< PreviousM&A ROUND-UP 10 Pharma Business International www.pbiforum.net intention to acquire Teneobio, a privately held, clinical stage biotechnology company developing a new class of biologics called Human Heavy-Chain Antibodies, for up to $2.5 billion. Under the terms of the agreement, Amgen will acquire all outstanding shares of Teneobio at closing in exchange for a $900 million upfront cash payment, as well as future contingent milestone payments to Teneobio equity holders potentially worth up to an additional $1.6 billion in cash. The acquisition includes Teneobio’s proprietary bispecific and multispecific antibody technologies, which will enable significant acceleration and efficiency in the discovery and development of new molecules that have the potential to treat a wide range of important diseases across Amgen’s core therapeutic areas. These platforms complement Amgen’s existing antibody capabilities with the addition of a heavy-chain only platform that allows a streamlined, sequence- based discovery approach for target binders, as well as Teneobio’s novel T-cell engager platform, which expands on Amgen’s existing leadership position in bispecific T-cell engagers by providing a differentiated, but complementary, approach to Amgen’s current BiTE platform. The acquisition will also add TNB-585, a Phase 1 bispecific T cell-engager for the treatment of metastatic castrate- resistant prostate cancer (mCRPC), and several preclinical oncology pipeline assets with the potential for near-term IND filings. TNB-585 complements Amgen’s existing prostate cancer portfolio, which includes acapatamab (formerly AMG 160) and AMG 509, both in Phase 1. Each of these three investigational therapies uses a different approach to treat a highly prevalent disease for which new treatment options are very much needed. In a second for deal completion this issue, Merck has completed the spinoff of Organon & Co. The goal was to create two patient-focused companies with enhanced strategic and operational focus, improved agility, simplified operating models, optimised capital structures and improved financial profiles. 08-11.qxp_Layout 1 13/08/2021 11:10 Page 3Pharma Business International 11 www.pbiforum.net M&A ROUND-UP Merck believes the transaction will deliver significant benefits for both Merck and Organon and create value for Merck shareholders. The spinoff is expected to allow Merck to increase its focus on key growth pillars, achieve higher revenue and EPS growth rates and enable incremental operating efficiencies of approximately $1.5 billion, which are expected to be achieved rateably over three years, with approximately $500 million realised during 2021. In connection with the spinoff, Merck received a distribution from Organon of approximately $9 billion. It’s hard to imagine that next issue, our penultimate of 2021, will have anything like this level of M&A activity across the pharmaceutical, biopharmaceutical and life sciences sector. But you’ll just have to keep an eye on our website for all the latest updates and be sure to check out our October issue when it’s live. Best of the rest Not forgetting a pair of other industry acquisitions coming in at over the billion-dollar mark. Novo Nordisk acquires Prothena’s ATTR amyloidosis programme for up to $1.2bn Novo Nordisk has acquired Prothena’s clinical stage antibody PRX004 and broader ATTR amyloidosis programme. PRX004 is a phase 2 ready anti-amyloid immunotherapy designed to deplete the amyloid deposits that are associated with the disease pathology of ATTR amyloidosis. ATTR amyloidosis is a rare, progressive and fatal disease characterised by the abnormal build-up of amyloid deposits composed of misfolded transthyretin protein in organs and tissues, most commonly the heart and/or nervous system. Prothena has completed a phase 1 study with PRX004 in patients with hereditary forms of ATTR, in which PRX004 was found to be safe and well tolerated. Novo Nordisk will initially focus on the clinical development of PRX004 in ATTR cardiomyopathy – an underdiagnosed and potentially fatal form of ATTR amyloidosis characterised by build-up of amyloid deposits in cardiac tissue. Novo Nordisk acquires Prothena’s wholly-owned subsidiary and gains full worldwide rights to the intellectual property and related rights of Prothena’s ATTR amyloidosis business and pipeline. PMI expands ‘Beyond Nicotine’ strategy with $1.2bn Vectura acquisition Philip Morris International (PMI) is acquiring Vectura, a provider of innovative inhaled drug delivery solutions that enable partners to bring their medicines to patients, for £852 million ($1.2 billion) accelerating its ‘Beyond Nicotine’ strategy and expanding its product pipeline development capabilities in inhaled therapeutics. “The acquisition of Vectura, following the recently announced agreement to acquire Fertin Pharma, will position us to accelerate this journey by expanding our capabilities in innovative inhaled and oral product formulations in order to deliver long-term growth and returns,” said Jacek Olczak, PMI CEO. “The market for inhaled therapeutics is large and growing rapidly, with significant potential for expansion into new application areas. PMI has the commitment to science and the financial resources to empower Vectura’s skilled teamto execute on an ambitious long-term vision. “Together, PMI and Vectura can lead this global category, bringing benefits to patients, to consumers, to public health, and to society-at- large.” Prothena is eligible to receive development and sales milestone payments totalling up to 1.2 billion US dollars including 100 million dollars in upfront and near-term clinical milestone payments. © Shutterstock /Michael V i 08-11.qxp_Layout 1 13/08/2021 11:10 Page 4A LIFE IN A DAY Q&A 12 Pharma Business International www.pbiforum.net A Life in a Day aims to support pharmaceutical and healthcare industries in developing patient- centric strategies and creating lasting change. Can you tell us how? A Life in a Day is a unique programme that nurtures what we believe is the key ingredient to successful patient centricity: empathy. Empathy helps healthcare and pharmaceutical professionals relate to the challenges that patients face every day and understand the reality of living with a chronic condition. It inspires the pharma industry to develop meaningful patient- centric strategies and have better patient- driven conversations with healthcare professionals. For healthcare, it means services and care are designed and delivered in a way that best suits patients’ needs. The end result? Patients’ lives are improved. Of course, that isn’t to say that pharmaceutical and healthcare professionals are not empathetic, but we know it’s difficult to fully appreciate the patient perspective without lived experience. A Life in a Day fills this knowledge gap by delivering unique, immersive experiences where people step into a patient’s shoes and face the challenges and choices patients deal with every day. These are designed hand-in-hand with patients and healthcare professionals to create emotive experiences that are as accurate as possible, and deliver them using a combination of live role play, physical items, multimedia materials and artificial intelligence through a smartphone app. Can you tell us a bit more about The Method, your company behind A Life in a Day? I co-founded The Method in 2004 with my business partner and friend, John Keates. With a background in theatre and film, we saw an opportunity to use our creative expertise in creating emotional connections with audiences to develop impactful learning and development programmes. A Life in a Day is our flagship, award-winning programme designed specifically for healthcare and pharmaceutical professionals. The pharma industry has taken great strides towards becoming more patient-centric in the work it does. How does A Life in a Day help them go further? We know pharma is committed to putting patients at the heart of its work, but a major issue is that a clear, consistent definition of patient centricity does not exist across the industry. This is where A Life in a Day can help. The programme’s focus on empathy supports people to define patient centricity for themselves and enables them to consider how their work can ultimately help to Q&A Mark Doyle, creator of A Life in a Day We spoke with Mark Doyle, co-founder of The Method and creator of the innovative learning and development programme, A Life in a Day. 12-13.qxp_Layout 1 13/08/2021 11:24 Page 1Pharma Business International 13 www.pbiforum.net A LIFE IN A DAY Q&A make patients’ lives better. By taking this approach, individuals can develop meaningful patient-centric activity that, in turn, delivers improved commercial performance through better conversations, patient-focussed product innovation and the use of emotional selling strategies. Patient-centric activity without empathy at its core will never realise its full potential. Why do you believe empathy is so important in healthcare? Empathy makes people’s lives better. Studies show it improves care and patient outcomes, helps people recover from illness quicker and builds trust between patients and healthcare professionals. Empathy also has mental health benefits - it has been shown to improve the mental and emotional wellbeing of both patients and healthcare professionals. Pharma has an important role to play here. Becoming more empathetic and having a holistic understanding of a patient’s experience will support everyone to work in a way that makes a difference. It will enable more effective patient-centric strategies across all pharma business units, which, in turn, should mean better products developed for patients and allow for more meaningful interaction with healthcare professionals. This all contributes to improving patients’ lives. The programme is designed to reflect the reality of living with a chronic health condition. What conditions does this currently include, and are there plans to expand this to include their conditions? We work with clients to develop experiences that fit their needs as well as offering other experiences more widely. So far, the therapy areas we have developed experiences for include: chronic heart failure, COPD, chronic kidney disease and renal cell carcinoma. We are about to launch other experiences focusing on lupus, asthma, diabetes, multiple myeloma and atopic dermatitis. The experiences you have developed sound very intense, taking place over a full 24 hours. How realistic is it really for you to expect busy pharma professionals to commit to such a time-consuming training? The experiences we have created as part of A Life in a Day allow people to learn in the flow of work. We take this approach because we want people to experience what it means to be a patient at home, at work, in social situations and at night. Patients aren’t just patients between 9am and 5pm; they live with their condition every hour of every day, so it was important to us to develop experiences that integrate into the working day. It is designed to be disruptive, but this reflects the reality of living with a chronic health condition. With A Life in a Day, the choices you make during the simulation determines what happens next, just like in real life, and many of our participants have gained valuable insight into the physical, personal, professional, social and emotional challenges that living with a chronic condition brings. How much of a difference can a programme like A Life in a Day make to pharma business? A Life in a Day has resulted in measurable improvements in patient centricity for all of our pharma clients so far - more than 4,000 professionals across 24 companies. Participants consistently report feeling more empathetic and having a deeper understanding of the full patient perspective. Companies have witnessed the development of new patient-centric activities and an increase in patient- focussed engagement with healthcare professionals, all as a result of our experiences. For example, clients have changed marketing and patient materials to centre much more on patients and their needs, are investigating how to make clinical trials more patient-centric and considering patients’ experiences to shape projects from the very beginning. Mark Doyle is co-founder of The Method, a British company offering innovative and immersive learning and development programmes to effect behaviour change, and creator of its award-winning A Life in a Day experience. Driven by the belief that healthcare works best when it centres around patients’ needs, Mark designed A Life in a Day to support the pharmaceutical and healthcare industries in developing patient-centric strategies for more impactful engagement. So far, A Life in a Day has been delivered to clients in more than 55 countries across the world. For more information about A Life in a Day, visit www.alifeinaday.co.uk. 12-13.qxp_Layout 1 13/08/2021 11:24 Page 2RESPIRATORY DISEASES 14 Pharma Business International www.pbiforum.net Respiratory diseases - such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary fibrosis, pneumonia, and lung cancer, amongst other conditions - can make even the most basic activities of ascending stairs and walking a challenge. Research to improve patient’s lives, though generally underfunded when compared to the impact of respiratory disease, continues, and is becoming more of a priority for some governments, with the UK for instance for the first time naming respiratory as a top priority in its Life Sciences Vision, which sets out how the country can tackle major health challenges and also boost the economy. The government’s ambition seeks to improve understanding of complex respiratory conditions, diagnosis and develop new treatments. Asthma, which is becoming more widespread, is a key area for research, with many new treatments coming to the fore. Just last year Trelegy Ellipta, a combination of fluticasone furoate (a corticosteroid to reduce inflammation), umeclidinium and vilanterol (bronchodilators) in a single inhaler, requiring once-a- day inhalation, was approved for patients aged 18 and over. Drug companies are also working on new injectable drugs for those with severe asthma that do not respond well to traditional inhalers. An experimental injectable drug showing promise against tough to manage asthma is tezepelumab. The monoclonal antibody targets an inflammatory protein thought to play an early role in many different types of asthma. A phase 3 clinical trial found it to be effective in quashing severe asthma with patients who had varying causes of shortness of breath. After a year of treatment, patients experienced less asthma attacks, better lung function and asthma control than those on a placebo. Tezepelumab is unlike other current biologic treatments for asthma, in that it is not just used in subsets of severe asthma, being effective regardless of eosinophil count or allergy status, and comes at a time when many asthma patients do not respond to current biologic medicines. A biologics license application has been accepted for tezepelumab by the Food and Drug Administration (FDA) and granted priority review. Moreover, work is progressing to treat severe asthma with personalised medicine. Recently, a phase 2 clinical trial treating patients with therapies based on genetics, family history, lifestyle and environmental factors got underway. Providing personalised therapies that can be adjusted based on patient response, the Precision Interventions for Severe and/or Exacerbation-Prone Respiratory disease research races ahead Pharma Business International details some of the most recent breakthroughs in respiratory disease research. 16 Á 14-17.qxp_Layout 1 13/08/2021 11:17 Page 1Pharma Business International 15 www.pbiforum.net RESPIRATORY DISEASES © Shutterstock /Zoran Milic 14-17.qxp_Layout 1 13/08/2021 11:17 Page 2RESPIRATORY DISEASES 16 Pharma Business International www.pbiforum.net © Shutterstock /Image Point Fr 14-17.qxp_Layout 1 13/08/2021 11:17 Page 3Pharma Business International 17 www.pbiforum.net RESPIRATORY DISEASES Asthma Network (PrecISE) study is assessing the effectiveness of six experimental asthma therapies; medium-chain triglyceride supplementation, clazakizumab, broncho- vaxom, imatinib mesylate, cavosonstat, and itacitinib. Similarly, a clinical trial applying precision medicine to the treatment of patients with idiopathic pulmonary fibrosis is underway. The trial aims to determine if N-Acetyl- cysteine (NAC) is an effective treatment in a subset of patients who carry a specific genetic variant. Treatments are also expanding for mesothelioma, though outlook tends to be poor. Last October (2020) the FDA approved a combination of immunotherapy drugs Opdivo and Yervoy for patients with malignant pleural mesothelioma that cannot be removed through surgery, providing more options to live longer with fewer side effects. A key breakthrough, the drug combination is the first new treatment for mesothelioma approved by the FDA in 16 years. The drugs are also the first immunotherapy treatments the FDA has approved for any type of mesothelioma. Other immunotherapies are making progress for mesothelioma too, with nivolumab being found to increase survival and make the disease more stable for patients who relapsed following standard treatment. The CONFIRM trial researchers say the study is the first to show that a treatment has been able to improve survival in patients with mesothelioma that has come back after chemotherapy and that until now, no treatment had been found that could significantly bolster outcomes for patients. Meanwhile novel treatments for COPD are making strides forward. Researchers at the National Institutes of Health, alongside collaborators, for example have found that inhaling unfragmented hyaluronan improves lung function in patients suffering from severe exacerbation of COPD. Hyaluronan - a sugar secreted by living tissue that acts as a scaffold for cells - shortened the amount of time COPD patients in intensive care needed breathing support and decreased number of days in the hospital. The research comes after co-senior author Stavros Garantziotis, M.D., medical director of the Clinical Research Unit at the National Institute of Environmental Health Sciences showed that exposure to pollution causes hyaluronan in the lungs to break down into smaller fragments, irritating lung tissue and activating the immune system, seeing constriction and inflammation of the airways. Garantziotis determined that inhalation of healthy, unfragmented hyaluronan reduces inflammation by outcompeting the smaller hyaluronan fragments. The treatment also improves mucus transport. As current treatments for lung disease include inhaled steroids, antibiotics, and bronchodilators, using a molecule already found in the body is a new concept. Garantziotis will now study the treatment in more patients to understand the optimal conditions and dosing that will produce the most benefit. Breakthroughs are also seeing diagnosis improved. For asthma, currently a wide-ranging complex investigation consisting of multiple elements is conducted, from interviews to blood and lungs tests, and x-rays. Researchers at Sweden’s Karolinska Institute (KI) have developed a non-invasive urine test to verify the type of asthma a patient has. Using mass spectrometry, the researchers are able to measure urinary metabolite levels of certain prostaglandins and leukotrienes - eicosanoid signalling molecules that are known mediators of asthmatic airway inflammation. Johan Kolmert, postdoctoral researcher at the Institute of Environmental Medicine, KI, and first author of the study, said: “We discovered particularly high levels of the metabolites of the mast cell mediator prostaglandin D2 and the eosinophil product leukotriene C4 in asthma patients with what is referred to as Type 2 inflammation. Using our methodology, we were able to measure these metabolites with high accuracy and link their levels to the severity and type of asthma.” The study shows promise for facilitating personalised diagnosis, provides clinicians with a better idea of which treatment is most likely to be effective, and the researchers state that the study illustrates measurement using a urine test offers better accuracy relative to other measurement methods, for example certain kinds of blood tests. These represent just a handful of the recent breakthroughs in respiratory disease research, with many more on the horizon. 14-17.qxp_Layout 1 13/08/2021 11:17 Page 4UMED Q&A 18 Pharma Business International www.pbiforum.net uMed’s mission statement is about trying to help GPs and their patients take part in important clinical research. How does the company undertake this? We want to help healthcare providers run patient research more efficiently and at scale, so we can better understand diseases and discover new treatments that will benefit patients. We do this by connecting health systems, GPs and life science sponsors, and automating the processes required to build groups or ‘cohorts’ of patients to participate in research. uMed works in three stages: • Our platform integrates with the healthcare provider’s Electronic Health Record (EMR) to match eligible patients to studies that are sourced by uMed or internal research teams. • The approval of the programs via the uMed dashboard triggers the automated outreach and remote consent of those patients on behalf of their recognised provider. • uMed remotely captures data from both the patient, the EHR and where necessary the clinician, linking this data back to the study dataset in a seamless process that maintains robust guarding of patient data, provider oversight and a safe patient experience. How will your approach impact the process of clinical trials for the better? COVID-19 has shown the power of clinical trials. It took less than 300 days for one vaccine to go from being an idea in a lab to be ready for administering to the general public. However, there is still a major roadblock to getting clinical trials for other diseases from off the shelf and into the world at speed – and that’s time and resources. GPs simply don’t have enough capacity which means clinical studies, although vital, often come second to delivering immediate patient outcomes. Sadly, many clinical trials also fail before they have even begun. Since March 2020, around 1,000 organisations supporting clinical trials have delayed the initiation of planned trials or withdrawn them completely, suspended enrolment in ongoing trials, or terminated these trials. Slow enrolment is largely to blame, with researchers struggling to recruit patients as volunteers. After all, without the volunteers to take part in clinical trials, there could be almost no research, which means it would be impossible to know which treatments are safe, let alone effective. Now, by automating the study processes, we have this huge opportunity to unlock massive capacity and scalability in vital health research – and at pace. We take on all the heavy lifting, from matching target cohorts of patients with clinical research opportunities through to engaging patients on behalf of the health system through an automated platform. What’s more, we collate the datasets for reporting while safeguarding Q&A Dr Matt Wilson, founder, uMed We spoke with Dr Matt Wilson, founder of uMed about the company’s mission of helping GPs and their patients take part in clinical research, as well as digital automation and much, much more. Dr Matt Wilson, founder, uMed 18-19.qxp_Layout 1 13/08/2021 11:17 Page 1Pharma Business International 19 www.pbiforum.net UMED Q&A patient data and ensuring regulatory compliance. Can you tell us a bit more about your medical background and how that has influenced your work with uMed? As a former A&E doctor, anaesthetist and Royal Marines medical officer, I know what clinicians are up against just in delivering patient care. When on shifts in the emergency department, I would sometimes go fourteen hours without eating anything, so the idea of doing research in these situations is simply unrealistic. The pandemic has made things worse. When I dashed back to clinical practice to support my local intensive care unit in the first wave of the virus this spring, I noticed operations that would take ten minutes were now taking up to an hour with all the PPE protocols, the cleansing of work stations, deployment of anti-viral vapours and that fact that some clinicians were also at too high risk for infection themselves to go into COVID wards. The time window for clinicians to undertake the meticulous, manual tasks associated with studies is just not there, so activity that could yield advances for treatments is lost. It’s this experience that led me to focusing on finding ways to automate clinical research that could short-circuit bureaucratic processes to build groups of patients that would accelerate studies. The thing that started to crystallise for me is that, if you want to do something serious with health data, you need to be able reach back to the patient. That changes everything if you can do it. Crucially, you can gain patient consent as well as validate and augment data that exists in the health record. And this is how uMed was born. uMed takes care of all the heavy lifting – how will this impact healthcare providers? By taking care of the heavy lifting, healthcare providers from GPs to hospitals can participate in dozens of programmes simultaneously without increasing their overhead or burden on staff. Medical research studies can cost many millions of pounds each, and up to 80% of these costs are associated with manual processes delegated to healthcare providers which uMed could eradicate. It means providers can focus on providing clinical care to their patients, while generating additional revenue which is shared among participating health systems and paid for by sponsors. Digital automation is at the heart of your platform. How can the pharmaceutical and healthcare benefit from a more widespread adoption of digital technologies? When used well, digital technologies can augment the capabilities of the healthcare and pharma workforce while also generating additional capacity within a system. For healthcare, this means being able to continue to focus on providing high quality patient care without the distraction of multiple other tasks. For pharma and research organisations, digital automation can lower the barrier to programmes that previously were financially and/or practically unviable. The real winners are therefore the patients who can benefit from better healthcare, and gain access to new treatments that would not have existed had digital technologies like uMed not existed. To find out more about uMed, visit www.umed.io, email hello@umed.io, or call +44(0) 2033 030329. 18-19.qxp_Layout 1 13/08/2021 11:17 Page 2Next >