Vivoryon Therapeutics (VVY) Status Update summary

Key clinical findings and scientific rationale

• Varoglutamstat, an oral QPCTL inhibitor, demonstrated statistically significant and sustained improvement in kidney function (eGFR) in two independent phase II studies, with effect sizes of 4.39 and 3.07 mL/min/1.73m² over placebo, and especially pronounced effects in diabetic subgroups (up to 9.41 mL/min/1.73m² improvement).

• Both VIVIAD and VIVA-MIND studies showed consistent and replicable increases in eGFR, with meta-analysis confirming homogeneity and robustness of results, particularly in diabetic patients.

• Responder analysis revealed over 70% of diabetes patients treated with 600 mg varoglutamstat experienced improved or stabilized eGFR, compared to 24% in placebo.

• The drug's unique mechanism targets upstream inflammatory and fibrotic pathways by inhibiting pyroglutaminylation, affecting multiple pro-inflammatory and pro-fibrotic mediators beyond CCL2.

• Inhibiting QPCTL offers a novel approach to halt kidney disease progression by targeting inflammation and fibrosis, addressing a significant unmet need as current treatments do not stabilize or improve kidney function.

Safety and additional health benefits

• Safety profile is favorable, with only minor, mostly temporary side effects, and overall incidence of adverse events similar to placebo; pooled safety analysis confirmed good tolerability at 600 mg BID.

• Varoglutamstat also showed beneficial effects on weight, blood pressure, and liver enzymes, supporting its use in patients with metabolic syndrome.

Competitive landscape and market opportunity

• Varoglutamstat is differentiated by oral availability, novel mechanism, single-agent activity, and demonstrated long-term improvement in kidney function; it is the only oral QPCTL inhibitor in clinical development to show eGFR improvement.

• No other compound in development matches its profile; only ProKidney cell therapy has shown similar eGFR stabilization or improvement.

• The initial target market is stage IIIb-IV diabetic kidney disease, estimated at 3-6 million patients in the US and Europe, with potential expansion to broader CKD and rare kidney diseases; diabetes affects over 500M adults globally, with 40% at risk for DKD.