Dr. Nick Blondin here from the Yale Cancer Center. We ran a phase one study of fb-PMT, which is a novel thyrointegrin inhibitor to treat patients with recurrent glioblastoma. The molecule fb-PMT, also known as NP751, is a thyrointegrin inhibitor targeting the alpha V beta 3 integrin, which is found overexpressed in glioblastoma tumors. By binding of the study drug fb-PMT to this integrin molecule, there’s multiple downstream pathways affected by this resulting in cancer cell apoptosis...
Dr. Nick Blondin here from the Yale Cancer Center. We ran a phase one study of fb-PMT, which is a novel thyrointegrin inhibitor to treat patients with recurrent glioblastoma. The molecule fb-PMT, also known as NP751, is a thyrointegrin inhibitor targeting the alpha V beta 3 integrin, which is found overexpressed in glioblastoma tumors. By binding of the study drug fb-PMT to this integrin molecule, there’s multiple downstream pathways affected by this resulting in cancer cell apoptosis. And that was kind of the preclinical rationale for the development of this product. So we did a three plus three type design of a phase one trial. We identified a starting dose of 0.08 milligrams per kilogram per day. Patients took the study treatment via subcutaneous injection that they self-administered daily. We treated three patients at each of the dose levels, again, starting at 0.08 milligrams per kilogram per day. It was level one. Level two was 0.24. Three was 0.48. Four was 0.96, and five was 1.44. We did an expansion at dose levels 4 and 5 to 6 patients total to further evaluate patients at those higher dose levels. We wanted to evaluate the safety and tolerability of the FBPMT and then evaluate pharmacokinetic profiling of the drug and establish the recommended phase two dose for this product. In a number of patients, we were also able to do some immunohistochemistry looking for the expression of alpha V beta three in patients. We looked at 14 samples and we found moderate to high expression of alpha V, beta 3 in patients. We looked at 14 samples, and we found moderate to high expression of AVB3 in 14 out of all 14 samples assessed. We found that the study drug was extremely well-tolerated. In terms of safety analysis, there were no treatment-related serious adverse events reported. Again, it seemed remarkably well-tolerated. There was no dose-limiting toxicities identified, and study treatment was well-tolerated. In regards to the PK analysis, the drug had rapid absorption with peak concentration observed within three to six hours post-dose, and there was detectable plasma concentration persisting through 24 hours in many subjects. And there was an expected correlate with the dose the patient received and, you know, drug level systemically. We found that patients in dose levels four and five, again, tolerated the drug really well. And particularly at dose level four, 0.96 milligram per kilogram, patients stayed on study treatment for several months on average. And so we’ve identified this as the dose that we want to move into phase two. We had two patients who were very long-term responders on study treatment with time on study 27 and 36 months respectively. So we are still trying to identify some other specific factors for those patients leading to those good outcomes. But with glioblastoma, particularly recurrent glioblastoma, having an average survival of less than one year, patients that are surviving two and three years, really, we thought are extraordinary outcomes and support the further development of this product.
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