Inozyme Pharma, Inc. (Nasdaq: INZY)
(“Inozyme” or the “Company”), a clinical-stage rare disease
biopharmaceutical company developing novel therapeutics for the
treatment of pathologic mineralization and intimal proliferation,
today announced positive interim 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 ENPP1 Deficiency and ABCC6 Deficiency (PXE, pseudoxanthoma
elasticum).
"We are pleased that these trials have achieved their primary
goals of demonstrating that INZ-701 was generally safe and well
tolerated and meaningfully increased PPi levels in patients with
ENPP1 Deficiency and ABCC6 Deficiency. We have also observed trends
of clinical improvement which gives us confidence that we can
design an informative pivotal trial in adults with ENPP1
Deficiency,” said Kurt Gunter, M.D., senior vice president and
chief medical officer of Inozyme Pharma. “The trends towards
improvement in clinically meaningful markers of bone metabolism in
adults with ENPP1 Deficiency point to the potential for INZ-701 to
treat rickets in our planned pivotal trial in pediatric patients
with the condition.”
“Data from these first-in-human trials of INZ-701 are highly
encouraging for both patients and physicians in the ENPP1
Deficiency and ABCC6 Deficiency communities. I am particularly
excited to see early signs that INZ-701 may address symptoms in the
adult population of ENPP1 Deficiency, which could translate to
clinical benefits in the infant and adolescent patients who are in
urgent need of a therapeutic option,” said Michael Levine, M.D.,
Professor Emeritus, Pediatrics and Medicine and Chief Emeritus,
Division of Endocrinology and Diabetes at the Center for Bone
Health at the Children’s Hospital of Philadelphia Research
Institute.
ENPP1 Deficiency
Nine patients were initially enrolled in the ongoing Phase 1/2
clinical trial across three dose cohorts of INZ-701 (0.2 mg/kg
(n=3), 0.6 mg/kg (n=3), and 1.8 mg/kg (n=3)). For trial design
details, please see the section entitled “INZ-701 in ENPP1
Deficiency Phase 1/2 Clinical Trial Design” below.
Exploratory Biomarker Data
Exploratory biomarker data were collected throughout the study
to provide evidence of the potential for disease modification with
ongoing treatment with INZ-701. Notable changes in key biomarkers
were observed and support the clinical hypothesis, including:
- Meaningful reduction of fibroblast growth factor-23 (FGF-23)
observed. 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.
- Serum phosphate (Pi) levels increased over time, in the absence
of phosphate and active vitamin D supplementation, which were
withheld from patients during the study.
- Statistically significant correlation between increase in
plasma pyrophosphate (PPi) and decrease in FGF-23 observed at one
week post first dose.
- Upward trends observed in bone specific alkaline phosphatase
(BSAP) levels from baseline, which signal biological activity in
bone tissue.
Exploratory Efficacy Data
Outcome measures were collected to assess potential clinical
benefit with ongoing treatment with INZ-701 and to inform the
design and patient selection of future trials in adolescents and
adults. Notable changes in PROs and functional outcomes were
observed in all cohorts, including:
- Concordant improvement in GIC scores reported by patients
(P-GIC) and clinicians (C-GIC), and no patient showed a
deterioration from baseline.
- High responder rates in Patient-Reported Outcome Measurement
Information Scales (PROMIS) of Pain Intensity, Fatigue and Pain
Interference.1
- Trend of improvement in 6-minute walk test (6-MWT). Subgroup
analysis of 6-MWT results showed greater improvement in patients
with lower baseline values and stable results over time in patients
with higher baseline values.
- Subgroup analysis of patients who presented with
arthritis/arthralgia at baseline showed improvement in 6-MWT, and
increased spine bone mineral density (BMD) and bone mineral content
(BMC), as measured by dual x-ray absorptiometry (DEXA).
Pharmacodynamic (PD) and Pharmacokinetic (PK)
Data
- Rapid, significant, and sustained increase in PPi levels
observed in all patients and significant elevation in PPi
maintained for up to 18 months.
- Long half-life of approximately 126 hours and drug accumulation
as shown by a greater than dose proportional exposure suggests the
potential for once weekly dosing.
Safety Data
- INZ-701 was generally well-tolerated and exhibited a favorable
safety profile, with no serious or severe adverse events attributed
to INZ-701 and no adverse events leading to study withdrawal.
- 3/9 patients experienced mild adverse events related to
INZ-701.
- Injection site reactions (bruising, hemorrhage, pain, pruritus,
and/or swelling) occurred in 2/9 patients.
- Other related adverse events included decreased appetite and
fatigue.
- There were two serious adverse events not related to
INZ-701.
- All nine patients enrolled in the Phase 2 portion of the trial,
two of whom subsequently withdrew from the study. The study
withdrawals were not related to an adverse event.
- Seven patients remain in the trial and continue on home
self-administration of INZ-701 treatment.
- Time on study ranged from 98 to over 638 days. Total time on
treatment across all cohorts corresponds to approximately 9
patient-years.
Anti-Drug Antibody (ADA) Data
INZ-701 exhibited a favorable immunogenicity profile with low
titers of non-neutralizing ADAs observed in 7/9 patients. The ADA
levels were transient in 3/7 patients.
ABCC6 Deficiency
Ten patients were enrolled in the ongoing Phase 1/2 trial across
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 Efficacy Data
Clinical outcome measures were collected to provide evidence of
clinical benefit and to inform the design of future trials in
adults. Notable changes in GIC, a PRO, were observed,
including:
- The majority of timepoints showed improvement in GIC scores
reported by P-GIC and C-GIC.
- All patients (9/9) showed improvement on C-GIC, and 7/9
patients showed improvement from baseline on P-GIC at last
follow-up.
Pharmacodynamic (PD) and Pharmacokinetic (PK)
Data
- Rapid and significant increase in PPi levels observed in all
cohorts with a dose response observed.
- PPi showed sustained increase in the highest dose cohort to
levels comparable to those observed in a study of healthy
subjects.2
- PK properties were consistent with those observed in the Phase
1/2 clinical trial in adults with ENPP1 Deficiency.
Safety Data
- INZ-701 was generally well-tolerated and exhibited a favorable
safety profile, with no serious or severe adverse events.
- All adverse events were mild to moderate in severity.
- 7/10 patients experienced adverse events related to INZ-701.
- Injection site reactions (discoloration, discomfort, erythema,
induration, pain, pruritus, warmth) occurred in 7/10 patients.
- Other related adverse events were fatigue, night sweats and
urticaria.
- One patient from the highest dose cohort was withdrawn from
Phase 1 at day 18 due to a moderate adverse event
(erythema/urticaria) related to INZ-701.
- One patient withdrew from the trial during Phase 2, which was
not related to an adverse event.
- Eight patients remain in the trial and seven continue on home
self-administration of INZ-701 treatment.
- Time on study ranged from 18 to over 518 days. Total time on
treatment across all cohorts corresponds to approximately 9.1
patient-years.
ADA Data
- INZ-701 exhibited a favorable immunogenicity profile with low
titers of non-neutralizing ADAs observed in 8/10 patients.
- The ADA levels were transient in 3/8 patients.
Webcast and Conference Call Details
Inozyme will host a conference call and webcast to discuss these
updates today, Tuesday, September 26th, 2023, at 8:00 a.m. ET.
The live webcast and replay will be accessible here and
through Inozyme’s website under News and Events. Alternatively, the
conference call may be accessed by dialing:
Domestic Dial-in Number: 1-877-270-2148International Dial-in
Number: 1-412-902-6510
Participants should ask to join the Inozyme
Pharma call.
About ENPP1 Deficiency
ENPP1 Deficiency is a progressive condition that manifests as a
spectrum of diseases. Individuals who present in utero or in
infancy are typically diagnosed with generalized arterial
calcification of infancy (GACI), which is characterized by
extensive vascular calcification and intimal proliferation
(overgrowth of smooth muscle cells inside blood vessels), resulting
in myocardial infarction, stroke, or cardiac or multiorgan failure.
Approximately 50% of infants with ENPP1 Deficiency 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 will primarily assess the
safety and tolerability of INZ-701 in adult patients with ENPP1
Deficiency, as well as characterize 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 ABCC6 Deficiency
ABCC6 Deficiency is a rare, severe, inherited disorder caused by
mutations in the ABCC6 gene, leading to low levels of PPi. PPi is
essential for preventing harmful soft tissue calcification and
regulating bone mineralization. ABCC6 Deficiency is a systemic and
progressively debilitating condition, which affects more than
67,000 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. In older individuals, ABCC6 Deficiency presents
as pseudoxanthoma elasticum (PXE), which is characterized by
pathological 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 ten
adult patients with ABCC6 Deficiency at sites in the United States
and Europe. The trial will primarily assess the safety and
tolerability of INZ-701 in adult patients with ABCC6 Deficiency, as
well as characterize the pharmacokinetic (PK) and pharmacodynamic
(PD) profile of INZ-701, including the evaluation of levels of
plasma 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 for further development that
increases PPi levels. 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 will include
evaluations of vascular, ophthalmologic, physical function and
patient-reported outcomes.
About INZ-701
INZ-701, a recombinant Fc fusion protein, is an ENPP1 enzyme
replacement therapy in development for the treatment of rare
disorders of the vasculature, soft tissue, and skeleton. In
preclinical studies, the experimental therapy has shown potential
to prevent pathologic mineralization and intimal proliferation (the
overgrowth of smooth muscle cells inside blood vessels), which can
drive morbidity and mortality in devastating genetic disorders such
as ENPP1 Deficiency and ABCC6 Deficiency. INZ-701 is currently in
clinical trials for the treatment of ENPP1 Deficiency and ABCC6
Deficiency.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 trials for the
treatment of ENPP1 Deficiency and ABCC6 Deficiency.
For more information, please
visit 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 availability of
data from clinical trials, 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 and ABCC6 Deficiency; 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 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 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.
ContactsInvestors:Inozyme PharmaStefan Riley,
Director of IR and Corporate Communications(857)
330-8871stefan.riley@inozyme.com
Media:SmithSolveMatt Pera(973)
886-9150matt.pera@smithsolve.com
1 “Responder” is defined as exhibiting improvement from baseline
in >50% of timepoints evaluated.2 Khursigara, et al, Bone
2023
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