Phase 2a Clinical TrialsPhase 2a clinical trials

Antios is building on clinical experience from the phase 2a studies to optimize treatment potential

To demonstrate the safety and evaluate the efficacy of ATI-2173, a 90-day, randomized, double-blind, placebo-controlled phase 2a study, ANTT201, was initiated in March 2021.1

ATI-2173 has been studied in multiple clinical trials, both as a monotherapy and as an integral component of combination regimens.

ANTT201 study design

Primary endpoint:

  • Adverse events
  • Time to HBV viral load relapse in HBV-infected subjects
  • Reduction of HDV RNA on treatment for HBV/HDV coinfected subjects

Four cohorts were broken up into 2 groups: SAVE-1 and SAVE-2.

SAVE-11

  • Cohort A: Hepatitis B virus (HBV) infected: 25 mg ATI-2173 + tenofovir disoproxil fumarate (TDF) 300 mg; once daily for 90 days
  • Cohort B: HBV infected: 50 mg ATI-2173 + TDF 300 mg; once daily for 90 days
  • Cohort C: HBV/HDV coinfected: 50 mg ATI-2173 + TDF 300 mg once daily for 90 days

SAVE-21

  • Cohort D: HBV infected: 25 mg ATI-2173 + TDF 300 mg; once daily for 90 days + 60 mg AB-729 subcutaneous injection from Arbutus on Day 28 and Day 90

*Results impacted due to the Russian invasion of Ukraine.

Safety results

ANTT201 study of ATI-2173 + TDF demonstrated safety with no treatment related adverse events (SAEs) or adverse events (AEs) leading to discontinuation

  • All subjects completed 90 days of dosing with no treatment related SAEs or AEs leading to study drug discontinuation
  • No clinical concerns in labs, myopathy questionnaire, or electrocardiography data
  • No safety concerns were identified by the blinded Safety Review Committee when combining ATI-2173 with TDF
  • Preliminary pharmacokinetic (PK) data analyses showed no drug interaction between ATI-2173 and TDF
  • Two patients on ATI-2173 + TDF had asymptomatic on-treatment ALT flares associated with significant HBV DNA reductions

ALT, alanine aminotransferase; AST, aspartate aminotransferase; MedDRA, Medical Dictionary for Regulatory Activities; TEAE, treatment-emergent adverse events.

In the ATI-2173 + TDF arms, ALT normalized on-treatment and no patients experienced ALT flares off-treatment

  • Patients receiving ATI-2173 combined with TDF experienced no off-treatment ALT flares, while patients on TDF alone experienced off-treatment flares
  • ATI-2173 also demonstrated 24 weeks of sustained viral response post treatment
  • There was no evidence of myopathy in either arm of ATI-2173 + TDF

Safety results are still pending for the SAVE-2 cohort.

Efficacy results

ATI-2173 + TDF demonstrated prolonged off-treatment DNA suppression compared to TDF alone following 90 days of treatment

HBV DNA Table
HBV DNA Graph

ATI-2173 + TDF demonstrated a durable antiviral effect compared to TDF alone

  • At 16 weeks off-treatment all of TDF alone subjects had virologic rebound versus 44% of the ATI-2713 + TDF subjects
  • At week 24 off-treatment, 75% of the ATI-2173 + TDF subjects had not met TDF restarting criteria
Virologic Rebound Data
TDF Restart Data

Virologic Rebound: time of 1st confirmed detectable HBV DNA for subjects previously BLQ or time of HBV DNA increase to 1 log10 IU/ml from nadir if not previously BLQ

TDF Restarting Criteria: Confirmed (2 values) HBV DNA >2,000 IU/ml if HBeAg- or HBV DNA >20,000 IU/ml if HBeAg+, OR ALT >3 x baseline or post treatment nadir value

Study summary

ATI-2173 demonstrated safety and off-treatment efficacy compared to TDF alone

All patients completed 90 days of dosing

ATI-2173 + TDF was safe and well tolerated

ATI-2173 demonstrated potent HBV DNA suppression that was sustained off treatment and differentiated from TDF alone

At 24 weeks off- treatment 75% of ATI-2173 + TDF patients did not meet re-start criteria vs. 0% in the TDF alone arm

In the ATI-2173 + TDF arms, ALTs normalized on-treatment and there were no off-treatment ALT flares

The 25 mg and 50 mg cohorts of ATI-2173 + TDF continue to demonstrate similar on- and off-treatment safety and antiviral efficacy1

Data from phase 2 study support longer duration and additional combination studies

References: 1. Data on file. Antios Therapeutics, Doylestown, PA.

Improving lives through the treatment of HBV About our therapies