4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company),
a leading clinical-stage genetic medicines company focused on
unlocking the full potential of genetic medicines to treat large
market diseases, today announced an update on its regulatory
interactions and development path for 4D-710, an aerosolized
genetic medicine for the treatment of CF lung disease.
Given high-level cystic fibrosis transmembrane conductance
regulator (CFTR) transgene expression in all lung airway biopsies
disclosed to date (significantly above normal lung CFTR levels),
dose exploration continues with the evaluation of lower doses in
the 4D-710 Phase 1/2 AEROW clinical trial in pwCF dosed
at 5E14 vg (Cohort 3; n=1) and 2.5E14 vg (Cohort 4; n=1); nine pwCF
total have been dosed to date (dose range 2.5E14 to 2E15 vg). Phase
2 Expansion Cohort dose selection is expected in Q2 2024 based on
all clinical and lung biopsy data; the Company anticipates
enrolling a total of six to nine pwCF in the Phase 2 Expansion
Cohort. The Company submitted an AEROW trial amendment to the
Cystic Fibrosis Therapeutics Development Network (TDN) as follows:
1) to enroll pwCF with lower baseline percent predicted forced
expiratory volume in 1 second (ppFEV1) (50-90%) to assess ppFEV1
response to 4D-710, and 2) to add a second lung biopsy procedure at
a longer-term timepoint (12 months or later) to study long term
durability of 4D-710 CFTR transgene expression and optimal timing
for redosing. The Company plans to share the following at the 47th
European Cystic Fibrosis Conference (ECFS) held on June 5-8, 2024
in Glasgow, United Kingdom: 1) interim AEROW clinical and lung
biomarker data on all nine pwCF dosed to date, 2) update on AEROW
trial amendment status, and 3) development plan update for pwCF who
are on modulators.
In addition, the Company recently had discussions with the U.S.
Food and Drug Administration (FDA) and European Medicines Agency
(EMA), regarding the registrational path for 4D-710 for treatment
of CF lung disease in pwCF who are ineligible for or cannot
tolerate approved CF modulator therapies. With regards to a full
product approval in this patient population, the Company
anticipates a Phase 3 randomized, controlled pivotal study
enrolling approximately 60-80 pwCF with low baseline ppFEV1
(planned to be approximately 40-80%). Phase 3 clinical endpoints
include changes after 4D-710 treatment in ppFEV1, quality-of-life
(Cystic Fibrosis Questionnaire Revised Respiratory Domain,
CFQ-R-RD) and frequency of pulmonary exacerbations. 4DMT is
preparing for initiation of a Phase 3 clinical trial in H2
2025.
Given the high unmet need in this CF population, an accelerated
approval path may be feasible. The Company intends to have
discussions with the FDA and EMA on an accelerated approval
pathway, in parallel with Phase 3 planning, following additional
AEROW clinical and lung biomarker data in pwCF with low baseline
ppFEV1. 4D-710 is the first genetic medicine product candidate to
demonstrate widespread and high-level CFTR expression (both RNA and
protein) in the airways of pwCF; the Company will continue to
evaluate the correlation between clinical endpoints and biomarker
endpoints in participants with low baseline ppFEV1 in anticipation
of further interactions on an accelerated approval pathway.
In addition, the Company has completed in-house process
development of a suspension GMP-ready manufacturing process for
4D-710 at 500 liter scale for the pivotal study and potential
commercialization. This process, in combination with investigating
lower doses, enables potentially lower cost of goods. The Company
anticipates initiation of technology transfer to a commercial
contract development and manufacturing organization (CDMO) in H1
2025.
“We are encouraged by our productive interactions with the FDA
and EMA on pivotal development plans for 4D-710, which we believe
has the potential to be a transformative therapy for people with
the highest unmet medical need for CF lung disease,” said David
Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “We are
committed to advancing 4D-710 into pivotal trial development
efficiently, while maintaining our current focus on initiation and
completion of two Phase 3 wet AMD studies with 4D-150. Our goal is
to initiate Phase 3 development in H2 2025 with 4D-710 suspension
GMP process clinical trial material. We look forward to sharing
interim clinical data from the AEROW Phase 1/2 clinical trial at
the ECFS conference in June 2024.”
About Cystic Fibrosis Lung Disease and
4D-710
Cystic fibrosis (CF) is an inherited, progressive disease caused
by mutations in the CFTR gene. It affects the lungs, pancreas, and
other organs. According to the Cystic Fibrosis Foundation, close to
40,000 people in the United States and an estimated 105,000 people
people have been diagnosed with CF across 94 countries, with
approximately 1,000 new cases of CF diagnosed in the United States
each year. Lung disease is the leading cause of morbidity and
mortality in people with CF. CF causes impaired lung function,
inflammation and bronchiectasis and is commonly associated with
persistent lung infections and repeated exacerbations due to the
inability to clear thickened mucus from the lungs. People with CF
require lifelong treatment with multiple daily medications. The
complications of the disease result in progressive loss of lung
function, increasing need for IV antibiotics and hospitalizations,
ultimately leading to end-stage respiratory failure.4D-710 is
comprised of our targeted and evolved next generation vector, A101,
and a codon-optimized CFTR∆R transgene. 4D-710 has the potential to
treat a broad range of people with CF, 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 for the approximately 10-15% of people whose
disease is not amenable to existing CFTR modulator medicines (based
on variant-eligibility and/or drug intolerance) targeting the CFTR
protein. In people with CFTR mutations whose disease is amenable to
modulator medicines, and in some people with CF the improvement in
lung function is incomplete and is variable. We therefore expect to
potentially develop 4D-710 in this broader population, as a single
agent and/or in combination with CFTR modulator small molecule
medicines. 4D-710 has received the Rare Pediatric Disease
Designation and Orphan Drug Designation from the FDA.
About 4DMT
4DMT is a leading clinical-stage genetic medicines company
focused on unlocking the full potential of genetic medicines to
treat large market diseases in ophthalmology and pulmonology.
4DMT’s proprietary invention platform, Therapeutic Vector
Evolution, 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 wholly owned and partnered product
candidates. Our product design, development, and manufacturing
engine helps us efficiently create and advance our diverse product
pipeline with the goal of revolutionizing medicine with potential
curative therapies for millions of patients. Currently, 4DMT is
advancing five clinical-stage and two preclinical product
candidates, each tailored to address rare and large market diseases
in ophthalmology, pulmonology, and cardiology. In addition, 4DMT is
also advancing programs in CNS through a gene editing partnership.
4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™,
and the 4DMT logo are trademarks of 4DMT.
All of our product candidates are in clinical or preclinical
development 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 our product candidates for the
therapeutic uses for which they are being studied.
Learn more at www.4DMT.com and follow us on LinkedIn.
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 4D-710. 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 SmithInizio Evoke
CommsKatherine.Smith@inizioevoke.com
Investors:
Julian PeiHead of Investor Relations and Corporate
FinanceInvestor.Relations@4DMT.com
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