Boehringer Ingelheim 2021: Keeping its focus on steady innovation

Boehringer Ingelheim enjoyed a profitable 2020, and the company has been bolstering R&D activities with acqusitions and partnerships.

By Christiane Truelove • [email protected]

 

Boehringer Ingelheim

Binger Strasse 173  

55216 Ingelheim am Rhein 

Telephone: +49-6132-77 0

Website: boehringer-ingelheim.com

 

 

OUTCOMES CREATIVITY INDEX SCORE: 5

Manny Awards — N/A 

Cannes Lions — N/A

Clio Health — 1

Creative Floor  Awards — N/A

MM+M Awards — 4

One Show — N/A

 

Financial Performance

(All figures are in millions of dollars except EPS and were translated using the Federal Reserve Board’s average rate of exchange in 2020: €1.141.)

2020  

Revenue $22,325  

Group profit $3,494  

R&D expense $4,217  

1H 2021  

Revenue $11,182  


Best-Selling Products

(All sales are in millions of dollars and were translated using the
Federal Reserve Board’s average rate of exchange in 2020: €1.141.)

2020  

Jardiance $2,830  

Ofev $2,345  

Spiriva $2,046  

Trajenta/Jentadueto $1,725  

Pradaxa $1,702 

1H  2021 

Jardiance $1,597  

Ofev $1,369 

 

“COVID-19 is a test the likes of which the world has not seen for a long time. Research-based pharmaceutical companies – whether they are involved in vaccine development or, like us, in the development of treatments to address SARS-CoV-2 induced symptoms and life-threatening complications – are a key industry in the pandemic. We are aware that many hopes rest on our industry and we take many extra efforts to address these,” says Hubertus von Baumbach, chairman of the board of managing directors. 

“These efforts come on top of the continued fight against other deadly diseases like cancer for instance and, unfortunately, they bear the same risk of failure that is inherent to all our research. Nevertheless, the industry has provided solutions at unprecedented speed and has collaborated in unequaled ways to ramp up supply – all on top of our usual work,” he says. 

Financial Performance

In 2020, Boehringer Ingelheim, while operating under the pressures of the pandemic, achieved success, executives say. 

Total net sales amounted to €19.57 billion ($22.32 billion). As reported, sales grew 3 percent but adjusted for currency effects, net sales increased by 5.6 percent compared with 2019. 

Operating income increased to €4.6 billion ($5.28 billion), 22 percent more than the previous year. Executives say two factors are mainly responsible for this – the positive sales trend and lower operating costs. Group profit after taxes for 2020 went up by 13 percent from 2019 to €3.06 billion ($3.49 billion). 

The company’s lead product in 2020 sales continued to be the SGLT-2 inhibitor Jardiance, which recorded sales of €2.48 billion ($2.83 billion), 15 percent more than in 2019. First-half 2021 sales increased by 17.2 percent (year on year and adjusted for currency effects) to €1.4 billion ($1.6 billion). 

The second best-selling pharmaceutical product in 2020 was the respiratory medicine Ofev, which generated €2.06 billion ($2.34 billion), 38 percent more than in 2019. Sales in the first half of 2021 totaled €1.2 billion ($1.37 billion), an increase of 28.9 percent (year on year and adjusted for currency effects). 

Third in sales during 2020 was the asthma and COPD medicine Spiriva, at €1.79 billion ($2.05 billion), a decrease of 13 percent from 2019. 

Boehringer Ingelheim operates in three main areas: Human Pharmaceuticals, Animal Health, and Biopharmaceutical Contract Manufacturing. 

In 2020, Human Pharmaceuticals sales totaled €14.42 billion ($16.45 billion), 3.3 percent more than in 2019. 

Animal Health, driven by sales of products such as NexGard, generated €4.04 billion ($4.7 billion), 2 percent more than in the year before.

Biopharmaceutical Contract Manufacturing recorded revenue of €837 million ($955 million), 6.5 percent more than in 2019.

Executives say Boehringer Ingelheim continued its positive trend during the first half of 2021. In the first six months, the company generated net sales of €9.8 billion ($11.18 billion), up 5.8 percent (year on year and adjusted for currency effects). All three business areas (Human Pharma, Animal Health, Biopharmaceutical Contract Manufacturing) contributed to the net sales growth. 

“Together with our employees, we achieved solid financial results in the first half of the year, even when the COVID-19 pandemic continues to have an impact,” says Michael Schmelmer, member of the board of managing firectors with responsibility for Finance & Group Functions. “We see that in a lot of countries, people avoid seeing their doctors because of COVID-19, even if they are in urgent need of diagnosis and treatment. This non-treatment poses a serious medical problem, which we must take into consideration even more when fighting the pandemic.”

In Human Pharma, Boehringer Ingelheim achieved net sales of €7.1 billion ($8.1 billion) in the first half of 2021, equal to last year in the same period. Adjusted for currency effects, net sales increased by 5 percent year on year.

In the first half of 2021, Boehringer Ingelheim generated strong net sales of around €2.3 billion ($2.62 billion) in the Animal Health business area. “Adjusted for currency effects, year-on-year sales were up 9.6 percent in this highly competitive market,” executives say.

The company reported that demand in Biopharmaceutical Contract Manufacturing remains high, with net sales increasing 1.1 percent (year on year and adjusted for currency effects) to €322 million ($367 million). Boehringer Ingelheim is further expanding its biopharmaceutical production capacity to continue to meet growing demand, management says, and the company will inaugurate its large-scale cell culture (LSCC) facility in Vienna, Austria, in October. This facility includes up to 150,000L manufacturing capacities for Boehringer Ingelheim products and contract manufacturing.

R&D Progress

According to company executives, Boehringer Ingelheim’s R&D pipeline in Human Pharma comprises more than 60 new substances and around 100 clinical and pre-clinical projects. The company believes this pipeline has the potential to deliver up to 15 medicines for approval by 2025.

In July 2021, Boehringer Ingelheim reported a breakthrough in the treatment of heart failure with Jardiance. More than 60 million patients worldwide suffer from this disease, approximately half of them from heart failure with preserved ejection fraction (HFpEF). Heart failure with left ventricular preserved ejection fraction occurs when the left ventricle of the heart is unable to fill properly, resulting in less blood being pumped to the body. A trial showed a significantly lower risk with Jardiance of hospitalization for heart failure or cardiovascular death in adults with HFpEF. 

If approved, Jardiance would become the first and only clinically proven therapy to improve outcomes across the full spectrum of heart failure patients regardless of ejection fraction. In June, the European Commission granted marketing authorization for Jardiance as a treatment for adults with symptomatic chronic heart failure with reduced ejection fraction (HFrEF). 

“Despite all the medical progress made in recent decades, there are still many diseases for which there is yet no adequate treatment available,” von Baumbach stated. “That is why we at Boehringer Ingelheim focus on areas where the need for medical innovation is high. Our strong R&D pipeline has made further, decisive progress in the first half of 2021. These medical successes have the potential to improve the lives of millions of patients worldwide.”

Boehringer Ingelheim also made progress in the area of neuropsychiatric disorders, including two ongoing Phase II trials. At the end of May 2021, Boehringer Ingelheim announced that the U.S. Food and Drug Administration granted Breakthrough Therapy Designation (BTD) for BI 425809, a key component of the company’s mental health research program, for the treatment of cognitive impairment associated with schizophrenia (CIAS).

Boehringer Ingelheim also announced the planned initiation of the innovative CONNEX Phase III clinical trial program assessing the safety and efficacy of BI 425809, a novel glycine transporter-1 (GlyT1) inhibitor, for improving cognition in adults with schizophrenia. 

Also in June, Boehringer Ingelheim and Zealand Pharma A/S announced that FDA granted Fast Track Designation to the GLP-1/glucagon dual agonist BI 456906 for adults with non-alcoholic steatohepatitis (NASH). The Fast Track Designation facilitates the development and expedites the review of new therapies to treat serious conditions and fill an unmet medical need. BI 456906 is currently being evaluated in a Phase II study in adults with NASH and liver fibrosis (F2/F3) with and without diabetes. The drug has the potential to be a new, once-weekly treatment that may offer therapeutically relevant benefits compared to currently available treatments. It is also being investigated as a potential treatment option for adults living with diabetes and for adults living with obesity.

“The FDA Fast Track Designation for our dual agonist is an important step forward in addressing the high unmet medical need among the up to 444 million adults estimated to be living with NASH,” says Waheed Jamal, M.D., corporate VP and head of CardioMetabolic Medicine, Boehringer Ingelheim. “Together with our partner Zealand Pharma, we look forward to working closely with the FDA as we explore the potential of the GLP-1/glucagon agonist to improve outcomes for adults with NASH.”

Executives say Boehringer Ingelheim also remains committed to the search for potential therapeutics against the SARS-CoV-2 virus. 

In July, the company announced that it will focus BI’s COVID-19 therapy research on the development of alteplase as a potential treatment for COVID-19 patients with severe breathing problems, called acute respiratory distress syndrome (ARDS). The decision is based on favorable safety and efficacy data from an interim analysis of the TRISTARDS Phase II/III study, following completion of the Phase IIb part of the study including 62 patients. 

However, the BI 767551 SARS-CoV-2 neutralizing antibody development program is being discontinued. According to management, the current state of the pandemic makes it challenging to further progress clinical development of this antibody and make it available to patients within a reasonable time frame to contribute against the COVID-19 pandemic.

Acquisitions & Partnerships

To expand its work in oncology and other areas of the pipeline, Boehringer Ingelheim has been investing in acquisitions and partnerships. In September, the company announced that it had acquired Abexxa Biologics Inc., a biopharmaceutical company taking a new approach in the fields of immuno-oncology and oncology research to develop the next generation of precision medicines designed to revolutionize cancer treatments. 

Executives say the acquisition will allow Boehringer Ingelheim to access Abexxa’s expertise in targeting cancer-specific proteins that are located inside the cell, rather than those expressed on the cell membrane. This enlarges the pool of potential cancer antigen targets. In particular, Abexxa’s technology could lead to the development of cancer immunotherapies that are effective in a broader range of patients and cancer types.

“The acquisition of Abexxa bolsters our commitment to tumor-antigen discovery and new ways of targeting intracellular antigens,” says Clive R. Wood, Ph.D., corporate senior VP and global head of discovery research, Boehringer Ingelheim. “Their cutting-edge knowhow and technologies for antigen discovery and novel antibody generation strongly complement the current approaches we have been applying successfully to enable immune-targeting of cancer cells. By expanding our portfolio of antibodies binding novel intracellular tumor antigens, we are striving to develop unique and broadly applicable new immunotherapeutic approaches for cancer patients.”

Abexxa’s platform unlocks the ability to target intracellular antigens of cancer cells by recognizing their presentation on the cell surface by MHC class 1 molecules. 

Although the Abexxa platform addresses the more common HLA-A2 peptide presentation, executives say the company has developed specific expertise in the nonclassical MHC class 1 molecule HLA-E, which has the potential to impact a broader set of cancer patients’ antigens. More specifically, Abexxa has developed a first-in-class T-cell receptor (TCR)-like antibody that can be used to disrupt the NKG2A:HLA-E immune checkpoint axis in oncology. Abexxa molecules are also being formulated to recruit immune cells targeting HLA-E peptide complexes on tumors. 

In 2016, Boehringer Ingelheim’s Venture Fund, the arm of the company that invests in ground-breaking therapeutic and digital health approaches, awarded Abexxa initial investment funding. 

Later that year, Abexxa won Boehringer Ingelheim’s Innovation Prize, which facilitates business growth and rewards new companies for their dedication to innovation. The prize allowed Abexxa to expand operations into a shared lab space in Cambridge, Mass., to continue its research. 

Leaders say Boehringer Ingelheim’s investment in Abexxa demonstrates how the company is seeking to foster innovation across leading biotech communities, including the Dallas-Fort Worth area.

“The investment by Boehringer Ingelheim’s Venture Fund in 2016 was a defining moment for Abexxa,” says Debra Wawro Weidanz, co-founder and CEO of Abexxa. 

According to Jon Weidanz, Ph.D., co-founder and chief science officer of Abexxa, “The acquisition by Boehringer Ingelheim allows our team to access the company’s expertise and capabilities in immuno-oncology and antibody development and to have the opportunity to translate Abexxa technology into a clinical asset.”

Also in September, Boehringer Ingelheim announced a clinical Phase I collaboration with Amgen (see profile on page 24) to evaluate the combination of BI 1701963, the first and most advanced SOS1::pan-KRAS inhibitor exhibiting activity against a broad spectrum of KRAS alleles, and Lumkaras (sotorasib), the first FDA-approved KRASG12C inhibitor for adult patients with locally advanced or metastatic non-small cell lung cancer. 

The trial will investigate potential synergistic effects of this combination, possibly improving therapeutic outcomes beyond those of KRASG12C inhibitor therapy alone, specifically for people living with lung and colorectal cancers.

“We are excited to partner with Amgen, who have pioneered KRAS G12C inhibition, and to further expand our program to make a difference for people living with KRAS-driven cancers,” says Francesco Di Marco, Ph.D., corporate senior VP, global therapy area head, Oncology, at Boehringer Ingelheim. “Boehringer Ingelheim follows an ‘all-in’ research approach to taking cancer on, including the first and most advanced SOS1::pan-KRAS inhibitor which we investigate in several combinations and cancer types to realize even more opportunities to deliver potential therapeutic benefits to cancer patients.” 

Under the terms of the non-exclusive collaboration, Amgen will be the sponsor of the trial and Boehringer Ingelheim and Amgen will jointly share the costs of and oversee clinical development for the combined therapy.

BI 1701963 is an investigational, orally available small molecule, that binds to the catalytic domain of SOS1 preventing the interaction with inactive KRAS. This reduces the formation of active KRAS and in consequence inhibits MAPK pathway signaling in KRAS-dependent cancers.

In another collaboration announced in September, Twist Bioscience Corp., a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, entered a broad-based research collaboration with Boehringer Ingelheim to use Twist’s proprietary antibody libraries to discover therapeutic antibodies against multiple targets provided by Boehringer Ingelheim.

“Boehringer Ingelheim believes Twist’s ability to generate potent, diverse therapeutic antibodies by mining its comprehensive libraries, combined with our extensive capabilities and experience in drug discovery and development, will enable us to deliver breakthrough opportunities to patients,” Dr. Wood says. “We look forward to working with Twist on molecular targets in a broad range of disease areas.” 

Under the terms of the agreement, Twist Biopharma – a division of Twist – will utilize its “Library of Libraries,” a panel of synthetic antibody phage display libraries derived only from sequences that exist in the human body, to identify potential therapeutic antibody candidates. Twist and Boehringer Ingelheim will work together to validate and optimize any resulting new antibody candidates, which could be researched against a range of therapeutic areas. Boehringer Ingelheim retains exclusive worldwide rights to develop and commercialize any therapeutic antibodies discovered as part of the collaboration. 

Twist will receive an upfront payment for each program entry. In addition, Twist has the potential to earn up to a total of $710 million in success-based clinical, regulatory and commercial milestone payments for the multiple target discovery programs.

Another notable partnership announced by Boehringer Ingelheim is in the fields of quantum computing and data science. 

In June, Boehringer Ingelheim became a founding member of the Quantum Technology and Application Consortium (QUTAC), which unites 10 of the leading German companies in exploring industrial applications for quantum computing. Experts say quantum computing holds enormous potential for pharmaceutical research and development, particularly for early research processes in which Boehringer Ingelheim has a high level of expertise. 

In April, Boehringer Ingelheim and The University of Texas MD Anderson Cancer Center today announced the extension and expansion of their joint Virtual Research and Development Center (VRDC) to explore new molecules from Boehringer Ingelheim’s KRAS (Kirsten rat sarcoma) and TRAILR2 (TNF-related apoptosis-inducing ligand receptor 2) portfolios for the potential treatment of lung cancer, particularly non-small cell lung cancer. 

According to executives, the collaboration, launched in 2019, has successfully combined MD Anderson’s innovative clinical research infrastructure and the patient-driven drug development capabilities of the Therapeutics Discovery division with Boehringer Ingelheim’s pipeline of innovative cancer medicines and expertise in advancing breakthrough therapies. Under the new agreement, joint research will continue for five additional years.

“Our collaboration with MD Anderson strengthens our determination to find solutions for the most difficult-to-treat cancers, and this latest commitment marks an important step forward, especially in our holistic KRAS program,” says Norbert Kraut, Ph.D., head of Global Cancer Research at Boehringer Ingelheim. “We are delighted to extend our collaboration with MD Anderson. With our shared dedication to patients and like-minded approach to innovation, we have the potential to bring the medicines to lung and gastrointestinal cancer patients that they so much need.”

Boehringer Ingelheim and the Lieber Institute for Brain Development (LIBD) in March announced a joint research and licensing collaboration focused on the development of novel centrally acting COMT (catechol-O-methyltransferase) inhibitors for the potential treatment of cognitive deficits in a spectrum of neuropsychiatric disorders, including schizophrenia. 

Aligning with a circuitry-based approach to precision psychiatry, the collaboration will leverage Boehringer Ingelheim’s deep experience in central nervous system (CNS) drug discovery and development alongside Lieber’s expertise in centrally acting COMT inhibitors. Executives say ultimately, the partnership will focus on advancing novel COMT inhibitor candidates into the clinic.

“Psychiatric disorders including cognitive impairment in schizophrenia have historically been difficult indications to treat and continue to remain areas of high unmet need,” says Dr. Hugh Marston, Ph.D., head of Department CNS Diseases Research at Boehringer Ingelheim. “This collaboration with the Lieber Institute further expands our innovative neuropsychiatric research program, a key focus area at Boehringer Ingelheim, with a first-in-class mechanism that may have the potential to address these symptoms. By combining our expertise, we hope to make significant steps forward to finding solutions for patients for which there currently is no treatment.”

Boehringer Ingelheim and Enara Bio in January announced that they have entered into a strategic collaboration and licensing agreement to research and develop novel targeted cancer immunotherapies, leveraging Enara Bio’s Dark Antigen discovery platform. 

According to company leaders, this collaboration combines Boehringer Ingelheim’s approach to tackle cancer through pairing leading science with innovative immune-oncology platforms, such as oncolytic viruses and cancer vaccines, with Enara Bio’s expertise in cancer antigen identification. The aim is to provide potential new therapies for patients with difficult to treat lung and gastrointestinal cancers. 

“We are excited to partner with Enara Bio as part of our mission to bring transformative new treatments to cancer patients,” says Jonathon Sedgwick, Ph.D., senior VP and global head, Cancer Immunology & Immune Modulation Research, Boehringer Ingelheim. “We are advancing a unique pipeline of cancer cell-directed agents, immuno-oncology therapies and intelligent combination approaches to help combat cancer. Enara Bio’s unique discovery platform offers a novel and highly differentiated approach that will allow us to look beyond the known proteome to identify and characterize Dark Antigens to support the development of T-Cell Receptor (TCR)-directed immunotherapies and therapeutic vaccines. We believe this is a highly innovative and promising approach to the development of the next wave of cancer immunotherapies.” 

Enara Bio’s proprietary Dark Antigen Platform Technology (EDAPT) will be used to discover and validate novel Dark Antigens in up to three tumor types in the lung and gastrointestinal cancer space. Executives say the discovery of shared antigens could lead to the development of vaccines that can be readily utilized to help a broader group of cancer patients.

Dark Antigens represent a new class of cancer-associated antigens that derive from the genomic dark matter, or the portion of the human genome that is normally not expressed as protein. Dark Antigen-encoding sequences are usually silenced in healthy cells but are activated and presented on tumor cells. They are associated with specific cancer types and, importantly, are shared across patients. Since they are typically not visible to the immune system, Dark Antigens represent a large potential repertoire of novel antigens that can be developed as targets for new immunotherapies.

In December 2020, Boehringer Ingelheim announced the signing of a binding agreement for acquiring all shares of NBE-Therapeutics, a private, clinical stage Swiss biotechnology company focused on antibody-drug conjugates and advancing targeted cancer therapies derived from its immune stimulatory iADC platform. 

NBE-Therapeutics’ lead compound, NBE-002, is in Phase I clinical studies for triple negative breast cancer and other solid tumors. Importantly, Boehringer Ingelheim gains access to an innovative and unique platform that it will use to build a leading ADC portfolio and develop potential combinations with other assets from its cancer immunology portfolio.

“NBE-Therapeutics’ iADC platform adds exceptional tumor targeting capabilities to our oncology portfolio. Together with our immune cell-targeting assets, this could enable new powerful combinations that will allow for efficacious and durable treatments for patients,” Pairet says. “This acquisition is a further example of Boehringer Ingelheim’s long-term strategy to enhance our position as an innovator of novel cancer therapies for patients in need. We welcome NBE-Therapeutics’ richly talented team to Boehringer Ingelheim and we look forward to collaborating with them on this important work.” 

The total transaction value is €1.18 billion and also includes contingent clinical and regulatory milestones.

Boehringer Ingelheim leaders state that the company’s cancer cell directed research is focused on the development of targeted therapies for the treatment of difficult-to-treat solid tumors. Inducing tumor cell death is a key component, and ADC based approaches have emerged as a powerful targeted therapy with potential for induction of immunogenic cell death at reduced systemic exposure and toxicity. 

Executives say the acquisition of NBE-Therapeutics will significantly strengthen Boehringer Ingelheim’s strategic focus on targeted cancer cell-directed therapies and complements existing capabilities in antigen discovery as well as antibody and T-cell engager technologies. By combining its world-class, in-house research and development with that of highly innovative biotechnology companies, Boehringer Ingelheim is developing innovative therapies and accelerating the delivery of the next generation of cancer treatments. This builds on recent strategic acquisitions and collaborations, including the acquisition of ViraTherapeutics and AMAL Therapeutics, which are additionally contributing assets.