Delving into the 24-week results for UBX1325 for the treatment of chronic DME, wet AMD

,

At ASRS 2022, Raj K. Maturi, MD, presented a talk entitled, “UBX1325, A Novel Senolytic Therapy for Treatment- Experienced Patients With Chronic DME or Wet AMD: 24-Week Results of a Phase 1 Study.”

Video transcript

David Hutton [DH]: I'm David Hutton of Ophthalmology Times. The American Society of Retina Specialists is holding its annual meeting in New York. At the meeting, Dr. Raj Maturi is presenting UBX1325, A novel senolytic therapy for treatment-experienced patients with chronic DME or wet AMD: 24-week results of a Phase 1 study. Thank you for joining us, Dr. Maturi. Tell us about this presentation.

Raj K. Maturi, MD: Thank you for having me, David. So senolytic therapy and senolytic medicines are an entirely new paradigm for the treatment of any retinal disease as well as some other systemic diseases.

In summary, we know that when cells undergo stress, many of them accumulate senescence cells, that is these vascular tissue cells fail to divide and replicate; they stop that process. When that happens, they release some senescence associated factors, such as inflammatory mediators, vascular endothelial growth factors and other tissue. And this goes on to cause fibrosis and all of the other pathology that we see.

When we eliminate these senolytic cells, specifically by targeted therapy, then we can allow the tissue to resume its normal homeostatic functions and go back to normal.

So that's the theory, and we wanted to see if it would work in humans. Prior to that bunch of animal models and studies were done. And very convincingly, it was shown that this drug product UBX1325, can actually decrease senescence cell burden in the mouse OIR model. In fact, it decreased the burden significantly an increased retinal caspase activation, which is another sign of cell death by almost 10 times.

So essentially, what the drug is doing is eliminating any cell that's not properly functioning, and therefore allowing normal tissue to regenerate and grow again. Similarly, in the OIR model, it decreased vascularization as with any anti-VEGF product.

However, unlike anti-VEGF products, this therapy decreased the amount of a vascular tissue. In fact, tissue vascularization was almost 4 times better than before compared to the vehicle control in the OIR model. Based on this very convincing and very good preclinical data, a Phase 1 study in treatment experienced patients with diabetes as well as macular degeneration was undertaken.

And then we looked at the data in two separate ways. We did all of the diabetics together, and then all of the wet AMD patients together. And the DME patients, all of whom had had multiple previous treatments with anti-VEGF, the senolytic therapy with single dose at baseline caused on average visual acuity improvement between 5 and 10 letters, and the mean gain was approximately 10 letters in the high dose treatment group.

Again, this was a single drug treatment, visual acuity gain was rapid and was more or less sustained through 24 weeks without any additional therapy.

A couple of patients did require rescue. And all of these rescues are eliminated in the testing in terms of will be used last observation carried forward. So you could see this visual gain despite or 2 of the 8 patients requiring rescue.

At the end of the day about 60% gained 5 letters, and half the subjects gain 2 lines or 10 letters.

And then we also looked at the diabetic and macular degeneration population separately and then the AMD population. Similar to the diabetic macular edema population, there was an immediate and rapid increase in visual acuity of about 5 letters by week 2, and most of this was sustained through week 24.

Unlike the diabetic patients, more of these patients required rescue. 4 required rescue 12 weeks and 2 additional patients required rescue at 22 weeks. Again, this was a six-month study with just one single dose at baseline.

The OCT differences were somewhat more marked and somewhat longer lasting in the AMD population. Although the diabetic population had a significant improvement in OCT initially, this did not last for the 24 weeks, even though visual acuity improved.

The Phase 1 study with a completely novel mechanism of action showed very promising results and showed that the drug was completely safe in patients; there were no significant SAEs or significant AAs of note, and therefore, two separate Phase 2 studies the ongoing: one in the diabetic one population, which is fully enrolled, and a second in the AMD population.

The AMD population as it required more rescue patients in Phase 1, and Phase 2 will receive two separate treatments of UBX. We look forward to seeing how this new paradigm of treatment can potentially supplement and potentially replace traditional anti-VEGF treatment, in at least a segment of this vast population with significant disease.

DH: Excellent. Thank you so much.

Note: This transcript has been lightly edited for clarity.