Slides
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1 UBX1325 Phase 2B ASPIRE Study 24- and 36-Week Data in DME March 24, 2025 Robert Bhisitkul, M.D., Ph.D. Professor of Ophthalmology, UCSF Anirvan Ghosh, CEO Federico Grossi, CMO Lynne Sullivan, CFO Alicia Tozier, Chief Strategy Officer
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2 Special Note Regarding Forward-Looking Statements This presentation and the accompanying oral commentary contain forward -looking statements including statements related to Unity Biotechnology Inc.’s (“UNITY’s”) understanding of cellular senescence and the role it plays in retinal diseases and diseases of aging, the potential for UNITY to develop therapeutics t o slow, halt, or reverse diseases of aging, including for ophthalmologic and neurologic diseases, UNITY’s expectations regarding potential benefits, activity, effectiveness, safety, and market oppor tunity 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 enrollment and res ults of the clinical trials in UBX1325, and UNITY’s expectations regarding the sufficiency of its cash runway. These statements involve substantial known and unknown risks, uncertainties, an d 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 relating to the uncertainties inherent in the drug development process, the risk that interim results of our clinical studies may not be indicative of future results, risk s related to UNITY’s ability to raise funding, and risks relating to UNITY’s understanding of senescence biology. This presentation and the accompanying oral commentary also contain data from third part ies 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. We may not actually achieve the plans, intentions, or expectations disclosed in our 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 presentation represent our views as of the date of this presentation. 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 presentation. For a further description of the risks and uncertainties that could cause actual results to differ from those e xpressed in these forward-looking statements, as well as risks relating to the business of UNITY in general, see UNITY’s most recent Annual Report on Form 10 -K for the year ended December 31, 2024, filed with the Securities and Exchange Commission on March 7, 2025, as well as other documents that may be filed by UNITY from time to time with the Securities and Exchange Commission. This presentation concerns drug candidates that are under clinical investigation which have not yet been approved for marketing by the U.S. Food and Drug Administration. They are currently limited by Federa l law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. This presentation does not constitute a n offer or invitation for the sale or purchase of securities and has been prepared solely for informational purposes.
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3 ASPIRE Ph2B Study in DME: Topline Results ASPIRE Study Data Highlights UBX1325 Could Provide an Important Treatment Option for DME Patients with Poor Vision with Inadequate Response to Anti -VEGFs, if Approved • Patients on UBX1325 gained 5.2 letters at week 24 and 5.5 letters at week 36 • UBX1325 was Non-Inferior to Aflibercept at 9 out of 10 time points through 36 weeks (did not meet non-inferiority analysis at average of weeks 20 and 24*) • About 40% of UBX1325 patients did not need supplemental anti-VEGF through week 36 • UBX1325 generally outperformed Aflibercept in subjects who had less aggressive disease • Patients with poor vision who switched from prior Aflibercept to UBX1325 had the most consistent gains in BCVA and less variable CST • UBX1325 was well-tolerated with no instances of inflammation *primary analysis
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4 Senolytic Therapeutic Hypothesis Mechanism of Action
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5 UNITY is Developing Senolytic Medicines to Eliminate Senescent Cells to Restore Vascular Health and Improve Vision UNITY illustration of proposed mechanism of action Disease State Increased senescence burden Elevated inflammatory markers Loss of vascular integrity Loss of vision Repaired State (intended results) Senescent cells removed Resolution of inflammation Retinal vasculature restored Improvement in vision
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Ph2B ASPIRE Study in DME Patients 24- and 36-week Results Following Treatment with UBX1325
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7 ASPIRE: DME Phase 2b Study Design (Head-to-head against aflibercept) * Primary endpoint: BCVA change from baseline to average of weeks 20 and 24 (noninferiority) Secondary endpoints include: BCVA change from BL over time • CST change from BL over time • proportion of patients gaining ≥15, ≥10, ≥5, or ≥0 letters from BL • safety and tolerability • proportion of participants who do not require anti-VEGF rescue * Weeks 0 4 8 12 16 20 24 Screening ≥6 mo aVEGF Treatment UBX1325 10 µg IVT 24-Week Safety & Efficacy Data 4-6 weeks 36-Week Safety & Efficacy Data Patient Population: Participants with NPDR who have active DME despite treatment with ≥3 anti-VEGF injections in preceding 6 months; BCVA 70 – 30 ETDRS letters; CST >325µm • Duration: 36 Weeks; Randomization: 1:1 • Size: n=50 (25 /arm) Run-in aflibercept Endpoints = Aflibercept injection = UBX1325 injection = Sham procedure 28 32 36 Aflibercept control 2mg IVT every 8 weeks Q1 2025 Q2 2025
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8 Patient Baseline Characteristics Patients in BEHOLD Study came in with DME duration ~3.5y Parameter, Units (SD) Aflibercept 2 mg (N=26) UBX1325 10 µg (N=26) Age, Years 65.9 (8.73) 66.2 (7.57) HBA1c, % 7.5 (1.50) 7.9 (1.87) Diabetes Dx, Years 14.4 (12.17) 21.1 (13.35) DME Dx, Years 3.4 (2.93) 4.7 (3.36) BCVA, ETDRS letters 63.3 (8.75) 61.6 (7.24) CST , µm 405.4 (118.61) 374.8 (101.78) Anti VEGF prior 190 days Aflibercept - n (%) 15 (57.7) 13 (50) Bevacizumab - n (%) 6 (23.1) 7 (26.9) Faricimab - n (%) 2 (7.7) 6 (23.1) Ranibizumab - n (%) 3 (11.5) 0
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9 BCVA Change from baseline through week 36* (excluding data post-rescue) *Data from all subjects through week 24 and majority of subjects through week 36
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10 BCVA Change from baseline through week 36* (including post-rescue data) *Data from all subjects through week 24 and majority of subjects through week 36
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11 UBX1325 was Non-Inferior to Aflibercept across Multiple Analyses UBX1325 Aflibercept Confidence Interval (NI -4.5) At 24 weeks (excl. post-rescue data) 5.2 4.8 >90% Avg of weeks 20 and 24 (excl. post-rescue data) 3.6 5.1 ~88% At 24 weeks (incl. post-rescue data) 5.2 4.8 >90% Avg of 20 and 24 weeks (incl. post-rescue data)* 3.7 5.1 ~88%* At 36 weeks (excl. post-rescue data) 4.9 2.9 >90% Avg of 32 and 36 wks (excl. post-rescue data) 3.9 2.7 >90% At 36 weeks (incl. post-rescue data) 5.5 5.3 >90% Avg of 32 and 36 wks (incl. post-rescue data) 4.7 4.3 >90% *primary analysis
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12 BCVA Changes in CST<400 m (at Baseline) Group* *Data from all subjects through week 24 and majority of subjects through week 36 *excluding post-rescue data Pre-specified analysis, 60% of study population
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13 BCVA Changes in CST<400 m (at Baseline) Group* *Data from all subjects through week 24 and majority of subjects through week 36 *including post-rescue data Pre-specified analysis, 60% of study population
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14 BCVA Changes in CST<400 m (at Run-in) Group* *Data from all subjects through week 24 and majority of subjects through week 36 *excluding post-rescue data Pre-specified analysis
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15 BCVA Changes in CST<400 m (at Run-in) Group* *Data from all subjects through week 24 and majority of subjects through week 36 *including post-rescue data Pre-specified analysis
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CST Changes and Supplemental Anti-VEGF use
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17 CST Change from baseline through week 36* (including data post-rescue) *Data from all subjects through week 24 and majority of subjects through week 36
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18 Patients who Switched from Prior Aflibercept to UBX1325 had Stable CST* Prior Aflibercept Patients had greater CST stability Prior Faricimab Patients had poor CST control and skewed rescues in UBX1325 arm *pre-specified analysis Switched from Aflibercept to UBX1325 -majority of patients in our study Overall CST Increase Driven by severe patients, previously on faricimab
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19 Safety and AE Summary Source: t_14_3_1_1 Parameter Aflibercept (N = 26) UBX1325 10 µg (N = 26) Subjects with at least one TEAE 13 (50.0) 19 (73.1) Non-Ocular TEAE 9 (34.6) 9 (34.6) Grade >=3 TEAE 3 (11.5) 5 (19.2) Serious TEAE 2 (7.7) 5 (19.2) Ocular TEAE for Study Eye 10 (38.5) 17 (65.4) Treatment-related Ocular TEAE for Study Eye 7 (26.9) 8 (30.8) TEAE leading to death 0 0 Intraocular inflammation, endophthalmitis, retinal artery occlusion, or vasculitis 0 0
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20 ASPIRE Ph2B Study in DME: Key Insights • Patients on UBX1325 gained over 5 letters of vision through 36 weeks in a difficult to treat patient population • UBX1325 generally outperformed Aflibercept in subjects who had less aggressive disease (baseline CST < 400 m) • Patients who switch from Aflibercept to UBX1325 had the most consistent and durable vision gains • Patients who switched from Aflibercept to UBX1325 had generally stable CST ASPIRE Study Data Highlights UBX1325 Has a High Likelihood of Showing Numerical Superiority to Aflibercept with Fewer Injections in Subsequent Studies
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Unmet Need in DME and Current Treatment Paradigm
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22 Unmet Needs Exist for Patients with Diabetic Macular Edema 58% Consider this…DME Market Opportunity 50%+ discontinue aVEGF treatment by 6 months³ $ 4.8 billion Global Market $ 2.8 billion US Market Non-responders to anti-VEGF2,5 Suboptimal Response (BCVA)2,3,4,5,8 Declining Vision >24 mos3,5,6 Frequent Dosing Q4wk 28% of patients7 High treatment burden with chronic anti-VEGF 35.5 million people with DME worldwide 1 $9.6b global DME market by 2031 1 1.7 million in the US1 $5.5b in the US by 2031 1 DME=Diabetic Macular Edema; BCVA=Best Corrected Visual Acuity 1. Global Data. Diabetic Macular Market 2021-2031. 2022 Aug 01 and Downs P. Global Retinal Pharmaceuticals Market Report. Market Scope, 2023 ; 2. Sharma D et al. Mechanisms of Acquired Resistance to Anti-VEGF. iovs.arvojournals.org; ISSN: 1552-5783; May 2023 ; 3. Kuo B, et al. Long-term Treatment Patterns for Diabetic Macular Edema – Up to 6 Year Follow-up in the IRIS Registry. Ophthalmology Retina. Articles in Press. 2024 Jun 01; 4. Gonzales V et al. Early and Long-Term Responses to Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema. American Journal of Ophthalmology. 2016 Dec. 172:72:79; 5. Glassman AR et al, Diabetic Retinopathy Clinical Research Network.Ophthalmol. 2020 Aug; 127 (9): 1201-10; 6. Emami-Naeini, P et al. Ophthalmology Retina. 2024 Apr. Volume 8, Issue 4, 388 – 398. 7. Giust J et al. Treat and Extend Versus Bi-monthly Dosing with Aflibercept for the Treatment of Diabetic Macular Edema, One Year Outcomes (EVADE STUDY). ARVO Annual Meeting Abstract. 2018; 8. Sun J et al. Defining “Strong” versus “Weak” Response to Anti-VEGF Treatment for Center-Involved Diabetic Macular EdemaRetina. 2023 April 01; 43(4): 616–623.
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23 A Targeted Offering Designed to Address Patient Unmet Needs Focus UBX1325 efforts on the sub -optimal responder segment, while expanding to the declining vision patient segment No aVEGF Response Initial BCVA Improvement Tx Experienced Patients (Diabetic Macular Edema) Current DME Treatment Paradigm & Key Patient Segments Suboptimal Vision Vision Decline Maintained BCVASub-optimal Vision UBX1325 UBX1325 UBX1325
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Discussion with Dr. Bhisitkul