Adagene (ADAG) investor relations material

ADG126 clinical development

• Randomized Phase II under Project Optimus tests two ADG126 doses with pembrolizumab; data expected in H1 2027.

• Phase II aims to replicate Phase I-B response rates of 17% and 25% for the two tested dose schedules.

• After Phase II, plans to meet FDA; best-case next step is randomized Phase III with OS as primary endpoint and control therapy based on treatment line.

• Potential Phase III controls include fruquintinib or regorafenib in later lines, TAS-102 plus bevacizumab in third line, or physician’s choice for a mixed-line population.

Mechanism and safety

• ADG126 unmasks in the tumor microenvironment; expected activity is weighted toward Treg depletion, with some immune priming also possible.

• SAFEbody masking requires both mask cleavage and high CTLA-4 expression for activation; CTLA-4 is highly expressed on Tregs.

• ADG116 binds a different epitope than ipilimumab and tremelimumab; its ADCC is reported as 10x higher than ipilimumab.

• Phase I-B adverse-event discontinuation rate was below 10% at doses up to 20 mg/kg with PD-1 combination; safety events still rose with dose.

Dosing and clinical context

• A 20 mg/kg Q6W schedule has slightly higher AUC than 10 mg/kg Q3W; the initial bolus is viewed as potentially important for rapidly progressive disease.

• The loading-dose schedule was not carried into metastatic Phase II and is being evaluated in the Singapore neoadjuvant study.

• Median OS benchmarks in later-line CRC were characterized as low teens; immunotherapy combinations may show a survival plateau unlike regorafenib, fruquintinib or TAS-102.

• Cross-trial comparisons are difficult given small cohorts; responses were seen in two patients with peritoneal metastases in the 20 mg/kg Q6W Phase I-B cohort.