Unity Biotechnology has recently announced the launch of its Phase 1 study of UBX1325 for patients with diabetic macular edema. The drug is designed to remove problematic senescent cells from the body which accumulate as we get older and are a reason we age.
UBX1325 is a senolytic agent that targets the BCL-xL pathway to destroy senescent cells, much like Navitoclax, which is known to clear senescent cells via this pathway but has serious side effects; UBX1325 may even be a modified version of Navitoclax. The BCL-2 family of proteins includes BCL-1, BCL-w and BCL-xL and prevents the cell from entering apoptosis.
Diabetic macular edema is due to leaky blood vessels in the eye, causing fluid to accumulate in the macula, the central area of the retina. It is a complication of diabetic retinopathy and has an outcome similar to adult wet macular degeneration. The researchers at UNITY believe that senescent cells play a key role in the development of this disease and that it may be addressed by removing them with senolytics.
SAN FRANCISCO, Oct. 12, 2020 (GLOBE NEWSWIRE) — UNITY Biotechnology (“UNITY”) [NASDAQ:UBX], a biotechnology company developing therapeutics to extend healthspan by slowing, halting or reversing diseases of aging, today announced that the first patient has been dosed in a Phase 1 study of UBX1325 in patients with diabetic macular edema (DME).
“There is strong evidence of association between disease progression in DME and accumulation of senescent cells. There’s additional evidence that senescent cells secrete factors that can be damaging to the eye and lead to vascular leakage, a pathological hallmark of DME,” said Anirvan Ghosh, Ph.D., chief executive officer of UNITY. “Bcl-xL inhibition, a novel senolytic mechanism, has been shown in our preclinical tests to lead to an impact on senescent cells, reduction in vascular leakage, and improvement in retinal function. Our preclinical observations give us confidence in UBX1325 and we are excited to bring this therapeutic candidate into clinical development.”
The Phase 1, first-in-human, open-label, single-ascending dose study is designed to evaluate the safety, tolerability and pharmacokinetics of UBX1325 in patients with advanced DME. The trial is designed to enroll approximately 15 patients, with safety and tolerability data expected in the first half of 2021. UNITY anticipates initiating a proof of concept study in the first half of 2021.
UBX1325 is a potent and selective small molecule inhibitor of Bcl-xL, an anti-apoptotic regulatory protein and a BCL-2 family member. Preclinically, UBX1325 has been shown to eliminate senescent cells and have a positive impact on inflammation, vascular leakage and visual function. UBX1325 is currently being evaluated in a first-in-human trial designed to treat patients with advanced diabetic macular edema. To learn more at clinicaltrials.gov about the Phase 1 clinical trial of UBX1325.
Will this time be different?
This announcement comes in the wake of disappointing news for UNITY Biotechnology, as its Phase 2 trial of UBX0101, another senolytic drug, failed to deliver the desired results. That study involved 183 patients with moderate-to-severe osteoarthritis of the knee given UBX0101, which targets the p53/MDM2 pathway, another way in which some senescent cells avoid apoptosis. Unfortunately, the study found no statistically significant difference in pain reduction between UBX0101 and placebo.
As with the previous clinical trial, success hinges a great deal on the tissue being targeted and the heterogeneity of the senescent cells within. It turns out that there are a number of different types of senescent cells, and they all use different pathways to evade destruction.
Success will depend on whether this drug targets the same pathway that the bulk of the senescent cells in the eye are using to survive. Let us hope that the right pathway has been chosen and more disappointing results can be avoided.
October 14, 2020
maybe you can try to find new molecules from the insects bios.
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