4D 150 DME Clinical Trial: Part 1 Interim 32 week Results

Published: 2025-01-10 12:16:11 ET FDMT

Intravitreal 4D-150

DME Clinical Trial: Part 1 Interim 32-week Results

January 10, 2025

Positive Interim Data & FDA

Feedback Supports

Advancement of 4D-150 to

Phase 3 in DME

Interim data support potential for maintenance of vision and anatomy improvements with substantially fewer injections than standard of care

Additional details at

Corporate Webcast February

10, 2025

Data cutoff date, December 13, 2024. DME, diabetic macular edema; BCVA, best corrected visual acuity; CST, central subfield thickness.

Part 1: Designed to Enroll Patients with High CST and Employed Stringent Supplemental Criteria, with Focus on Safety & Dose Selection

Key Objectives

Key Eligibility Criteria

Evaluate safety & tolerability

Identify dose level for further evaluation

Diagnosis within 2 years, CST ≥350 μm (includes treatment naïve)

Confirmed anti-VEGF response (CST decrease ≥40 μm at Week -1 versus Week -8)*

32-week Results

Durezol®

(40 weeks from baseline)

16-week taper starting at Day -3

Week

-8

-4 D1

12 16 20 24 28 32 36 40 44 48 52 104

4D-150 3E10 vg/eye(n=9)

                

4D-150 1E10 vg/eye(n=12)

                

4D-150 5E9 vg/eye(n=1)

                

Baseline

Reference for

Supplemental

Aflibercept

Supplemental Aflibercept Criteria (starting at Week 8)

Primary

 CST increase ≥50 μm

endpoint†

*Assessed by SD-OCT and confirmed by independent reading center.

† Safety and tolerability (frequency and severity of treatment emergent adverse events). CST, central subfield thickness: defined as thickness of 1mm area from ILM to BM.

SPECTRA Disease Activity Criteria for Supplemental Treatment Are Stringent Compared to Other Trials and Did Not Require Vision Decrease

Product

Trial

Disease Activity Criteria for Supplemental Treatment or Shortened Dose Interval

VIVID/VISTA1

≥10 letter loss on 2 consecutive visits or ≥15 letter loss at any visit from the best previous

measurement ANDBCVA worse than baseline

PHOTON2

>10 letter loss in BCVA from Week 12 due to persistent or worsening DME AND>50 µm increase

in CRT from Week 12

YOSEMITE/RHINE3

≥5 letter loss in BCVA AND≥10% increase in CST from reference CST

≥20% increase in CST from reference CST independent of any BCVA change

≥10 letter loss in BCVA due to DME

VERONA4

5-9 letters loss in BCVA AND>75 µm of new fluid at two consecutive visits

≥100 µm increase in CST (new fluid) vs. baseline

Lack of 10% reduction in CST compared to baseline†

≥50 µm increase in CST‡

4D-150

SPECTRA Part 1

(supplemental injections continue until change in CST is ≤30 μm on 2 consecutive visits or CST

≤325 µm)

*After Week 24. † After Week 12. ‡After Week 8. BCVA, best corrected visual acuity; CST, central subfield thickness; ETDRS, Early Treatment Diabetic Retinopathy Study.

1. Korobelnik et al. Ophthalmology 2014;121:2247-54. 2. Brown et al. Lancet 2024;403:1153-63. 3. Wykoff et al. Lancet 2022;399:741-55. 4. EyePoint Corporate Presentation, October 2024.

Study Population: Baseline CST, BCVA, and Prior Treatment Status Balanced Across Dose Arms

3E10 vg/eye

(n=9)

1E10 vg/eye

(n=12)

5E9 vg/eye

(n=1)

Total

(N=22)

Central subfield thickness, ∝m

Mean

513

488

515

499

(range)

(382-671)

(356-669)

(356-671)

BCVA, ETDRS letters

Mean

(range)

(41-79)

(32-84)

Treatment Experienced, n (%)

7 (78)

9 (75)

16 (73)

BCVA, best corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study.

SPECTRA Designed With Fewer Loading Doses and Enrolled Population With High CST and Majority Treatment Experienced

Selected

4D-150

Studies:

VIVID/VISTA1

PHOTON2

YOSEMITE/RHINE3

VERONA4

Phase 3

Phase 1/2

Anti-VEGF Loading Doses

Mean CST at Baseline (µm)

Treatment Experienced at Baseline (%)

520

500

480

460

440

420

400

~500

~480

~450

~410

~500

100%

80%

60%

40%

20%

100%

73%

VISTA ~43%

~44%

~25%

VIVID ~9%

CST, central subfield thickness; BCVA, best corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study.

Sources: 1. Korobelnik et al. Ophthalmology 2014;121:2247-54. 2. Brown et al. Lancet 2024;403:1153-63. 3. Wykoff et al. Lancet 2022;399:741-55. 4. EyePoint Corporate Presentation, October 2024. *Given concurrently with DURAVYU.

4D-150 Continues to be Well Tolerated

Data cutoff date, December 13, 2024.

No Intraocular Inflammation and All Patients Completed Prophylactic Topical Steroids on Schedule and Remained Completely Off Steroids

Anterior Chamber Cells

Vitreous Cells

Topical

Corticosteroid

3E10 vg/eye

(N=9)

NEI/SUN Score 0 (none) 1+ 2+ 3+ 4+

1E10 vg/eye*

(N=11)

5E9 vg/eye

Week

Data cutoff date, December 13, 2024. *Excludes patient with early termination due to death (unrelated to 4D-150) prior to completion of a post-baseline assessment. NEI, National Eye Institute; SUN, Standardization of Uveitis Nomenclature; TR, trace (not observed); PC, pigmented cells (not observed); X, missed visit.

4D-150 3E10 vg/eye: Sustained Improvement in Visual Acuity Through 32 Weeks (+8.4 Letters vs Baseline)

4D-150

Estimated gene

expression ramp-up

period

3E10 vg/eye (n=9)

Aflibercept

1E10 vg/eye (n=11)*

Mean change in BCVA

(ETDRS letters)

Illustrative residual effect of

Week 2 loading dose

+8.4

+7.1

-8

-4

Week

Mean per

patient

Supplemental Injections**, n

3E10 vg/eye (n=9)

0.6

1E10 vg/eye (n=11)

1.4

Data cutoff date, December 13, 2024.

*Excludes patient with early termination due to death (unrelated to 4D-150) prior to completion of a post-baseline assessment. **No patient in 3E10 or 1E10 vg/eye arm would have received a supplemental injection based on disease activity measurement at time of first supplemental injection based on disease activity worsening criteria in VIVID/VISTA or PHOTON.

BCVA, best corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study.

Disclaimer

4D Molecular Therapeutics Inc. published this content on January 10, 2025, and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on January 10, 2025 at 17:15:33.433.