The company’s financial success of 2019 was quickly followed by measures to cope with the COVID-19 pandemic.
By Christiane Truelove • [email protected]
Boehringer Ingelheim GmbH
Binger Strasse 173
55216 Ingelheim am Rhein, Germany
Telephone: +49 6132 77 0
(All figures are in millions of dollars except EPS and were translated using the Federal Reserve Board’s average rate of exchange in 2019: €1.1194)
Net income $3,046
R&D expense $3,875
BEST-SELLING Rx PRODUCTS
(All sales are in millions of dollars and were translated using the Federal Reserve Board’s average rate of exchange in 2019: €1.1194)
Micardis product family $822
Outcomes Creativity Index Score: 14
Manny Awards – N/A
Cannes Lions – N/A
LIA: Health & Wellness – 3
Clio Health – 4
One Show: HW&P – N/A
MM&M Awards – 3
Global Awards – 4
Creative Floor Awards – N/A
For family-owned Boehringer Ingelheim, 2019 was another successful financial year. “Our medicines have improved the quality of life and given patients more years to live,” says Christian Boehringer, chairman of the shareholders’ committee. “This is possible because we have relied on the power of innovation for many decades. We invest sustainably, continuously, and to an increasing extent. Our innovative strength is the basis of our company’s independence. To reach patients, we need to have a competitive offer. We need to fulfill our promise of quality and convince with the value of our contribution. Over the past few years, we have done this well.”
2020 was supposed to be a special year for the company as the Making More Health (MMH) initiative is celebrating its tenth anniversary. But then came COVID-19.
As many pharma companies did, Boehringer Ingelheim stepped up with efforts to combat the pandemic. Starting in April, the company began offering support and relief through multiple initiatives under its Global Support Program.
“As a research-driven pharmaceutical company, Boehringer Ingelheim is an active partner in the global movement to fight COVID-19,” says Hubertus von Baumbach, chairman of the board of managing directors. We are pleased that our business performance last year allows us to contribute to finding solutions to combat the virus. At the same time, we remain fully dedicated to reliable drug supply. And we are also working hard to minimize the impact of the pandemic on our global research and development programs.”
Baumbach adds, “These are extraordinary times, but they make us acutely aware of our purpose to serve where the medical need is high.”
Because millions of patients around the world are dependent on the company’s medicines, management says Boehringer Ingelheim is doing everything possible to keep production running, including treatments for pets and livestock.
To fight COVID-19, Boehringer Ingelheim is using the company’s considerable knowledge in various therapeutic areas, such as respiratory diseases and virology to find medical solutions to the pandemic. Management says the company’s scientists are searching for novel virus-neutralizing antibodies, as well as screening its entire molecule library for compounds that could target the virus. Furthermore, Boehringer Ingelheim actively participates with its COVID-19 projects in several research consortia, the Innovative Medicines Initiative of the European Union and an initiative led by the Bill and Melinda Gates Foundation, for example.
Other elements of the Global Support Program include a €5.8 million donations fund, paid leave for BI’s 51,000 employees to volunteer for COVID-19 relief, and a €580,000 relief fund for social entrepreneurs and their communities in Kenya and India, supported by the company through the Making More Health program.
Boehringer Ingelheim executives say the COVID-19 Global Support Program follows a strong business performance in 2019. Net sales increased by 9 percent to €19 billion ($21.27 billion). Research and development investments increased 9 percent to €3.46 billion ($3.88 billion), or 18.2 percent of net sales, mainly driven by new products and pipeline advances in existing projects.
In 2019, BI invested a company-record €1.1 billion ($1.23 billion) in fixed assets, compared with €950 million ($1.06 billion) in 2018. Operating income at the Boehringer Ingelheim Group level rose by around 9 percent to €3.78 billion ($4.23 billion), while net income after tax increased to €2.72 billion ($3.05 billion). Cash flow from operating activities increased by €356 million ($399 million) to €3.3 billion ($3.69 billion). At the end of 2019, the equity ratio was at 44 percent compared with 40 percent in 2018.
“Our solid capital base has allowed us to shield our operations and workforce from the impact of COVID-19,” says Michael Schmelmer, member of the board of managing directors with responsibility for Finance and Group Functions. “We are seeing the fruits of our past investments into our IT infrastructure and digital technology. Nearly 40,000 of our employees have been able to work uninterrupted from home. We can be in contact with physicians through our online platforms. And we can offer veterinarians to diagnose pets remotely through our PetPro digital platform in the U.S. In times where social distancing is so important, we are digitally close to our colleagues, our customers and our partners.”
According to BI management, the Human Pharma business was the company’s main growth driver in 2019. At €13.96 billion ($15.63 billion), human pharmaceuticals grew by 11.2 percent and made up 74 percent of total net sales. All regions contributed to the strong results in Human Pharma. Medicines against respiratory diseases, as well as cardiovascular and metabolic diseases remain the most important contributors to net sales. For the first time, Jardiance, a medicine for the treatment of type 2 diabetes, which also reduces the risk of cardiovascular diseases for patients with type 2 diabetics with pre-existing cardiovascular conditions, was the biggest revenue contributor in Human Pharmaceuticals. In 2019, Jardiance generated €2.15 billion ($2.41 billion), 47 percent more than in 2018.
BI’s second best-selling product in 2019 was the COPD drug Spiriva, which had €2.06 billion ($2.3 billion) in sales, a decrease of 15 percent.
The type 2 diabetes product family Trajenta/Jentadueto registered 2019 sales of €1.56 billion ($1.75 billion), an increase of 12 percent.
The fourth best-selling pharma product was the blood thinner Pradaxa, with sales of €1.53 billion ($1.71 billion), 3 percent more than in 2018.
The company’s Animal Health business is one of the largest providers of veterinary vaccines and medicines and has a strong presence in the livestock and pets segments. BI executives say while net sales increased in the pets segment, sales in the swine segment were negatively impacted by the outbreak of African swine fever, especially in China. Overall, the Animal Health business delivered a solid performance with net sales of €4.04 billion ($4.52 billion) in 2019, almost 2 percent less than in 2018. The antiparasitic Nexgard was the division’s best-selling product, with net sales of €740 million ($828 million), 21 percent more than in 2018.
Boehringer Ingelheim is one of the leading manufacturers of biopharmaceuticals, with 70 percent of the top 20 pharmaceutical companies and innovative biotech firms as clients. Known as Boehringer Ingelheim BioXcellence, the business achieved net sales of €786 million ($880 million) in 2019, an increase of 7.1 percent.
For the first half of 2020, Boehringer Ingelheim generated net sales of €9.7 billion ($10.86 billion), which adjusted for currency effects equates to year-on-year growth of 4.4 percent. Each of the three business areas contributed to this net sales growth, and BI executives believe that some of this growth in the first half was driven by increased safety stock in the health care systems.
“The performance in the first half year, driven by the desire to continue delivering the products needed by patients, reflects an exceptional effort by the whole organization in this very challenging time of the pandemic,” Schmelmer says. “We expect the market demand to remain very volatile in the coming months due to COVID-19. This will continue to require much attention on our part.”
The Human Pharma business achieved net sales of €7.1 billion ($7.95 billion) in the first half of 2020, 4.6 percent more than in first-half 2019. The company’s diabetes portfolio of products remains one of the growth drivers in Boehringer Ingelheim’s portfolio. According to BI, net sales of Jardiance increased by a currency-adjusted 22.7 percent to €1.2 billion ($1.34 billion compared with €1 billion ($1.12 billion) in first-half 2019. Boehringer Ingelheim markets the company’s diabetes medicines with Eli Lilly and Co.
BI executives say the other growth driver in the company’s Human Pharma portfolio is the respiratory product Ofev, which is approved in more than 80 countries for the treatment of people living with idiopathic pulmonary fibrosis (IPF) and in more than 40 countries for systemic sclerosis-associated ILD (SSc-ILD). Ofev also obtained approval in the United States, the EU, Canada, and Japan for a third indication, as the first treatment for people living with chronic fibrosing interstitial lung diseases with a progressive phenotype. Net sales in the 2020 first half for Ofev rose to €975 million ($1.09 billion) from €677 million ($758 million) in same-time 2019.
Boehringer Ingelheim generated net sales of around €2.2 billion ($2.46 billion) in the Animal Health business area during the first six months of 2020 compared with €2.1 billion ($2.35 billion) in January-June 2019. Sales of Nexgard grew 12.2 percent to €446 million ($499 million). Net sales of the swine vaccine Ingelvac Circoflex, which were under pressure throughout 2019 due to the African swine fever outbreak in China and Southeast Asia, recovered in the first half of 2020, growing 9.9 percent to €127 million ($142 million). According to management, with a new disease centric approach in its innovation strategy, Boehringer Ingelheim will rebalance the Animal Health business and put more emphasis on parasiticides and therapeutics.
Net sales of Biopharmaceutical Contract Manufacturing were significantly higher compared to the previous year’s level, at €318 million ($356 million) compared with €273 million ($306 million), due to favorable phase effects.
According to BI, 2019 R&D investments in the Human Pharma business amounted to €3.04 billion ($3.41 billion), or 21.8 percent of net sales. There are about 100 projects across all phases of research. The goal is for 75 percent of these projects to be either the first molecule in their active ingredient class or in a new therapeutic area. The focus of R&D in Human Pharma lies on cardiovascular and metabolic diseases, oncology, respiratory, immunology, diseases of the central nervous system, and retinal health.
The company entered into two research partnerships in September 2020, one for a cancer therapy and another for a digital therapeutic in schizophrenia.
Boehringer Ingelheim and Mirati Therapeutics Inc. are evaluating the combination of BI 1701963, a SOS1::pan-KRAS inhibitor blocking KRAS independent of mutation type, and MRTX849, a KRAS G12C selective inhibitor in patients with solid tumors that harbor the KRAS G12C mutation. The collaboration is investigating the potential of this combination to provide more effective and durable responses for patients with lung and colorectal cancers who have limited treatment options.
Preclinical data suggest that the combination of a KRAS G12C inhibitor with a SOS1::pan-KRAS inhibitor results in increased anti-tumor activity based on the complementary mechanisms of these targeted oncology agents. By shifting the equilibrium from active KRAS(ON) towards the inactive KRAS(OFF) form, SOS1::pan-KRAS inhibitors have the potential to sensitize KRAS G12C mutant tumors to covalent KRAS G12C inhibitors that bind to KRAS(OFF).
“We are excited to partner with Mirati in our ambition to make a difference for people living with KRAS-driven cancers,” says Victoria Zazulina, M.D., global medical head for oncology at Boehringer Ingelheim. “Combining our SOS1::pan-KRAS inhibitor with the mutation specific G12C inhibitor could be a win-win approach enhancing the response to therapy. We have a comprehensive KRAS program including the first SOS1::pan-KRAS inhibitor in the clinic, BI 1701963, for which we are exploring several combinations to optimize its therapeutic benefit in broad patient populations.”
Under the terms of the non-exclusive collaboration, Mirati is sponsoring the trial and Boehringer Ingelheim and Mirati are jointly sharing the costs of and overseeing clinical development for the combined therapy.
Boehringer Ingelheim is working with Click Therapeutics to develop and commercialize a prescription-based digital therapeutic. BI will use cognitive and neurobehavioral mechanisms delivered through Click’s proprietary engagement platform with the goal of reducing cognitive deficits and impaired social functioning in patients with schizophrenia. Together, the two companies will join their expertise to develop a novel mobile application, CT-155, which combines multiple clinically validated therapeutic interventions to help schizophrenia patients modify their behavior to achieve positive clinical outcomes alone and in combination with pharmaceutical therapy options.
The partnership with Click aims to provide better tools and resources to those living with schizophrenia, where there remains a huge unmet need due to lack of access to psychosocial intervention therapies.
“At Boehringer Ingelheim we believe that digital technologies can offer exciting new ways to help patients in need,” says Jan Stefan Scheld, M.D., corporate senior VP, therapeutic area head CNS, Retinopathies & Emerging Areas, Boehringer Ingelheim. “Therefore, we are pleased to partner with Click Therapeutics on the advancement of a prescription-based digital therapeutic, which will hopefully provide better treatment for patients with schizophrenia.”
According to Cornelia Dorner-Ciossek, Ph.D., director CNS Diseases Research at Boehringer Ingelheim, CT-155 is an excellent addition to the company’s CNS pipeline portfolio, and has the potential to be prescribed together with Boehringer Ingelheim’s schizophrenia pipeline compounds, possibly enhancing the benefit of pharmacotherapy for patients.
In another advance in the CNS pipeline, Boehringer Ingelheim in September announced the results from a 12-week, placebo-controlled Phase II trial that demonstrated BI 425809 met its primary endpoint. The data showed improvement in cognition in stable adult patients with schizophrenia. The results were presented at the 33rd European College of Neuropsychopharmacology (ECNP) Congress. A Gly-T1 inhibitor, BI 425809, forms a key component of Boehringer Ingelheim’s central nervous system research program. The latest trial results, along with an ongoing combination Phase II study of BI 425809 and adjunctive computerized cognitive training, will help determine the direction for BI 425809 in further schizophrenia research.
Boehringer Ingelheim entered into a research collaboration in July with Numab Therapeutics. The collaboration started with two projects aimed at novel therapies for difficult-to-treat lung and gastrointestinal cancers and patients with geographic atrophy, a progressive, irreversible retinal disease that occurs in patients with age-related macular degeneration (AMD) for which there is no current treatment. The collaboration brings together Boehringer Ingelheim’s leading expertise in the research and development of life-changing breakthrough therapies with Numab’s multi-specific antibody platform.
Management says the novel T-cell engager to be developed with Numab adds to Boehringer Ingelheim’s growing cancer immunology portfolio and supports the strategy to take cancer on by targeting “cold” tumors with synergistic combination approaches. In retinal diseases, Boehringer Ingelheim is pursuing a holistic approach leveraging existing expertise in oncology, inflammation, neurodegeneration, fibrosis, and cardiometabolic diseases. The new GA program with Numab further broadens the company’s comprehensive portfolio of next generation retinal therapy approaches in various stages of development up to Phase II in macular degeneration and diabetic retinal diseases.
“We are thrilled to work with the excellent team at Numab to advance our portfolio assets. Numab’s technology platform fits well with our internal antibody discovery and engineering capabilities and will enhance our efforts to deliver transformative antibody-based therapeutics to patients,” says Paige Mahaney, senior VP and US Discovery Research Site head at Boehringer Ingelheim.
Under the terms of the alliance, the partners are working together to discover one novel multi-specific antibody drug candidate in each area. Boehringer Ingelheim receives from Numab an exclusive worldwide license to develop and commercialize the resulting candidates in exchange for upfront and milestone payments, as well as tiered royalties on net sales of all products resulting from the alliance.
In July, Boehringer Ingelheim announced that the European Commission approved an additional indication for Ofev (nintedanib) in adults for the treatment of other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype beyond IPF. The approval came after the Committee for Medicinal Products for Human Use adopted a positive opinion in May 2020. The U.S. Food and Drug Administration, Health Canada, and the Japanese Pharmaceuticals and Medical Devices Agency have approved Ofev as the first treatment for the same patient population.
The approval is based on the results of INBUILD, which was a randomized, double-blind, placebo-controlled, parallel-group Phase III trial that evaluated the efficacy, safety and tolerability of nintedanib in patients with chronic fibrosing ILDs with a progressive phenotype. The primary endpoint was the annual rate of decline in forced vital capacity (FVC) in mL assessed over a 52-week period. Patients on placebo lost 188mL lung volume over a year, while patients on nintedanib lost 81mL. This was measured as adjusted annual rate of decline over 52 weeks and meant that nintedanib slowed the lung function decline by 57 percent versus placebo. The treatment effect of nintedanib in slowing FVC decline compared with placebo seen in INBUILD was consistent for all patients, regardless of the fibrotic pattern on high-resolution computed tomography (HRCT) and it was also consistent with the results in nintedanib trials studying patients with IPF and SSc-ILD.
“We are very pleased with the European Commission’s decision to approve nintedanib as the first treatment in the EU for a group of chronic fibrosing ILDs that are progressing,” says Peter Fang, senior VP and head of Therapeutic Area Inflammation at Boehringer Ingelheim. “Living with fibrotic diseases greatly impacts the lives of the affected. Various underlying diseases can lead to the development of pulmonary fibrosis and until now, no treatment option was available. Bringing new hope to those patients constitutes a therapeutic breakthrough.”
In May, Boehringer Ingelheim announced the acquisition of Northern Biologics Inc., a wholly owned subsidiary of Northern LP. BI executives say by acquiring this entity, which focuses on therapeutic antibodies targeting the tumor microenvironment, Boehringer Ingelheim is now positioned at the forefront of the stromal biology space – an emerging area in cancer immunology. The seller retains the Northern Biologics name and will continue to drive certain preclinical efforts on one of the programs, while Boehringer Ingelheim is responsible for clinical, regulatory and commercial development of the acquired programs.
The total transaction includes an upfront payment, milestones, and other consideration payments.
The first program, now in late preclinical development, is an antibody inhibitor of periostin, a secreted matricellular protein overexpressed in the immunosuppressive stroma microenvironment of many solid tumor types. Targeting these stromal cells can help turn previously “cold” tumors – non-reactive, immunologically inactive tumors – to “hot” tumors – those that are susceptible or accessible to host immune system attack. The antibody program targeting periostin has emerged as a promising therapy to overcome stromal mechanisms of immune exclusion and suppression, BI executives say.
The second program targets a key regulator of myeloid cells that is important for enhancing anti-tumor T-cell function. Targeting myeloid cells is a focus area of research and clinical development for Boehringer Ingelheim and the acquired program offers combination opportunities across the company’s product portfolio.
“This acquisition provides Boehringer Ingelheim with two complementary assets to our existing cancer immunology portfolio and supports our strategy to target ‘cold’ tumors with synergistic combination approaches,” says Jonathon Sedgwick, Ph.D., senior VP and global Head, Cancer Immunology & Immune Modulation Research, Boehringer Ingelheim. “Driving innovation in tumor stroma and myeloid cell biology is yet another example of how we are ‘Taking Cancer On’ by exploring first-in-class approaches to provide the best treatment options for cancer patients.”
Also in May, Boehringer Ingelheim and CDR-Life announced that they entered into a collaboration and licensing agreement to research and develop antibody fragment-based therapeutics for geographic atrophy (GA). GA is a progressive, irreversible retinal disease that occurs in patients with age-related macular degeneration (AMD) for which there is no current treatment. Management says with Boehringer Ingelheim’s expertise in the therapeutic development of biologics and CDR-Life’s strong know-how in antibody engineering, the two companies will progress CDR-Life’s preclinical candidate, with the aim to preserve sight for patients with GA.
Company executives say Boehringer Ingelheim takes a holistic approach to the development of novel retinal disease therapies, targeting key mechanisms in the pathogenesis of retinal diseases. By leveraging existing expertise in oncology, inflammation, neurodegeneration, fibrosis and cardiometabolic diseases, the company has built a comprehensive portfolio of next-generation retinal therapy approaches in various stages of development up to Phase II in macular degeneration and diabetic retinal diseases.
According to executives, CDR-Life’s preclinical program, which uses antibody fragment-based technology, complements this growing portfolio, providing an innovative approach to treat GA.
Under the terms of the agreement, Boehringer Ingelheim receives an exclusive, worldwide license to develop certain compounds based on CDR-Life´s technology against a specific target and is responsible for global development and commercialization. CDR-Life is eligible to receive up to CHF 474.5 million in upfront and success-based milestone payments, as well as research funding and royalties on sales.
Boehringer Ingelheim and Trutino Biosciences in February announced a research collaboration and worldwide licensing agreement based on Trutino’s innovative On-Demand-Cytokine (ODC) platform. Under the terms of strategic alliance, Boehringer Ingelheim gains access to Trutino’s ODC platform technology for the generation and development of up to three new ODC candidates.
According to management, this collaboration combines Boehringer Ingelheim’s long-term strategy to provide first-in-class, breakthrough therapies for cancer patients with Trutino’s unique knowledge and expertise in increasing the safety and efficacy of cytokine therapies.
“Developing a strong and innovative cytokine therapeutic program as an additional component of our cancer immunology portfolio, demonstrates how we are ‘Taking Cancer On,’ and provides a high-potential combination partner for our existing cancer vaccine, oncolytic virus, T cell engager and myeloid-targeting therapeutics portfolio,” says Jonathon Sedgwick, Ph.D., Senior VP and Global Head, Cancer Immunology & Immune Modulation Research at BI. “We are very pleased to partner with Trutino and harness the potential of their innovative scientific platform to develop treatment breakthroughs that will transform the lives of cancer patients.”
Trutino’s ODC platform masks the activity of cytokines until they reach the tumor site and become fully activated, sparing systemic exposure and potentially leading to a higher margin of safety and greater efficacy than conventional cytokine treatments. Trutino will generate the new ODC molecules and carry out preclinical validation, handing over development to Boehringer Ingelheim for late preclinical testing through the rest of development.
Trutino’s clinical potential was initially recognized by Boehringer Ingelheim through its grass roots programs, including the “BI Innovation Prize,” where the ODC platform technology was an early-stage standout in the 2019 program held in San Diego. Launched in 2015, the grass roots programs comprise “BI Office Hours,” “BI Academy,” and the “BI Innovation Prize.” Through Office Hours, Boehringer Ingelheim has provided more than 200 early-stage companies in the life-sciences community with mentoring and direct access to relevant expertise and industry perspective from senior leaders within the company.
Management says the partnership with Trutino strengthens Boehringer Ingelheim’s next-generation immune oncology portfolio, which combines cancer vaccines, oncolytic viruses, T Cell engagers, and myeloid targeting platforms with the aim of making “cold” tumors that are invisible to the immune system “hot” to rally the immune system against the tumor. Under the terms of the agreement, Boehringer Ingelheim is providing an upfront payment, near-term preclinical milestone payments and clinical, regulatory and commercial milestone payments, including royalties on future product sales.