4D-150 / 4D Molecular Therap, Otsuka - LARVOL DELTA

4D Molecular Therapeutics…announced a strategic partnership with Otsuka Pharmaceutical Co., Ltd. (Otsuka) to develop and commercialize 4D-150 for the treatment of wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME) in the greater Asia-Pacific (APAC) region including Japan (GlobeNewswire) - "4DMT to receive $85 million upfront cash payment and expect to receive at least $50 million of cost sharing from Otsuka over the next three years for development activities supporting global registration. Up to $336 million in potential regulatory and commercial milestones and tiered double-digit royalties depending on net sales in Otsuka’s territories. Proceeds and cost sharing expected to support global Phase 3 clinical trial in DME and pre-commercial activities."

Licensing / partnership • Diabetic Macular Edema • Wet Age-related Macular Degeneration

4D-150 in Patients With Diabetic Macular Edema (clinicaltrials.gov) - P2 | N=72 | Active, not recruiting | Sponsor: 4D Molecular Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2028 ➔ Feb 2029 | Trial primary completion date: Feb 2028 ➔ Feb 2029

Enrollment closed • Trial completion date • Trial primary completion date • Diabetic Macular Edema • Diabetic Retinopathy • Gene Therapies • Ophthalmology • Retinal Disorders

4FRONT-2: Single Intravitreal Injection of 4D-150 in Patients With Macular Neovascularization Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: 4D Molecular Therapeutics

New P3 trial • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

PRISM: 4D-150 in Patients With Neovascular (Wet) Age-Related Macular Degeneration (clinicaltrials.gov) - P1/2 | N=215 | Recruiting | Sponsor: 4D Molecular Therapeutics | Trial completion date: Nov 2026 ➔ Jan 2031 | Trial primary completion date: Nov 2025 ➔ Mar 2027

Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

4DMT Announces RMAT Designation Granted by FDA for 4D-150 for DME (GlobeNewswire) - "4D Molecular Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted the Regenerative Medicine Advanced Therapy (RMAT) designation to 4D-150 for the treatment of diabetic macular edema (DME)....'The RMAT designation is based on the review of our results to-date from our ongoing 4D-150 SPECTRA DME study...'"

FDA event • Diabetic Macular Edema

Interim results from the phase 2b population extension cohort in the PRISM clinical trial evaluating 4D-150 in adults with neovascular (wet) age-related macular degeneration (ARVO 2025) - P1/2 | "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 • Age-related Macular Degeneration • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC

4DMT Announces First Patients Enrolled in 4FRONT-1 Phase 3 Clinical Trial Evaluating 4D-150 in Wet AMD (GlobeNewswire) - "4D Molecular Therapeutics...today announced that the first patients have been enrolled across multiple sites in the 4FRONT-1 Phase 3 clinical trial evaluating 4D-150 for the treatment of wet age-related macular degeneration (wet AMD)."

Trial status • Wet Age-related Macular Degeneration

4D-150 in Patients With Macular Neovascularization Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: 4D Molecular Therapeutics

New P3 trial • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

4D-150 Program Milestones (GlobeNewswire) - "4FRONT-1 and 4FRONT-2 expected to initiate in Q1 and Q3 2025, respectively; Two-year Phase 1/2a and 18-month Phase 2b PRISM data expected in Q4 2025; Primary endpoint 52-week topline data from both 4FRONT-1 and 4FRONT-2 expected in H2 2027."

Clinical data • New P3 trial • Wet Age-related Macular Degeneration

4DMT Presents Positive 52-Week Results from Phase 2b Cohort of PRISM Wet AMD Study and Long-term Durability Data Supporting 4D-150 4FRONT Global Registration Program (GlobeNewswire) - P1/2 | N=215 | PRISM (NCT05197270) | Sponsor: 4D Molecular Therapeutics | "Topline 52-Week Efficacy Results for 4D-150 3E10 vg/eye (Planned Phase 3 Dose) from Phase 2b Population Extension Cohort of PRISM (Data Cut-Off January 15, 2025): Phase 2b (n=30): Broad Wet AMD Disease Activity...Supplemental aflibercept injections: 83% reduction, representing 0.97 mean supplemental injections per patient over 52-weeks vs. 6.0 injections projected with on-label aflibercept 2 mg Q8W; 70% 0-1 injection; 57% injection-free...Phase 2b (n=15): Recently Diagnosed Subgroup...Supplemental aflibercept injections: 94% reduction, representing 0.33 mean supplemental injections per patient over 52-weeks vs. 6.0 injections; projected with on-label aflibercept 2 mg Q8W; 87% 0-1 injection; 80% injection-free....4D-150 Safety Update from PRISM (Data Cut-Off January 15, 2025)...2.8% (2 of 71) had 4D-150–related 1+ intraocular inflammation (IOI) (SUN/NEI scales)..."

P2b data • Wet Age-related Macular Degeneration

4DMT Announces Corporate Webcast to Review Interim 52-week Results from the Phase 2b Cohort of PRISM in a Broad Wet AMD Population (GlobeNewswire) - P1/2 | N=215 | NCT05197270 | Sponsor: 4D Molecular Therapeutics | "4D Molecular Therapeutics...announced that the Company will present the initial interim 52-week data from the Phase 2b Population Extension cohort of the PRISM clinical trial evaluating 4D-150 in a broad wet age-related macular degeneration (wet AMD) patient population at Angiogenesis, Exudation, and Degeneration 2025 being held virtually on February 8, 2025. The Company will host a webcast to discuss the PRISM interim data and additional analyses from the 4D-150 program in wet AMD and diabetic macular edema (DME) on Monday, February 10, 2025 at 8:00 a.m. ET."

P2b data • Diabetic Macular Edema

4DMT Announces Positive Interim Data from 4D-150 SPECTRA Clinical Trial in DME and Alignment with FDA on Registrational Path (GlobeNewswire) - P2 | N=72 | NCT05930561 | "Efficacy Results Through 32 Weeks: i) 3E10 vg/eye arm: Sustained gain of best corrected visual acuity (BCVA) of +8.4 letters; Sustained reduction of CST, as measured by optical coherence tomography (OCT), of -194 µm; ii) Supplemental injections: Post-aflibercept loading doses (3), 3E10 vg/eye achieved substantially fewer supplemental injections compared to 1E10 vg/eye and projected on-label aflibercept 2mg Q8W...Results to be presented in a corporate webcast on February 10, 2025; 52-week interim data update expected at a scientific conference in mid-2025...Next steps for DME development to be presented in a corporate webcast on February 10, 2025."

P2 data • Diabetic Macular Edema

Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies. (PubMed, Invest Ophthalmol Vis Sci) - "These findings support further development of 4D-150. Clinical trials are underway to establish the safety and efficacy of 4D-150 in individuals with wet AMD and DME."

Journal • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFB • VEGFC

PRISM: 4D-150 in Patients with Neovascular (Wet) Age-Related Macular Degeneration (clinicaltrials.gov) - P1/2 | N=215 | Recruiting | Sponsor: 4D Molecular Therapeutics | N=150 ➔ 215 | Trial completion date: Nov 2025 ➔ Nov 2026 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Enrollment change • Gene therapy • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

4DMT Announces Positive Phase 2 PRISM Interim Results for Intravitreal 4D-150 in a Broad Wet AMD Population Affirming Favorable Safety Profile and Robust Clinical Activity (GlobeNewswire) - P1/2 | N=150 | PRISM (NCT05197270) | Sponsor: 4D Molecular Therapeutics | "The cohort evaluated 4D-150 in wet AMD patients with broad disease activity (no minimum or maximum central subfield thickness (CST)) and prior anti-VEGF treatment (1-6 anti-VEGF injections in the prior 12 months)...The dose arms enrolled in the cohort were generally well-balanced. Mean CST was 329 μm and mean number of actual injections in the prior 12 months was 4.4; All three Phase 1 patients treated with 3E10 vg/eye previously reported as injection-free beyond 52 weeks remain injection-free through ~2 to 2.5 years of follow-up; 4D-150 continues to be safe and well tolerated across all patients dosed to date (n=139) in both PRISM (wet AMD, n=117) and SPECTRA (DME, n=22) clinical trials"

P2 data • Wet Age-related Macular Degeneration

4DMT Presents Injection-Free Subgroup Analyses from 4D-150 Phase 2 PRISM Randomized Dose Expansion Cohort in Wet AMD Patients with Severe Disease Activity & High Treatment Burden at the Clinical Trials at the Summit 2024 Meeting (GlobeNewswire) - "Upcoming 4D-150 Milestones: (i) Phase 2 PRISM Population Extension cohort (N=32) in the broader wet AMD patient population: Initial interim 24-week landmark analysis expected to be presented at the ASRS Annual Scientific Meeting on July 17, 2024; (ii) Phase 3 planning: Update on Phase 3 clinical trial design expected in Q3 2024; First Phase 3 clinical trial initiation expected in Q1 2025."

New P3 trial • P2 data • Wet Age-related Macular Degeneration

4DMT Presents Injection-Free Subgroup Analyses from 4D-150 Phase 2 PRISM Randomized Dose Expansion Cohort in Wet AMD Patients with Severe Disease Activity & High Treatment Burden at the Clinical Trials at the Summit 2024 Meeting (GlobeNewswire) - P1 | N=150 | PRISM (NCT05197270) | Sponsor: 4D Molecular Therapeutics |"4D Molecular Therapeutics...presented supplemental aflibercept injection-free subgroup analyses of the previously reported 24-week landmark results from the randomized Dose Expansion cohort from the Phase 2 PRISM clinical trial evaluating intravitreal 4D-150 in wet age-related macular degeneration (wet AMD) patients with severe disease activity and a high treatment burden....Stable visual acuity observed through Week 24 in both 4D-150 dose groups (n=22 injection-free patients); BCVA equal to or numerically higher than bimonthly aflibercept (n=10 patients) at all six time points through Week 24; High dose (3E10 vg/eye; n=12 patients): Sustained reduction and stabilization of CST fluctuations compared to bimonthly aflibercept at all six timepoints through Week 24."

P2 data • Wet Age-related Macular Degeneration

Interim results from the PRISM randomized phase 2 dose expansion trial evaluating 4D-150 in high anti-VEGF need individuals with neovascular (wet) age-related macular degeneration (ARVO 2024) - P1/2 | "Initial safety results from the PRISM phase 2 dose expansion study evaluating 4D-150 in adults with nAMD were consistent with observations from the dose exploration study, with no evidence of clinically significant ocular adverse events during follow-up for 12–36 weeks. 24-week interim safety and efficacy data will be presented."

Clinical • P2 data • Age-related Macular Degeneration • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC

4DMT links gene therapy to drop in Eylea injections, fueling plans to enter phase 3 (FierceBiotech) - P1/2 | N=150 | NCT05197270 | Sponsor: 4D Molecular Therapeutics | "4D Molecular Therapeutics has linked its gene therapy to a 90% reduction in treatment burden in wet age-related macular degeneration (AMD), emboldening it to start planning to enter phase 3 next year. 4D-150 uses an adeno-associated virus vector to deliver transgenes encoding aflibercept, the molecule that Regeneron sells as Eylea, and RNAi that inhibits VEGF-C....By the 24-week analysis, 4DMT had tracked an 89% and 85% reduction in annualized anti-VEGF injection rates in the high and low 4D-150 dose arms, respectively."

New P3 trial • P1/2 data • Age-related Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

4DMT Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for 4D-150 Genetic Medicine for Intravitreal Treatment of Wet AMD, the First RMAT Designation in Wet AMD (GlobeNewswire) - P1 | N=150 | PRISM (NCT05197270) | Sponsor: 4D Molecular Therapeutics | "4D Molecular Therapeutics...today announced that the U.S. Food and Drug Administration (FDA) has granted the RMAT designation for the investigational genetic medicine candidate 4D-150 for intravitreal treatment of wet age-related macular degeneration (wet AMD). The FDA granted RMAT designation based on the potential of 4D-150 to address the unmet medical need within this population...The designation follows interim Phase 1 PRISM clinical data for 4D-150 that demonstrated an encouraging safety, tolerability and clinical activity profile....4DMT is currently working with the FDA and EMA on preliminary Phase 3 clinical trial plans and expects to provide an update in February 2024 along with 4D-150 interim randomized Phase 2 PRISM trial data."

FDA event • New P3 trial • P1 data • P2 data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

4D-150 in Patients With Neovascular (Wet) Age-Related Macular Degeneration (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: 4D Molecular Therapeutics | N=65 ➔ 150 | Trial completion date: Sep 2026 ➔ Nov 2025 | Trial primary completion date: May 2026 ➔ Nov 2024

Enrollment change • Gene therapy • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

4D-150 in Patients With Diabetic Macular Edema (clinicaltrials.gov) - P2 | N=72 | Recruiting | Sponsor: 4D Molecular Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • Diabetic Macular Edema • Diabetic Retinopathy • Gene Therapies • Ophthalmology • Retinal Disorders

4DMT Completes Enrollment of Phase 2 PRISM Clinical Trial for Intravitreal 4D-150 in Patients with Wet AMD and Reports Interim Safety and Tolerability Data (GlobeNewswire) - "4D Molecular Therapeutics...announced that it has completed enrollment of the Phase 2 Dose Expansion stage of the PRISM clinical trial for patients with wet age-related macular degeneration (wet AMD) over approximately two quarters, and that no significant 4D-150 safety events or inflammation have been reported to date....Initial interim Phase 2 clinical activity data, and further safety data updates, are expected to be reported in H1 2024. We expect to have initial discussions with the FDA on Phase 3 pivotal trial design for 4D-150 for patients with wet AMD in Q4 2023, and we expect to provide an update on pivotal trial plans in Q1 2024."

Enrollment closed • New P3 trial • P2 data • Age-related Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

4D-150 in Patients With Diabetic Macular Edema (clinicaltrials.gov) - P2 | N=72 | Not yet recruiting | Sponsor: 4D Molecular Therapeutics

Gene therapy • New P2 trial • Diabetic Macular Edema • Diabetic Retinopathy • Gene Therapies • Ophthalmology • Retinal Disorders

Interim results for the Phase 1/2 PRISM Trial evaluating 4D-150, a dual-transgene intravitreal genetic medicine in individuals with neovascular (wet) age-related macular degeneration (ARVO 2023) - P1/2 | "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 • P1/2 data • Age-related Macular Degeneration • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC