carbon footprint www.blmgroup.co.uk VOLUME 4 ISSUE 1 W W W. R E N E W A B L E S A N D E N V I R O N M E N T. C O M E A S T M I D L A N D S L E A E A D I N G B U S I N E S S M A G A A Z I N E APRIL 2020 0 £3. .50 BUS SUP SINES T PPOR SS TING B THCART HEAL YY FACTOR RE OFF FICE ea Stopping the spr THCAR WW HEAL d thinkin Forwar TT AUTOMA Y AFACTOR ad WW EASTMIDL RE A hea SOL OFF ng factories LANDSBUSINE TION ficef althy of LUTIONS ESSLINK CO U FICE w UK www.blmgroup.co.uk EMPOWER Your Business Focus on T A Pharm rld o our guide to the pharmaceutical w Y B U S I N E S S I N T E R N A L ma olume 8 Issue 1 V T I O N declares g rrld Hea oooW coron F ganisa gg l b l g l h O virus na g gency ti medi Nucle Prev aaccin V The nuclea b f treatment ve The P l t k aage n e t eelopment t vv om de rF w w w di i k . p b i f o r u m . n yorkshire & lincolnsh hire’s leading business ma magazine april 2020 £3.5 50 TO T RES C THE SPOND CRISIS DING S YY FACTOR C TT HEAL OFF THCARE FICE safety Ensuring e TT HEAL e of factories The futur TION T AUTOMA YY AFACTOR fices healthy f Keeping of SOLUTIONS OFFICE employee THCARE V w VOLUME 35 ISSUE 4 .blmgroup.co.uk www Often Imitated - Never Equalled www.blmgroup.co.uk 02.qxp_Layout 1 08/02/2021 13:44 Page 1Contents Volume 9 Issue 1 12 16 20 32 Group Editor: Steve Fisher (s.fisher@blmgroup.co.uk) Editor: Michael Fisher (m.fisher@blmgroup.co.uk) Assistant Editor: Dominic Cuthbert (d.cuthbert@blmgroup.co.uk) Journalist: Tess Egginton (t.egginton@blmgroup.co.uk) Sales Director: Angie Cooper (a.cooper@blmgroup.co.uk) Sales: Vicky Hunt (v.hunt@blmgroup.co.uk) Tel: +44 (0) 1472 310302 Accounts & Subscriptions: Angela Sharman (a.sharman@blmgroup.co.uk) Design & Production: Gary Jorgensen, Mark Casson, (studio@blmgroup.co.uk) Editorial: Tel: +44 (0) 1472 310305, Fax: +44 (0) 1472 310317 Part of BLMGroup: Armstrong House, Armstrong Street, Grimsby, North East Lincolnshire DN31 2QE England All rights reserved. No part of this publication may be reproduced, transmitted, photocopied, recorded or otherwise without express permission of the copyright holder, for which application should be addressed first to the publisher. While every reasonable care is taken, neither the publisher nor its participating agents accept liability for loss or damage to prints, colour transparencies, negatives or other material of whatever nature submitted to this publication. The views expressed in this publication are not necessarily the views of those held by the publisher. News4 Stay up to date with the latest industry updates from the global pharmaceutical technology industry. A cure for COVID-19?7 Vaccines continue to be the main topic of conversation when it comes to COVID-19. Several have now been approved, while there are over 230 candidates. Talking Medicines Q&A10 Pharma Business International spoke with Jo Halliday, CEO of Talking Medicines, the world’s first social intelligence company designed specifically for the pharmaceutical industry. M&A round-up12 A slew of major pharma deals prevented us from rounding up the 2020 M&A space in our final issue of the year. Instead, we stated that we would use our first issue of the new year, but in the two months since our last issue, there has been a host of multi-billion-dollar deals to explore. Collaboration16 Collaboration has been fundamental to the pharmaceutical R&D space for years, as we explore, but in the wake of the COVID outbreak, collaboration is more important than ever. RNAi therapies20 Following a number of obstacles, RNA interference (RNAi) therapies are seeing renewed interest and investment alongside more approvals. Licensing24 Licensing has been part and parcel of pharmaceutical dealmaking for decades, but it has become critical in combatting coronavirus as companies share resources and intellectual property. Delivery systems28 Logistical delivery of pharmaceuticals is in the news at the moment due to the slow rollout of the COVID-19 vaccine, but systems of delivery treatment to the human body are just as important, and just as impacted by the lockdown. Digital therapeutics32 In the wake of COVID-19, technology is being well utilised to keep people safe, as Pharma Business International explores. Events 36 We give a rundown of pharma events happening around the world. @pbiforum www.pbiforum.net company/pbiforum Cover photo courtesy: Shutterstock / Moonhonor 03.qxp_Layout 1 09/02/2021 11:26 Page 1Consultancy to fund research into mental health impact of rare disease diagnosis RBW Consulting, a life science and technology search consultancy, is funding, in full, a clinical research project in partnership with Rare Disease Research Partners. The research will provide much-needed insight into how a rare disease diagnosis can affect the mental health of the patient, their family, and carers. The research will involve a group of experts including psychologists and family groups, and will be published in the second half of 2021. Dr Tom Kenny said: “While rare diseases individually affect a small number of people, the total rare disease community is significant and largely underserviced by existing healthcare systems. My aim for this research is to have a positive impact on the quality of life for all those that are affected by a rare disease.” 4 Pharma Business International www.pbiforum.net Latest news Lilly and Merus to develop novel T-Cell re-directing bispecific antibodies Loxo Oncology, an R&D group of Eli Lilly, will leverage oncology specialist Merus’ proprietary Biclonics to develop novel T-cell re- directing bispecific antibody therapies. Merus will lead discovery and early stage research activities while Loxo Oncology at Lilly will be responsible for additional research, development and commercialisation activities. Merus will receive an upfront cash payment of $40 million, as well as an equity investment by Lilly of $20 million in Merus common shares. Merus is also eligible to receive up to $540 million in potential development and commercialisation milestones per product, for a total of up to approximately $1.6 billion for three products, as well as tiered royalties ranging from the mid-single to low-double digits on product sales should Lilly successfully commercialise a therapy from the collaboration. Boehringer & Enara Bio forge cancer immunotherapy agreement Boehringer Ingelheim and Enara Bio have entered into a strategic collaboration and licensing agreement to research and develop novel targeted cancer immunotherapies, leveraging the latter’s Dark Antigen discovery platform. This new collaboration combines Boehringer Ingelheim’s approach to tackle cancer through pairing leading science with innovative immune-oncology platforms, such as oncolytic viruses and cancer vaccines, with Enara Bio’s expertise in cancer antigen identification. The aim is to provide potential new therapies for patients with difficult to treat lung and gastrointestinal cancers. Enara Bio’s proprietary Dark Antigen Platform Technology (EDAPT) will be used to discover and validate novel Dark Antigens in up to three tumour types in the lung and gastrointestinal cancer space. The discovery of shared antigens could lead to the development of vaccines that can be readily utilised to help a broader group of cancer patients. © Shutterstock/Emily frost © Shutterstock/vitstudio © Shutterstock / CI Photos 04-06.qxp_Layout 1 08/02/2021 13:47 Page 1Reach Separations enters purification alliance with NovAliX Purification specialists Reach Separations and drug discovery contract research organisation (CRO), NovAliX, have entered into a unique alliance to develop supercritical fluid chromatography (SFC) capabilities at the NovAliX facility near Strasbourg. Formed in support of Reach Separations’ strategy to grow its European presence, and in response to a sustained rise in demand for purification expertise from NovAliX’s clients, Reach has made a significant investment at NovAliX’s Strasbourg premises to install new analytical SFC instrumentation. SFC expert Stéphane Dubant will join the team to ensure a smooth transition of projects between Strasbourg and Nottingham. The alliance involves Reach Separations providing chiral separation and sophisticated purification capabilities, utilising its specialist purification expertise that will provide NovAliX with access to molecules of higher structural complexity with multiple chiral centres, in order to deliver even greater success in medicinal chemistry programmes. Pharma Business International 5 www.pbiforum.net Latest news Lonza to manufacture Aruvant’s potential curative sickle cell treatment for trial Aruvant Sciences, a private company focused on developing gene therapies for rare diseases, has chosen Lonza to manufacture ARU-1801, a potentially curative treatment for sickle cell disease, for a pivotal trial. Aruvant is building a hybrid supply model that is led by the company’s cell and gene therapy scientists and leverages specialized external suppliers. The company has expanded the internal technical and operational organization with experts in vector and cell manufacturing, analytics, quality, supply and regulatory affairs. To complement the internal capabilities, Aruvant is partnering with world-leading contract development manufacturing organizations. The strategic long-term manufacturing agreement with Lonza is a critical step to advancing the clinical development of ARU-1801 for sickle cell patients. Under Aruvant’s direction, Lonza has begun process development and technology transfer activities from its Houston center of excellence to help establish robust manufacturing for ARU-1801. Once complete, Lonza will deliver cGMP material supply for the pivotal clinical trial. Research project to develop novel protein expression systems Mogrify, a UK company aiming to transform the development of ex vivo cell therapies and pioneer the field of in vivo reprogramming therapies, and the MRC Laboratory of Molecular Biology (LMB), a research laboratory dedicated to understanding important biological processes at the molecular level, have formed an exploratory research collaboration. The project aims to develop novel protein expression systems by leveraging recent advances in direct cell reprogramming to help improve the production of proteins which are not produced sufficiently well in existing expression systems. The MOGRIFY® technology will be applied to predict combinations of transcription factors to induce trans-differentiation from one cell type to another. The resulting target cell types could provide researchers with improved access to important proteins found in human cell types that are difficult to obtain and allow for more efficient protein production. Mogrify will receive access to any intellectual property and know- how developed during the project, further enabling the commercialisation of the technology in areas of therapeutic value. © Shutterstock / paulista © Shutterstock / anyaivanova © Shutterstock / Kateryna Kon 04-06.qxp_Layout 1 08/02/2021 13:47 Page 2Biogen & Sage collaborate on breakthrough therapy for depression Biogen and Sage Therapeutics are jointly collaborating to develop and commercialise zuranolone (SAGE-217) for depression and other neurological disorders and SAGE-217 for movement disorders. Specifically, the potential breakthrough treatment will be investigated for use in major depressive disorder (MDD), postpartum depression (PPD) and other psychiatric disorders. SAGE-217, meanwhile, will be investigated for essential tremor and other. “Through this collaboration, Sage and Biogen have the potential to build something greater together than either could have done alone,” said Mike Cloonan, Chief Operating Officer at Sage Therapeutics. Zuranolone, a potential first-in-class, two-week, once-daily oral therapy in development for the treatment of MDD and PPD, is currently in Phase 3 development as part of the LANDSCAPE and NEST clinical programs. Zuranolone has breakthrough therapy designation from the FDA for MDD and, if successfully developed and approved, has the potential to be a novel treatment paradigm in depression. The vision for zuranolone in MDD and PPD is based on its potential, being evaluated in the LANDSCAPE and NEST development programs, to work rapidly and to continue providing sustained benefit beyond the period of dosing. Together, these two features, if supported by positive clinical efficacy and safety data, could provide an alternative option to how depression is treated today based on a target profile of an “as-needed” short course of treatment for a depressive episode, with rapid and sustained efficacy and favourable tolerability. The development of an “as-needed” treatment for depression may help ease the difficulties associated with chronic use of antidepressants and may enhance quality of life and patient adherence. If approved, zuranolone would also be highly complementary to several of Biogen’s therapeutic areas of focus, including multiple sclerosis (MS), Alzheimer’s disease (AD), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Depression is a common co-morbidity in patients with these neurological disorders and their caregivers. 6 Pharma Business International www.pbiforum.net Latest news Major study launches to better understand link between genetics & human disease A consortium of ten biopharmaceutical companies will perform a study to measure circulating concentrations of almost 1,500 plasma proteins in approximately 53,000 UK Biobank participants, launched by UK Biobank. It will be one of the world’s largest studies of blood protein concentrations conducted to date and aims to significantly enhance the field of ‘proteomics’, enabling better understanding of disease processes and supporting innovative drug development. Over the last few years, UK Biobank, one of the world’s largest and most comprehensive biomedical databases and research resources, has, with consent, made de-identified genetic data on its 500,000 participants available to scientists in order to identify potential DNA hotspots associated with human diseases. These genetic variants can serve as powerful ‘signposts’ for scientists in drug discovery and development. The measurement of a wide range of circulating proteins represents the next major step for UK Biobank, as these data will enable research into the association between genetic variation and circulating protein levels, which in turn, will help to understand the links between genetics and human disease. Studying the levels of many different proteins in UK Biobank participants will allow scientists to assess the extent to which particular proteins are involved in the development or progression of different diseases. The study has been commissioned and funded by a consortium of leading biopharmaceutical companies including Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Roche, GlaxoSmithKline (GSK), Johnson & Johnson, Pfizer, Regeneron and Takeda Pharmaceutical. The laboratory work to measure the proteins will be conducted by Olink, a Swedish proteomics company, using its proprietary technology, which combines high throughput and high-quality protein-level data from very small sample volumes. The resulting de-identified dataset will be added to the UK Biobank research resource and, after an initial 9-month exclusivity period for the companies funding the assays, made available to all approved researchers. © Shutterstock / gopixa © Shutterstock / Illustration Forest 04-06.qxp_Layout 1 08/02/2021 13:47 Page 3Pharma Business International 7 www.pbiforum.net A CURE FOR COVID-19? With the number of confirmed COVID-19 cases passing 105 million (at time of writing), and deaths passing 2.2 million, efforts to develop vaccines and treatments continue to push ahead. Several vaccines have now been authorised around the world with a wealth of others still in development. In total there are over 230 vaccine candidates, according to WHO, utilising various techniques. The “big three” vaccines approved include the Oxford-AstraZeneca adenovirus vaccine, the Pfizer/BioNTech mRNA vaccine, and Moderna’s mRNA vaccine. As new variants (B.1.1.7, first identified in the UK, N501Y.V2/B.1.351, first identified in South Africa, P.1, first identified in Brazil) are uncovered, however, there is widespread concern over how effective the vaccines approved so far will be against these, especially as the variants are considered more transmissible with the three named above carrying the mutation N501Y, which allows the virus to bind more tightly to human cells. The South Africa and Brazil variants also carry two other mutations, K417T and E484K, which help the virus evade the immune system. Evidence has indicated the new variants are covered by existing vaccines, but some mutations may reduce efficacy. A lab study has found Pfizer and BioNTech’s vaccine to be largely effective against mutations first identified in the UK and South Africa, though antibodies generated by the vaccine worked less well against the South African variant. The same was found by Moderna. In response to emerging variants Moderna and Pfizer have announced they are working on booster shots, and the team behind the Oxford-AstraZeneca jab has said vaccines protecting against the new variants should be ready by Variants and new vaccines Vaccines continue to be the main topic of conversation when it comes to COVID-19. Several have now been approved, while there are over 230 candidates. 8 Á © Shutterstock /Lightspring 07-09.qxp_Layout 1 08/02/2021 13:49 Page 1A CURE FOR COVID-19? 8 Pharma Business International www.pbiforum.net autumn. In further good news from the Oxford-AstraZeneca camp, recent results show that its vaccine may substantially reduce the spread of COVID-19 (by sixty-seven per cent) - the first time a vaccine has been shown to reduce transmission of the virus. The study additionally indicated that the vaccine offers up to seventy-six per cent effective protection from a single dose for three months. Upon administration of the second dose, efficacy rises to eighty-two per cent if the interval between injections is three months. On top of the variant issue is distribution, with the popular mRNA vaccines, though effective, requiring very low storage temperatures. In the case of the Pfizer vaccine, a temperature between -80 and -60°C is needed. The spreading out of doses also adds hurdles, with all these factors together presenting challenges for low- and middle-income countries. This is calling for a wider variety of vaccines that are easier logistically, like conventional vaccines. Without the cold-chain distribution problems of mRNA vaccines, the Oxford-AstraZeneca jab can have better reach in areas with less infrastructure. A number of other vaccines are edging closer to approval as fresh results are announced, whereas some are hitting delays. Novavax’s nanoparticle vaccine is close to the milestone, showing 89.3 per cent efficacy in Phase 3. In its UK study of 15,000 participants, fifty-six COVID-19 cases occurred in the placebo arm, in comparison to six in the vaccine arm. In the wake of new variants, a post hoc analysis puts efficacy against the B.1.1.7 variant at 85.6 per cent, while the jab is 49.4 per cent effective against the South African variant (according to data from a Phase 2b study of 4,400 subjects), and 95.6 per cent effective in older variants. Like the Oxford- AstraZeneca jab, this vaccine only needs to be kept at fridge temperature, making distribution easier. Johnson & Johnson’s single-dose vector vaccine candidate on the other hand has been shown to be less effective in Phase 3 data – sixty-six per cent overall in moderate to severe cases, rising to eighty-five per cent in severe cases. The vaccine was seventy- two per cent effective at preventing moderate to severe COVID-19 in the US, but outside of the country this decreased. In Latin America efficacy was sixty-six per cent, and in South Africa, fifty-seven per cent. Authorised/approved vaccines NameType of vaccineMain developersAuthorisation/approval Comirnaty/BNT162b2mRNA-based vaccinePfizer, BioNTech, Fosun PharmaUK, Bahrain, Canada, Mexico, US, Singapore, Costa Rica, Ecuador, Jordan, Panama, Chile, Oman, Saudi Arabia, Argentina, Switzerland, Kuwait, EU, Philippines, Pakistan, Colombia, Iraq, Israel, Qatar, Singapore, UAE, Faroe Islands, Greenland, Iceland, Malaysia, Norway, Serbia, Hong Kong, Albania, Australia Moderna COVID19 Vaccine/mRNA-based vaccineModerna, BARDA, NIAIDCanada, Israel, Saudi Arabia, Switzerland, UK, US, EU, Faroe Islands, mRNA-1273Greenland, Iceland, Norway COVID-19 Vaccine AstraZeneca/Adenovirus vaccineBARDA, OWSUK, Argentina, El Salvador, Dominican Republic, India, Bangladesh, AZD1222Mexico, Nepal, Pakistan, Brazil, Saudi Arabia, Iraq, Hungary, Thailand, South Africa, EU CoronaVacInactivated vaccine SinovacChina, Bolivia, Turkey, Indonesia, Brazil, Chile (formalin with alum adjuvant) No nameInactivated vaccineWuhan Institute of Biological Products, China China National Pharmaceutical Group (Sinopharm) Sputnik VNon-replicating viral vectorGamaleya Research Institute, Russia, Belarus, Argentina, Guinea, Bolivia, Algeria, Palestine, Venezuela. Acellena Contract Drug Research Paraguay, Turkmenistan, Hungary, UAE, Serbia, Iran and Development BBIBP-CorVInactivated vaccineBeijing Institute of Biological China, Bahrain, UAE, Egypt, Jordan, Iraq, Pakistan, Serbia, Peru Products, Sinopharm EpiVacCoronaPeptide vaccineFederal Budgetary Research Russia Institution State Research Centre of Virology and Biotechnology CovaxinInactivated vaccineBharat Biotech, ICMRIndia 07-09.qxp_Layout 1 08/02/2021 13:49 Page 2Pharma Business International 9 www.pbiforum.net A CURE FOR COVID-19? Meanwhile, GlaxoSmithKline is coming together with CureVac to develop second-generation mRNA vaccines against COVID-19, focusing on emerging variants and developing numerous candidates to serve as boosters if immunity wanes or to protect those who haven’t been vaccinated. GSK will also help produce up to 100 million doses of CureVac’s current shot candidate. Recent preclinical data for CVnCoV, an mRNA vaccine, demonstrates the induction of robust antibody and T cell responses in non-human primates. Furthermore, rhesus macaques were shown to be protected from challenge infection with SARS-CoV-2 following vaccination with 8μg of CVnCoV. The data provided important evidence on the immunogenicity and protective efficacy of CVnCoV at low doses, supporting the ongoing international clinical Phase 2b/3 efficacy study applying a 12μg dose. CureVax’s CVnCoV vaccine also entered a Phase 3 trial in December. On the other side of the coin, Sanofi and GSK delayed their adjuvanted recombinant protein-based COVID-19 vaccine programme in December to improve immune response in the elderly. Other vaccines making progress include Inovio’s INO-4800 DNA vaccine. Peer-reviewed Phase 1 data shows INO- 4800 to be immunogenic in 100 per cent of subjects, inducing neutralising antibody and/or T cell responses. It also demonstrated favourable safety and tolerability, with no serious adverse events reported. INO-4800 is claimed to be stable at room temperature for more than a year, at 37°C for more than a month, has a five-year projected shelf life at normal refrigeration temperature and does not need to be frozen during transport or storage - useful for timely global distribution. Inovio is currently conducting the Phase 2 segment of its planned Phase 2/3 clinical trial for INO- 4800, called INNOVATE, and recently announced the dosing of its first subject in its Phase 2 clinical trial for INO-4800 in China, in collaboration with Advaccine. As the vaccine race continues, treatments are being tested for those with COVID-19 to aid and speed up recovery. For example, following an announcement at the beginning of January, patients across the UK who are admitted to intensive care units due to COVID-19 are to receive new life-saving treatments which can reduce the time spent in hospital by up to 10 days. Results from the government-funded REMAP-CAP clinical trial showed tocilizumab and sarilumab reduced the relative risk of death by twenty-four per cent, when administered to patients within twenty-four hours of entering intensive care. Most of the data came from when the drugs were administered in addition to a corticosteroid. Patients receiving these drugs, typically used to treat rheumatoid arthritis, left intensive care between seven to ten days earlier on average. Also in the UK, a large-scale trial of a new treatment is underway to prevent COVID patients developing severe illness. It involves inhaling interferon beta in the hopes of stimulating the immune system. Early findings indicate the treatment decreases the likelihood of a patient developing severe disease - like requiring ventilation - by just under eighty per cent. © Shutterstock /Moonhonor 07-09.qxp_Layout 1 08/02/2021 13:49 Page 3Next >