< PreviousM&A ROUND-UP 10 Pharma Business International www.pbiforum.net Chairman and CEO at Amgen. Moving on to Bayer who is offloading its Animal Health business in a $7.6 billion deal to Elanco Animal Health. Broken down, the deal is comprised of $5.3 billion in cash and $2.3 billion in Elanco stock. Bayer said that the divestment is expected to conclude in mid-2020 subject to the typical closing conditions. The exit of the Animal Health business marks the largest transaction in the series of portfolio measures initiated by Bayer in November 2018. This move has also seen the company divest its Consumer Health brands – Coppertone and Dr. Scholl’s – and a sixty per cent stake in German site services provider Currenta. But that’s not the only appearance of Bayer this issue, with the company having recently reached an agreement to fully acquire BlueRock Therapeutics. BlueRock is a privately-held US biotech focussed on developing engineered cell therapies using a prosperity induced pluripotent stem cell (iPSC) platform. Following a 2016 joint venture with Versant Ventures to establish BlueRock Therapeutics, Bayer will now acquire the remaining stake for approximately $240 million in cash to be paid upfront at closing and an additional $360 million payable upon achievement of pre- defined development milestones. With Bayer currently holding a 40.8 per cent stake, the investment corresponds to a total company value of BlueRock Therapeutics of approximately $1 billion. Elsewhere, an affiliate of the Permira funds has acquired life sciences company Cambrex Corporation in a deal worth $2.4 billion. The deal, slated to close in the fourth quarter of the year, sees Cambrex shareholders receive $60 8-11.qxp_Layout 1 07/10/2019 12:02 Page 3Pharma Business International 11 www.pbiforum.net M&A ROUND-UP © Shutterstock /Sergey Nivens in cash for each share of common stock. Cambrex has become an attractive option of late, having acquired Halo Pharma in 2018 and Avista Pharma Solutions in 2019, deals which added drug product manufacturing and a full range of early stage and analytical testing services to its pipeline. This allowed the company to broaden its customer relationship over the full product lifecycle. The last of the billion-dollar-plus deals covered this issue sees Danish pharma, Lundbeck, bolster its brain disease portfolio with the $1.96 acquisition of clinical-stage migraine specialists Alder BioPharmaceuticals. Alder is developing eptinezumab for the preventive treatment of migraine in adults. If approved by the FDA, it will be the first IV CGRP therapy for migraine prevention. It is also developing ALD1910, a mAb designed to inhibit pituitary adenylate cyclase-activating polypeptide (PACAP) for migraine prevention. Lundbeck said that adding both of these therapies to its portfolio will establish it is as an emerging leader in migraine and other pain syndromes. Alder submitted a Biologics License Application (BLA) to the FDA for eptinezumab in February 2019 and the FDA has set a Prescription Drug User Fee Act (PDUFA) action date of 21 February 2020. Lundbeck said expects to submit eptinezumab for approval to regulatory authorities in the European Union during 2020, followed by submissions for approval in other regions around the world including China and Japan. Next issue, we’ll round-up the biggest deals of the year and look at what 2020 might bring for M&A activity in the pharmaceutical industry. PARKINSON'S EXPOSÉ 12 Pharma Business International www.pbiforum.net Parkinson’s disease is a neurodegenerative condition affecting thirty-five million people worldwide. In 2018, 145,000 people were diagnosed in the UK alone, a figure that’s expected to increase by a fifth by 2025. Unlike some other neurogenerative conditions, Parkinson’s affects men more than women, though like much about the disease, the exact reasons why are unclear, though it’s thought to be a combination of biological and lifestyle factors. But whether men or women, the age bracket most at risk is between fifty and eighty-nine, but a small percentage of sufferers do develop Parkinson’s before their fifties. The disease is caused by a loss of nerve cells in the substantia nigra in the mid brain. This leads to a reduction of dopamine, which plays a vital role in regulating movement of the body. Exactly what causes the loss of nerve cells isn’t entirely understood, though most experts believe it’s down to a combination of genetic and environmental factors. However it develops, there are three main symptoms: tremors, slow movement, and stiff and inflexible muscles. It can also trigger several other physical and psychological issues, including depression, loss of sense of smell and memory issues, among others. At present, there is no cure for Parkinson’s. There are, however, treatments to reduce the main symptoms and for sufferers to maintain quality of life. Supportive treatments, including physiotherapy, occupational therapy, medication and brain surgery, are also available to help control and manage the symptoms. Individuals can also help to reduce their chances of developing the disease by taking preventative measures, such as diet and exercise. Lesser known is the removal of one’s appendix, an organ which contains high Parkinson’s related alpha-synuclein aggregates. As there is no cure yet, this area is ripe with innovation, though there are several challenges that first need to be overcome. The most pressing roadblocks are that the disease still isn’t fully understood and, more often than not, it’s diagnosed too late. There’s also multiple types of Parkinson’s and clinical trials often fail. Yet perhaps the biggest challenge is that there Issues around funding, understanding and diagnosis need to be overcome if there’s ever to be a cure for Parkinson’s. Fortunately, there’s plenty of encouraging research taking place. 14 Á PuttingPharma Business International 13 www.pbiforum.net PARKINSON'S EXPOSÉ © Shutterstock /angellodeco in its placePARKINSON'S EXPOSÉ 14 Pharma Business International www.pbiforum.net just isn’t enough funding and investment, though organisations like The Michael J. Fox Foundation is helping in this regard. In fact, the Foundation recently launched the ‘Ken Griffin Alpha-synuclein Imaging Competition’, a $10 million programme intended to spur the development of an imaging tracer to visualise the key protein alpha-synuclein in the living brain. Meeting all these challenges will be critical to unlocking new therapies and, potentially, a cure for Parkinson’s. Currently, there are researchers and organisations exploring ways of diagnosing the disease earlier. Investigators at Stanford University School of Medicine have pinpointed a molecular defect that, they say, seems almost universal amongst patients with Parkinson’s and those at high risk of developing it. This could potentially prove a means of detecting the disease before symptoms manifest as well as offering a tentative roadmap to halting the disease’s progression. Parkinson’s is known to involve a defect in mitochondrial function. Mitochondria spend much of their time attached to a grid of protein ‘roads’ that crisscross cells but, when defective, mitochondria must be removed. Our cells have a technique for removing them in the form of a series of proteins that usher them to the cell’s recycling centres. But first, those proteins must remove an adaptor molecule called Miro that attaches mitochondria, damaged or otherwise, to the grid. In this study, published in Cell Metabolism, Xinnan Wang, MD, PhD, associate professor of neurosurgery and the study’s senior author, and her team obtained skin samples from eighty-three Parkinson’s patients, five asymptomatic disorders and fifty-two health control subjects. They extracted fibroblast – cells commonly found in skin tissue – from the samples, cultured them in petri dishes and subjected them to a stressful process that messes up mitochondria. The test should have resulted in their clearance, necessarily preceded by the removal of Miro molecules tethering them to the grid. However, the researchers found the Miro-removal defect in ninety-four per cent Parkinson’s fibroblasts and in all five of the ‘high risk’ samples, but not in any of the fibroblasts from the control group or from patients with other movement disorders. Following this stage, the investigators then screened almost seven million small molecules in collaboration with San Francisco-based biotechnology company, Atomwise. The company’s software predicted that eleven of those molecules would bind to Miro in a way that would facilitate its separation from mitochondria and would, additionally, be non-toxic, orally available and able to cross the blood-brain barrier. These compounds were then fed to fruit flies for seven days after which time the researchers determined that four of them significantly reduced the flies’ Miro levels without toxicity. They tested one compound, which they say appeared to target Miro most exclusively, on fibroblasts from a patient with sporadic Parkinson’s. The study revealed that this substantially improved Miro clearance in these cells after their exposure to mitochondria- damaging stress. Wang said she believes clinical trial of the compound, or a close analogue, are no more than a few years off. “Our hope is that if this compound or similar one process nontoxic and efficacious and we can give it, like a statin drug, to people who’ve tested positive for the Miro-removal defect but don’t yet have Parkinson’s symptoms, they’ll never get it,” she says. These encouraging findings open an entirely new avenue for approaching Parkinson’s disease and help to overcome one of the key challenges preventing new treatments, cures and preventative measures from coming forward. Of course, there is still a long way to go towards beating Parkinson’s, but all the evidence suggests we’re closer now than ever. 12-15.qxp_Layout 1 07/10/2019 12:03 Page 3Pharma Business International 15 www.pbiforum.net PARKINSON'S EXPOSÉ © Shutterstock /TriffETHICS 16 Pharma Business International www.pbiforum.net Creativity in compliance training Let’s be honest, compliance training has traditionally often missed the mark. The use of legalese and tone around consequences has failed to engage its audience – and mandatory training is perceived as a ‘must do’ activity. But does it have to be that way? We are all striving to achieve organisation-wide compliance and an ethical culture, as well as mitigating risk. To do this we need to start engaging, motivating and empowering our employees. It’s time to do things differently. The case for change When PwC surveyed 825 risk and compliance executives across various industries globally, less than a fifth of them (17%) said they were ‘very satisfied’ with their compliance programmes. PwC terms these companies as compliance ‘leaders’. According to the poll, these ‘leaders’ are using progressive methods in all aspects of risk management to develop effective procedures and practices. The report highlighted that for compliance programmes to be successful, a culture of values needs to span the whole organisation, from the boardroom to the frontline. It also says we must look more deeply into compliance and ethics. Why? Because we want to do what’s right for patients and for the wider community. We shouldn’t simply be embracing the regulations; we should be embracing the spirit of the regulations. If, like AstraZeneca, your organisation has tens of thousands of globally dispersed employees, then you’re going to have to be creative in order to transcend the physical and cultural barriers to reach and engage everyone from the CEO to the janitor. And, when it comes to compliance, you still need training that motivates and engages employees. Changing the conversation The planning and preparation of new compliance and ethics training is critical. Firstly, if you feel that what you’re doing now isn’t working as well as it should, consider looking outside of the organisation for inspiration. Getting external expertise helps you to challenge your own conventions to come up with innovative approaches. In our case, we worked with digital learning provider, Sponge, to embed an ethical culture into the company’s DNA, delivered via training for our 60,000+ employees and third parties. We wanted something completely different, exciting and creative, and they met that brief. Secondly, to discover why existing training is failing to engage, ditch assumptions and ask your employees. Set up focus groups and conduct learner interviews; ask people to share their feedback and invite suggestions about how it could be made more engaging and relevant to them in terms of content and delivery. This also makes employees feel invested in the training throughout its roll-out. Thirdly, and this is really important, change the tone of compliance to be more positive and inclusive. For example, moving from ‘you must/must not’ to ‘we will’ and ‘we do’. Help employees understand the role that they can play in making a positive difference whatever they do in the organisation. In 2017, reflecting a shift in our Injecting creativity in compliance training Louise Vamvoukaki, Director, Sustainability Education and Engagement at AstraZeneca, explores the importance of creativity in compliance training for the pharmaceutical industry. Louise VamvoukakiPharma Business International 17 www.pbiforum.net ETHICS organisational culture, which placed greater emphasis on ‘values’ and ‘behaviours’, we moved from a ‘Code of Conduct’ to a ‘Code of Ethics’ – a change of just one word made a huge difference. For compliance training this allowed us to start to think differently – putting our core company values and behaviours at the heart of the Code. Empowered by these positive concepts, employees are now more motivated. Training has started to shift from a ‘must do’ to a ‘want to do’ exercise. Positive language has the power to shift the perception of compliance and ethics from a ‘blocker’ (negative) to an ‘enabler’ (positive). Removing the ‘fear factor’ is also essential for pharmaceuticals that want to encourage people, in their day-to-day work, to make decisions that are based on doing things right. How to introduce creativity in compliance training Great training alone often isn’t enough to motivate people. To truly embed our values and ethics, we stopped thinking about our Code of Ethics training as a one-off event and moved it to a whole campaign with a piece of mandatory training at the heart of it. We did this using a three-stage journey: pre-launch activities, the training, and continuing the conversation. Working with Sponge, the approach comprises key elements based on the latest learning theories and design principles and included these five key elements: • Create a buzz: Before the launch of the Code of Ethics, we created a teaser campaign. This included a pre-launch trailer which, by launch, had over 2,300 views on our internal social platform. • Convey empathy and emotion: We used storytelling and emotion to create ‘empathy videos’ with the aim of bringing the message home and making the concept ‘real’. • Win hearts and minds: We want employees to live and breathe our values. By emphasising ownership and personal accountability, we empower learners to take responsibility for their own behaviours and decisions. • Keeping the conversation alive: To reinforce the messaging, we made use of our plasma screens and ambient media in our offices around the world to show campaign materials. • Sustainability in compliance: The key is to look beyond rolling out just another piece of compliance training. The results Creativity in compliance shouldn’t and needn’t make it any more expensive. In partnership with Sponge, we created reusable assets such as videos, illustrations and animations – some were image-led with no need for words or translations, which works well for a global audience. We used digital technology delivered on multiple devices for maximum ‘reach’. But, while tech is important when it comes to the delivery of learning, the impact of the training is down to the content. And what of that impact? Our training completion rates were up 13% in 2018 compared to the previous training in 2017 and there was a 21% increase in the number of people who completed the training on day one. Almost a quarter (23%) did the training on mobile devices. Of the 2,226 employees who completed a feedback survey, 86% said their understanding of AstraZeneca’s values had increased or greatly increased; 94% were likely or very likely to recommend the training and 90% felt ‘very’ or ‘extremely engaged’ with the learning. © Shutterstock /ShidlovskiDIGITAL THERAPEUTICS 18 Pharma Business International www.pbiforum.net We live in a digital world, with almost everyone having access to a mobile phone and many now to a smartphone. It is expected that as the current generation ages, this will only become more prevalent, allowing people to be more connected than ever. While this no doubt means a lot for our social lives – and with social lives promoting health this is a good thing – it also offers opportunities to manage, treat and care for illness, and to help people self-care and self-monitor. Enter the world of digital therapeutics – digital software, apps or even hardware that allows patients to monitor, self- treat and access information that can help them deal with potentially lifechanging conditions from the comfort of their own home. Digital products used to improve health have existed since 2000 but were only officially recognised as digital therapeutics in 2015. A digital world 20 Á As people become more digitally connected, the pharma industry sees opportunities to tackle big diseases through information. Pharma Business International 19 www.pbiforum.net DIGITAL THERAPEUTICS © Shutterstock /Alexey BoldinNext >