4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company), a
clinical-stage genetic medicines company with three novel, highly
targeted next generation AAV vectors currently in the clinic, today
announced alignment with the U.S. Food and Drug
Administration (FDA) on a plan to lift the clinical hold on
the Phase 1/2 INGLAXA clinical trial in the United States for
4D-310 for Fabry disease cardiomyopathy.
“We are delighted to have reached an agreement with the FDA on
our proposed plan to address the clinical hold and continue trial
development,” said David Kirn, M.D., Co-founder and Chief Executive
Officer of 4DMT. “We have shared with the FDA the totality of the
most up to date clinical activity and safety data already generated
from INGLAXA trials, as of August 2023, and look forward to
progressing this critical work on behalf of all patients with Fabry
disease.”
In January 2023, the Company announced that it would pause
enrollment in both the United States and Asia-Pacific trials after
observing instances of atypical hemolytic uremic syndrome (aHUS).
Consistent with the Company’s plans, the FDA subsequently notified
the Company of a clinical hold in the U.S. The Asia-Pacific
clinical trial program was not placed on clinical hold by any
regulatory agency.
The Company’s plan includes a single non-clinical study,
currently underway, that will evaluate the safety and
biodistribution in NHPs of IV 4D-310 with the R/S immunosuppressive
regimen compared to the prior prednisone regimen. 4DMT expects to
submit the results to the FDA in Q2 2024. In addition, the INGLAXA
clinical trial protocol has been amended to minimize the risk of
aHUS following IV 4D-310 dosing, including requiring the R/S
immunosuppressive regimen.
In February 2023, the Company presented positive interim
clinical activity data of 4D-310 from 3 patients with 12 months of
follow-up, which demonstrated improvements in multiple
FDA-recommended cardiac endpoints along with selective and
widespread transgene expression within ~50% of cardiomyocytes in a
cardiac biopsy. Additional interim cardiac biopsy and clinical
efficacy data, with follow-up of at least 12 -18 months for all 6
patients dosed with 4D-310 from the INGLAXA clinical trials, is
expected to be presented in Q1 2024.
Clinical investigators have previously demonstrated that the R/S
immunosuppressive regimen is well-tolerated and is able to prevent
the development of aHUS following IV administration of AAV gene
therapeutics.
About 4D-310 and Fabry Disease
Cardiomyopathy
4D-310 utilizes the cardiac targeted and evolved C102 vector to
efficiently deliver a functional copy of the GLA gene (encodes for
AGA enzyme) to the heart after a single low dose IV administration.
The product candidate is designed to generate high local levels of
AGA directly within heart tissue, as well as other affected organs,
with the goal of reversing the cardiomyopathy in Fabry patients.
Cardiomyopathy is the leading cause of death in the Fabry disease
population.
Affecting more than 50,000 people in the United States and
European Union, Fabry disease is a genetic disorder of the GLA gene
that results in the body’s inability to produce AGA, causing
accumulation of the substrate globotriaosylceramide (Gb3) in
critical organs, including the heart, kidney, and blood vessels.
Cardiomyopathy is the leading cause of death in the Fabry disease
patient population. Such substrate accumulation can lead to
life-threatening hypertrophic cardiomyopathy, heart failure,
arrhythmias, various degrees of kidney dysfunction and
cerebrovascular stroke. Significant unmet medical needs remain for
these patients despite enzyme replacement therapy (ERT), the
current standard of care. ERT requires biweekly intravenous dosing
which markedly decreases patients’ quality of life. In addition,
while benefit has been demonstrated in the kidney, ERT has not been
shown to clearly benefit the heart.
About 4DMT
4DMT is a clinical-stage biotherapeutics company with three
novel, highly targeted next generation AAV vectors currently in the
clinic targeting multiple large market diseases in ophthalmology
and pulmonology, plus other therapeutic areas. 4DMT seeks to unlock
the full potential of genetic medicines using its proprietary
invention platform, Therapeutic Vector Evolution, which combines
the power of the Nobel Prize-winning technology, directed
evolution, with approximately one billion synthetic AAV
capsid-derived sequences to invent customized and evolved vectors
for use in our product candidates. All of our vectors are
proprietary to 4DMT and were invented at 4DMT, including the
vectors utilized in our clinical-stage and preclinical pipeline
product candidates: R100, A101, and C102. The Company is initially
focused on five clinical-stage product candidates in three
therapeutic areas for both rare and large market diseases:
ophthalmology, pulmonology, and cardiology. The 4DMT customized 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. 4DMT is currently advancing five product
candidates in clinical development: 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
4D preclinical product candidates in development are: 4D-175 for
geographic atrophy and 4D-725 for AATLD.
4D-150, 4D-710, 4D-310, 4D-125, and 4D-110 are our product
candidates in clinical development and have not yet been approved
for marketing by the US FDA or any other regulatory authority. No
representation is made as to the safety or effectiveness of 4D-150,
4D-710, 4D-310, 4D-125, or 4D-110 for the therapeutic uses 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 of 4DMT’s product candidates, as well as the
plans, announcements and related timing for the clinical
development of and regulatory interactions and expectations
regarding 4D-310. 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 Securities and Exchange Commission. In addition, any
forward-looking statements represent 4D Molecular Therapeutics'
views only as of today and should not be relied upon as
representing its views as of any subsequent date. 4D Molecular
Therapeutics explicitly disclaims any obligation to update any
forward-looking statements. No representations or warranties
(expressed or implied) are made about the accuracy of any such
forward looking statements.
Contacts:
Media:
Katherine SmithEvoke CanaleKatherine.Smith@evokegroup.com
Investors:
Julian PeiHead of Investor Relations and Corporate
CommunicationsInvestor.Relations@4DMT.com267-644-5097
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