Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 988 |
| INN | Tozorakimab |
| Status | Clinical |
| Drug code(s) | MEDI3506 |
| Brand name | None |
| mAb sequence source | mAb human |
| General Molecular Category | Naked monospecific |
| Format, general category | Full length Ab |
| Format details | None |
| Isotype (Fc) | IgG1 |
| Light chain isotype | lambda |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | None |
| Target(s) | IL-33 |
| Indications of clinical studies | Acute respiratory failure, Chronic Obstructive Pulmonary Disease/Chronic bronchitis. COVID-19, Atopic dermatitis, diabetic kidney disease, Phase 1 in Healthy Adult Subjects With a History of Mild Atopy and as Multiple Ascending Doses in Subjects COPD |
| Primary therapeutic area | Respiratory diseases |
| Most advanced stage of development (global) | Phase 3 |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | May 15, 2017 |
| Start of Phase 2 | November 18, 2019 |
| Start of Phase 3 | January 04, 2022 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | AstraZeneca |
| Licensee/Partner | None |
| Comments about company or candidate | Sep 2024: Primary endpoint missed in the phase 2 FRONTIER-4 study; data presented at the European Respiratory Society 2024 Congress in Vienna, Austria. NCT06040086 Phase 3 in Chronic Obstructive Pulmonary Disease started in Sep 2023. Phase 3 studies for Chronic obstructive pulmonary disease (NCT05166889, NCT05158387, NCT05742802) are recruiting as of May-June 2023; Acute respiratory failure (NCT05624450) is recruiting as of March 10, 2023. Fast track designation for acute respiratory failure. NCT05624450 Phase 3 in Acute Respiratory Failure started in Dec 2022. NCT05166889 Phase 3 in COPD started in Jan 2022; NCT05742802 Phase 3 to start in Feb 2023. NCT04570657 Phase 2 in asthma started in Sep 2020. Phase-II clinical trials in COVID-2019 infections in United Kingdom (IV) (EudraCT2020-001736-95). NCT04170543 Phase 2 in Diabetic Kidney Disease recruiting as of Nov 20, 2019. Listed in AZ pipeline dated July 25, 2019. NCT03096795 Phase 1 study Suspended (Pending protocol amendment) as of January 2018, but recruiting as of Aug 2018 |
| Full address of company | Cambridge, United Kingdom Europe United Kingdom https://www.astrazeneca.com/our-company/contact-us.html |
We describe the identification of tozorakimab (MEDI3506), a potent, human anti-IL-33 monoclonal antibody, which can inhibit reduced IL-33 (IL-33red) and oxidized IL-33 (IL-33ox) activities through distinct serum-stimulated 2 (ST2) and receptor for advanced glycation end products/epidermal growth factor receptor (RAGE/EGFR complex) signalling pathways. We hypothesized that a therapeutic antibody would require an affinity higher than that of ST2 for IL-33, with an association rate greater than 107 M-1 s-1, to effectively neutralize IL-33 following rapid release from damaged tissue. An innovative antibody generation campaign identified tozorakimab, an antibody with a femtomolar affinity for IL-33red and a fast association rate (8.5 × 107 M-1 s-1), which was comparable to soluble ST2. Sci Rep. 2023 Jun 17;13(1):9825. doi: 10.1038/s41598-023-36642-y. IgG1 lambda2
| Anticipated events | Marketing application possible for acute respiratory failure in 2025+ |
| Factor(s) contributing to discontinuation | None |