THE SCIENCE
Revolutionizing immunotherapy through Nanobody® technology

Nanobodies® represent a new generation of antibody-derived targeted therapies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies (VHH).
Nanobodies® have a number of potential advantages over traditional antibodies, including their small size, enhanced tissue penetration, resistance to temperature changes, ease of manufacturing, and the ability to design multivalent therapeutic molecules with bespoke target combinations.
Sonelokimab is a novel ~40 kDa humanized Nanobody® consisting of three VHH domains covalently linked by flexible spacers. With two domains, sonelokimab selectively binds with high affinity to IL-17A and IL-17F, thereby inhibiting the naturally occurring IL-17A/A, IL‑17A/F, and IL-17F/F dimers that are central drivers of inflammatory disease. A third central domain binds to human albumin, facilitating further enrichment of sonelokimab at sites of inflammatory edema.
Sonelokimab is designed to more directly target sites of inflammation and penetrate difficult-to-reach inflamed tissues by synergistically combining the power of Nanobody® technology with optimized inhibition of the IL-17 inflammatory pathway to move the clinical paradigm beyond traditional antibodies.
The terms Nanobody® and Nanobodies® are trademarks of Ablynx, a Sanofi company. Sonelokimab is not yet approved for use in any indication.
References: Papp KA, et al. Lancet. 2021; 397:1564-1575; Svecova D. J Am Acad Dermatol. 2019;81:196–203
1. Jovcevska I, Muyldermans S. The Therapeutic Potential of Nanobodies. BioDrugs. 2020;34(1):11–26.
2. Coppieters K, Dreier T, Silence K, et al. Formatted anti-tumor necrosis factor alpha VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen-induced arthritis. Arthritis Rheum. 2006;54(6):1856–1866.
3. Tijink BM, Laeremans T, Budde M, et al. Improved tumor targeting of anti-epidermal growth factor receptor Nanobodies through albumin binding: taking advantage of modular Nanobody technology. Mol Cancer Ther. 2008;7(8):2288–2297.
4. Sun S, Ding Z, Yang X, et al. Nanobody: A Small Antibody with Big Implications for Tumor Therapeutic Strategy. Int J Nanomedicine. 2021;16:2337–2356.
5. Papp KA, Weinberg MA, Morris A, Reich K. IL17A/F nanobody sonelokimab in patients with plaque psoriasis: a multicentre, randomised, placebo-controlled, phase 2b study. Lancet. 2021;397(10284):1564–1575.
6. Svecova D, Lubell MW, Casset-Semanaz F, Mackenzie H, Grenningloh R, Krueger JG. A randomized, double-blind, placebo-controlled phase 1 study of multiple ascending doses of subcutaneous M1095, an anti-interleukin 17A/F nanobody, in moderate-to-severe psoriasis. J Am Acad Dermatol. 2019;81(1):196–203.
7. Durham LE, Kirkham BW, Taams LS. Contribution of the IL-17 Pathway to Psoriasis and Psoriatic Arthritis. Curr Rheumatol Rep. 2015;17(8):55.
8. Taams LS, Steel KJA, Srenathan U, Burns LA, Kirkham BW. IL-17 in the immunopathogenesis of spondyloarthritis. Nat Rev Rheumatol. 2018;14(8):453–466.
9. Fletcher JM, Moran B, Petrasca A, Smith CM. IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa. Clin Exp Immunol. 2020;201(2):121–134.
10. Sleep D. Albumin and its application in drug delivery. Expert Opin Drug Deliv. 2015;12(5):793–812.
11. Cheloha RW, Harmand TJ, Wijne C, Schwartz TU, Ploegh HL. Exploring cellular biochemistry with nanobodies. J Biol Chem. 2020;295(45):15307–15327.
12. Wunder A, Muller-Ladner U, Stelzer EH, et al. Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. J Immunol. 2003;170(9):4793–4801.
13. Goepfert A, Lehmann S, Wirth E, Rondeau JM. The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties. Sci Rep. 2017;7(1):8906.
14. Wright JF, Bennett F, Li B, et al. The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. J Immunol. 2008;181(4):2799–2805.
15. Acelyrin. Our Pipeline: Izokibep. 2022. https://acelyrin.com/our-pipeline [Accessed February 2022].
16. Liu L, Lu J, Allan BW, et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J inflamm Res. 2016;9:39–50.
17. Kolbinger F, Di Padova F, Deodhar A, et al. Secukinumab for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis: Physical and pharmacological properties underlie the observed clinical efficacy and safety. Pharmacol Ther. 2022;229:107925.