ABL Bio - medicine for A Better Life

• Overview
• ABL301
• ABL503
• ABL111
• ABL102
• ABL103
• ABL104
• ABL105
• ABL501

• Pipeline

  ABL503 (Ragistomig)

• Program Target

  PD-L1 x 4-1BB

• Disease Indication

  Solid Tumor

• Development Stage

  Clinical Development
  (Phase 1)

Summary

ABL503 is a bispecific antibody combining PD-L1 checkpoint pathway with 4-1BB agonistic activity to overcome the current limitation of PD-(L)1 therapy and 4-1BB related toxicity. ABL503 is full length anti-PD-L1 mAb (Fc-silenced human IgG1) fused with scFv of anti-4-1BB engaging mAb. ABL503 possesses unique properties that 4-1BB activation signal is only induced in the presence of PD-L1 expressing tumors. ABL503 shows superior anti-tumor activity in an animal model system than PD-L1 alone, 4-1BB alone or combination of both with immunological memory resistant to rechallenge with same tumors.

Structure and Mechanism of Action

Encouraging anti-tumor activity at potential efficacious dose level (3 mg/kg and 5 mg/kg)

All responses were observed at the potential efficacious dose level. (7 out of 26 efficacy-evaluable patients at 3 and 5 mg/kg): 1 complete response (CR) and 6 partial responses (PRs)

Best percent change from baseline in tumor size

Promising response in prior checkpoint inhibitor (CPI) refractory/relapsed patients

5 out of 7 responders had received prior anti-PD-(L)1 inhibitors and all were relapsed or refractory to anti-PD-(L)1 inhibitors

Dose-limiting toxicities (DLT-evaluable set)

Induced effector memory T cells by ragistomig

A representative case is that one patient achieved sustained tumor regression over 6 months, even after treatment discontinuation. It might be linked to the observed activation and expansion of effector memory T cell induced by ragistomig (Duration of response: 39 weeks)

Tolerable safety profiles

Some treatment related adverse event related to PD-L1 or 4-1BB targeting antibody occurred, but improved and manageable with corticosteroid once applied or ABL503 interruption

Pharmacokinetics(PK): Dose proportional PK was observed

Pharmacodynamic biomarker

Dose-dependent increase of PD biomarker, s4-1BB was observed, demonstrating target engagement, and sustained at optimal dose level