Aerovate Therapeutics Presents Phase 1 Data for AV-101, A Novel Dry Powder Inhaled Formulation of Imatinib Being Developed for the Treatment of Patients with Pulmonary Arterial Hypertension (PAH)
AV-101 is being developed to address cellular hyperproliferation and resistance to apoptosis in the pulmonary vasculature, which are key features of the pathophysiology of PAH
PAH is an area of high unmet need, and currently approved therapies are limited by acting primarily through vasodilation
These Phase 1 results show that AV-101 delivered by dry powder inhalation was generally well tolerated and significantly reduced systemic exposure compared with oral imatinib in healthy adult participants
WALTHAM, Mass., May 16, 2022 (GLOBE NEWSWIRE) -- Aerovate Therapeutics, Inc. (Nasdaq: AVTE), a clinical-stage biopharmaceutical company focused on developing drugs that meaningfully improve the lives of patients with rare cardiopulmonary disease, today presents Phase 1 results at the American Thoracic Society (ATS) International Conference in San Francisco. Aerovate’s data show that AV-101, a novel inhaled dry powder formulation of imatinib, was generally well-tolerated by healthy adult volunteers with no serious adverse events reported.
“We are pleased these Phase 1 data showed that AV-101 was generally well-tolerated in this trial of healthy adult volunteers across a dose range we believe may overlap or exceed lung exposures from 400 mg of oral imatinib, the dose used in the Novartis global Phase 3 IMPRES trial, while simultaneously reducing systemic exposure,” said Timothy Noyes, Chief Executive Officer at Aerovate. “These findings represent an important step forward in our clinical development of AV-101, and support the selection of doses being evaluated in our ongoing Phase 2b/Phase 3 IMPAHCT trial.”
Imatinib previously demonstrated a statistically significant and clinically meaningful benefit in PAH patients in the global Phase 3 IMPRES trial, conducted by Novartis, when administered orally as a tablet but was poorly tolerated due to adverse events. The development of oral imatinib for PAH was discontinued. Aerovate designed AV-101, a dry powder inhaled formulation of imatinib, to target imatinib’s anti-proliferative activity in the pulmonary vasculature by direct delivery to the lungs while potentially avoiding the treatment-limiting systemic toxicities seen with oral imatinib.
Aerovate’s Phase 1 trial evaluated single and multiple ascending doses of AV-101 administered by inhalation for safety, tolerability, and pharmacokinetics in healthy adult volunteers. The single ascending dose (SAD) portion of Aerovate’s trial included 5 cohorts of 8 subjects each (6 randomized to AV-101, 2 placebo), who were administered a planned progression of 1 mg, 3 mg, 10 mg, 30 mg, and 90 mg single doses of inhaled AV-101 or placebo, compared to an additional cohort of 8 participants receiving 400 mg oral imatinib, the dose used in the IMPRES trial. The multiple ascending dose (MAD) portion consisted of 3 cohorts of up to 12 subjects each (9 randomized to AV-101, 3 placebo) who received AV-101 or placebo at either 10 mg, 30 mg, or 90 mg twice daily for 7 days. Only the morning dose was delivered on Day 7 so pharmacokinetics could be followed. Due to its known tolerability profile, the predicted steady-state exposure data for multiple doses of oral imatinib were obtained using a population pharmacokinetics model and data for oral imatinib 400 mg from the SAD study. At all doses, AV-101 demonstrated lower systemic exposure than oral imatinib. No serious treatment-emergent adverse events (TEAEs) were reported in either the SAD or the MAD cohorts. In the SAD portion of the trial, the most common TEAEs were dizziness and headache, whereas in the MAD portion of the trial, the most common TEAEs were short periods of cough and headache, primarily in the 90 mg cohort.
“Formulated as a dry powder for inhalation, AV-101 is designed to deliver high concentrations of imatinib throughout the airways and straight to diseased blood vessels,” said Hunter Gillies, M.B.Ch.B., Chief Medical Officer at Aerovate. “By limiting systemic exposure and directly targeting the disease process of hyperproliferation in the pulmonary vasculature, AV-101 has the potential to make a meaningful difference for the PAH community.”
A copy of the conference presentation will be avalable in the “Presentations > Events” section of Aerovate’s website at ir.aerovatetx.com.
Session: B106 – Union Square: Observational Studies and Clinical Trials in Pulmonary Hypertension
About the IMPAHCT Trial
About Aerovate Therapeutics, Inc.
Cautionary Note Regarding Forward-Looking Statements
Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the therapeutic potential of AV-101; the timing associated with site activation, patient recruitment, initiation and continuation of our Phase 2b/Phase 3 trial of AV-101 in PAH patients and timing of top-line results; the impact of the ongoing COVID-19 pandemic on our business, clinical trial, operations and goals; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in the United States and foreign countries as well as those risks and uncertainties set forth more fully under the caption “Risk Factors” in our most recent Annual Report on Form 10-K filed with the SEC and subsequent filings with the SEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date.