UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02 Results of Operations and Financial Condition.
On January 10, 2025, 4D Molecular Therapeutics, Inc. (the “Company”) announced a strategically focused pipeline and resulting updated cash runway guidance.
As a result of its strategically focused pipeline, resource reallocation, and discontinued future investment plans on non-core product candidates, each of which is described in further detail in Item 8.01 of this Current Report on Form 8-K, the Company has extended its expected cash runway. Under the updated operating plan, based on unaudited cash, cash equivalents and marketable securities of $506 million as of December 31, 2024, the Company now expects its current cash to fund operations into 2028. Cash runway includes full execution and topline 52-week data from 4FRONT-1 and 4FRONT-2 Phase 3 clinical trials in wet age-related macular degeneration (“wet AMD”), and ongoing early-stage development for diabetic macular edema (“DME”) and cystic fibrosis (“CF”). Additionally, the Company will explore value-creating partnership opportunities and other strategic financing options.
Item 8.01 Other Events
INTERIM DATA FROM 4D-150 SPECTRA PART 1 CLINICAL TRIAL
On January 10, 2025, the Company reported positive topline interim data from Part 1 of the SPECTRA clinical trial evaluating 4D-150 in DME and alignment with the U.S. Food and Drug Administration (“FDA”) on registrational pathway for 4D-150 in DME.
Clinical Trial Design & Interim Data from 4D-150 SPECTRA Part 1 Clinical Trial (Data Cutoff of December 13, 2024):
4D-150 DME Phase 3 Regulatory Update & Next Steps
As a result of the interim data from Part 1 of the SPECTRA clinical trial, the Company has selected 3E10 vg/eye as the Phase 3 dose for 4D-150 in DME. Based on data generated to date for 4D-150 in both the SPECTRA and PRISM clinical trials, FDA is aligned that a single Phase 3 clinical trial, combined with data from the two planned Phase 3 clinical trials in the 4FRONT wet AMD program, would be acceptable as the basis of a BLA submission for 4D-150 in DME. Per FDA feedback, the Company may proceed to Phase 3 (with SPECTRA Part 2 no longer needed) and is aligned with key design elements of a Phase 3 clinical trial with approximately 300-400 patients total with a primary endpoint of BCVA noninferiority vs. on-label aflibercept 2mg (5 loading doses and Q8W), and revised supplemental injection criteria (less stringent compared to Part 1 SPECTRA, in line with prior successful Phase 3 DME clinical trials).
The Company plans to present the next steps for DME development in a corporate webcast on February 10, 2025.
On January 10, 2025, the Company posted an investor presentation on its website containing topline interim data from Part 1 of the SPECTRA clinical trial. The investor presentation is furnished as Exhibit 99.1 of this Current Report on Form 8-K and is incorporated herein by reference. The presentation furnished as Exhibit 99.1 hereto shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any registration statement or other document filed under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
PIPELINE FOCUS AND CASH RUNWAY
On January 10, 2025, the Company announced a strategically focused pipeline, updated Phase 3 4FRONT program plans, initial 4FRONT guidance and resulting updated cash runway guidance.
Strategically Focused Pipeline
Core Programs: Updates & Upcoming Milestones
Large Market Ophthalmology Focus
4D-150 is a potential backbone therapy that is designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) targeted to the retina with a single, well tolerated, intravitreal injection. 4D-150 is being developed for wet AMD and DME, each of which affects millions of patients globally, with the goal of preserving vision and relieving patients from burdensome repeated bolus injections, which can total up to 12 per year. The Company will focus the majority of its research and development resources and operations on global development and pre-commercial planning for 4D-150 in wet AMD.
Pulmonology Program
The Company’s proprietary A101 vector is the first known AAV vector to demonstrate successful delivery and expression of the CFTR transgene in the lungs of people with CF following aerosol delivery. Given A101-enabled product candidate 4D-710’s proof of delivery, safety data and initial clinical activity signals, and ongoing support from the Cystic Fibrosis Foundation and collaboration with Therapeutics Development Network, the Company intends to complete Phase 1 enrollment in H1 2025, approach the FDA with a pivotal trial proposal mid-2025, and evaluate additional funding options to further advance 4D-710 into late-stage development.
Programs with Reduced Capital Allocation
While the Company believes the therapeutics below hold significant potential, at this time no further significant investment is expected on these programs, pending additional financing or partnerships.
Following a comprehensive review of its portfolio, the Company has decided to terminate the development of the early-stage rare disease clinical programs evaluating 4D-110 for Choroideremia and 4D-125 for X-Linked Retinitis Pigmentosa.
Given the promising portfolio of product candidates and vectors owned and developed by the Company, the Company will not be investing additional capital into new preclinical product candidates at this time.
Forward-Looking Statements
This Current Report on Form 8-K contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, but are not limited to, statements regarding the Company’s clinical development plans for its product candidates, including 4D-150 and 4D-710, timing for the announcement of results from ongoing clinical trials, anticipated resource allocations and cash runway, the therapeutic
potential, and clinical benefits and market potential of 4DMT’s product candidates, as well as the regulatory interactions regarding 4D-150. In some cases you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including risks and uncertainties that are described in greater detail in the section entitled “Risk Factors” in the Company’s most recent Quarterly Report on Form 10-Q as well as any subsequent filings with the Securities and Exchange Commission. The Company expressly disclaims any intent or obligation to update these forward-looking statements, except as required by law.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
Exhibit Number |
Description |
99.1 |
Investor Presentation of 4D Molecular Therapeutics, Inc., dated January 10, 2025 |
104 |
Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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4D MOLECULAR THERAPERUTICS, INC. |
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Date: |
January 10, 2025 |
By: |
/s/ Uneek Mehra |
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Uneek Mehra |
Intravitreal 4D-150 DME Clinical Trial: Part 1 Interim 32-week Results January 10, 2025 EXHIBIT 99.1
Legal Disclaimer This Presentation contains forward looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this Presentation, including statements regarding our clinical development plans, strategy, future operations, future financial position, prospects, plans, objectives of management, and implied and express statements regarding the therapeutic potential, clinical benefits of and market potential of our product candidates are forward looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward looking statements, although not all forward looking statements contain these identifying words. We may not actually achieve the plans, intentions, or expectations disclosed in these forward looking statements, and you should not place undue reliance on these forward looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward looking statements. In addition, the forward looking statements included 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 in the future, we specifically disclaim any obligation to do so. These forward looking statements should not be relied upon as representing our views as of any date subsequent to the date of this Presentation. This Presentation discusses our product candidates that are under preclinical study and in clinical trials, and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of our product candidates for the therapeutic use for which they are being studied. This Presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. This Presentation shall not constitute an offer to sell or the solicitation of an offer to buy securities.
4D-150 continues to be well tolerated: No intraocular inflammation observed at any timepoint or dose level All patients completed the 16-week topical steroid taper on schedule and remained completely off steroids No hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions 4D-150 (3E10 vg/eye, n=9) 32-week efficacy results: Sustained gain in BCVA: +8.4 letters Sustained reduction of CST: –194 µm 86% reduction in injection burden vs. projected on-label aflibercept 2mg Q8W 61% reduction in injection burden vs. 1E10 vg/eye, dose response observed FDA alignment: Single Phase 3 clinical trial acceptable for BLA submission in DME, based on review of interim data from SPECTRA and PRISM and planned global Phase 3 program for wet AMD Company may proceed to Phase 3 per FDA feedback, SPECTRA Part 2 no longer needed Next steps: 3E10 vg/eye selected as Phase 3 dose Detailed results to be presented in corporate webcast on February 10, 2025 SPECTRA 52-week interim data update: Mid-2025 at scientific conference 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 *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. Supplemental Aflibercept Criteria (starting at Week 8) CST increase ≥50 μm Injections continue until change in CST is ≤30 μm on 2 consecutive visits or CST is ≤325μm Primary endpoint† Durezol® 16-week taper starting at Day -3 Baseline Diagnosis within 2 years, CST ≥350 μm (includes treatment naïve) Confirmed anti-VEGF response (CST decrease ≥40 μm at Week –1 versus Week –8)* Key Eligibility Criteria Evaluate safety & tolerability Identify dose level for further evaluation Key Objectives 32-week Results (40 weeks from baseline) Reference for Supplemental Aflibercept
SPECTRA Disease Activity Criteria for Supplemental Treatment Are Stringent Compared to Other Trials and Did Not Require Vision Decrease *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. 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 AND BCVA 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 VERONA4 ≥10 letter loss in BCVA due to DME 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† 4D-150 SPECTRA Part 1 ≥50 µm increase in CST‡ (supplemental injections continue until change in CST is ≤30 µm on 2 consecutive visits or CST ≤325 µm)
Study Population: Baseline CST, BCVA, and Prior Treatment Status Balanced Across Dose Arms BCVA, best corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study. 1 patient in 1E10 vg/eye arm terminated the study due to death unrelated to 4D-150 prior to completion of a post-baseline assessment 3E10 vg/eye (n=9) 1E10 vg/eye (n=12) 5E9 vg/eye (n=1) Total (N=22) Central subfield thickness, mm Mean (range) 513 (382–671) 488 (356–669) 515 499 (356–671) BCVA, ETDRS letters Mean (range) 63 (41–79) 62 (32–84) 68 63 (32–84) Treatment Experienced, n (%) 7 (78) 9 (75) 0 16 (73)
SPECTRA Designed With Fewer Loading Doses and Enrolled Population With High CST and Majority Treatment Experienced 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. Anti-VEGF Loading Doses Mean CST at Baseline (µm) Treatment Experienced at Baseline (%) Selected Studies: 4D-150 PHOTON2 VIVID/VISTA1 YOSEMITE/RHINE3 VERONA4 VIVID VISTA Phase 3 Phase 1/2
4D-150 Continues to be Well Tolerated Data cutoff date, December 13, 2024. 4D-150 continues to be well tolerated with no intraocular inflammation at any timepoint at any dose level All patients completed the 16-week topical steroid taper on schedule and remained completely off steroids No hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions
No Intraocular Inflammation and All Patients Completed Prophylactic Topical Steroids on Schedule and Remained Completely Off Steroids 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. Anterior Chamber Cells Vitreous Cells X X X X 0 2 8 12 16 20 24 28 32 X X X X 0 2 8 12 16 20 24 28 32 Week X 0 (none) 1+ 3+ 4+ 2+ 5E9 vg/eye Topical Corticosteroid NEI/SUN Score 3E10 vg/eye (N=9) 1E10 vg/eye* (N=11) Missed Visit
4D-150 3E10 vg/eye: Sustained Improvement in Visual Acuity Through 32 Weeks (+8.4 Letters vs Baseline) Week Supplemental Injections**, n 3E10 vg/eye (n=9) 0 0 2 0 2 1 0 0.6 1E10 vg/eye (n=11) 1 2 2 4 2 1 3 1.4 +8.4 +7.1 Aflibercept Mean per patient 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. Estimated gene expression ramp-up period 2 4D-150 Illustrative residual effect of Week 2 loading dose
Eylea Phase 3 Studies in DME1 Compared 5 Loading Doses + Q4W or Q8W vs. Laser On-label Eylea Improves CST ~165 µm But Requires High Treatment Burden 1. Korobelnik et al. Ophthalmology 2014;121:2247–54. Aflibercept 2mg 5 Load + Q8W Eylea consistently achieved CST improvements of ~165 µm in DME patients Eylea saw CST rebounds ~8 weeks after last dose of the loading dose regimen, rebounds continue in Q8W arms 1 2 1 1 2 2
4D-150 3E10 vg/eye: Sustained Improvement in Anatomic Control Through 32 Weeks (–194 µm vs Baseline) -194 -153 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. CST, central subfield thickness. Supplemental Injections**, n 3E10 vg/eye (n=9) 0 0 2 0 2 1 0 0.6 1E10 vg/eye (n=11) 1 2 2 4 2 1 3 1.4 Mean per patient 4D-150 2 Aflibercept Illustrative residual effect of Week 2 loading dose Estimated gene expression ramp-up period
3E10 vg/eye Post-loading Phase: 86% Reduction in Treatment Burden vs. Projected On-label Aflibercept 2mg Q8W; Dose Response in Favor of 3E10 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. **Excludes n=1 patient who did not receive the Week 2 aflibercept. This patient received 1 supplemental injection through 32 weeks. Mean cumulative function from Cox proportional hazard regression model for recurrent events was used to estimate the mean cumulative number of supplemental aflibercept injections. Loading Phase 1 injection 2 injections 0 injections Cumulative Injections (Weeks 8–32) 3E10 vg/eye (n=9) 0.6 1.4 4.0 86% reduction vs. projected on-label aflibercept 2mg Q8W 5 of 8 Injection-free in patients treated per protocol** 61% reduction vs. 1E10 vg/eye
4D-150 continues to be well tolerated: No intraocular inflammation observed at any timepoint or dose level All patients completed the 16-week topical steroid taper on schedule and remained completely off steroids No hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions 4D-150 (3E10 vg/eye, n=9) 32-week efficacy results: Sustained gain in BCVA: +8.4 letters Sustained reduction of CST: –194 µm 86% reduction in injection burden vs. projected on-label aflibercept 2mg Q8W 61% reduction in injection burden vs. 1E10 vg/eye, dose response observed FDA alignment: Single Phase 3 clinical trial acceptable for BLA submission in DME, based on review of interim data from SPECTRA and PRISM and planned global Phase 3 program for wet AMD Company may proceed to Phase 3 per FDA feedback, SPECTRA Part 2 no longer needed Next steps: 3E10 vg/eye selected as Phase 3 dose Detailed results to be presented in corporate webcast on February 10, 2025 SPECTRA 52-week interim data update: Mid-2025 at scientific conference 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.
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On-label Aflibercept Improves CST by ~150-180 µm with 7 Total Injections Through 40 Weeks; Rebound Observed at Week 24 Despite 5 Loading Doses 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. PHOTON2 Aflibercept 2mg Q8W results through week 40 achieved with 7 injections Despite 5 loading doses, rebound observed 8 weeks later 1 1 3 3