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 updated interim safety and
efficacy data on six adults with Fabry disease cardiomyopathy
treated with a single intravenous (IV) infusion of 4D-310 (1E13
vg/kg) with follow-up of 12-33 months overall, including 12-24
month follow-up data on cardiac contractility, exercise capacity,
quality of life and cardiac biopsy data. The data was presented in
a late-breaking session at WORLDSymposium™ 2024 in San Diego,
California on Friday, February 9, 2024.
“We are pleased to see 4D-310 continue to consistently
demonstrate clinical activity across multiple important cardiac
endpoints including cardiac function, exercise capacity and quality
of life,” said Robert Kim, M.D., Chief Medical Officer of 4DMT.
“Current therapies do not adequately address Fabry-related
cardiovascular manifestations, and cardiovascular disease is the
most common cause of death in these patients. 4D-310 continues to
be well tolerated, with the previously reported cases of aHUS
having fully resolved and no new drug-related adverse events over
Grade 1 reported.”
“These promising clinical results continue to validate our
Therapeutic Vector Evolution platform, as well as the potential of
the C102 vector for targeted IV delivery to cardiomyocytes. Cardiac
biopsies also showed robust and durable delivery and transgene
expression from 4D-310, and remarkably, a reduction in Gb3
substrate in cardiomyocytes,” said David Kirn, M.D., Co-founder and
Chief Executive Officer of 4DMT. “No approved therapy has been
shown to definitively clear accumulated Gb3 from cardiomyocytes in
patients with Fabry disease, which speaks to 4D-310’s highly
differentiated profile. We remain on-track to submit results from
the non-clinical study to evaluate 4D-310 in NHPs with the R/S
immunosuppressive regimen to the FDA in Q2 2024 to address the
clinical hold.”
INGLAXA Phase 1/2 Clinical Trial Design &
Enrollment
- Dose escalation and
dose expansion trial assessing a single IV infusion of 4D-310 in a
broad and diverse Fabry disease patient population
- Enrolled six
patients, each treated with 1E13 vg/kg of 4D-310 and a prophylactic
corticosteroid immunosuppressive regimen
- Protocol amended to
change immunosuppressive regimen to rituximab and sirolimus
(enrollment on this amendment pending)
- Cardiac biopsies allowed at week 6
and 26 in the INGLAXA-2 trial (to date, one patient had biopsies
performed)
INGLAXA Phase 1/2 Interim Data Summary (Data Cutoff:
December 5, 2023)
- Safety and
Tolerability
- Previously reported cases of aHUS
(n=3) have fully resolved
- No clinically significant cardiac or
liver toxicities
- No new 4D-310–related adverse events
> Grade 1 since the last interim update in February 2023
- Echocardiography
Contractility Assessments (Global Longitudinal Strain,
GLS)
- Improved GLS in all five evaluable
patients by month 12
- Two patients who reached 24 months
of follow-up both showed clinically meaningful improvement with
change from baseline exceeding the minimal detectable difference of
-1.5% (-2.8 and -2.9%, respectively)
- Cardiopulmonary Exercise
Testing (CPET) Peak VO2
Assessments
- 3 of 4 evaluable patients
demonstrated clinically meaningful improvement by CPET peak VO2
with change from baseline exceeding the minimal clinically
important difference (MCID) of +1.5 at month 12 (+1.8, +2.0 &
+7.0)
- One patient who reached 24 months of
follow up continued to show meaningful improvement with change from
baseline exceeding the MCID of +1.5 (+7.8)
- Cardiac Quality of Life
Assessments (Kansas City Cardiomyopathy Questionnaire)
- Two patients had low baseline scores
<90 (scale 0-100); both patients had clinically meaningful
improvements in QOL (exceeding the MCID of +5)
- One patient had 12 months follow-up:
Clinical & Overall Summary Scores improved by +5.7 and +11.7,
respectively
- One patient had 24 months follow-up:
Clinical & Overall Summary Scores improved by +12.5 and +8.3,
respectively
- Three patients had baseline values
>90 (92.7, 100 & 100); all remained stable through 12-24
months (+1.1 to -1.6).
- Cardiac Biopsy Assessments
of Transgene Expression and Substrate Clearance
- Cardiac biopsies at week 6 and 26
from one patient showed robust & durable 4D-310–mediated
transgene expression in cardiomyocytes
- All samples positive for transgene
RNA (ISH) & AGA protein (IHC)
- At week 26, mean Gb3 inclusion body
volume per cardiomyocyte was reduced 15% from week 6 and 61% vs.
historical sample collected approximately 7 years prior to
enrollment and analyzed independently by investigator
Detailed results can be found in the Scientific Posters and
Publications section of our website here.
Next Steps for Development of 4D-310
- FDA submission of data from the NHP
study evaluating the safety and biodistribution of IV 4D-310 with
the R/S immunosuppressive regimen compared to the prior prednisone
regimen expected in Q2 2024
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 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 our clinical and preclinical product candidates, and
related timing for the clinical development of 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 SmithInizio Evoke
CommsKatherine.Smith@inizioevoke.com
Investors:
Julian PeiHead of Investor Relations and Corporate
CommunicationsInvestor.Relations@4DMT.com267-644-5097
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