Vir Biotechnology (VIR) Status Update summary

Oncology Program and Platform Overview

• PRO-XTEN™ dual-masked T-cell engager platform is clinically validated, showing broad activity and promising safety in solid tumors, including HER2 and PSMA targets, by reducing off-tumor toxicity and enabling longer half-life for less frequent dosing.

• VIR-5818 (HER2-targeted) and VIR-5500 (PSMA-targeted) are the most advanced assets, both demonstrating efficacy and low rates of severe adverse events in heavily pretreated populations.

• Dual masking technology enables selective activation in the tumor microenvironment, reducing off-tumor toxicity and cytokine release syndrome (CRS), and potentially expanding the therapeutic index.

• Platform supports rapid pipeline expansion, every three-week dosing, and improved patient convenience.

• Robust financial position with ~$1.1 billion in cash and investments as of January 1, 2025, supporting continued R&D and dose escalation.

Clinical Data Highlights: HER2 and PSMA Programs

• VIR-5818 Phase 1 enrolled heavily pretreated HER2+ solid tumor patients; 50% observed tumor shrinkage at efficacious doses, with a 33% response rate in colorectal cancer and up to 18.1 months duration of response.

• Minimal CRS observed (no grade 3 or higher), and only 16% grade 3 or higher treatment-related adverse events for VIR-5818; no dose-limiting toxicities for either agent.

• VIR-5500 in mCRPC shows 100% PSA decline and 58% PSA50 response at early dose cohorts, with no grade 3 or higher CRS and no prophylactic steroids required.

• Durable responses observed, including a patient with 18+ months of sustained benefit and significant radiographic and symptomatic improvement in high-burden patients.

• ctDNA analysis shows 54% molecular response rate for VIR-5818, supporting anti-tumor activity beyond imaging.

Technology and Mechanism

• PRO-XTEN™ masking technology keeps T-cell engagers inactive until reaching the tumor microenvironment, reducing off-tumor toxicity and increasing drug half-life.

• Early pharmacokinetic data show minimal systemic unmasking, linear pharmacokinetics, and desirable half-lives (6–10 days), supporting every three-week dosing.

• Dual-masking technology provides a significant therapeutic index advantage over unmasked or single-masked TCEs.

• No requirement for prophylactic corticosteroids or anti-IL-6 premedication in early clinical testing.

• Maximum tolerated dose has not been reached for either agent; dose escalation is ongoing.