Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” or “Inozyme”), a
clinical-stage rare disease biopharmaceutical company developing
novel therapeutics for the treatment of pathologic mineralization
and intimal proliferation, today announced positive topline safety,
pharmacokinetic (PK), pharmacodynamic (PD) and exploratory efficacy
data from the Company’s ongoing Phase 1/2 clinical trials of
INZ-701 in adults with ABCC6 Deficiency (PXE, pseudoxanthoma
elasticum) and ENPP1 Deficiency.
“We are excited by the excellent safety and preliminary efficacy
profile of INZ-701 in adults with ABCC6 Deficiency,” said Douglas
A. Treco, Ph.D., CEO of Inozyme Pharma. “Our investigations into
the natural history of this disease have identified a substantial
and previously overlooked pediatric population with a high risk of
stroke. We believe these patients represent a critical unmet need
in this genetic disease and that changes observed in adults treated
with INZ-701 will translate to clinical benefits in a future trial
in children.”
“The high risk of ischemic stroke in pediatric patients with
ABCC6 Deficiency and its devastating consequences represents a
serious unmet need in this population,” commented Professor Zulf
Mughal, M.D., Consultant in Paediatric Bone Disorders at Al Jalila
Children's Specialty Hospital, Dubai, UAE. “I am very encouraged to
see that INZ-701 may improve vascular pathology and believe that
this effect may translate to clinical benefits in patients of all
ages.”
ABCC6 Deficiency Data
The ongoing Phase 1/2 trial in ABCC6 Deficiency enrolled 10
adults with heavy disease burden, as evidenced by serious
cardiovascular disease and retinal disease. The patients were
assigned to three dose cohorts of INZ-701: 0.2 mg/kg (n=3), 0.6
mg/kg (n=3), and 1.8 mg/kg (n=4). For trial design details, please
see the section entitled “INZ-701 in ABCC6 Deficiency Phase 1/2
Clinical Trial Design” below.
Exploratory Clinical and Efficacy Data
Exploratory markers of clinical benefit were collected throughout
the study to provide evidence of the potential for disease
modification with ongoing INZ-701 treatment. Notable changes were
observed, including:
Carotid intima-media
thickness (cIMT) stabilized and decreased
- cIMT, a predictive marker for cardiovascular disease and
stroke, increases at a faster rate in people with PXE than in the
general population. Reduction or stabilization of cIMT was observed
across all dose cohorts (seven of eight evaluable patients),
indicating a potential beneficial effect of INZ-701 on vascular
pathology.
Choroidal thickness
increased
- The choroid is the vascular layer between the sclera and
retina. Choroidal thinning is associated with degenerative retinal
changes in people with PXE and progresses with age. Increased
choroidal thickness was observed across all dose cohorts (seven of
eight evaluable patients), which indicates a potential beneficial
effect of INZ-701 on retinal disease.
Global Visual Function
Questionnaire (VFQ-25) scores indicated preservation and
improvement of visual function over 48 weeks
- Four of six evaluable patients with VFQ-25 scores below normal
at baseline improved over 48 weeks. Improvement in visual function
was greater in older patients. A correlation between improvements
in VFQ-25 and increases in choroidal thickness was preserved after
48 weeks.
Global Impression of Change
Scale (GIC): Concordant improvement in GIC scores reported by
patients (P-GIC) and clinicians (C-GIC) observed
in all three dose cohorts
- All evaluable patients (nine of nine) showed improvement from
baseline on C-GIC, and seven of nine evaluable patients showed
improvement from baseline on P-GIC.
PD and PK Data
- Rapid increase in plasma pyrophosphate (PPi) levels observed at
1.8 mg/kg dose level and was sustained to levels comparable to
those observed in Inozyme’s study of healthy subjects (n=10).
Safety Data
- INZ-701 was generally well tolerated and exhibited a favorable
safety profile, with no serious or severe adverse events
(AEs).
- All AEs were mild to moderate in severity. For previously
reported data on AEs, please read here.
- Eight patients remain in the trial and seven continue on home
self-administration of INZ-701 treatment.
- Time on study ranged from 45 to over 631 days. Total time on
treatment across all cohorts corresponds to approximately 12+
patient-years.
Anti-Drug Antibody (ADA) Data
- INZ-701 exhibited a favorable immunogenicity profile with low
titers of non-neutralizing ADAs observed in eight of 10
patients.
- The ADA levels were transient in three of eight patients.
Natural History StudiesThe Company conducted a
comprehensive retrospective, natural history study, and a
prospective, longitudinal, observational study to characterize the
natural progression of early-onset ABCC6 Deficiency and inform
future clinical trial design. Findings indicate a substantial
disease burden among pediatric patients with ABCC6 Deficiency,
manifesting in a high incidence of major clinical events, notably
stroke, severe neurological disease, and severe cardiovascular
disease, occurring early in life. Seven out of 12 patients across
the natural history studies either experienced stroke or are at
risk, with strokes resulting in severe outcomes such as seizure
disorders, paresis, and significant disability. Furthermore, 10 out
of 12 patients were diagnosed with GACI Type 2, underscoring the
considerable morbidity risk among pediatric survivors beyond the
critical infancy period.
Development Plans for INZ-701 in Pediatric ABCC6
DeficiencyGiven the high risk of cerebrovascular disease
in the pediatric population, the Company believes that endpoints
predictive of ischemic stroke (for example, progression of cerebral
vasculopathy) may provide a suitable basis for Accelerated Approval
in the US and Conditional Marketing Authorisation in the EU of
INZ-701 in children with ABCC6 Deficiency. The Company plans to
work expeditiously with the U.S. Food and Drug Administration (FDA)
and the European Medicines Agency (EMA) on a pivotal trial design.
Subject to regulatory review and sufficient funding, the Company
expects to initiate a pivotal trial in pediatric patients with
ABCC6 Deficiency in Q1 2025.
ENPP1 Deficiency Data
Thirteen adults with ENPP1 Deficiency were enrolled in the
ongoing Phase 1/2 trial across three twice weekly dose cohorts (0.2
mg/kg [n=3], 0.6 mg/kg [n=3], and 1.8 mg/kg [n=3]) and one
once-weekly dose cohort (1.2 mg/kg [n=4]) of INZ-701. For trial
design details, please see the section entitled “INZ-701 in ENPP1
Deficiency Phase 1/2 Clinical Trial Design” below.
Exploratory Biomarker DataExploratory biomarker
data were collected throughout the study to provide evidence of the
potential for disease modification with ongoing treatment with
INZ-701. For previously reported exploratory biomarker data, please
read here. Notable changes in key biomarkers were observed and
support Inozyme’s clinical hypothesis, including:
- Significant reduction of fibroblast growth factor-23 (FGF-23)
in the 1.8 mg/kg dose cohort (Cohort 3) through week 48. Most
patients with ENPP1 Deficiency have elevated levels of FGF-23,
which leads to increased phosphate wasting and hypophosphatemia, a
key driver of osteomalacia and rickets.
- Increase in bone specific alkaline phosphatase (BSAP) levels
and decrease in c-telopeptide (CTX) in the 1.8 mg/kg dose cohort
(Cohort 3) through week 48, which indicate the restoration of
proper bone mineralization.
Exploratory Efficacy DataOutcome measures were
collected to assess the potential clinical benefit of ongoing
treatment with INZ-701 and to inform the design and patient
selection of future trials in adolescents and adults. For
previously reported exploratory efficacy data, please read here.
Notable changes in PROs and functional outcomes were observed in
all three twice-weekly dose cohorts, including:
- Favorable responses on the
Patient-Reported Outcome Measurement Information Scales (PROMIS) of
Pain Intensity, Fatigue and Pain Interference and P-GIC were
maintained.
PD and PK Data
- Data from the once-weekly dose cohort showed increased PPi
levels comparable to those observed in Inozyme’s study of healthy
subjects (n=10).
- Consistent exposure was observed with 1.2 mg/kg once weekly
dosing when compared to 0.6 mg/kg twice weekly dosing.
- Long-term data showed a sustained increased PPi levels in the
once-weekly dose cohort.
Safety Data
- INZ-701 was generally well-tolerated and exhibited a favorable
safety profile, with no serious or severe AEs attributed to INZ-701
and no AEs leading to study withdrawal. For previously reported
data on adverse events, please read here.
- Eleven patients remain in the trial and 10 continue on home
self-administration of INZ-701 treatment.
- Time on study ranged from 22 to over 742 days. Total time on
treatment across all dose cohorts corresponds to approximately 12+
patient-years.
ADA Data
- INZ-701 exhibited a favorable immunogenicity profile with low
titers of non-neutralizing ADAs observed in 11/14 patients.
- The ADA levels were transient in three of 11 patients.
Conference Call and Webcast Details
The live webcast and replay will be accessible through the
Investor Relations section of Inozyme’s website under Events.
Alternatively, the conference call may be accessed by
dialing:Domestic Dial-in Number: 1-833-816-1110International
Dial-in Number: 1-412-317-0686
Participants should ask to join the Inozyme
Pharma call.For those unable to participate live, a replay
will be available in the Investor Relations section of
Inozyme’s website for a limited time following the event.
About ABCC6 Deficiency
ABCC6 Deficiency is a progressively debilitating condition of
the vasculature and soft tissue that is estimated to affect
approximately 1 in 25,000 to 1 in 50,000 individuals worldwide.
Infants with ABCC6 Deficiency are diagnosed with generalized
arterial calcification of infancy (GACI Type 2), a condition that
resembles GACI Type 1, the infant form of ENPP1 Deficiency.
Pediatric patients who survive the first year of life may develop
neurological disease, including stroke, and cardiovascular disease
secondary to ongoing vascular calcification and stenosis. In older
individuals, ABCC6 Deficiency presents as pseudoxanthoma elasticum
(PXE), which is characterized by pathologic mineralization in blood
vessels and soft tissues clinically affecting the skin, eyes, and
vascular system. There are no approved therapies for ABCC6
Deficiency.
INZ-701 in ABCC6 Deficiency Phase 1/2 Clinical Trial
Design
The ongoing Phase 1/2 open-label clinical trial enrolled 10
adult patients with ABCC6 Deficiency at sites in the United States
and Europe. The trial is primarily assessing the safety and
tolerability of INZ-701 in adult patients with ABCC6 Deficiency, as
well as characterizing the pharmacokinetic (PK) and pharmacodynamic
(PD) profile of INZ-701, including the evaluation of levels of
plasma pyrophosphate (PPi) and other biomarkers. In the Phase 1
dose-escalation portion of the trial, Inozyme assessed INZ-701 for
32 days at doses of 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg
administered via subcutaneous injection twice weekly, with three
patients per dose cohort. Doses were selected based on preclinical
studies and PK/PD modeling. The Phase 1 dose-escalation portion of
the trial sought to identify a safe, tolerable dose that increases
PPi levels for further development. The open-label Phase 2
extension portion of the trial is assessing long-term safety, PK,
and PD of continued treatment with INZ-701 for at least 48 weeks,
where patients may self-administer INZ-701. Exploratory endpoints
include evaluations of vascular, ophthalmologic, physical function,
and patient-reported outcomes.
About ENPP1 Deficiency
ENPP1 Deficiency is a progressively debilitating condition of
the vasculature, soft tissue, and skeleton with a prevalence of
approximately 1 in 64,000 pregnancies worldwide. Although ENPP1
Deficiency was initially described in patients with biallelic ENPP1
Deficiency (homozygous or compound heterozygous mutations), many
patients with monoallelic ENPP1 Deficiency (heterozygous mutations)
have clinical symptoms, potentially increasing the worldwide
prevalence. Individuals who present in utero or in infancy are
typically diagnosed with generalized arterial calcification of
infancy (GACI Type 1) and approximately 50% of infants die within
six months of birth. Children with ENPP1 Deficiency typically
develop rickets, a condition diagnosed as autosomal-recessive
hypophosphatemic rickets type 2 (ARHR2), while adolescents and
adults can develop osteomalacia (softened bones). ARHR2 and
osteomalacia lead to pain and mobility issues. Patients can also
exhibit signs and symptoms of hearing loss, arterial and joint
calcification, and cardiovascular complications. There are no
approved therapies for ENPP1 Deficiency.
INZ-701 in ENPP1 Deficiency Phase 1/2 Clinical Trial
Design
The ongoing Phase 1/2 open-label clinical trial initially
enrolled nine adult patients with ENPP1 Deficiency at sites in
North America and Europe. The trial is primarily assessing the
safety and tolerability of INZ-701 in adult patients with ENPP1
Deficiency, as well as characterizing the pharmacokinetic (PK) and
pharmacodynamic (PD) profile of INZ-701, including evaluation of
the PD marker, plasma pyrophosphate (PPi) and other biomarker
levels. In the Phase 1 dose-escalation portion of the trial,
Inozyme assessed INZ-701 for 32 days at doses of 0.2 mg/kg, 0.6
mg/kg, and 1.8 mg/kg administered via subcutaneous injection twice
weekly, with three patients per dose cohort. Doses were selected
based on preclinical studies and PK/PD modeling. The Phase 1
dose-escalation portion of the trial sought to identify a safe,
tolerable dose that increases PPi levels and that can be used for
further clinical development. Following completion of the Phase 1
portion of the first three cohorts, Inozyme dosed patients in a
fourth cohort at 1.2 mg/kg to investigate the potential for
once-weekly dosing of INZ-701. The open-label Phase 2 extension
portion of the trial is assessing long-term safety, PK, and PD of
continued treatment with INZ-701 for at least 48 weeks, where
patients may self-administer INZ-701. Exploratory endpoints include
evaluations of skeletal, vascular, physical function, and
patient-reported outcomes.
About INZ-701
INZ-701, a recombinant Fc fusion protein, is an ENPP1 enzyme
replacement therapy (ERT) in development for the treatment of rare
disorders of the vasculature, soft tissue, and skeleton. INZ-701
metabolizes ATP to generate PPi, a natural inhibitor of
mineralization, and AMP, which can be processed to phosphate and
adenosine, the latter being a natural inhibitor of intimal
proliferation. In preclinical studies, the experimental therapy has
shown potential to prevent pathologic mineralization and intimal
proliferation, which can drive morbidity and mortality in
devastating disorders such as ENPP1 Deficiency, ABCC6 Deficiency
and calciphylaxis. Clinical data to date have demonstrated that
INZ-701 was generally well tolerated, exhibited a favorable safety
profile, and meaningfully increased PPi levels in multiple clinical
trials.
About Inozyme Pharma
Inozyme Pharma, Inc. is a clinical-stage rare disease
biopharmaceutical company developing novel therapeutics for the
treatment of diseases impacting the vasculature, soft tissue, and
skeleton. Inozyme is developing INZ-701, an enzyme replacement
therapy, to address pathologic mineralization and intimal
proliferation, which can drive morbidity and mortality in these
severe diseases. INZ-701 is currently in clinical development for
the treatment of ENPP1 Deficiency, ABCC6 Deficiency and
calciphylaxis.
For more information, please
visit https://www.inozyme.com/ or follow Inozyme
on LinkedIn, X (formerly Twitter), and Facebook.
Cautionary Note Regarding Forward-Looking
Statements
Statements in this press release about future expectations,
plans, and prospects, as well as any other statements regarding
matters that are not historical facts, may constitute "forward-
looking statements" within the meaning of The Private Securities
Litigation Reform Act of 1995.
These statements include, but are not limited to, statements
relating to the timing and contents of our planned topline data
update, the initiation, timing, and design of our planned clinical
trials, our regulatory strategy, including our plan to seek
accelerated approval in the U.S. and conditional approval in the
E.U, and the potential benefits of INZ-701. The words "anticipate,"
"believe," "continue," "could," "estimate," "expect," "intend,"
"may," "plan," "potential," "predict," "project," "should,"
"target," "will," "would," and similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements are based on management's current
expectations of future events and are subject to a number of risks
and uncertainties that could cause actual results to differ
materially and adversely from those set forth in, or implied by,
such forward-looking statements. These risks and uncertainties
include, but are not limited to, risks associated with the
Company's ability to conduct its ongoing clinical trials of INZ-701
for ENPP1 Deficiency, ABCC6 Deficiency and calciphylaxis; enroll
patients in ongoing and planned trials; obtain and maintain
necessary approvals from the FDA and other regulatory authorities;
continue to advance its product candidates in preclinical studies
and clinical trials; replicate in later clinical trials positive
results found in preclinical studies and early-stage clinical
trials of its product candidates; advance the development of its
product candidates under the timelines it anticipates in planned
and future clinical trials; obtain, maintain, and protect
intellectual property rights related to its product candidates;
manage expenses; comply with the covenants under its outstanding
loan agreement; and raise the substantial additional capital needed
to achieve its business objectives. For a discussion of other risks
and uncertainties, and other important factors, any of which could
cause the Company's actual results to differ from those contained
in the forward-looking statements, see the "Risk Factors" section
in the Company's most recent Annual Report on Form 10-K and
Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission, as well as discussions of potential risks,
uncertainties, and other important factors, in the Company's most
recent filings with the Securities and Exchange Commission. In
addition, the forward-looking statements included in this press
release represent the Company's views as of the date hereof and
should not be relied upon as representing the Company's views as of
any date subsequent to the date hereof. The Company anticipates
that subsequent events and developments will cause the Company's
views to change. However, while the Company may elect to update
these forward-looking statements at some point in the future, the
Company specifically disclaims any obligation to do so.
Contacts
Investors:Inozyme PharmaStefan Riley, Senior Director of IR and
Corporate Communications(857) 330-8871stefan.riley@inozyme.com
Media: SmithSolve Matt Pera(973)
886-9150matt.pera@smithsolve.com
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