European Biotechs Pushing the Frontiers in Immunotherapy

Cancer remains the leading cause of death worldwide. The approval of immune checkpoint inhibitors (ICIs), which target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and programmed cell death protein 1 (PD-1) receptors on T and B immune cells, has transformed the landscape of cancer treatment.1However, they are not effective against all cancers, have variable efficacy, and some patients may develop resistance to treatment.2

Researchers have identified several new targets that could overcome resistance and restore T-cell immune responses (Figure 1). These include B and T lymphocyte attenuator (BTLA), B7 homologue 3 protein (B7-H3), CD112R, also known as poliovirus receptor (PVR)-related Ig domain (PVRIG),glucocorticoids-induced TNF receptor family-related protein (GITR), inducible co-stimulatory receptor (ICOS), indoleamine 2,3-dioxygenase 1 (IDO-1), natural killer (NK) group 2A (NKG2A), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin and mucin-containing protein-3 (TIM-3), and V-domain Ig suppressor of T cell activation (VISTA).3These findings have paved the way for potential new treatments to be used as monotherapies or, more likely, in combination with existing ICIs.4

There has been significant progress in understanding how cells evade the immune system.3 Researchers at Lund University, Sweden, have discovered a new immune evasion mechanism regulated by signaling lymphocytic activation molecule 6 (SLAMF6, also known as Ly108).6 SLAMF6 receptors are primarily expressed on progenitor or stem-like exhausted T cells and show both activating and inhibitory functions, which could be effectively utilized in immunotherapy.6 Preliminary data with SLAMF6-targeting monoclonal antibodies (mAbs) have demonstrated improvements in the functional integrity of T cells in vivo and in mouse models; this is a vital finding, because ICI blockade can cause T cell exhaustion.7,8,9

What ICI Therapies Are the Pharma Industry Investing In?

Many large pharmaceutical companies have invested in this area. Leading commercial products include Merck & Co’s Keytruda (pembrolizumab), Bristol-Myers Squibb's (BMS) Opdivo (nivolumab), Roche/Genentech’s Tecentriq (atezolizumab), and AstraZeneca’s Imfinzi (durvalumab), which together represent the majority share of global ICI revenues.5Leading pharma firms continue to expand their oncology pipelines and have formed strategic collaborations and acquisitions to access new ICIs. For example, BioNTech acquired Biotheus to gain full global rights to BNT327/PM8002 (PD-L1 × VEGF-A bispecific) and has since established a global strategic partnership with BMS to co-develop and co-commercialize BNT327.10,11In October 2024, AbbVie and EvolveImmune Therapeutics signed a collaboration and option-to-license agreement to develop multispecific T cell-engaging antibodies in oncology.12

What Are Some European Players to Watch Out for in the ICI Space?

Several European biotechs are evaluating next-generation ICIs that target a variety of pathways (Table I).

BioNTech (Germany) is a global biotechnology company that has developed a comprehensive oncology portfolio comprising three therapeutic modalities: mRNA cancer immunotherapies; next-generation immunomodulators, such as antibody-drug conjugates (ADCs) and chimeric antigen receptor (CAR) T cell therapies; and targeted therapies. The company is developing a range of immunomodulators, including gotistobart (optimised Fc anti-CTLA4), pumitamig (anti PD-L1/anti VEGF A), BNT314 (anti 4-1BB/anti-EpCAM), BNT317 (anti-PD-1/CD39), and BNT3213 (anti-TIGHT/OVRIG) bi-specific antibodies.13 It is also evaluating HER2, TROP2, B7H3, HER3, EGFRxHER3, and ADCs as combination partners for cancer therapies. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including BMS, Duality Biologics, Fosun Pharma, Genentech, Genmab, MediLink, OncoC4, Pfizer, and Regeneron.13

GenMab (Denmark) is an international biotechnology company established in 1999. It has developed a broad range of antibody-based therapeutic formats, including bispecific antibodies, ADCs, immune-modulating antibodies, and other next-generation modalities. It has a strategic focus on novel drug combinations, including ICIs with immunomodulators, such as TIGIT and LAG-3. In 2025, it terminated development of acasunlimab, a PD-L1x4-1BB bispecific antibody; BioNTech withdrew from its development in August 2024. 14,15Meanwhile, in September 2025, Genmab acquired Merus for approximately US$8 billion to expand its late-stage pipeline, gaining access to petosemtamab, an EGFRxLGR5 bispecific antibody in phase 3 for head and neck cancer and MCLA‑145, a bispecific antibody targeting CD137 and PD-1/PD-L1 for solid tumours.16,17

Innate Pharma SA (France) is a global clinical-stage oncology-focused biotech company. It is pioneering NK cell checkpoint modulators and monalizumab, an anti-NKG2A antibody, in collaboration with AstraZeneca, in non-small cell lung cancer.18Innate Pharma has also established a collaboration with Sanofi, as well as renowned academic and research institutions, to advance innovation in immuno-oncology. 19

Lead Biologics (Switzerland) was founded in 2022 by Thoas Fioretos, MD, PhD, Niklas Landberg, MD, PhD, Carl Sandén, PhD, and Kjell Sjöström, MSc, a life science entrepreneur and founder of Innovagen AB. The company has raised US$770,000 from Seed Venture Capitalists.20 It is currently evaluating several mAbs that target different ICI pathways, including LB01, which targets SLAMF6, T-cell mediated elimination of cancer cells for the treatment of leukaemia and solid tumours; LB02, which targets C3AR, which is located on leukemic stem cells; and LB03, which targets SIRPα-CD47, which is important in the regulation of macrophage function.21In 2025, the company published a study showing that LB01 inhibits a previously unknown immune escape mechanism and eliminates acute myeloid leukaemia (AML) cells in advanced experimental models.7,8 Based on the promising results, clinical trials are expected to start within 2 to 3 years.21 The company has forged strategic partnerships with Lunds University, Medicon Village, RISE, SciLife Lab, Smile Venture Hub, and Vinnova to drive the development of its pipeline products.

Future Opportunities in ICI Development

Over the past decade, significant progress has been made in cancer immunotherapy, including ICIs and CAR T-cell therapy, leading to improved management of various cancers.22Treatment continues to advance as innovative biotech companies explore new ICI pathways that can enhance and combine the effects of existing therapies.23 The global ICI market was valued at US$42.3 billion in 2024 and is expected to reach US$49.7 billion in 2025, expanding further to US$156.5 billion by 2033, with a compound annual growth rate of 15.4% from 2025 to 2033. The increasing global cancer burden will drive this robust growth, with more ICI approvals across different tumour types and earlier treatment lines, higher adoption of combination therapies, and broader access to treatments in emerging markets.1Many large pharmaceutical companies, including AstraZeneca, BMS, Genentech, Merck & Co., Roche, and Sanofi, have already made significant investments in this area. Innovative European biotech firms such as BioNTech, GenMab, Innate Pharma SA, and Lead Biologics have been quick to capitalise on investor interest, enabling them to explore new targets that could be used as monotherapies or in combination with approved therapies to improve clinical outcomes in a broader range of cancers.

References

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7. Li B; Zhong MC; Galindo CC; et al. SLAMF6 as a drug-targetable suppressor of T cell immunity against cancer. Nature. 2026.
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10. BioNtech. BioNTech to acquire Biotheus to boost oncology strategy. Press Release. November 13, 2025.
11. Bristol Myers Squibb. BioNTech and Bristol Myers Squibb announce global strategic partnership to co-develop and co-commercialize next-generation bispecific antibody candidate BNT327 broadly for multiple solid tumour types. Press Release. June 2, 2025.
12. AbbVie. AbbVie and EvolveImmune Therapeutics announce collaboration and option-to-license agreement to develop next-generation cancer biotherapeutics. Press Release. October 31, 2024.
13. BioNTech. Q2 2025 BNTX Presentation. Company Presentation. November 11, 2025.
14. Genmab A/S. Genmab Portfolio Prioritization Update. Press Release. December 29, 2025.
15. Genmab A/S. Genmab Takes Full Control of Acasunlimab Development Program. Press Release. August 5, 2024.
16. Genmab A/S. Genmab to Acquire Merus, Expanding Late-Stage Pipeline and Accelerating into a Wholly Owned Model. Press Release. September 29, 2025.
17. Mittag D; Laus G; Yan C; et al. Phase I study of MCLA-145, a bispecific antibody targeting CD137 and PD-L1, in solid tumors, as monotherapy or in combination with pembrolizumab. Journal of Clinical Oncology, 2024;42(16), 2520.
18. Innate Pharma. 2026 Financial Calendar. Press Release. December 11, 2025.
19. Innate Pharma. Innate Pharma announces €15m investment by Sanofi. Press Release. April 24, 2025.
20. CREATE Health. Spin-off companies. December 2, 2025.
21. Lead Biologics, Science. (accessed March 4, 2026).
22. Rebaudi F; De Franco F; Goda R; et al. The landscape of combining immune checkpoint inhibitors with novel Therapies: Secret alliances against breast cancer. Cancer Treat Rev. 2024;130:102831.
23. Park CL and Bedard PL. Moving the needle on immune checkpoint inhibitors with novel targets: are we being TIMid or LAGging behind?, The Oncologist, 2025;30,7.oyaf145.

About the author

Cheryl Barton, PhD, is founder and director of PharmaVision, Pharmavision.co.uk.