Healthcare

Patients are at the center of all our research and development efforts. We are committed to innovation in science to bring more medicines to more patients, faster. We will continue our internal discovery engine, while more than 50% of future launches are expected to result from external co-development partnerships and strategic in-licensing of assets. In 2024, our Healthcare business devoted roughly 17.8% of total sales to R&D activities aimed at discovering and developing new therapies.

Oncology

In Oncology, our scientific curiosity and dedication to patients are at the heart of our efforts to improve the lives of people living with cancer. As a key focus area within our R&D portfolio, we are dedicated to delivering transformative treatments. Translational research is integrated throughout the entire R&D process, with several projects addressing unmet needs in difficult-to-treat cancers through innovative treatment approaches and novel combinations.

Marketed therapies

We are committed to setting new standards of care for multiple tumor types and making the corresponding therapies accessible to as many patients as possible globally. Therefore, in 2024, we continued to explore the impact of our marketed therapies by continuously analyzing data from our pivotal studies and generating real-world evidence. Additionally, we are evaluating these treatments in new clinical settings to allow more cancer patients to partake in their potential benefits.

To date, Bavencio^® (avelumab), an anti-PD-L1 antibody, has been approved in over 70 countries as a first-line maintenance treatment for locally advanced or metastatic urothelial carcinoma (UC) in adult patients whose disease has not progressed following platinum-based chemotherapy. New analyses presented at congresses throughout 2024 continued to strengthen the robust evidence supporting its use in this setting. This includes data from the pivotal Phase III JAVELIN Bladder 100 study shared at the 2024 American Society of Clinical Oncology (ASCO^®) Annual Meeting, confirming the benefit of Bavencio^® in key subgroups of patients with advanced urothelial carcinoma that has not progressed on platinum-based chemotherapy, including those who have low tumor burden and those with mixed histologic subtypes.

In addition, findings from long-term responders in JAVELIN Bladder 100 treated with Bavencio^® plus best supportive care for ≥1 year and ≥2 years were presented at the European Society for Medical Oncology (ESMO) Congress. Further analyses from Japan and France presented at the ESMO Congress added to the extensive real-world evidence of Bavencio^® as a maintenance treatment, demonstrating that the clinical trial outcomes can be translated into real-world practice across a range of settings and geographies.

In the Phase II JAVELIN Bladder Medley study, we are continuing to evaluate whether optimizing first-line maintenance treatment by combining a novel therapy with avelumab could further improve outcomes for patients with advanced UC whose disease did not progress following first-line platinum-based chemotherapy. Initiated in 2022, this randomized umbrella study assesses avelumab monotherapy versus avelumab in combination with our investigational anti-TIGIT antibody (M6223), avelumab in combination with Nektar Therapeutics’ interleukin-15 (IL-15) receptor agonist (NKTR-255) and avelumab in combination with Gilead Sciences’ Trodelvy^®.

Bavencio^® is also approved as a monotherapy for the treatment of metastatic Merkel cell carcinoma (MCC) in 63 countries. Additionally, Bavencio^® is approved for the treatment of advanced renal cell carcinoma (RCC) in combination with axitinib in 60 countries.

Tepmetko^®

In February 2024, the U.S. Food and Drug Administration (FDA) granted full approval to the oral MET inhibitor Tepmetko^® (tepotinib) for adult patients with metastatic METex14-skipping non-small-cell lung cancer (NSCLC). The conversion from accelerated to full approval was based on the VISION study, which encompassed 161 further patients and was presented at the 2024 ASCO^® Annual Meeting as well as a follow-up spanning an additional 28 months to assess duration of response.

In 2024, we presented further data on health-related quality of life (HRQoL) in patients treated with Tepmetko^®. Data from the Phase II VISION study showed that patients with METex14-skipping NSCLC with brain, liver, adrenal, or bone metastases maintained stable HRQoL during treatment with Tepmetko^® with improvements in symptoms, such as coughing, that were consistent with results for the overall population.

In August 2024, the Phase II INSIGHT 2 primary analysis manuscript was published in The Lancet Oncology, showing that tepotinib combined with osimertinib offered promising clinical benefit with a manageable safety profile in patients with EGFR-mutated NSCLC whose disease had progressed on first-line osimertinib and had experienced MET amplification.

Novel medicines

In 2024 we made significant progress in advancing our novel medicines, including our antibody-drug conjugates (ADC) discovered in-house and assets from our portfolio of DNA damage response (DDR) inhibitors.

At the 2024 ASCO^® Annual Meeting, we presented first-in-human data for M9140, an investigational ADC targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) that features a novel exatecan payload. This is the first ADC developed in our labs to enter clinical development. Data from 40 patients treated across seven dose levels in Part 1A of the study demonstrated encouraging clinical activity with a manageable and predictable safety profile in this population. Updated results, including biomarker analyses, were presented at the ESMO Congress 2024. M9140 entered the randomized dose optimization part of the study for metastatic colorectal cancer in 2024, with further explorative analyses in patients with CEACAM5-expressing tumors including gastric, pancreatic and NSCLC to start in 2025.

We also advanced M3554, our GD2 (disialoganglioside expressed on tumors)-targeted ADC from our platform, into clinical development, with the first-in-human study beginning in November 2024.

Within our DDR portfolio, we are continuing to advance the development of tuvusertib (M1774), our potent and selective inhibitor of ataxia telangiectasia and Rad3-related (ATR), and M9466, the selective PARP1 (poly ADP-ribose polymerase 1) inhibitor licensed from Jiangsu Hengrui Pharmaceuticals Co. Ltd in 2023, opening new studies in 2024 to explore the potential of these medicines in different tumors. The Phase II DDRiver EOC 302 study evaluates tuvusertib in combination with our ataxia telangiectasia-mutated (ATM) inhibitor, lartesertib, or with niraparib, a PARP inhibitor, in PARP-resistant ovarian cancer. For M9466, we opened the Phase I DDRiver 501 study, exploring M9466 in combination with tuvusertib in solid tumors with relevant mutations and/or prior PARP inhibitor exposure, with a focus on castration-resistant prostate and ovarian cancers. Additionally, the DDRiver 511 study was initiated, combining M9466 with FOLFIRI chemotherapy.

Throughout the year, we have presented several abstracts at congresses that form the foundation of Phase II combination studies of tuvusertib. These included data from the Phase Ib DDRiver Solid Tumors 320 study evaluating tuvusertib in combination with lartesertib or our immune checkpoint inhibitor Bavencio^®, which were first presented at the ASCO^® Annual Meeting 2024. The findings confirm that both DDRi assets are well positioned for the development of combinations in therapeutic areas in which we have experience. At the 2024 ASCO^® Annual Meeting, we shared findings from Part B1 of the Phase I DDRiver Solid Tumors 301 study, which demonstrated a manageable safety profile and preliminary efficacy for different dosing regimens of tuvusertib in combination with niraparib, a PARP inhibitor, in patients with advanced solid tumors. We shared additional data from this study with translational, pharmacokinetic, pharmacodynamic, and immunophenotyping analyses at ESMO 2024.

In June, we announced the discontinuation of the randomized Phase III TrilynX^® study evaluating xevinapant plus chemoradiotherapy (CRT) in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). The decision followed a pre-planned interim analysis performed by the study’s Independent Data Monitoring Committee, which found that the trial would be unlikely to meet its primary objective of prolonging event-free survival. The company also discontinued the Phase III XRay Vision^® study of xevinapant versus placebo in combination with adjuvant, post-operative radiotherapy in patients with resected LA SCCHN.

In November, our partners at Abbisko Therapeutics Co. Ltd., Shanghai, China, announced that Abbisko’s investigational treatment for tenosynovial giant cell tumor (TGCT), pimicotinib, significantly improved objective response rate (ORR) compared to placebo in the Abbisko-led pivotal Phase III MANEUVER study, meeting its primary endpoint. We entered into a licensing agreement with Abbisko in December 2023, granting us an exclusive license to commercialize products comprising or containing pimicotinib for all indications in mainland China, Hong Kong, Macau, and Taiwan, as well as an exclusive option for global commercial rights of pimicotinib.

Building on our expertise in the treatment of colorectal cancer (CRC), in January we announced a licensing agreement with Inspirna, Inc. for the development and commercialization of ompenaclid, a potentially first-in-class oral inhibitor of the creatine transport channel SLC6A8 and SLC6A8-targeting follow-on compounds outside of the United States. Ompenaclid is currently being evaluated by Inspirna in a Phase II study for the second-line treatment of RAS-mutated (RASmut) advanced or metastatic CRC.

Neurology & Immunology

We have been committed to people living with multiple sclerosis (MS) for more than 25 years. Our ongoing dedication to science drives us to continue to push the boundaries of knowledge through our research in neurological and immune-mediated disease areas.

Beyond MS, we are continuing to expand the therapeutic focus areas of our Neurology & Immunology franchise by developing potential first-in-class treatments for conditions with high unmet medical needs. We have a pipeline focusing on discovering new therapies that have potential in other neuroinflammatory and immune-mediated diseases, including systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE) and generalized myasthenia gravis (gMG).

Enpatoran, an investigational highly specific potential first-in-class immune modulator, is being developed as a new investigational oral therapy for SLE and CLE in a Phase II study. It aims to overcome limitations of currently available lupus therapies by providing selective inhibition of Toll-like-receptors (TLR) 7 and 8, that are known as key lupus-relevant disease drivers, which may increase efficacy while preserving immunity against infections. Analysis from the CLE cohort of a Phase II study indicates that enpatoran met the primary endpoint with a good safety profile. We anticipate Phase II results for enpatoran in systemic lupus in early 2025, which would then complete the data.

We are also exploring the potential of cladribine capsules for the treatment of gMG, which affects an estimated 700,000 people worldwide and where a high unmet need remains, particularly with regard to oral treatment options. Cladribine is expected to selectively target B and T lymphocytes, which are thought to be the root cause of gMG. In June 2023, the FDA granted orphan drug designation for cladribine capsules for the treatment of gMG. We began a global Phase III clinical trial program in June 2024.

In 2024, we also presented new data from our portfolio in MS at numerous scientific meetings, including the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum in February, the Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting in May and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in September.

At ACTRIMS, we presented two new post-hoc analyses from the M AGNIFY-MS clinical program. The first presentation suggested the potential of Mavenclad^® to maintain or improve cognitive function in patients with highly active relapsing multiple sclerosis (RMS). Additionally, the second presentation with interim findings from year three of the M AGNIFY-MS extension trial underscored the continued efficacy and safety profile of Mavenclad^® following the completion of the two-year treatment course.

At ECTRIMS, we showcased data on the long-term safety profile, sustained efficacy, and durable effect of Mavenclad^® in RMS with 40 abstracts and two oral presentations. Mavenclad^® data from several M AGNIFY-MS sub-studies demonstrate the benefits of early treatment and the drug’s sustained efficacy across multiple measures of disease activity, such as its impact on both peripheral and central inflammation, on promoting immune cell reconstitution effects and on disability progression, including freedom from progression independent of relapse activity for most patients.

Building on data presented at the 2024 CMSC Annual Meeting, which showed that Mavenclad^® can reduce or eliminate oligoclonal bands in the cerebrospinal fluid, additional data presented at ECTRIMS suggested that immune reconstitution following treatment with Mavenclad^® may shift the immune system to a less pathogenic state.

Fertility

As a global market leader in fertility drugs and treatments, our Fertility franchise plays a crucial role in our Healthcare business. Infertility is a growing challenge globally due to demographic change and lifestyle adjustments such as delayed childbearing.

According to the latest data, more than six million babies have been born worldwide with the help of Gonal-f^®, a leading therapeutic within our Fertility portfolio. It contains the active ingredient follitropin alfa (r-hFSH alfa), which is a recombinant form of the natural hormone FSH and is available in a convenient and ready-to-use pre-filled injection pen. Treatment with Gonal-f^® can result in increased follicles, oocytes and embryos compared with urinary gonadotropins, thereby improving the chances of pregnancy and live birth. Recent real-world evidence studies based on key European registries (D.I.R., SNDS) showed increased likelihood of live birth with Gonal-f^® compared with urinary gonadotropins and biosimilar preparations of follitropin alfa.

Cardiovascular, Metabolism & Endocrinology

Chronic diseases such as diabetes, prediabetes, hypertension and cardiovascular disease, growth hormone disorders, and thyroid disorders are having a significant and growing impact on health and society in the 21^st century. In view of this development, we are committed to helping patients living with these conditions.

The new formulation of Euthyrox^® (levothyroxine) for the treatment of hypothyroidism obtained further regulatory approvals in 2024 and is available in more than 90 countries where this incremental innovation is registered. With its characteristics of delivering precise, fine-tuned, and stable natural thyroid hormone thyroxine doses due to the tightened specification, Euthyrox^® may help optimize disease management.

Glucophage^®, containing the active ingredient metformin, is the most widely prescribed non-insulin diabetes treatment worldwide for first-line treatment of type 2 diabetes. We are continuing to deploy our strategy on the early stages of the diabetes continuum, taking advantage of the fact that Glucophage^® is now approved in more than 80 countries.

Our pipeline