tozorakimab

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Ligands
tozorakimab

GtoPdb Ligand ID: 12964

Synonyms: MEDI-3506 | MEDI3506

Compound class: Antibody

Comment: Tozorakimab (MEDI3506) is a high-affinity anti-IL-33 monoclonal antibody. It inhibits IL-33-induced signalling to produce a anti-inflammatory effects [3]. Tozorakimab blocks the actions of both reduced IL-33 (IL-33^red) and oxidized IL-33 (IL-33^ox) metabolites through their respective downstream pathways (ST2 for IL-33^red, RAGE/EGFR complex for IL-33^ox) [1,7,9]. Activation of the RAGE/EGFR signaling cascade affects mucus production, which is a known driver of both disease exacerbations, and epithelial pathogenesis in COPD patients [8].

References
1. Cohen ES, Scott IC, Majithiya JB, Rapley L, Kemp BP, England E, Rees DG, Overed-Sayer CL, Woods J, Bond NJ et al.. (2015) Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation. Nat Commun, 6: 8327. [PMID:26365875]
2. Corren J, Reid F, Moate R, Jimenez E, Sadiq MW, Williams A, Rytelewski M, Cameron-Christie S, Muthas D, Georgi B et al.. (2026) FRONTIER-3: a randomised phase 2a study to investigate tozorakimab, an anti-interleukin-33 monoclonal antibody, in early-onset asthma. ERJ Open Res, 12 (1). [PMID:41736737]
3. England E, Rees DG, Scott IC, Carmen S, Chan DTY, Chaillan Huntington CE, Houslay KF, Erngren T, Penney M, Majithiya JB et al.. (2023) Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction. Sci Rep, 13 (1): 9825. [PMID:37330528]
4. Reid F, Singh D, Albayaty M, Moate R, Jimenez E, Sadiq MW, Howe D, Gavala M, Killick H, Williams A et al.. (2024) A Randomized Phase I Study of the Anti-Interleukin-33 Antibody Tozorakimab in Healthy Adults and Patients With Chronic Obstructive Pulmonary Disease. Clin Pharmacol Ther, 115 (3): 565-575. [PMID:38115209]
5. Silverberg JI, Mustapa MN, Reid F, Lei A, Smith R, Moate R, Kelly A, Chen R, Gavala M, Jimenez E et al.. (2025) Efficacy and safety of tozorakimab in moderate-to-severe atopic dermatitis: A Phase 2a randomized controlled trial (FRONTIER-2). J Eur Acad Dermatol Venereol, 39 (6): 1126-1133. [PMID:39535462]
6. Singh D, Guller P, Reid F, Doffman S, Seppälä U, Psallidas I, Moate R, Smith R, Kiraga J, Jimenez E et al.. (2025) A phase 2a trial of the IL-33 monoclonal antibody tozorakimab in patients with COPD: FRONTIER-4. Eur Respir J, 66 (1). [PMID:40154559]
7. Strickson S, Houslay KF, Negri VA, Ohne Y, Ottosson T, Dodd RB, Chaillan Huntington C, Li J, Killick H, Rees DG et al.. (2022) Oxidised IL-33 signals via RAGE/EGFR to drive a COPD-associated phenotype. European Respiratory Journal, 60: 2482. DOI: 10.1183/13993003.congress-2022.2482
8. Strickson S, Houslay KF, Negri VA, Ohne Y, Ottosson T, Dodd RB, Huntington CC, Baker T, Li J, Stephenson KE et al.. (2023) Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex. Eur Respir J, 62 (3). [PMID:37442582]
9. Tominaga S. (1989) A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor. FEBS Lett, 258 (2): 301-4. [PMID:2532153]
10. Wilkinson T, Dixon R, Page C, Carroll M, Griffiths G, Ho LP, De Soyza A, Felton T, Lewis KE, Phekoo K et al.. (2020) ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial. Trials, 21 (1): 691. [PMID:32736596]

References

1. Cohen ES, Scott IC, Majithiya JB, Rapley L, Kemp BP, England E, Rees DG, Overed-Sayer CL, Woods J, Bond NJ et al.. (2015)
Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation.
Nat Commun, 6: 8327. [PMID:26365875]

2. Corren J, Reid F, Moate R, Jimenez E, Sadiq MW, Williams A, Rytelewski M, Cameron-Christie S, Muthas D, Georgi B et al.. (2026)
FRONTIER-3: a randomised phase 2a study to investigate tozorakimab, an anti-interleukin-33 monoclonal antibody, in early-onset asthma.
ERJ Open Res, 12 (1). [PMID:41736737]

3. England E, Rees DG, Scott IC, Carmen S, Chan DTY, Chaillan Huntington CE, Houslay KF, Erngren T, Penney M, Majithiya JB et al.. (2023)
Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction.
Sci Rep, 13 (1): 9825. [PMID:37330528]

4. Reid F, Singh D, Albayaty M, Moate R, Jimenez E, Sadiq MW, Howe D, Gavala M, Killick H, Williams A et al.. (2024)
A Randomized Phase I Study of the Anti-Interleukin-33 Antibody Tozorakimab in Healthy Adults and Patients With Chronic Obstructive Pulmonary Disease.
Clin Pharmacol Ther, 115 (3): 565-575. [PMID:38115209]

5. Silverberg JI, Mustapa MN, Reid F, Lei A, Smith R, Moate R, Kelly A, Chen R, Gavala M, Jimenez E et al.. (2025)
Efficacy and safety of tozorakimab in moderate-to-severe atopic dermatitis: A Phase 2a randomized controlled trial (FRONTIER-2).
J Eur Acad Dermatol Venereol, 39 (6): 1126-1133. [PMID:39535462]

6. Singh D, Guller P, Reid F, Doffman S, Seppälä U, Psallidas I, Moate R, Smith R, Kiraga J, Jimenez E et al.. (2025)
A phase 2a trial of the IL-33 monoclonal antibody tozorakimab in patients with COPD: FRONTIER-4.
Eur Respir J, 66 (1). [PMID:40154559]

7. Strickson S, Houslay KF, Negri VA, Ohne Y, Ottosson T, Dodd RB, Chaillan Huntington C, Li J, Killick H, Rees DG et al.. (2022)
Oxidised IL-33 signals via RAGE/EGFR to drive a COPD-associated phenotype.
European Respiratory Journal, 60: 2482. DOI: 10.1183/13993003.congress-2022.2482

8. Strickson S, Houslay KF, Negri VA, Ohne Y, Ottosson T, Dodd RB, Huntington CC, Baker T, Li J, Stephenson KE et al.. (2023)
Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex.
Eur Respir J, 62 (3). [PMID:37442582]

9. Tominaga S. (1989)
A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor.
FEBS Lett, 258 (2): 301-4. [PMID:2532153]

10. Wilkinson T, Dixon R, Page C, Carroll M, Griffiths G, Ho LP, De Soyza A, Felton T, Lewis KE, Phekoo K et al.. (2020)
ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial.
Trials, 21 (1): 691. [PMID:32736596]