- Expands Large Market Ophthalmology Portfolio Following Positive Clinical Data in wet Age-Related Macular Degeneration to Include Diabetic Macular Edema Clinical Program and Geographic Atrophy Preclinical Program
- Expands Large Market Pulmonology Portfolio Following Positive Clinical Data in Cystic Fibrosis to Include Alpha-1 Antitrypsin Deficiency Preclinical Program
- Reports Program Updates and Interim Clinical Data from Phase 1/2 Fabry Disease Cardiomyopathy Trials; Full Clinical Data to be Reported at WORLDSymposium in
February 2023 - Cash Guidance Unchanged and Sufficient to Fund Operations into H1 2025
“These updates highlight 4DMT’s diversified and growing product pipeline that is driven by our underlying directed evolution vector platform and our robust product design and development engine for genetic medicines,” said
Ophthalmology Product Candidate Portfolio
4D-150 for the Intravitreal Treatment of Patients with Wet Age-Related Macular Degeneration (wet AMD) and Patients with Diabetic Macular Edema (DME)
Filed IND Application for Phase 2 SPECTRA Clinical Trial with Intravitreal 4D-150 in Patients with DME:
4DMT filed an Investigational New Drug (IND) Application for 4D-150 in patients with DME in
Initiated Randomized Phase 2 of PRISM Clinical Trial of Intravitreal 4D-150 in Patients with Wet AMD:
The Phase 2 stage of the Phase 1/2 PRISM clinical trial of 4D-150 in patients with wet AMD consists of three treatment groups. Patients will be randomized in masked fashion to receive a single intravitreal injection at one of two dose levels of 4D-150 (3E10 and 1E10 vg/eye) or aflibercept in a 2:2:1 ratio (n=50 patients). This Phase 2 stage of the trial was initiated in
Expanded Portfolio with Preclinical Product Candidate 4D-175 for Geographic Atrophy (GA):
Geographic atrophy is a highly prevalent disease with significant unmet medical need. It is estimated that there are over one million individuals with GA in
Preclinical development was initiated for a new product candidate designed for single dose intravitreal treatment of patients with GA; the product candidate will utilize 4DMT’s proprietary R100 intravitreal vector currently used in the wet AMD and DME programs, and a transgene payload that addresses a complement pathway target (undisclosed). We anticipate that development and manufacturing activities will benefit from prior clinical experience and GMP manufacturing of three other R100-based ophthalmology product candidates that have been dosed in ophthalmology patients with wet AMD, X-Linked Retinitis Pigmentosa (XLRP) and choroideremia.
Arshad M Khanani, M.D., M.A., FASRS, Managing Partner and Director of Clinical Research at
Program Updates on Rare Disease Product Candidates 4D-125 for XLRP and 4D-110 for Choroideremia:
Enrollment on the Phase 1/2 clinical trials for 4D-125 and 4D-110 was completed in the fourth quarter of 2022: 14 patients have been treated with 4D-125, and 13 with 4D-110. The safety and tolerability profiles for both product candidates remain unchanged from prior data releases. We will continue to follow these patients for 24 months to assess the magnitude and durability of key imaging endpoint changes in evaluable patients. We anticipate providing program and clinical data updates in 2024.
Pulmonology Product Portfolio
4D-710 for the Aerosol Treatment of Patients with Cystic Fibrosis (CF) Lung Disease
Treated First Patient in High Dose Cohort on Phase 1/2 Clinical Trial with Aerosol Delivered 4D-710 in Patients with Cystic Fibrosis Lung Disease that is Not Amenable to Treatment with CFTR Modulator Therapy:
Following three patients dosed in cohort 1 (1E15 vg), the first patient in the high dose cohort (2E15 vg) was treated in
Expanded Portfolio with Initiation of
Preclinical research was initiated with the combination of 4D-710 with CFTR modulator therapy to support development of 4D-710 in the approximately 85% of CF patients amenable to CFTR modulator therapy.
Expanded Portfolio with Addition of Preclinical Product Candidate 4D-725 for Alpha-1 Antitrypsin Deficiency:
Alpha-1 Antitrypsin Deficiency is a prevalent disease, affecting approximately 200,000 individuals in
Preclinical development was initiated for a new product candidate designed for single dose aerosol treatment of patients with alpha-1 antitrypsin lung disease; this product candidate utilizes 4DMT’s proprietary A101 aerosol vector currently used in the CF program and expresses a genetically-validated transgene. We anticipate that development and manufacturing activities will benefit from prior clinical experience and GMP manufacturing of the A101-based 4D-710 product candidate that has been dosed in CF patients.
“We are excited by the demonstration of widespread CFTR∆R transgene expression in the airways of the first three Phase 1/2 study participants with CF lung disease, previously reported at NACFC, as well as the initial favorable safety results,” said
4D-310 for Fabry Disease Cardiomyopathy
Interim 4D-310 INGLAXA Phase 1/2 Clinical Trials Data in Patients with Fabry Disease:
Two clinical trials, one in the
Cardiac Functional, Imaging, and Biopsy Data Promising in Patients Based on Evaluable Data to Date:
Cardiac clinical endpoint assessments (functional and imaging) were performed over time, and the
One patient underwent cardiac biopsy at week 6 (n=1 in
Cardiac Clinical Endpoint Methods and Results
- Cardiopulmonary Exercise Testing to assess exercise function by peak VO2 (FDA-recommended primary endpoint): Improvement in two of three patients
- KCCQ QOL to assess cardiomyopathy-associated quality-of-life (FDA-recommended primary endpoint): Improvement in two of two patients abnormal at baseline; third patient remained stable at 100% through 12 months
- Echocardiography to assess left ventricular function by global longitudinal strain: Improvement in three of three patients (FDA-recommended supportive clinical trial endpoint)
- Cardiac MRI to assess substrate in heart: Improvement in two of two patients (one pending)
4D-310 Cardiac clinical endpoints results summary (data cut-off date of
Pts ( | Native T1 (CMR) (ms) | GLS (Echo) | Peak VO2 (CPET) (mL/kg/min) | Cardiac QoL (KCCQ-23) | ||||||
Baseline | Week 52 | Baseline | Week 52 | Baseline | Week 52 | Baseline | Week 52 (Overall Summary Score) | Week 52 (Clinical Summary Score) | ||
1 | Abnormal | Improved (+30.6) | Borderline | Improved (-2.5%) | Abnormal | Improved (+2.0) | Normal | Stable 100% | Stable 100% | |
2 | Abnormal | Improved (+9.1) | Normal | Improved (-1.1%) | Abnormal | Improved (+7.0) | Abnormal | Improved (+11.7) | Improved (+5.7) | |
3 | Abnormal | Pending | Borderline | Improved (-3.3%) | Abnormal | -2.2 | Abnormal | Improved (+7.3) | Improved (+10.4) | |
ERT natural history | Worsened (-4.0)1 | Worsened (+1.1%)1 | Worsened (-1.8)2 | n.a. | n.a. |
- Minimal detectable difference (MDD): native T1 (29 ms); GLS (1.5%); Borderline: GLS range of -16 to -18%
- Minimal clinically important difference (MCID): peak VO2 (1.5 mL/kg/min); KCCQ (summary scores 5 points)
- References: 1. Nordin et al. Circ Cardiovasc Imaging 2019:e009430; 2. Lobo,
Internal Medicine Journal 2008;38:407
Oral presentation and full clinical trial data release planned for WORLDSymposium on
Alignment with FDA on Pivotal Clinical Trial Primary Endpoints for 4D-310 for Fabry Disease Cardiomyopathy:
4DMT proposed, and FDA communicated alignment with, use of the following endpoints in a potential pivotal trial:
- Primary endpoint: Change from baseline at 12 and 24 months in cardiopulmonary exercise testing (peak VO2).
- Primary endpoint: Kansas City Cardiomyopathy Questionnaire (KCCQ; quality of life).
- Supportive endpoint: Left ventricular function as assessed by global longitudinal strain on echocardiography.
Next Steps for 4D-310 Clinical Development:
As of
About 4D-150 and wet AMD and DME
4D-150 is comprised of our targeted and evolved intravitreal vector, R100, and a payload that expresses both aflibercept and a VEGF-C RNAi. R100 was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform; we created this platform utilizing principles of directed evolution, a Nobel Prize-winning technology. This dual transgene payload inhibits 4 angiogenic factors: VEGF A, B, C and PlGF. 4D-150 is designed for a single low dose intravitreal delivery.
Wet AMD is a highly prevalent disease with estimated incidence rate of 200,000 new patients per year in
DME is a highly prevalent disease with significant unmet medical need. It is estimated that there are approximately one million individuals with DME in
About 4D-710 and Cystic Fibrosis
4D-710 is comprised of our targeted and evolved vector, A101, and a codon-optimized CFTR∆R transgene. A101 was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform; we created this platform utilizing principles of directed evolution, a Nobel Prize-winning technology. 4D-710 has the potential to treat a broad range of patients with cystic fibrosis, independent of the specific CFTR mutation, and is designed for aerosol delivery to achieve CFTR expression within lung airway epithelial cells. 4D-710 is being initially developed in the approximately 15% of patients whose disease is not amenable to existing CFTR modulator medicines targeting the CFTR protein. In patients with CFTR mutations whose disease is amenable to modulator medicines, the improvement in lung function is incomplete and is variable. We therefore expect to potentially develop 4D-710 in this broader patient population, as a single agent and/or in combination with CFTR modulator small molecule medicines.
Cystic fibrosis is a major inherited disease caused by mutations in the CFTR gene. According to the
About 4D-310 and Fabry Disease
4D-310 utilizes the targeted and evolved C102 vector to deliver a functional copy of the GLA gene and was designed for a unique mechanism of action, specifically to directly correct the AGA enzyme function within cardiomyocytes (heart muscle cells) after a single IV administration. C102 was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform; we created this platform utilizing principles of directed evolution, a Nobel Prize-winning technology. The product is designed to generate both high local production of AGA directly within critically affected organs, including heart, blood vessels and kidney, as well as the potential for sustained blood levels of AGA for systemic cross-correction. This product design has the potential to address the cardiomyopathy in these patients that is the leading cause of death, as well as other significant unmet medical needs in patients with Fabry disease.
Affecting more than 50,000 people in the
About 4DMT
4DMT is a clinical-stage biotherapeutics company harnessing the power of directed evolution for targeted genetic medicines. 4DMT seeks to unlock the full potential of genetic medicines using its proprietary vector invention platform, Therapeutic Vector Evolution, which combines the power of the Nobel Prize-winning technology directed evolution. We invented synthetic vector libraries with approximately one billion synthetic AAV capsid-derived sequences to invent targeted and evolved vectors for use in our products. All of our vectors are proprietary to 4DMT and were invented at 4DMT, including the vectors utilized in our clinical-stage and preclinical pipeline products: R100, A101 and C102. The company is initially focused on five clinical-stage products in three therapeutic areas for both rare and large market diseases: ophthalmology, pulmonology and cardiology (Fabry disease cardiomyopathy). The 4DMT targeted and evolved vectors were invented with the goal of being delivered at relatively low doses through clinically routine, well tolerated and minimally invasive routes of administration, transducing diseased cells in target tissues efficiently, having reduced immunogenicity and, where relevant, having resistance to pre-existing antibodies. The five 4DMT product candidates in clinical development are as follows: 4D-150 for wet AMD and DME, 4D-710 for cystic fibrosis lung disease, 4D-310 for Fabry disease cardiomyopathy, 4D-125 for XLRP and 4D-110 for choroideremia. The 4DMT preclinical product candidates in development are as follows: 4D-175 for geographic atrophy and 4D-725 for alpha-1 antitrypsin deficiency.
4D-150, 4D-310, 4D-710, 4D-125 and 4D-110 are in clinical trials and have not yet been approved for marketing by the FDA or any other regulatory authority. No representation is made as to the safety or effectiveness of 4D-150, 4D-310, 4D-710, 4D-125, and 4D-110 for the therapeutic use for which they are being studied. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the therapeutic potential and clinical benefits, as well as the plans and related timing for the clinical development of 4D-150, 4D-310, 4D-710, 4D-125 and 4D-110. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including risks and uncertainties that are described in greater detail in the section entitled "Risk Factors" in 4D Molecular Therapeutics’ most recent Quarterly Report on Form 10-Q, as well as any subsequent filings with the
Contacts:
Media:
Evoke Canale
Katherine.Smith@evokegroup.com
Investors:
Chief Financial Officer
amoretti@4dmt.com
ikoffler@lifesciadvisors.com
917-734-7387
![](https://ml.globenewswire.com/media/MGM5MDIyNmQtODY1NC00ZmQ3LWJmMTMtN2Q5Yzg2ODA1NmVkLTEyMDE2Njk=/tiny/4D-Molecular-Therapeutics-Inc-.png)
2023 GlobeNewswire, Inc., source