Monitoring the Safety of WHISTLE-PF in IPF Across Diverse Populations

PE: Given the progressive and life threatening-nature of IPF, how soon do you anticipate ENV-101 might be available to patients if the Phase IIb trial meets its objectives?

Hood: That’s going to be up to the date from the IIb trial. If it replicates what we saw in 101, that would be amazing. At that point, it’s up to the regulatory authorities, which makes it a really tough question. Obviously, as the sponsor of the trial, we're going to do everything possible to get the drug to patients as soon as possible. Since IPF is actually more deadly than most cancers, I would hope that the regulatory authorities are also keen to help us get it to patients as soon as possible.

PE: The Phase IIa trial highlighted a favorable safety profile for ENV-101. What steps are being taken in WHISTLE-PF to monitor and further validate its safety across a larger and more diverse population?

Hood: The drug was very well tolerated in the IIa trial. and also, in the additional 200 subjects that have previously been treated with the drug. So, we have a pretty robust database of 230 patients, and it's been very well tolerated the in the IPS studies and there were no serious adverse events, o grade three or higher events, and most of the tolerability signals were considered mild. When we go into the IIb study, we'll explore an additional two doses going even lower, which could actually be efficacious, based on what we know those doses, and we'll have regular monitoring of all side effects, including an independent review board that looks at it as well at the end of the day.

The other difference with IIb is that we're going to allow standard of care this time, which wasn’t in the IIa trial, it was just monotherapy. At the end of the day, we'll increase the number of patients on drug. We'll have patients at lower doses, and to the patient's benefit, most of the patients will actually be on active drug in the trial.

Full Interview Summary: The initiation of the WHISTLE PF trial for ENV-101 aligns with the company’s broader strategic goals by advancing its priority of addressing idiopathic pulmonary fibrosis (IPF) with transformative therapies. ENV-101 targets the Hedgehog signaling pathway, directly addressing the disease’s underlying pathology by reducing fibrosis and potentially reversing lung damage, distinguishing it from current IPF treatments that only slow disease progression.

Phase IIa trials have demonstrated both clinical and statistical significance in improving lung function, structure, and reducing fibrosis. With a favorable safety profile observed across 230 patients, including oncology studies, the WHISTLE PF trial will further validate these findings in a larger, more diverse population. The Phase IIb trial will explore additional lower doses to optimize efficacy and tolerability while permitting standard-of-care therapies, ensuring comprehensive data collection. Safety monitoring will include an independent review board to oversee adverse events.

The company is also collaborating with patient advocacy organizations like the Pulmonary Fibrosis Foundation (USA), PF Warriors, and international groups in Australia, Europe, and the UK to raise awareness and facilitate trial participation. Given IPF’s life-threatening nature and the drug’s promise to outperform standard care in both efficacy and tolerability, these partnerships aim to engage more patients, ultimately expanding access to ENV-101.

While regulatory timelines remain uncertain, the company is committed to expediting the process, acknowledging the severe prognosis of IPF. The potential for accelerated approval, typically rare in pulmonary conditions, underscores the drug’s unique position as a game-changer for this devastating disease.