APG777: A Promising Breakthrough in IL-13 Targeted Therapy

Interleukin-13 (IL-13) is a pivotal T helper type 2 (Th2) cytokine implicated in the development of atopic dermatitis, asthma, and various inflammatory conditions. APG777 (Apogee Therapeutics), a humanized IgG1 monoclonal antibody, specifically engineered to bind with high affinity to IL-13, holds promise in interrupting downstream inflammatory signaling. With a unique amino acid modification in its Fc region, APG777 demonstrates an extended half-life in nonhuman primates, potentially revolutionizing treatment approaches.

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Data was presented in the poster session “APG777, a high-affinity humanized IgG1 mAb targeting IL-13, demonstrates prolonged half-life in non-human primates” at the 2023 Fall Clinical Dermatology Conference in Las Vegas, Nevada October 19-22.

Study Materials and Methods

The pharmacokinetics of APG777 and a monoclonal antibody analogous to lebrikizumab were evaluated in female cynomolgus monkeys. A single bolus dose of 3 mg/kg was administered via both intravenous (IV) and subcutaneous (SC) routes. Blood samples were collected serially over a span of 2160 hours post-dose.

Results

APG777 exhibited a striking average half-life (t1/2) of 27.6 days and a clearance (Cl) rate of 1.45 (mL/day/kg) in nonhuman primates. In comparison, lebrikizumab demonstrated an average t1/2 of 18.0 days and a Cl rate of 2.93 (mL/day/kg) in the same population. Notably, APG777 showed a high level of absorption, with a subcutaneous bioavailability (F) of 81.22%, and a Volume of Distribution at steady-state (Vss) of 55.65 (mL/kg). Lebrikizumab displayed similar strong absorption characteristics, with an F of 75.70% and a Vss of 52.10 (mL/kg).

Conclusions

The exceptional pharmacokinetic profile of APG777, characterized by an extended half-life, increased exposure, and reduced clearance compared to lebrikizumab, is promising for patients with IL-13-driven diseases. This extended half-life may allow for less frequent dosing, alleviating the injection burden on patients. These results pave the way for a Phase 1 study of APG777 in healthy volunteers, a milestone that has already been initiated in Australia. The potential implications of APG777 in revolutionizing the treatment landscape for atopic dermatitis and other IL-13-driven diseases are substantial, offering renewed hope for patients and clinicians alike.

Reference

Zhu E, Oh J, Dambkowski C, et al. APG777, a high-affinity humanized IgG1 mAb targeting IL-13, demonstrates prolonged half-life in non-human primates. Poster presented at: 2023 Fall Clinical Dermatology Conference; October 19-22, 2023; Las Vegas, Nevada.