Previous Clinical Trial Results

Haduvio™ (oral nalbuphine ER) achieved statistically significant reductions in cough frequency in patients with idiopathic pulmonary fibrosis (IPF) and in patients with refractory chronic cough (RCC).

We are currently developing Haduvio to help patients suffering from serious chronic cough conditions. We completed a Phase 2b trial in patients with IPF suffering from chronic cough and a Phase 2a trial in patients with RCC. We are planning for future trials in these patient populations as well as in patients with non-IPF interstitial lung disease who experience chronic cough. All trials are expected to initiate by the first half of 2026. 

%

of IPF Patients Experience Chronic Cough

Phase 2b Cough Reduction with Nalbuphine ER (CORAL) Trial

In June 2025, we announced positive results from our Phase 2b CORAL trial for the treatment of chronic cough in patients with Idiopathic Pulmonary Fibrosis (IPF). The results from this trial supported the previous positive results seen in the Phase 2a CANAL trial for this same population.

Haduvio (nalbuphine ER/NAL ER) is an investigational drug
mITT population
Primary efficacy analysis conducted on log-transformed cough frequency data
^One placebo patient with an extreme outlier value at Week 6 was excluded from the modified intent-to-treat mITT population. Inclusion of the patient in the placebo group would have resulted in an increased cough frequency from baseline in the placebo group and much greater placebo-adjusted differences.
PBO: placebo

Statistically Significant Difference vs Placebo At All Doses

Haduvio met the primary endpoint with statistically significant reductions in 24-hour cough frequency across all dose groups. The 108 mg BID, 54 mg BID and 27 mg BID dose groups achieved reductions from Baseline of 60.2% (p<0.0001), 53.4% (p<0.0001), and 47.9% (p<0.01), respectively, compared to a placebo reduction from Baseline of 16.9%^.

Statistically Significant Difference vs Placebo At All Doses

Haduvio (nalbuphine ER/NAL ER) is an investigational drug
mITT population
Primary efficacy analysis conducted on log-transformed cough frequency data
^One placebo patient with an extreme outlier value at Week 6 was excluded from the modified intent-to-treat mITT population. Inclusion of the patient in the placebo group would have resulted in an increased cough frequency from baseline in the placebo group and much greater placebo-adjusted differences.
PBO: placebo

Haduvio met the primary endpoint with statistically significant reductions in 24-hour cough frequency across all dose groups. The 108 mg BID, 54 mg BID and 27 mg BID dose groups achieved reductions from Baseline of 60.2% (p<0.0001), 53.4% (p<0.0001), and 47.9% (p<0.01), respectively, compared to a placebo reduction from Baseline of 16.9%^.

Broad Response

Majority of patients achieved at least a 50% reduction in objective cough frequency. A 50% reduction in 24-hour cough frequency at Week 6 vs Baseline was seen in 65% of patients on 108 mg BID Haduvio (p<0.001), 63% of patients on 54 mg BID Haduvio (p<0.001) and 60% of patients on 27 mg BID Haduvio (p<0.001) dose groups, compared to 19% of placebo patients.

mITT population, Primary efficacy analysis conducted on log-transformed cough frequency data.
^One placebo patient with an extreme outlier value at Week 6 was excluded from the modified intent-to-treat (mITT) population. Inclusion of the patient in the placebo group would have resulted in an increased cough frequency from baseline in the placebo group and much greater placebo-adjusted differences.
Responder is defined those subjects meeting the pre-specified threshold.

Broad Response

mITT population, Primary efficacy analysis conducted on log-transformed cough frequency data.
^One placebo patient with an extreme outlier value at Week 6 was excluded from the modified intent-to-treat (mITT) population. Inclusion of the patient in the placebo group would have resulted in an increased cough frequency from baseline in the placebo group and much greater placebo-adjusted differences.
Responder is defined those subjects meeting the pre-specified threshold.

 

Majority of patients achieved at least a 50% reduction in objective cough frequency. A 50% reduction in 24-hour cough frequency at Week 6 vs Baseline was seen in 65% of patients on 108 mg BID Haduvio (p<0.001), 63% of patients on 54 mg BID Haduvio (p<0.001) and 60% of patients on 27 mg BID Haduvio (p<0.001) dose groups, compared to 19% of placebo patients.

mITT population, Primary efficacy analysis conducted on log-transformed cough frequency data
^One placebo patient with an extreme outlier value at Week 6 was excluded from the modified intent-to-treat (mITT) population. Inclusion of the patient in the placebo group would have resulted in an increased cough frequency from baseline in the placebo group and much greater placebo-adjusted differences.
Responder is defined those subjects meeting the pre-specified threshold

Rapid Onset of Effect

A rapid reduction was seen in 24-hour cough frequency at Week 2 with Haduvio, the first time point measured.

Rapid Onset of Effect

mITT population, Primary efficacy analysis conducted on log-transformed cough frequency data
^One placebo patient with an extreme outlier value at Week 6 was excluded from the modified intent-to-treat (mITT) population. Inclusion of the patient in the placebo group would have resulted in an increased cough frequency from baseline in the placebo group and much greater placebo-adjusted differences.
Responder is defined those subjects meeting the pre-specified threshold
A rapid reduction was seen in 24-hour cough frequency at Week 2 with Haduvio, the first time point measured.

Phase 2a Refractory Chronic Cough Improvement Via Nalbuphine ER (RIVER) Trial

In March 2025, we announced positive results from our Phase 2a RIVER trial in patients with RCC, including patients with unexplained chronic cough. The results from this trial supported Haduvio’s potential in treating chronic cough across indications through both the objective cough monitor and patient reported outcomes.

Statistically Significant Primary Endpoint

Haduvio met the primary endpoint with a statistically-significant reduction in 24-hour cough frequency with a 67% reduction from baseline (p<0.0001), and a 57% placebo-adjusted change.

Statistically Significant Primary Endpoint

Haduvio met the primary endpoint with a statistically-significant reduction in 24-hour cough frequency with a 67% reduction from baseline (p<0.0001), and a 57% placebo-adjusted change.

Rapid Reduction in Cough Frequency

Haduvio demonstrated a statistically significant reduction in 24-hour cough at Day 7 (27 mg BID), the earliest objective cough reading with the lowest assessed dose.

Rapid Reduction in Cough Frequency

Haduvio demonstrated a statistically significant reduction in 24-hour cough at Day 7 (27 mg BID), the earliest objective cough reading with the lowest assessed dose.

Broad Clinically Meaningful Effect

84% of those treated with Haduvio saw a clinically meaningful reduction in their 24-hour cough frequency compared to 29% of those treated with placebo. 77% of Haduvio treated patients achieved a 50% or greater reduction in their cough frequency compared with 15% on Placebo.

Broad Clinically Meaningful Effect

84% of those treated with Haduvio saw a clinically meaningful reduction in their 24-hour cough frequency compared to 29% of those treated with placebo. 77% of Haduvio treated patients achieved a 50% or greater reduction in their cough frequency compared with 15% on Placebo.

Consistency Across Baseline Cough Frequency

Haduvio demonstrated a statistically-significant reduction in 24-hour cough frequency with a placebo adjusted change of 51% in the severe cough (20+ coughs/hour) subgroup (p<0.0001) and 75% in the moderate cough (10-19 coughs/hour) subgroup (p<0.0001).

Safety

Over 1,000 patients have been dosed with Haduvio across various indications with some patients treated for up to 1-year.

The safety results of the CORAL and RIVER trials were generally consistent with the known safety profile of Haduvio from previous trials.

Adverse events most commonly observed during the CORAL trial included nausea, vomiting, constipation, dizziness, headache, fatigue, somnolence and dry mouth. Serious adverse events (all non-fatal) were reported for four patients (10.0%) in the placebo group and for two patients (1.6%) across all Haduvio doses combined.

Adverse events most commonly observed during the RIVER trial were constipation, nausea, somnolence, headache, dizziness, and fatigue and there were no treatment emergent serious adverse events.