Unity Biotechnology, Inc.

SOUTH SAN FRANCISCO, Calif., April 23, 2025 (GLOBE NEWSWIRE) -- UNITY Biotechnology, Inc. (“UNITY”) [NASDAQ: UBX], a biotechnology company developing therapeutics to slow, halt or reverse diseases of aging, today announced that the peer-reviewed journal NEJM Evidence published results from the Phase 2 BEHOLD study of UBX1325 in patients with diabetic macular edema (DME). As reported in the article titled, “Safety and Efficacy of Senolytic UBX1325 in Diabetic Macular Edema,” the results suggested that the selective clearance of senescent cells in the retina provided disease-modifying and long-lasting improvements in vision in patients with DME, supporting the potential of UBX1325 as a novel modality for retinal diseases. “By targeting senescent cells, we expect to remodel the retinal vasculature, which should lead to improvements in retinal function,” said Anirvan Ghosh, Ph.D., chief executive officer of UNITY and an author of the paper. “We see the impact of this approach in action in the BEHOLD study, in which patients experienced meaningful and sustained improvements in their visual acuity for 1 year after a single injection of UBX1325. By selectively targeting an underlying cause of inflammation and disease progression, senolytic therapies could provide a valuable future treatment option for DME patients.” As previously disclosed and presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Annual Meeting, a single injection of the senolytic candidate UBX1325 led to a statistically significant and clinically meaningful improvement in vision with extended durability through 48 weeks in patients with advanced DME. UNITY is currently conducting a Phase 2b ASPIRE study to evaluate multiple doses of UBX1325 in a head-to-head comparison to aflibercept. Topline 24-week and 36-week data was disclosed on March 24, 2025 and full 36-week data is expected in the second quarter of 2025. About the BEHOLD StudyThe proof-of-concept Phase 2 BEHOLD study is a multi-center, randomized, double-masked, sham-controlled study designed to evaluate the safety, tolerability, efficacy and durability of a single 10 mcg dose of UBX1325 in patients with DME. The study enrolled 65 patients who, despite being on anti-VEGF treatment for at least 6 months, displayed persistent visual acuity deficits (73 ETDRS letters, approximately 20/40, or worse) and residual retinal fluid (CST ≥300 microns). At baseline, patients in the study had an average visual acuity of 61.4 ETDRS letters and a CST of approximately 439.6 microns. In the 6 months prior to study enrollment, patients received an average of 4 anti-VEGF injections, with the last anti-VEGF injection occurring 3-6 weeks prior to randomization. Fifty patients completed the 48-week study extension. More information about the study is available here (NEJM Evidence) and here. About UBX1325 UBX1325 is an investigational compound being studied in retinal diseases, including DME, and is not approved for any use in any country. UBX1325 is a potent small molecule inhibitor of BCL-xL, a member of the BCL-2 family of apoptosis regulating proteins. UBX1325 is designed to inhibit the function of proteins that senescent cells rely on for survival. The Phase 2 BEHOLD study in patients with DME demonstrated that a single injection of UBX1325 resulted in a statistically significant and clinically meaningful improvement in mean BCVA through 48 weeks compared to sham treatment. In preclinical studies, UNITY has demonstrated that targeting BCL-xL with UBX1325 preferentially eliminated senescent cells from diseased tissue while sparing cells in healthy tissue. Multiple doses of UBX1325 are currently being evaluated in the ASPIRE Phase 2b study for people with DME who are not achieving optimal benefit from anti-VEGF drugs (NCT06011798). UNITY’s goal with UBX1325 is to transformationally improve real-world outcomes for patients with retinal disease. About UNITYUNITY is developing a new class of therapeutics to slow, halt, or reverse diseases of aging. UNITY’s current focus is on creating medicines to selectively eliminate or modulate senescent cells and thereby provide transformative benefit in age-related ophthalmologic and neurologic diseases. More information is available at www.unitybiotechnology.com or follow us on X and LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements including statements related to UNITY’s understanding of cellular senescence and the role it plays in diseases of aging, the potential for UNITY to develop therapeutics to slow, halt, or reverse diseases of aging, including for ophthalmologic and neurologic diseases, UNITY’s expectations regarding potential benefits, activity, effectiveness, safety, and market opportunity of UBX1325, the potential for UNITY to successfully commence and complete clinical studies of UBX1325 for DME and other ophthalmologic diseases, the expected timing of results of the clinical trial in UBX1325, and UNITY’s expectations regarding the sufficiency of its cash runway. These statements involve substantial known and unknown risks, uncertainties, and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements, including risks related to delay or disruption in clinical trials, risks relating to the uncertainties inherent in the drug development process, risks relating to UNITY’s understanding of senescence biology, and risks related to UNITY’s ability to raise funding. This press release also contains data from third parties relating to market size and treatment outcomes, which involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. The Company may not actually achieve the plans, intentions, or expectations disclosed in its forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements in this press release represent our views as of the date of this release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this release. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general and the sufficiency of its cash runway, see UNITY’s most recent Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, filed with the Securities and Exchange Commission on April 22, 2025, as well as other documents that may be filed by UNITY from time to time with the Securities and Exchange Commission. Media ContactInizio Evoke CommsKatherine SmithKatherine.Smith@inizioevoke.com Investor ContactLifeSci Advisors, LLCJoyce Allairejallaire@lifesciadvisors.com

iStock, White Bear Studio The Eylea franchise was in need of a win after an appellate court last week denied the pharma’s bid to block Amgen’s biosimilar from the U.S. Two investigational eye therapies, from Opthea Limited and UNITY Biotechnology, were unable to unseat Regeneron ’s blockbuster anti-VEGF therapy Eylea on Monday as the standard of care in two different ophthalmic indications. The news comes as Regeneron last week lost its court appeal to prevent Amgen’s biosimilar Pavblu from entering the U.S. market. In a March 15 note to investors, BMO Capital Markets analysts said the failed appeal “reads as a modest negative to Regeneron” and compounds the existing risk to its Eylea franchise. Presenting topline data from the Phase III COAST study, Australian biotech Opthea revealed that its investigational VEGF blocker sozinibercept failed to significantly outperform Eylea at improving vision in patients with wet age-related macular degeneration (AMD). At 52 weeks, best-corrected visual acuity (BCVA) in those treated with sozinibercept improved by 12.8 letters on average from baseline, while mean improvement in Eylea counterparts was 13.7 letters. Like Eylea, sozinibercept is designed to be injected into the eye and also works by binding VEGF, a protein involved in the formation of new blood vessels. Uniquely, however, sozinibercept targets the VEGF-C and VEGF-D subtypes (Eylea binds to VEGF-A and placental growth factor), which according to Opthea is highly expressed in patients receiving the standard VEGF-A therapies, in turn leading to leaky blood vessels that could ultimately also harm vision. Sozinibercept is Opthea’s only clinical candidate , and wet AMD is its most advanced indication. Monday’s Phase III stumble thus presents a financial problem for the biotech, which in its news release revealed that it “has been assessing its rights and obligations” to investors. Opthea could be on the hook for certain payments that “would have a material adverse impact on the solvency of the company,” it wrote. The biotech is in “active discussions” with its investors, trying to determine “whether there is a pathway that represents the best outcome for the company and its shareholders,” according to Monday’s release. Opthea has yet to reach a decision but is mulling over terminating the COAST trial or unmasking a separate wet AMD trial. Also on Monday, California-based UNITY Biotechnology announced that its investigational eye injection UBX1325 likewise fell to Eylea in patients with diabetic macular edema. Topline data from the Phase IIb ASPIRE study showed that UBX1325 improved visual acuity by more than five letters at 24 and 36 weeks versus baseline. These gains, according to UNITY, were “non-inferior” to Eylea at almost all time points through 36 weeks except at the average of weeks 20 and 24. At this time point, UBX1325 showed non-inferiority at an 88% confidence interval—just shy of the 90% prespecified threshold for the study’s primary endpoint. Despite missing its target, UNITY CEO Anirvan Ghosh sang an optimistic tune in a statement on Monday, noting that UBX1325 “showed robust vision improvements in a difficult to treat patient population.” The biotech will continue to advance the candidate into late-stage studies.

The primary endpoint miss was driven fully by the 20-week data, which was the only measure out of 10 in which UBX1325 was inferior to aflibercept.\n Unity Biotechnology’s investigational eye treatment failed to match Eylea at 20 weeks—part of the mid-stage trial’s primary endpoint and the only time stamp out of 10 in which the candidate was inferior to Regeneron’s blockbuster.Despite the miss, Mizuho analysts still highlighted possible paths forward for the candidate in a March 24 note.Investors didn\'t appear to be buying this optimistic outlook, sending Unity’s stock sliding 33% from $1.82 per share at market close last Friday to $1.20 as of 11 a.m. ET Monday.The topline results come from the California company’s phase 2b study, dubbed Aspire, which is evaluating intravitreal UBX1325, a small molecule designed to inhibit BCL-xL. The double-masked trial enrolled 52 patients with previously treated, active diabetic macular edema (DME).Participants were randomized to receive either 10 μg of UBX1325 or 2 mg of aflibercept—sold under brand names Eylea and Zaltrap—every eight weeks for six months.The study missed the primary endpoint, which measured non-inferiority compared to aflibercept using the average Best Corrected Visual Acuity (BCVA) letter change from baseline at 20 and 24 weeks.Across the 20- to 24-week average, patients in the UBX1325 arm gained 3.7 letters from baseline versus a 5.1 gain for patients in the control arm. The 88% confidence interval narrowly missed the 90% pre-specified threshold. While the combined measure was the study’s main endpoint, the miss was driven fully by the 20-week data, which was the only measure out of 10 across 36 weeks in which UBX1325 was inferior to aflibercept.At 24 weeks, the investigational treatment was tied to a 5.2 letter gain in visual acuity, compared to 4.8 in the control arm.Though complete data for 36-week treatment is expected later this quarter, a 5.5 letter gain was recorded for the patients (about 75% of total) included so far.Furthermore, the biotech’s data found that UBX1325 was actually superior to aflibercept at seven of the 10 time points in a pre-specified population with moderately aggressive disease. The population represents about 60% of patients and is a group Mizuho analysts flagged as a potential path forward for the drug.“We are excited that UBX1325 showed robust vision improvements in a difficult to treat patient population,” Unity CEO Anirvan Ghosh, Ph.D., said in a March 24 release. “The results also suggest that UBX1325 may provide greater vision gains than standard of care in patients with moderately aggressive disease. We look forward to advancing UBX1325 to late-stage studies against aflibercept in DME patients with inadequate response to anti-VEGF therapies.”The investigational treatment demonstrated a favorable safety and tolerability profile, with no cases of intraocular inflammation, retinal artery occlusion, endophthalmitis or vasculitis reported across multiple studies, according to Unity. Mizuho analysts pointed to the primary endpoint measure likely favoring aflibercept, more prior Vabysmo patients in the investigational arm and a longer average time of DME diagnosis for the UBX1325 arm as all possibly contributing to the study’s primary endpoint fail.  Previously, Unity tested out UBX1325 in wet age-related macular degeneration—also against Eylea. The candidate passed the main goal of a phase 2 trial that measured safety but failed to significantly improve vision for all patients when compared to the Regeneron blockbuster.It’s a great day for Regeneron as Unity is the second biotech to report a miss against its eye injection. Just this morning, Australia-based Opthea’s asset failed to match Eylea in a phase 3 test, leaving the biotech to question its own future.