foselutoclax (UBX1325) / Unity Biotech, Ascentage Pharma - LARVOL DELTA

Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE) (clinicaltrials.gov) - P2 | N=52 | Completed | Sponsor: Unity Biotechnology, Inc. | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders

UNITY Biotechnology Announces Complete 36-Week Results from the ASPIRE Phase 2b Study of UBX1325 in Diabetic Macular Edema and Provides Corporate Updates (GlobeNewswire) - P2b | N=52 | ASPIRE (NCT06011798) | Sponsor: Unity Biotechnology, Inc. | "UBX1325 demonstrated vision gains that were comparable and statistically non-inferior to aflibercept at week 36 in a difficult-to-treat DME patient population; UBX1325 generally outperformed aflibercept in a pre-specified subgroup of patients entering the study with CST <400 microns (60% of enrolled patients); Company to explore strategic alternatives to advance UBX1325, Tie2/anti-VEGF bispecific, and Tie2 agonistic antibody assets and reduce operational cash burn....The Company will present full 36-week results from the ASPIRE study at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting on Wednesday, May 7, 2025."

P2b data • Diabetic Macular Edema

Safety and Efficacy of Senolytic UBX1325 in Diabetic Macular Edema. (PubMed, NEJM Evid) - P2 | "In this sham-controlled trial there were no TEAEs that led to discontinuation of treatment with UBX1325 compared with sham. There were trends suggestive of potential efficacy; larger trials are needed to further evaluate these findings. (Funded by UNITY Biotechnology; ClinicalTrials.gov number, NCT04857996.)."

Clinical • Journal • B Cell Lymphoma • Diabetic Macular Edema • Diabetic Retinopathy • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Ophthalmology • Retinal Disorders

Foselutoclax (UBX1325) for Diabetic Macular Edema - A Potential Novel Therapy? (PubMed, NEJM Evid) - No abstract available

Journal • Diabetic Macular Edema • Ophthalmology

UNITY Biotechnology Announces Publication in NEJM Evidence Highlighting the Potential of Senolytic Therapeutics to Provide Long-Term Improvements in Vision in DME (GlobeNewswire) - P2a | N=65 | BEHOLD (NCT04857996) | Sponsor: Unity Biotechnology, Inc. | "UNITY Biotechnology, Inc...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....full 36-week data is expected in the second quarter of 2025."

P2a data • Diabetic Macular Edema

Safety and Efficacy of Senolytic Candidate UBX1325 for Diabetic Macular Edema: The BEHOLD Phase 2 and ASPIRE Phase 2b Trials (ARVO 2025) - P2 | "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • P2b data • Diabetic Macular Edema • Diabetic Retinopathy • Ophthalmology • Retinal Disorders • BCL2L1

UNITY Biotechnology Announces Topline Results from the ASPIRE Phase 2b Study in Diabetic Macular Edema (GlobeNewswire) - P2b | N=52 | ASPIRE (NCT06011798) | Sponsor: Unity Biotechnology, Inc. | "Treatment with UBX1325 resulted in vision gains comparable to aflibercept at weeks 24 and 36 in difficult-to-treat patient population; UBX1325 was non-inferior to aflibercept at week 24 (>90% confidence interval), but did not meet statistical non-inferiority on the average of weeks 20 and 24, the primary analysis endpoint (met at 88% confidence interval); UBX1325-treated patients had a +5.2 letter gain in visual acuity at 24 weeks and a +5.5 letter gain at 36 weeks; UBX1325 was numerically superior to aflibercept at 7 out of 10 time points in a pre-specified population with moderately aggressive disease; UNITY anticipates the complete 36-week data results of the remaining patients in the second quarter of 2025."

P2b data • Diabetic Macular Edema

UNITY Biotechnology, Inc. Reports Fourth Quarter and Full Year 2024 Financial Results and Business Updates (GlobeNewswire) - "UNITY anticipates receiving 24-week primary endpoint data in the first quarter of 2025 and 36-week data in the second quarter of 2025. The Phase 2b ASPIRE study in DME is a multi-center, randomized, double-masked, active-controlled study designed to evaluate the safety and efficacy of UBX1325 in a head-to-head comparison to aflibercept."

P2b data • Diabetic Macular Edema

UNITY Biotechnology, Inc. Reports Third Quarter 2024 Financial Results and Business Updates (GlobeNewswire) - "UNITY expects topline 24-week primary endpoint data in the first quarter of 2025 and 36-week data in the second quarter of 2025....Research and development expenses decreased by $1.8 million, to $2.8 million for three months ended September 30, 2024, from $4.6 million for the three months ended September 30, 2023. The decrease was primarily due to $0.9 million in personnel costs due to our reduced headcount related to our reduction in force, $0.8 million in direct research and development expenses mainly due to the completion of the Phase 2 BEHOLD study of UBX1325 in patients with DME and the Phase 2 ENVISION study of UBX1325 in patients with AMD, and $0.1 million in operating costs due to reduced fixed assets depreciation and reduced office space."

Commercial • P2b data • Age-related Macular Degeneration • Diabetic Macular Edema • Ophthalmology

Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues. (PubMed, Eye (Lond)) - "Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and Ang-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC • VEGFD

Multifocal Electroretinography Changes after UBX1325 (Foselutoclax) Treatment in Neovascular Age-Related Macular Degeneration. (PubMed, J Clin Med) - "The mean change in BCVA demonstrated statistical significance in Weeks 4 and 8, showing increases of 5 (p = 0.02) and 6.2 (p = 0.02) letters, respectively. Foselutoclax treatment was shown to have the potential to recover outer retinal function as determined by mfERG and BCVA at approximately Week 8 of treatment."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE) (clinicaltrials.gov) - P2 | N=52 | Active, not recruiting | Sponsor: Unity Biotechnology, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders

UNITY Biotechnology, Inc. Reports Second Quarter 2024 Financial Results and Business Updates (GlobeNewswire) - "...'Having expanded and extended our ASPIRE study to 50 patients and 36 weeks, respectively, to better assess the efficacy and durability of UBX1325 compared to aflibercept, we have been laser-focused on enrollment and execution this quarter'....UNITY expects topline 24-week primary endpoint data in the first quarter of 2025 and 36-week data in the second quarter of 2025. The Phase 2b ASPIRE study in DME is a multi-center, randomized, double-masked, active-controlled study designed to evaluate the safety and efficacy of UBX1325 in a head-to-head comparison to aflibercept."

P2b data • Trial status • Diabetic Macular Edema

Safety, Tolerability and Evidence of Activity Study of UBX1325 in Patients With Diabetic Macular Edema (BEHOLD) (clinicaltrials.gov) - P2 | N=65 | Completed | Sponsor: Unity Biotechnology, Inc. | Phase classification: P2a ➔ P2

Phase classification • Diabetic Macular Edema • Ophthalmology

Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE) (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Unity Biotechnology, Inc. | Phase classification: P2b ➔ P2 | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025

Phase classification • Trial completion date • Trial primary completion date • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders

UNITY Biotechnology Announces Upcoming Presentations at the ARVO 2024 Annual Meeting (GlobeNewswire) - "UNITY Biotechnology, Inc...today announced that the Company will present two poster presentations at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Annual Meeting being held on May 5-9, 2024 in Seattle, Washington."

Clinical • P2 data • Diabetic Macular Edema • Macular Edema • Ophthalmology

Senolytic drug candidate in wet AMD demonstrates benefit with Multifocal ERG testing (ARVO 2024) - "The results of this study support foselutoclax's capacity to maintain retinal physiological functioning with potential for focal areas of improvement as noted in mfERG responses. This study also presents mfERG as a potential endpoint in retinal clinical trials. As well as excellent consistency in data, total responses in waveforms for each subject remained relatively stable, indicative of standardized testing conditions and reliability."

Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • BCL2L1

Effect of Patient Baseline Characteristics on Response to UBX1325, a Novel Senolytic Candidate For Patients With DME: BEHOLD Phase 2 Study 48 weeks follow-up (ARVO 2024) - "The study achieved Proof-of-Concept based on pre-specified criteria for the use of UBX1325 as a potential treatment for DME ."

Clinical • P2 data • Ophthalmology • BCL2L1

Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results. (PubMed, Nat Med) - P1 | "We then conducted a phase 1 single ascending dose safety study of UBX1325 (foselutoclax), a senolytic small-molecule inhibitor of BCL-xL, in patients with advanced DME for whom anti-vascular endothelial growth factor therapy was no longer considered beneficial...This hypothesis will need to be verified in larger clinical trials. ClinicalTrials.gov identifier: NCT04537884 ."

Journal • P1 data • Preclinical • Diabetes • Diabetic Macular Edema • Inflammation • Metabolic Disorders • Ophthalmology • BCL2L1

UBX1325 A Novel Senolytic Candidate for Patients With Diabetic Macular Edema: 48-Weeks Results for BEHOLD Phase 2 Study (AAO 2023) - No abstract available

Clinical • Late-breaking abstract • P2 data • Diabetic Macular Edema • Ophthalmology

Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE) (clinicaltrials.gov) - P2b | N=40 | Recruiting | Sponsor: Unity Biotechnology, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders

Safety, Tolerability, and Efficacy Study of UBX1325 in Patients With Neovascular Age-Related Macular Degeneration (ENVISION) (clinicaltrials.gov) - P2 | N=51 | Completed | Sponsor: Unity Biotechnology, Inc. | Active, not recruiting ➔ Completed

Trial completion • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

ASPIRE: Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (clinicaltrials.gov) - P2b | N=40 | Not yet recruiting | Sponsor: Unity Biotechnology, Inc.

New P2b trial • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders

ENVISION Trial 24-Week Data: Phase 2 Study of UBX1325, a New Senolytic Agent for Patients With Wet AMD (ASRS 2023) - No abstract available

Clinical • P2 data • Wet Age-related Macular Degeneration

Safety, Tolerability, and Efficacy Study of UBX1325 in Patients With Neovascular Age-Related Macular Degeneration (ENVISION) (clinicaltrials.gov) - P2 | N=51 | Active, not recruiting | Sponsor: Unity Biotechnology, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2023 ➔ Aug 2023

Enrollment closed • Trial completion date • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration