Michael Weickert, PhD: [00:00:00] So the first thing I want to explain is Zelenirstat is a first in class therapy targeting a new target that’s never been drugged before for any indication. So this is the first time it’s been studied in patients and we do what’s called a phase one study which is primarily to identify safety. Is it safe to dose this new drug which has never been dosed before at a new target that’s never been drugged before?
So our study was designed to escalate the dose gradually in a series of patients that are not selected for their potential to respond to the drug, but are simply patients that are willing to volunteer to let us study safety of a new drug. These are usually heavily pre treated patients. The average patient in our study had four prior lines of therapy that had failed, and they’re looking for new options because they’ve run out of their conventional options.
And we are definitely a new option. So the study identified what we call a recommended phase 2 dose that we are taking on and have begun dosing in phase [00:01:00] 2. It identified a stopping dose at which patients were experiencing dose limiting toxicities. And it has allowed us to continue the development of the drug because the side effects we observed were tolerable by the patients.
The efficacy we observed in phase 1 was unexpected and surprising and very welcome because we didn’t Pick these patients. They picked the study and we were willing to take all comers.
OncologyTube: Fantastic. So our audience are oncologists and hematologists. What were the key findings regarding the safety and tolerability of Zelenirstat in the phase one dose escalation study?
And how did these findings impact its potential as a cancer treatment option?
Michael Weickert, PhD: Yes. So the side effects that were observed in the study were all gastrointestinal in nature, which is very common in oncology drugs. Zelenirstat is a once a day oral therapy. So we identified loss of appetite in a minority of patients.
[00:02:00] We saw some nausea some vomiting, some diarrhea in a minority of patients. Usually these are self limiting. that the patient didn’t need medicine. They actually often came into the doctor’s appointment and reported when they asked, how are you feeling that? Oh, I, you know what, I had a loss of appetite for last week.
I was a little nauseous, a couple weeks ago. A little bit of it required drug, but most of it was self limiting. It’s the same side effects we saw in animal studies. So when we did animal toxicology studies before getting into the clinic to authorize us to do studies in patients, we saw the same kinds of experiences in the animals.
GI side effects, nausea, vomiting, diarrhea, that was what was limiting in animals as well. The good news is in animals when it was serious, you could take the animals off the drug and the side effects would resolve on their own, and then you could resume dosing with the drug safely. The net effect is that this drug looks safe and well tolerated in patients, and looks ready to take on into Phase II, [00:03:00] which is why we have commenced a Phase II study in lymphoma, and are prepared to commence a Phase II study in solid tumor cancers, including GI cancers, as well as a study in leukemia patients as well.
OncologyTube: Excellent. Could you elaborate on the clinical outcomes observed with Zelenostat in the Phase 1 study, particularly in terms of progression free survival and overall survival and how these outcomes compared to existing treatment options?
Michael Weickert, PhD: Sure. Be glad to. First off, this is a safety study. We did not have efficacy endpoints as the endpoints for the study, prospectively.
But when we conducted the study, when patients got to the dose that we predicted would be an effective dose, instead of having progressive disease, the patients stayed on the study drug, which they can only do if the drug is preventing any further tumor growth, or is causing the tumor to shrink. So when we got to that dose, which we’ve now taken on into phase two, most of the patients stayed on drug.
[00:04:00] In fact, our GI patients, we had an appendiceal carcinoma and a colorectal cancer patient with seven prior lines of therapy, they’re still on drug. They haven’t come off because their cancers are under control or are shrinking. thAt was a very exciting and unexpected result. So we took a retrospective analysis of the Phase I study, looking at the efficacy we observed or the duration of treatment we observed in the patients receiving that effective dose.
versus the patients that received all the lower doses. And it turns out there’s a statistical significant progression free survival and overall survival benefit to patients who received the effective dose of Zelenirstat. This is a very small N of patients. There’s only 7 in the dose level that we’ve taken to phase 2.
There’s only 17 in the other doses, so only 24 patients in the analysis, despite that low number. And despite the fact that this is not the intention of the study, and despite the fact [00:05:00] that we didn’t pick the patients for potential to respond, and despite the fact that they had four prior lines of therapy that they had, on average, had failed before going into the study, we still observed this benefit.
So that was exciting, the fact that GI cancers appear to have Potentially the most benefit of the solid tumor patients that we enrolled in the study means that we are looking at expanding our study into solid tumor cancers and GI cancers in particular as soon as we can afford to do now the fact that patients have failed all other available lines of therapy before they come on the study means that even though other therapies are not effective, we still look to have a benefit.
The other thing that I’ll mention is that because we’re a new mode of action, a new method of action, and a new first in class therapy, we have the potential to be synergistic with other therapies. And [00:06:00] so that potential for synergy comes because we are orthogonal to other therapies. We are working through a different mechanism.
And that’s also an exciting prospect for the future. Excellent.
OncologyTube: What is the significance of initiating a Phase IIa expansion study in patients with B cell non Hodgkin’s lymphoma, and how might the findings from this study contribute to the development of Zelenirstat as a targeted therapy for hematologic and solid tumors?
Michael Weickert, PhD: So with Zelenirstat in the animal studies, when we looked at models of hematologic cancers, acute myeloleukemia, Burkitt’s lymphoma, diffuse large B cell lymphoma. We saw in all those cancers complete regression of the tumor with treatment by Zell and Zelenirstat. So that’s our lead indications because with monotherapeutic applications, we are hoping to reproduce that complete regression in patients.
And that’s why the first phase two study is in diffuse large B cell lymphoma patients. [00:07:00] Now at the same time, given the results we’ve observed in the phase one study We’re primarily solid tumor patients who are enrolled because of the ease of enrollment and the availability of those patients. We’re now looking at maybe we need to expand our clinical program to include solid tumor patients much earlier than we’d planned.
We had planned to develop hematologic cancers, and then later when we could afford, we would go back to solid tumor cancers. But now, it looks like GI cancer patients should be one of the arms that we’re investigating clinically as soon as we can afford to do
OncologyTube: all right. This has been an interview with Dr.
Michael Weikert, PhD, Chief Executive Officer of Pacylex Pharmaceuticals. Dr.Michael Weikert, PhD thank you so much for joining us today.
Michael Weickert, PhD: Thank you so much for your questions.