Grünenthal Report 2018/19

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Letter from the CEO

The word historic is often overused –  but I use it deliberately when I say that 2018 was a truly historic year for Grünenthal.

With the acquisition of the pain-related brands Nexium™ and Vimovo™, we concluded the biggest single investment in the history of our company. By diligently executing our strategy – fundamentally improving our profit by delivering sustainable savings amounting to € 100 million, capturing sales opportunities, focusing our pipeline and building new capabilities – we were able to engage in a deal in the range of US$ 1 billion for the first time ever. This acquisition significantly strengthens our leading position in pain management and, most importantly, it helps us to address a high unmet patient need. The deal also has an immediate and lasting effect on our financial performance. We expect to double our EBITDA, in other words our ability to generate profit from our operations. This will enable us to further reinvest in building our company and developing life-changing treatments for patients.

The second historic moment came when we established our own commercial footprint in the world’s largest pharma market, the United States, for the first time. We acquired the US-rights for Qutenza™ (capsaicin) 8% patch and began building a US structure to commercialise the asset through Averitas Pharma. We had obtained global rights for Qutenza™ also in 2018.

Highlights in 2018 also included initiating a phase III program to investigate Neridronate for the treatment of Complex Regional Pain Syndrome (CRPS). The FDA has granted Breakthrough Therapy, Fast Track and Orphan Drug Designation for this investigational medicine. Also, we are now able to start a phase II program for a new compound, Neosaxitoxin, which is an innovative local/regional anaesthetic, to be used in peripheral nerve block and wound infiltration. Neosaxitoxin has the potential to be an alternative to post-operative pain control with systemic analgesics including opioids. And FLIX™, the investigational surgical sealant of our subsidiary Adhesys Medical, was granted CE-Certification in Europe.

In addition, we have obtained a label extension for Palexia™ Oral Solution to be used to treat moderate to severe pain in children from 2 years of age1.

“2018 was a decisive year for Grünenthal – both strategically and financially. Our success is based on the biggest transformation our company has ever undergone”
Gabriel Baertschi, Chief Executive Officer of Grünenthal

The progress we made in 2018 was made possible by our outstanding teams worldwide and our culture. This is shaped by our Values and Behaviours and our Code of Conduct, which define the way we interact and make decisions.

Our company is now in a much stronger position than it was last year in terms of turnover and profit, and we have also advanced our pipeline. We have achieved our financial targets, while also making strong progress in further executing our ambitious strategy at high pace. Above all, we’re working towards our vision of a world free of pain.

On behalf of the Executive Board, I’d like to invite you to join us on our journey in 2019 and beyond, as we seek to continue the successful development of our company – and improve quality of life for patients worldwide.

Best regards,

Gabriel Baertschi

1Restricted to hospital use where appropriate equipment to enable respiratory support is available and for a maximum treatment duration of 3 days

Image: Gabriel Baertschi, Chief Commercial Officer

Gabriel Baertschi, CEO

Corporate profile and strategy

Grünenthal is a global leader in pain management. Our purpose is to change lives for the better – and innovation is our passion. We’re driven to seek effective, life-changing medicines and solutions for patients with severe diseases and high unmet medical needs. We are focussing all of our activities and efforts on moving towards our vision of a world free of pain.

As a science-based, privately-owned pharmaceutical company, we have a long track record of bringing innovative treatments and state-of-the-art technologies to people living with pain worldwide. Strong ongoing partnerships with leading healthcare and development organisations bring our new products to life. We’re a fully integrated pharmaceutical company that offers support along the entire value chain – from drug development through to commercialisation.

Grünenthal is headquartered in Aachen, Germany, and has affiliates in 30 countries across Europe, Latin America and the US. Our products are sold in more than 100 countries. In 2018  Grünenthal employed around 4,900 people1 and achieved sales of € 1.3 billion.

1Status: end of December 2018

Key facts and figures

New strategy brings turnaround for Grünenthal

In view of a fast-paced, ever-changing market environment, Grünenthal has found relevant answers to current and future challenges and has consistently followed up on them as part of a new corporate strategy. Our strategy describes how we are approaching our vision of a world free of pain. It is built around four priorities: Transformation, Innovation, Growth and Culture.

All four elements are closely linked. Together, they help us build on our strengths and address headwinds such as expiring patents on some of our key revenue drivers, competition from generics, an increasingly challenging reimbursement environment in many markets and pharma-typical research and development risks.

Our strategic priorities

We have already achieved significant successes, making 2018 a turnaround year for Grünenthal. We have fundamentally improved our profit, captured sales opportunities, prioritised our R&D portfolio and built new capabilities. We’ve become more global, more efficient and work more effectively across functions and geographies. We are now able to deliver over € 100 million in sustainable savings per year, which open up exciting new options for our business in terms of both organic and inorganic growth. For the first time ever, we were in a position where we could close a deal in the range of US$ 1 billion with the recent acquisition of Nexium™ and Vimovo™.

Our company has gone through a significant transformation. And we will continue to further develop relevant change initiatives to make Grünenthal even stronger and more competitive – setting ourselves up for a sustainable future.

Our unique commitment to pain

Pain is a huge burden. It impacts patients – as well as their families, friends, caregivers and society as a whole. It is estimated that about one in five people worldwide suffers from chronic pain1, which equates to around 1.4 billion people. Pain is one of the most common reasons people seek medical help2, which places an enormous economic burden on healthcare systems. For many conditions there is no standard of care, and in cases where they do exist, they have limited efficacy3. Chronic pain is one of the major reasons why people leave the labour market prematurely, and is also a significant contributor to disability retirement4. Although few people die of pain, many still die in pain, while even more live in pain.

Given the prevalence and debilitating effects of pain, Grünenthal considers it to be a disease in its own right rather than just a symptom. As a global leader in pain management for nearly 50 years, we’re fully aware that patients are still hugely underserved in this area. We’re driven to seek new solutions to relieve pain. We are also fully committed to transforming this field. We’re redefining and shaping the future of pain management through our own research, as well as by drawing on external innovation, collaborations and networks.

“Although few people die of pain, many still die in pain, while even more live in pain. We will leave no stone unturned to help these patients.”
Gabriel Baertschi, Chief Executive Officer of Grünenthal

1Goldberg, D.S. and McGee, S.J., 2011, Pain as a Global Public Health Priority. BMC Public Health, 11, 770.
2Gureje, O., Simon, G.E., Von Korff, M., 2001, A cross-national study of the course of persistent pain in primary care. Pain. 92: 195-200.
3Pain Alliance Europe, 2017, Survey on Chronic Pain 2017, Diagnosis, Treatment and impact of Pain.
4Saastamoinen, P. et al., 2012, Pain and disability retirement: a prospective cohort study.

Why pain matters

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Societal Impact of Pain (SIP)

Societal Impact of Pain (SIP) is an international platform created in 2009 as a joint initiative of the European Pain Federation (EFIC) and Grünenthal. It aims to raise awareness of the impact that pain has on our societies, as well as our health and economic systems. It does this by facilitating the exchange of information and best-practice sharing across all European Union member states, and by developing and fostering Europe-wide policy strategies and activities for improved pain care. The scientific framework of the SIP platform is under the responsibility of EFIC. Cooperation partners for SIP include the Pain Alliance Europe and the Active Citizenship Network.

www.sip-platform.eu

Innovation

Networked innovation for the benefit of patients

Pain is an area with significant unmet medical needs. Many patients suffer for too long before receiving the right diagnosis – and an effective treatment. In fact, there are several pain conditions for which no medical solution is available. With nearly 50 years of experience in the field of pain research, we feel a strong sense of determination to deliver medical solutions allowing patients to relieve unnecessary suffering from pain – constantly striving to get closer to our vision of a world free of pain.

We take a holistic approach to research and development to create innovations that make a difference to patients’ lives. And we know that this needs a strong team with many different skills. For this reason, we place a strong focus on networked innovation – reaching out to the international research community to connect the dots and facilitate innovation. As a result, we’re able to establish collaborative projects that drive progress in pain research. Everything we do is based on our firm belief in transparency, open-mindedness and cooperation with all relevant stakeholders in the field of pain research and management.

To further sharpen our research approach, we regularly organise Patient Days, which enable us to better understand the patient perspective and gain insights into their experiences of living with pain conditions. We’ve created PainSolve, a platform that brings together the global research community to exchange their ideas and jointly move their projects forward. And we also played a central role in establishing a framework that enables pain projects under the umbrella of the Innovative Medicines Initiative (IMI), the world’s largest public-private partnership for Life Sciences1.  

We'll continue to go the extra mile to change patients’ lives for the better. Leveraging our operational agility, our research capabilities, as well as networked innovation, we are shaping the future of pain management.

“Grünenthal is one of the few remaining strongholds where innovation in pain is truly supported and is at the core of what we do.”
Gabriel Baertschi, Chief Executive Officer of Grünenthal

1www.imi.europa.eu

Involving patients every step of the way

At Grünenthal, patients are at the centre of everything we do. For this reason, our research activities start by listening to their needs. Our vision is to have patients involved in every step of our R&D process, as partners seeking a shared goal. We’re entering open dialogue with patients and patient groups through a combination of focus group meetings, interviews, surveys, and the creation of pain assessments. Thus, we’re able to hear patients’ voices and integrate their insights into our research and development programs.

We value these insights incredibly highly. By combining our expertise with patients’ first-hand experience, we’re able to design truly patient-focused research programmes, including more patient-friendly trials. This leads to enhanced recruitment and retention rates, while also enabling us to translate the patients’ insights into relevant clinical endpoints that make sure new treatment options address the most disruptive symptoms of their disease and unmet needs.

Building long-term relationships with patient groups is a key element of our search for innovations that improve patients’ quality of life. We look forward to further opportunities for dialogue – and would be pleased to hear from patients around the world who share our passion for collaboration and open discussion. 

“The fact that the company is so genuinely interested in the patient and the patient voice, and wanting to get to know us better […] It's something that touches my heart.“
Nicole Hemmenway, CRPS Patient and Chair of the US Pain Foundation

For us science is a team sport

What we can't do alone, we can achieve together. Pain researchers at Grünenthal and around the world are connected by a common goal of creating innovative solutions and delivering them to patients in need. Science is a team sport – now more than ever in our connected world. That’s why we need to connect the dots to achieve breakthroughs for patients.

With PainSolve, we’ve created a platform that can do just that. It offers a community area that is reserved for scientists and provides a space for exchange and networking – from basic research or clinical research through to cognitive, behavioural and social science. If you want to create lifechanging solutions in pain research and management through networked innovation, PainSolve is where you can meet likeminded people, discuss your ideas, and find partners who will help you plan and execute your projects.

As thought leaders, we shared our PainSpectrum library on PainSolve. It contains in-depth information about almost 100 pain conditions. Complemented by expert-led webinars, surveys and articles, we’re convinced that our non-commercial PainSolve platform is a valuable tool that provides added value for researchers. If you want to join our cause, we’re looking forward to connecting with you at www.painsolve.com.

“Great solutions emerge when the best minds can come together, discuss their opinions and take each other's ideas to the next level.”
John Bothmer, Head of Translational Science at Grünenthal

Joining forces within the Innovative Medicines Initiative (IMI)

These examples demonstrate the fact that networked innovation is at the heart of our work. We’re an agile organization joining forces with relevant stakeholders and experts to work towards our vision of a world free of pain. To facilitate our collaborative approaches, our colleagues successfully achieved putting pain research on the agenda of the Innovative Medicines Initiative (IMI), the world’s largest public-private partnership in Life Science.

Under the umbrella of IMI, we are co-leading the “Pain Group”, which unites European pharmaceutical companies and the academia who are dedicated to better understand, treat and manage pain. Together, we define research projects, submit proposals and process approved projects with the relevant experts – who join us from small and medium-sized enterprises, universities, research institutions, hospitals and patient organisations. 

From the multitude of projects that have emerged from this group, we are particularly proud of IMI-PainCare, which comprises 40 institutions from 14 countries across Europe and the US. It proves our commitment to networked innovation and the success of our efforts – because the best international experts are joining together to conduct research that aims to create life-changing outcomes for the patients we serve.

“We’re keen to enter into pioneering projects, teaming up with innovators from across industry and academia.”
Petra Bloms-Funke, Head of Grants & Partnerships at Grünenthal

Pipeline Highlights

Neridronate

Complex Regional Pain Syndrome (CRPS) is a rare, debilitating medical condition that typically affects patients following a soft tissue, bone, or nerve injury. CRPS is characterised by severe, continuous, burning or throbbing pain, frequently persistent and ranked as the most painful form of chronic pain that exists today on the McGill Pain Index. Currently, with no FDA or EMA approved medication, there are only very limited therapeutic solutions available. Thus, patients suffering from CRPS report lower quality of life scores than patients with most other chronic pain conditions.

Neridronate is an investigational product which has demonstrated efficacy in Complex Regional Pain Syndrome in a trial conducted in Italy1.  We’re currently running global phase III trials with the intention to file for approval with the US Food and Drug Administration (FDA). The FDA has granted Breakthrough Therapy, Fast Track and Orphan Drug Designation for Neridronate. It could be the first medication to receive FDA approval specifically for CRPS with the potential to alleviate pain and other CRPS symptoms with one treatment course.

Neosaxitoxin

Surgical procedures are commonplace, but still 55% of patients are dissatisfied with the pain management they received, while 30% report that their pain management was inadequate.2 Inadequate post-surgical pain management may delay rehabilitation, prevent patients from early mobilization and ultimately result in a longer stay in the hospital. This may bring further cost to society.

With Neosaxitoxin – a biotechnology-derived substance from a marine source and (atypical) local and regional anaesthetic – we’re developing a new medicine to address these unmet needs. In combination with the current standard of care (Bupivacaine) Neosaxitoxin has the potential to provide long-lasting post-operative pain relief and to reduce the need for post-operative systemically acting analgesics including opioids. The innovative (non-opioid) post-surgical pain treatment was in-licensed by Grünenthal in 2015 from Proteus S.A. (Chile) and Boston Children’s Hospital (US). It is currently in clinical development in peripheral nerve block and wound infiltration.

FLIX™ and VIVO

When traditional techniques for managing surgical incision do not deliver a high level of performance, the post-operative complications for patients can be severe and sometimes life threatening. Yearly, 50 million patients worldwide suffer from post-operative complications3, the most common being surgical wound infection4, a consequence of poor wound healing which affects over 500,000 patients per year in the US and leads to about 8,000 deaths annually. Life-threatening complications – such as postoperative anastomosis leakage for example – affect 20% of patients who undergo gastrointestinal surgery.5

We strive to address these issues by providing solutions for safer and improved clinical outcomes for patients and physicians with FLIX™ and VIVO – our innovative, fully synthetic investigational surgical sealants. FLIX™ is designed for topical use, while VIVO is one of the very few surgical sealants with a prospective use inside the body, carrying the potential to become an adjunct to current surgical suturing techniques. FLIX™ is currently undergoing clinical investigation for the United States, while VIVO is in preclinical and clinical development for a wide range of surgical procedures. FLIX™ was granted CE-Certification in Europe in January 2018; VIVO has been granted multiple academic research grants for its high and unique clinical potential.

1Varenna et al.; Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study; in: Rheumatology 2013, Volume 52, Issue 3, p. 534–542.
2Maier, C. et al., The quality of pain management in German hospitals; In: Dtsch Arztebl Int. 2010; 107(36): 607–614.
3Weiser TG, Haynes AB, Molina G, et al., Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes. Lancet 2015; 385: S11.
4Najar PA, Smink DS., Prophylactic antibiotics and prevention of surgical site infections. Surg Clin N Am 2015;95: 269-83.
5Alberts, et al., Predicting risk and diminishing the consequences of anastomotic dehiscence following rectal resection. Colorectal Dissection, September 2003, p 478 - 482.

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People and culture

Attracting the best and driving a vibrant, high-performing culture

Our business success is made possible by our people. As a player in a fast-paced, ever-changing market environment, we continuously question the way we do things and embrace change as an integral part of our daily work. Our employees demonstrate this agility every day. With their commitment, knowledge, skills and satisfaction, our teams drive our efforts to strengthen our position as a cutting-edge pharmaceutical company. We offer our employees an exciting working environment and wide-ranging individual development opportunities. It’s our goal to become a Great Place to Work® in all our markets. End of December 2018 Grünenthal employed around 4,900 people worldwide.

We invest in talent

To achieve our strategic priorities, we continue to attract, develop and retain a talented and diverse workforce that is united in the pursuit of our vision – and that brings our Values and Behaviours to life. Through our professional People Management, we’re growing our talents from within as well as identifying and recruiting emerging talents from outside of our company.

We support our employees in their development and encourage leaders to spend time supporting their employees’ career plans. We offer internal and external training to further build up capabilities. Alongside this, we’re building academies to make sure the employees in each of our functions have access to relevant technical knowledge and development opportunities.

Growing leadership capabilities and recognising outstanding results

As part of our efforts to achieve our strategic priorities, we aim to harness different perspectives, talents and ideas, while also ensuring that we develop a strong and diverse group of leaders. By embracing diversity, we ensure high-quality decisions and a better understanding of changing markets and consumer groups. In the last few months, we’ve achieved progress in making our Senior Level team – the level below our Corporate Executive Board – more diverse. Between 2016 and 2018, two-thirds of vacancies in our Senior Level were filled internally and one-third with external candidates. This reflects our commitment to developing high-quality leaders. We also increased the number of women in senior roles (the first two levels below the Corporate Executive Board) to 30 percent.

We promote a vibrant, high-performance culture. Every employee is required to have high-quality objectives that are aligned with our strategy. Performance is monitored through an active Performance Management Process that focuses on results – as well as the way those results were achieved. Our Performance Management Process also includes recognising and rewarding outstanding results.

Engaging our workforce

We want to make sure our employees understand and believe in our strategy. We offer several internal platforms on the global and country levels that provide all employees worldwide with opportunities to gather information and enter into dialogue with our Corporate Executive Board.

We also care for the wellbeing of our employees. For example, we regularly hold Health Day events at our headquarters in Germany, which include a range of activities related to mental and physical health. We also have our own internal Kindergarten, called Karlinis. It is located at our headquarters in Aachen and supports working parents in balancing their family and work life.

We use employee opinion surveys and leadership 360° feedback surveys to measure employee satisfaction and engagement, as well as the progress we’ve made towards our aim of becoming a Great Place to Work®.

Our Culture

Culture is one key pillar of our strategy, which supports our vision of moving towards a world free of pain. Our strategic focus has evolved over the last few months – and the framework for our company culture has changed just as much. We now have a set of five values that are defined by specific behaviours. Together, they guide our decision-making and give a clear indication of how we should act – as individuals and as an organisation. We embrace diversity, our people put patients at the centre of their decisions, we live entrepreneurship, join forces, drive performance and act with integrity. This all fosters our unique culture, “We are Grünenthal”.

Image: Corinne Pala, Regional Head Regulatory Affairs Europe at Grünenthal

Corinne Pala, Regional Head Regulatory Affairs Europe at Grünenthal

Markets and products

Extending our reach

In view of our vision of a world free of pain, Grünenthal strives to provide effective medication to patients worldwide. Therefore, we continuously grow and expand our market presence and product portfolio, and we collaborate with commercial partners and multiple stakeholders from the pain management field and beyond.

Grünenthal’s field force currently comprises around 1,600 people distributed across Europe, Latin America and the US. Their overall focus is on pain and also gout, while our teams in Latin America focus on other therapeutic areas as well, e.g. women’s health. In 2018, our field forces visited nearly 300,000 stakeholders, including physicians, pharmacists, and administrative staff within the health care system.

In addition, Grünenthal has built a strong network of commercial partners in countries where we do not maintain our own local sales organisation.

Map Grünenthal Affiiates & Partner Countries

In 2018, we achieved significant milestones in terms of executing our growth strategy and expanding our business across multiple therapeutic categories and geographies. Here are some highlights:

In January, Grünenthal entered into an agreement with Merck Sharp Dohme (MSD) for the commercialisation of their women’s health product portfolio in Latin America – complementing our existing presence in this therapeutic area and making us the second largest women’s health company in the region, with revenues of more than € 110 million.

In the same month, we signed a license and distribution agreement with Mundipharma for Tramal™ in China. The partnership strengthens our position and footprint in China, while also safeguarding our tramadol ampoules production capacities.

In March, we launched our first gout product Zurampic™ in Switzerland and Italy, with launches in Austria, Belgium and Spain following in the course of the year. The product is the first innovative uricosuric in gout treatment for over 40 years.

In August, we gained European marketing authorization for Duzallo™, a fixed-dose combination therapy for hyperuricemia in adult gout patients. Duzallo™ is planned to be launched in most European countries in 2019.

In October, we performed the biggest single investment in our history by acquiring the European rights to Nexium™ and the global rights to Vimovo™ (excluding the US and Japan) from AstraZeneca for a total consideration of up to US$ 922 million (€ 806 million). The two well-established brands are a perfect fit for our existing product portfolio and address a high unmet patient need (see chapter 8.1).

In November, we acquired global commercial rights for Qutenza™ (capsaicin) 8% patch and extended our commercial footprint to the United States through the US-based pharmaceutical company Averitas Pharma. Averitas Pharma will commercialise Qutenza™ for Grünenthal in the US.

To support healthcare professionals and patients in managing pain and related diseases Grünenthal has launched a number of initiatives and grants.

Change Gout

Change Gout is an initiative that aims to raise awareness of the burden of gout and improve the management of the disease by engaging both patients and physicians. Gout is the most common form of inflammatory arthritis in Europe. However, awareness is relatively low. For this reason, Grünenthal has collaborated with patients and clinical experts to design a pan-European survey to give people with gout a voice.

The 15-minute online survey was completed by 1,100 gout patients from 14 European countries. It collected information about the patient’s disease story, their (and the general public’s) knowledge about gout, the current status of their gout and the impact of the disease on their life. The design and content of the survey has been developed together with several patient and clinical experts. The initiative is supported by 13 European patient organisations.

The results of this survey demonstrate that gout has a significant impact not only on patients, but also on their families and society. Detailed findings will be presented at EULAR European Congress of Rheumatology in June 2019.

www.changegout.com

Change Pain

Change Pain is an initiative endorsed by the European Pain Federation, EFIC and Grünenthal. It aims to understand the needs of pain patients and develop solutions to improve the management of pain. Since the initiative was launched in 12 European countries in 2009, a great number of tools have been developed to make physicians’ daily practice easier, and more than 65,000 healthcare professionals have been involved in educational activities, either by completing web-based learning modules or attending workshops across Europe.

In 2018, we organised a Change Pain Advisory Board. It brought together representatives from the Latin American Federation of Associations for the Study of Pain (FEDELAT), the European Pain Federation (EFIC), the International Association for the Study of Pain (IASP), the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) and a group of key international opinion leaders specialised in the treatment of acute and chronic pain. The Advisory Board’s objective was to explore tangible ways of increasing the impact of the Change Pain initiative on patients’ outcomes, as well as to discuss future strategic collaboration based on alignment and partnership.

www.change-pain.com

My pain feels like…

Many patients have a difficult time describing their pain in a way that allows doctors to really understand the potential cause and the impact on their lives. As a result, patients endure a drawn out ‘trial and error’ treatment approach that can last months or even years.

The main goal of “my pain feels like…” is to improve the communication between patients and doctors. The focus is on nerve pain (also called neuropathic pain), which affects millions of people worldwide. One part of the initiative is the “my pain questionnaire” which supports pain patients in reflecting their symptoms, describing them more precisely, and preparing for doctors’ appointments. Another component is the so called “pain box”, a psychophysical experiment in which people can experience symptoms of localized neuropathic pain. The “pain box” was developed at the Montescano Pain School in Italy to teach doctors how localized neuropathic pain feels, and to improve empathy and understanding for patients.

www.mypainfeelslike.com

EFIC-Grünenthal Grant

These biennial grants from Grünenthal and the European Pain Federation EFIC, which total € 200,000, support young scientists early in their career in carrying out innovative clinical pain research in any member country of EFIC.

Individual research grants are worth up to € 40,000 per project for a duration of up to two years. Research grants are intended for clinical and human experimental pain research, including innovative educational initiatives aimed at improving diagnosis and treatment of pain. The decision on awarding grants is made independently by a sub-group of the Research Committee of the European Pain Federation EFIC.

The E-G-G 2018 received 59 applications from 16 countries – which promises to deliver interesting winning projects that benefit pain patients over the long-term. The winners will be announced in May 2019. During the EFIC congress, representatives from three of the winning projects that received  E-G-G funding in 2016 will present the results of their work.

www.e-g-g.info

Brain, Mind and Pain Grant

The Brain, Mind, and Pain Patient-Centred Innovation Grant was initiated by the Pain Alliance Europe and is supported by Grünenthal. Its main aim is to encourage patient-centred innovation that leads to improvements in the life conditions of pain patients.

The BMP Patient-Centred Innovation Grant jury announced three winners (out of 19 applicants) during a ceremony in Brussels on 20 June, 2018. The theme was “overcoming problems in access to treatments”. The three winning projects were:

MyBrainNet: a central platform for neurological brain diseases (Dystonia Europe)

Master your pain: improving access to personalised psychosocial treatment of pain caused by rheumatic diseases (Groningen University)

Reduce sensorial pain or stress in Autism Spectrum Disorder (ASPERGA Association)

The projects were assessed by a jury of patients and patient representatives, supported by scientific experts.

www.bmp-grant.eu

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Manufacturing and global operations

Lean manufacturing principles and excellence along the entire value chain

Our Global Operations organisation provides the backbone for Grünenthal’s ambitious plans for business growth. It creates value by applying lean principles and searching for continuous improvement opportunities along the entire value chain – from the raw materials we buy through to the logistics network we use to bring our medicines to patients around the world. Our global teams join forces to support our company’s growth by minimising costs, increasing efficiency and ensuring the highest quality standards.

Grünenthal operates six specialised plants in Germany, Switzerland, Italy, Ecuador and Chile. These sites manufacture our products and also support Grünenthal’s external customers, who account for around 50% of our overall production capacity. Our employees are passionate about making our internal and external customers happy – and making sure patients around the world can rely on our leading solutions to improve their quality of life.

Protecting patients against falsified pharmaceutical products

In 2018, Grünenthal implemented the requirements of a new EU legislation called the Falsified Medicines Directive (FMD), which aims to protect patients by preventing counterfeit medicines from being dispensed by pharmacies. It was a massive undertaking that is widely seen as one of the largest transformations in the history of our industry. Grünenthal was one of the first 20 companies to receive certification in line with this new legislation. This demonstrates our dedication to ensuring patients’ safety and providing innovative pain medicines that improve patients’ quality of life.

State-of-the-art production in Italy

One of our most ambitious projects in 2018 was the transformation of our production site in Origgio, Italy – because we had to complete this massive refurbishment while continuing to serve our customers from this location without any interruption. Our approach was coordinated by a special team of employees from across our business who worked together with suppliers and regulatory authorities to coordinate the comprehensive restructuring of the facility – and achieved success within a rapid timeframe.

This remarkable transition was made possible because the site began pre-producing our innovative medicines during the 12 months leading up to the installation of the new equipment. The local team increased their manufacturing volume by 50% during this period to create a stockpile of enough medicine to guarantee patients would continue to have uninterrupted access to the treatments they rely on. The refurbishment of the 2000-square-meter production hall was completed in just three months – without a single accident.

The local health authority officially approved the site in January 2019 after a two-month period of validation and on site auditing. Grünenthal Italy is now operating in line with best practice in our industry and in compliance with increasingly strict international regulations.

Contract manufacturing

Our contract manufacturing unit, Grünenthal PRO, offered services to 90 customers in the past year. Success in 2018 was built on in time implementation of the above mentioned Falsified Medicines Directive for the EU and similar requirements for other countries. In addition, we made investments into new capabilities such as new biopharma assembly and packaging lines at our site in Italy. The Italian team’s dedication to shortening lead times, offering flexible launch times and driving yield rates up was recognised by a major strategic customer – who presented Grünenthal with its best supplier award. A new cold storage warehouse of 1,500 pallets will further drive growth of this biopharma service in 2019.

Integrated Business Planning

Grünenthal has implemented a new standard for global demand and supply planning capabilities through our Integrated Business Planning (IBP) process. This monthly decision-making process balances demand and supply in a synchronised way to make sure we meet – or even exceed – our internal and external customers’ expectations. It integrates assumptions and drivers, ensures we avoid redundancies through transparent decision-making processes – especially when looking into root causes and gap closing opportunities to efficiently use our resources. IBP is fully integrated with our financial and brand planning processes, with plans in place to merge these processes on one common SAP platform in the future. In 2018, we increased demand planning accuracy in Europe by three percent points – which further strengthens our end-to-end processes to better serve customer and patient needs.

Image: Cindy Fuenzalida, Chemical Analyst at Grünenthal in Chile

Cindy Fuenzalida, Chemical Analyst at Grünenthal in Chile

Responsibility

Code of Conduct

Building trust through high ethical standards

At Grünenthal, we share the responsibility to act with integrity and conduct all of our research and business activities in compliance with applicable laws and regulations. Building trust through high ethical standards gives confidence to all of our stakeholders, including patients, customers, employees, partners, suppliers, investors and the communities we serve. Our compliance system provides a clear framework for our decisions and actions. It is built around our Code of Conduct, which we relaunched in 2018.

Our compliance framework covers our interactions with healthcare providers, patients, business partners, data privacy matters, competition and antitrust rules as well as financial compliance. Grünenthal’s compliance organisation is part of the Legal, Compliance, Risk and Audit team, which is led by our General Counsel.

You see it, you say it

Building a culture of compliance also means challenging any unethical, dishonest or otherwise unacceptable behaviour and speaking up when noticing anything that does not meet our high ethical standards. That’s why everyone – employees and external stakeholders alike – is asked to promptly report any compliance problems, concerns or misconduct. Concerns or questions can be reported personally or anonymously via our Ethics Helpline, which offers full confidentiality.

www.ethicshelpline.grunenthal.com

Image: Research building on the Grünenthal Campus in Aachen, Germany

Research building on the Grünenthal Campus in Aachen, Germany

Environment, health and safety

Driving progress towards a sustainable future

The world’s limited resources are becoming increasingly depleted and the environmental footprint of humankind is already more than the planet can sustain. That’s why we’re committed to driving progress towards environmental responsibility and sustainable development.

At Grünenthal, we actively support the United Nations 2030 Agenda for Sustainable Development and the 17 Sustainable Development Goals (SDGs). The SDGs aim to drive progress towards a sustainable future by acting as a call to action for politics, business and society on topics including inequality, climate change and justice. Our company’s efforts to promote sustainable development include defining sub-goals that are relevant for our operations and introducing management systems in line with leading international standards for environment, health and safety.

We collect and analyse data from our production sites and use it to continuously improve resource efficiency and occupational safety, while also cutting waste.


Grünenthal’s stance on opioids

It is widely accepted that the access to appropriate pain treatment is a basic human right, as stated for example in the 2011 Montreal declaration of the International Association for the Study of Pain (IASP). Opioid analgesics are one of the treatment options available.

Opioids can provide benefits for patients in pain, but may also carry a risk of inappropriate use including misuse, abuse, addiction and diversion. That’s why it is essential that physicians prescribe opioid analgesics after careful consideration of the benefits and risks of all of the available treatment options. At Grünenthal, we believe all physicians prescribing opioids should adopt an individual approach to opioid therapy for each patient, including a clear and realistic therapeutic objective and an agreement between the patient and her or his physician on treatment expectation and reporting of dose changes and side effects.

Grünenthal is highly committed to contributing to solving the challenges related to opioids worldwide. In particular, the opioid crisis in the US needs attention from both policy makers and pharmaceutical companies. We are actively involved in a range of measures and initiatives aiming to relieve the tragic impact opioid use disorder has on individuals, families and society. For example, we have engaged in the US Food & Drug Administration (FDA) Innovation Challenge program, which aims to encourage the development of innovative medical devices that prevent and treat opioid use disorders. We are also investing in R&D activities targeting opioids with less potential for abuse or misuse – including Abuse-Deterrent Formulations (ADF) that make opioid medicines more difficult to abuse, as well as innovative non-opioid solutions that offer equally effective treatment for patients in need.

Grünenthal will continue to further enhance its efforts to minimize the risk of inappropriate and illegitimate use of prescription opioids while striving to ensure that patients with a clear need are not denied access to effective and appropriate treatments. And above all, we are working tirelessly to bring innovative solutions to the market that bring us closer to our vision of a world free of pain for patients.

www.grunenthal.com/about-us/our_positions

Social responsibility

At Grünenthal, caring for the world around us is a big part of who we are. We have a long tradition of supporting projects that have a positive impact on people and communities, from palliative care and charity activities through to environmental protection. We actively engage in projects that help people increase their quality of life – in line with our vision of a world free of pain. Here are just a few examples.

Clean Workspace Week

Our team in Spain has been engaging in a unique project that combines recycling with support for people in need. In just one week, they collected 1,788 kilograms of paper for recycling through a “clean workspace” activity at our office in Madrid – and they then donated the same weight of food to the Food Bank Foundation of Madrid.

The partnership with this organisation has been in place since 2013. So far, Grünenthal employees have donated around 21,500 kilograms of food in total. As a result, the foundation presented Grünenthal with its 2018 Communication Award in recognition of our local team’s outstanding contribution to its cause.

Grünenthal employees also support this organisation through volunteering activities. In December and January, colleagues from our Madrid office went to the organisation’s warehouse to help classify the food collected during one of its campaigns – so that it could be redistributed to some of the 300,000 people living in poverty in Madrid.

Expanding access to palliative care

2018 marked the 50th anniversary of Grünenthal’s presence in Peru. Our innovative medicines are improving the lives of people in this country – and so is our commitment to improving palliative care, which is still very basic in many areas of Latin America. In Peru, for example, around 100,000 patients are seeking access to palliative medicine, but there are only about 100 qualified palliative care specialists. Improvement is urgently needed.

In October 2018, the Grünenthal Foundation for Palliative Medicine, the Department of Palliative Medicine at the Medical Faculty of RWTH Aachen University, Germany, the Peruvian Society for Palliative Care and the National University of San Marcos organised the international Congress on Palliative Care in Lima. It aimed to facilitate the exchange of knowledge and skills related to treating people in the final phase of life, while also raising awareness about the importance of providing high-quality palliative medicine among the scientific and political communities, as well as across society.

The Grünenthal Foundation for Thalidomide-affected People

The Grünenthal Foundation for Thalidomide-affected People runs support projects for people affected by a thalidomide-containing product from Grünenthal or its licensees. It aims to permanently improve their lives in a pragmatic way by providing specific, needs-based support. Since the Foundation was established, it has provided support for more than 2,000 individual cases – ranging from barrier-free bathrooms and kitchens through to specially adapted wheelchairs and cars, voice-controlled software for the remote use of computers and other devices, as well as investments in adapted hospital rooms.

One of the projects in 2018 involved supporting home improvements that give disabled people greater freedom in their day-to-day lives. Contributions from the foundation helped remodel kitchens, for example. The new facilities feature state-of-the-art technologies that make a range of everyday tasks easier – from sensors that activate the hot and cold water taps, through to remote controls for appliances and innovative designs that make cupboards and drawers easier to access.

The Grünenthal Foundation is open to all people suffering from Grünenthal’s thalidomide products or its licensees who are acknowledged by an official institution that applies similar eligibility criteria as the Contergan Foundation, a German federal foundation under public law, or the UK Thalidomide Trust.

Dynamo Camp

Under the motto “Un Sorriso per Chi Soffre" (A Smile for Those who Suffer), employees from Grünenthal Italy are taking a proactive approach to supporting social projects. One example is our partnership with a therapeutic recreation camp in Tuscany known as Dynamo Camp. It’s a free holiday camp for children aged six to seventeen who are either in therapy or in the post-hospitalisation period. By offering facilities such as a climbing wall that is specially designed to be suitable for disabled, wheelchair bound or recovering children, it provides a life-changing opportunity to experience a real recreational holiday complete with sport, play and relaxation.

An initial group of Grünenthal employees volunteered at Dynamo Camp in 2018, with more expected to join them in 2019. In fact, the team in Italy aims to further increase its contribution to social and community projects over the coming 12 months and beyond.

Image: Recreational activities at Dynamo Camp in Tuscany, Italy

Recreational activities at Dynamo Camp in Tuscany, Italy

Financials

Transforming our business to facilitate future growth

2018 was a decisive year for Grünenthal – both strategically and financially. We have achieved the financial turnaround, stabilised our EBITDA1 and significantly curbed cost – despite major headwinds due to generic competition and an increasingly challenging reimbursement environment.

This success is based on the biggest transformation our company has ever undergone. By rigorously implementing the efficiency programs we launched in 2017, we reduced costs by over € 100 million a year (see chapter 1) to make our company more sustainable. For instance, we reorganized our Commercial area to respond to the above-mentioned market trends, increased the efficiency of Global Operations and centralized global procurement activities to better leverage economies of scale.

We used part of the cash generated by these savings to make strategic investments such as acquiring global rights to Qutenza™ and establishing our own commercial presence in the US. Together with other major transactions, for instance the acquisition of global (ex Japan) rights to Zomig™ in 2017, we were able to enhance our company’s profit base. This substantial improvement in the operative financial results paved the way for us to finance the large-scale deals for Nexium™ and Vimovo™ (see chapter 8.1). We were able to finance this transaction with favourable conditions and a balanced maturity profile. Ultimately, all of these transactions are vital building blocks to future-proof Grünenthal and strengthen our leading position in the pain and analgesic market.

In addition, we have strengthened our early R&D partnerships with promising projects and re-focused our pipeline. We are convinced that there is great potential in investigational products such as Neridronate and Neosaxitoxin (see chapter 3). And we also expect a lot from the label extension for Qutenza™ in the US, which we are currently working towards.

The success of these projects and our external growth endeavors is important to sustain and grow our position in an increasingly challenging market environment. The influence of generics and the resulting decline in prices, as well as reimbursement hurdles are already reflected in the current sales2 development for our mature brands, including Versatis™. Nevertheless, we were able to increase our gross profit3 in 2018 through growth of our high-margin products such as Palexia™ and Qutenza™.

Outlook for 2019

We expect an overall unchanged market environment for 2019. The biggest priority and by far largest contributor to our EBITDA and cash flow are the various deals, which will continue to strengthen our leading position in the pain market and pave our way for future growth. They are expected to generate a significant portion of adjusted EBITDA per year and boost our financial performance.

“The substantial improvement in our operative financial results paved the way for us to finance the large-scale deals for Nexium™ and Vimovo™”
Fabian Raschke, Chief Financial Officer of Grünenthal
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Business development and licensing

Setting the course for growth

We believe in partnerships. Grünenthal is committed to open collaboration with like-minded players who share our passion for creating innovative medicines and making them accessible to patients worldwide. In today's fast-moving world, a single scientific organization or company alone can no longer successfully do research or commercialisation. That is why we build strong networks and share our unique expertise to drive progress towards our vision of a world free of pain.

Grünenthal is known for its proficiency in pain and adjacent fields. As a privately owned, mid-sized company with strong R&D and commercial capabilities, we are an attractive partner for other pharmaceutical companies seeking to develop breakthrough treatments for patients. And we do not only build partnerships in the field of research and development. To continuously grow our business and mitigate risks we leverage the potential of our pipeline while also seizing external growth opportunities. Therefore, cooperation and collaboration at Grünenthal also relates to sales partnerships, licensing agreements and acquisitions. And in this respect 2018 was a truly exciting year. Here are some of the highlights:

European rights to Nexium™ and global rights (ex US and Japan) to Vimovo™

In October 2018, we concluded the biggest single investment in the history of our company and acquired AstraZeneca’s European rights for Nexium™ and global (ex US and Japan) rights for Vimovo™ for a total consideration of up to US$ 922 million (€ 806 million). Complementing our extensive pain expertise with these well-established products is a perfect strategic fit. The acquisition significantly strengthens Grünenthal’s leading position in pain management and helps address a high unmet medical need, i.e. gastroprotection for patients on non-steroidal anti-inflammatory drugs (NSAIDs). The deal will have an immediate and lasting effect on our financial performance. We expect to double our EBITDA.

Nexium™ is one of the leading proton pump inhibitors (PPI) used, among others, for the prevention and healing of gastric ulcers associated with NSAID therapy. Vimovo™ is a proprietary pain product for the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, whilst offering gastro-intestinal protection.

Global rights to Qutenza™

In November, Grünenthal acquired additional global commercial rights for Qutenza™ (capsaicin) 8% patch from Acorda Therapeutics, Inc., making us the sole owner of the product worldwide. Qutenza™ is a local analgesic that complements our existing pain portfolio and offers a real alternative to the current standard of care. There is still a high unmet medical need in pain management, particularly for non-opioid and non-systemic treatments.

In Europe, Qutenza™ is approved for a broad peripheral neuropathic pain indication in adults, which includes post-surgical neuropathic pain, cancer-related neuropathic pain and painful diabetic peripheral neuropathy. In the US, it is currently only approved for the treatment of postherpetic neuralgia (PHN). We are therefore working towards a broader neuropathic pain label from the US Food & Drug Administration (FDA).

Extending our commercial footprint to the United States

We also established our own commercial presence in the world’s biggest pharma market, the US, for the first time and will commercialise the pain patch Qutenza™ through Averitas Pharma. Qutenza™ will serve as the vanguard brand for our new US business.

In the past, setting up the infrastructure to market our broad-based products in the US would have required massive investment. Now, with a specialty product like Qutenza™, we can take a focused approach by envisioning and building a flexible and scalable specialty commercial model. Our innovative approach to align the expertise of health care professionals with complementary sites of care will help improve access to Qutenza™ for appropriate patients.

“We continue executing our growth strategy and have been expanding our portfolio by a series of acquisitions with a total value of more than US$ 1.3 billion since 2016.”
Gabriel Baertschi, Chief Executive Officer of Grünenthal