Apogee Therapeutics, Inc. (Nasdaq: APGE), a clinical-stage
biotechnology company advancing differentiated biologics for the
treatment of atopic dermatitis (AD), chronic obstructive pulmonary
disease, asthma and other inflammatory and immunology (I&I)
indications, today announced positive interim Phase 1 data from its
first-in-human study of APG777, one of its lead product candidates
being developed as a frontline treatment for moderate-to-severe AD
and other inflammatory diseases. Pharmacokinetic (PK) data showed a
half-life of approximately 75 days across doses tested and
Pharmacodynamic (PD) data showed deep and sustained inhibition of
key AD biomarkers pSTAT6 and TARC for ~3 months (longest follow-up
available, with inhibition still ongoing at time of the data cut).
Results from the trial exceeded the Company’s trial objectives
and support the potential for APG777, a novel anti-IL-13 antibody,
to optimize exposure levels in 16-week induction and be dosed once
every three or six months in maintenance. These findings represent
the potential for improved clinical responses from greater
exposures in induction and significantly less frequent dosing in
maintenance compared to currently approved biologic therapies,
which are dosed at every two to four weeks, a potential major
advancement for patients with AD and other inflammatory diseases.
APG777, in single doses up to 1,200mg and multiple doses of 300mg,
was well tolerated and showed a favorable safety profile, in line
with the existing body of third-party evidence for the safety of
the anti-IL-13 class. Based on these data, the company plans to
initiate a randomized, placebo-controlled, Phase 2 clinical trial
in patients with moderate-to-severe AD in the first half of 2024
ahead of schedule.
“The positive PK, PD and safety findings from our Phase 1 trial
mark the first clinical data ahead of schedule from our portfolio
of potentially differentiated biologics and underscore the
promising potential of APG777 to offer patients a transformational
therapy that could drive improved clinical responses than the
current standard of care and extend dosing to every three or six
months,” said Michael Henderson, M.D., Chief Executive Officer of
Apogee. “We are excited to embark on the next phase of development
for APG777, with plans to initiate our Phase 2 clinical trial in
the first half of this year while rapidly progressing the rest of
our pipeline forward. At Apogee, we refuse to stop at good enough
and are dedicated to advancing innovative solutions for patients.
Today’s announcement brings us an important step closer to
achieving this goal."
“Currently approved therapies for atopic dermatitis and other
immunology indications typically call for injections every two to
four weeks, which can lead to poor treatment adherence and
long-term disease control,” said Jonathan Silverberg, MD, PhD, MPH,
Professor of Dermatology at The George Washington University School
of Medicine and Health Sciences. “I am very encouraged by the
initial data from this study, which demonstrate the potential for
APG777 as a well-tolerated treatment with a half-life that would
support less frequent injections.”
“Significant unmet need remains for patients with
moderate-to-severe AD, many of whom continue to have symptomatic
disease on current therapies,” said Emma Guttman-Yassky, MD, PhD,
the Waldman Professor of Dermatology and Immunology and Health
System Chair of Dermatology at the Icahn School of Medicine at
Mount Sinai in New York City. “APG777’s Phase 2 trial will test an
important hypothesis, greater inhibition of the pathway during
induction, to see if improved clinical responses can be delivered
for patients living with AD.”
APG777 is a novel, subcutaneous extended half-life monoclonal
antibody targeting IL-13 – a critical cytokine in inflammation and
a primary driver of AD. In our head-to-head preclinical studies,
APG777 demonstrated equivalent or better potency to lebrikizumab in
the inhibition of IL-13 signaling. Based on its potentially
best-in-class PK profile, APG777 has the potential for improved
clinical responses from greater exposures of drug in induction and
dosing as infrequently as once every three or six months. AD is a
chronic inflammatory skin disorder which can lead to sleep
disturbance, psychological distress, elevated infection risk and
chronic pain, all of which significantly impact quality of life.
Today’s treatments are associated with many challenges, including
frequent injection regimens that can lead to poor patient
compliance. APG777 represents the first clinical-stage product
candidate from the company’s strategic collaboration with Paragon
Therapeutics, Inc., an innovative discovery engine for
biologics.
Key Phase 1 Interim Findings
The Phase 1 trial is a first-in-human, randomized, double-blind,
placebo-controlled study designed to evaluate safety and PK of
APG777 in healthy volunteers. The study enrolled 40 healthy adult
participants into three single-ascending dose (SAD) and two
multiple-ascending dose (MAD) cohorts. Doses of subcutaneous APG777
evaluated in the study included 300mg, 600mg and 1,200mg. Detailed
findings from the SAD portion and interim results from MAD portion
of the Phase 1 trial are as follows:
- PK differentiation supports further development of
APG777 as a treatment for moderate-to-severe AD and other
inflammatory diseases
- Potentially best-in-class PK profile, including a half-life of
approximately 75 days, supporting:
- Testing higher exposures of drug in induction to potentially
achieve improved clinical responses
- Testing of maintenance dosing of every 3- or 6-months,
representing 2-4 injections per year compared to the current
treatment paradigm of 13-26 injections per year
- Dose-proportional increases in serum concentrations and key
parameters (e.g., Cmax, AUC) were observed in the Phase 1
trial
- PK was consistent across subjects with low variability
- Single doses of APG777 demonstrated a deep and
sustained effect on PD markers for ~3 months (longest follow-up
available with inhibition still ongoing at time of data
cut)
- Single doses of APG777 suppressed pSTAT6, one of the first
downstream markers of IL-13 pathway inhibition, with near-complete
inhibition for ~3 months
- Single doses of APG777 suppressed TARC, an inflammatory
mediator and the most strongly correlated biomarker to AD severity,
with deep and sustained inhibition for ~3 months
- Well tolerated across all dose groups. Single
doses of APG777 up to 1,200mg and multiple doses of 300 mg were
well tolerated with a favorable safety profile consistent with the
existing third-party data supporting the safety of the anti-IL-13
class.
- The most common treatment-emergent adverse events (TEAEs) were
vascular access site pain, vessel puncture site bruise, headache,
and vascular access bruising
- 60% of participants observed at least one TEAE; 15% of
participants observed at least one drug-related AE
- There were no Grade 3 TEAEs or severe adverse events (SAEs). No
AEs led to study discontinuation
“The interim results from this Phase 1 trial are tremendously
encouraging for APG777’s potential to meaningfully improve the
standard of care for patients with moderate-to-severe AD. On behalf
of the entire Apogee team, I’d like to extend our heartfelt
gratitude to the volunteers, investigator, and the study team for
their support in the successful execution of this important trial,”
said Carl Dambkowski, M.D., Chief Medical Officer of Apogee
Therapeutics. “We look forward to rapidly advancing APG777 into
Phase 2 clinical trials in AD and other inflammatory
conditions.”
Phase 2 trial in AD
Following today’s positive interim results, Apogee plans to
advance APG777 into a randomized, placebo-controlled, 16-week Phase
2 clinical trial in patients with moderate-to-severe AD.
- Phase 2 AD trial is expected to initiate in the 1H of
2024 with 16-week topline data from Part A expected in 2H
2025
- Part A is expected to enroll approximately 110 patients
randomized 2:1 to APG777 vs placebo with primary endpoint of mean
percentage changes in EASI score from baseline to Week 16
- Part B of the Phase 2 trial is a randomized, placebo-controlled
dose optimization with approximately 360 patients randomized
1:1:1:1 to high, medium, or low dose APG777 vs placebo with primary
endpoint of mean percentage changes in EASI score from baseline to
Week 16
- All patients benefiting from treatment will continue to APG777
maintenance, which will evaluate 3- to 6-month dosing
- Integrated design expected to provide for significant
timeline acceleration by combining Ph2a and Ph2b elements into a
single study protocol
- All Part A sites are also expected to participate in Part B,
avoiding delays for site startup between the two parts
- Doses in the Phase 2 trial are enabled by APG777’s
potentially best-in-class PK profile, extended half-life, and
high-concentration formulation
- 180 mg/mL formulation enables 44% higher dose of APG777 vs
lebrikizumab in the same volume
- APG777 Phase 2 induction regimen is designed to exceed
lebrikizumab (an IL-13 inhibitor with an overlapping epitope with
APG777) exposures by ~30 to 40% with potential for improved
clinical responses and maintenance regimen is designed to equal
lebrikizumab’s exposures
- In Phase 3 studies, ~30% higher exposure seen in lebrikizumab
low bodyweight group resulted in numerically higher efficacy than
the overall study population across all key endpoints, including
EASI-75 and more stringent endpoints such as EASI-90 and IGA
0/1
- ~30-40% higher induction exposures for APG777 than lebrikizumab
are based on a planned six injection induction regimen given in the
first sixteen weeks of APG777 treatment. This is approximately half
as many of the 11 injections of lebrikizumab given during the same
period
- At 52 weeks, exposures of APG777 dosed every three months are
designed to exceed those of lebrikizumab and exposures of APG777
dosed every six months are designed to equal those of
lebrikizumab
Conference Call and Webcast
Apogee will host a conference call and webcast today, March 5,
2024, at 7:00 a.m. ET to discuss the APG777 Phase 1 interim
results. A live webcast of the call will be available on the
Investor Relations page of Apogee’s website at
https://investors.apogeetherapeutics.com/news-events/events. The
webcast will be made available for replay on the company's website
following completion of the event.
About APG777
APG777 is a novel, subcutaneous extended half-life monoclonal
antibody targeting IL-13 for the potential treatment of atopic
dermatitis (AD). In head-to-head preclinical studies, APG777 showed
equivalent or better potency to lebrikizumab in the inhibition of
IL-13 signaling. AD is a chronic inflammatory skin disorder that
affects approximately 40 million adults and 18 million children in
the United States, France, Germany, Italy, Japan, Spain and the
United Kingdom, 40 percent of which have moderate-to-severe
disease. Based on initial clinical data, the company may initiate a
Phase 2 trial in asthma and plans to further evaluate opportunities
to develop APG777 for other I&I indications, including alopecia
areata, chronic rhinosinusitis with nasal polyps, chronic
spontaneous urticaria, eosinophilic esophagitis and prurigo
nodularis.
About Apogee
Apogee Therapeutics is a clinical-stage biotechnology company
seeking to develop differentiated biologics for the treatment of
atopic dermatitis (AD), chronic obstructive pulmonary disease
(COPD), asthma and other inflammatory and immunology indications
with high unmet need. Apogee’s antibody programs are designed to
overcome limitations of existing therapies by targeting
well-established mechanisms of action and incorporating advanced
antibody engineering to optimize half-life and other properties.
The company’s two most advanced programs are APG777 and APG808,
which are being initially developed for the treatment of AD and
COPD, respectively. Based on a broad pipeline and depth of
expertise, the company believes it can deliver value and meaningful
benefit to patients underserved by today’s standard of care. For
more information, please visit www.apogeetherapeutics.com.
Financial DisclosuresDr. Silverberg and Dr.
Guttman- Yassky receive financial compensation as a scientific
advisor for Apogee.
Forward Looking Statements
Certain statements in this press release may constitute
“forward-looking statements” within the meaning of the federal
securities laws, including, but not limited to, statements
regarding: the efficacy, safety, tolerability, PK and PD profile of
APG777, the potential dosing regimen of APG777, the potential
superiority of APG777 compared to current therapies, our
expectations regarding plans for our current and future product
candidates and programs, our plans for our current and future
clinical trials, including a Phase 2 trial for APG777, our plans
for clinical trial design, the anticipated timing of the initiation
of and results from our clinical trials, including data from our
Phase 2 trial of AP777, and the potential clinical benefit and
half-life of APG777. Words such as “may,” “might,” “will,”
“objective,” “intend,” “should,” “could,” “can,” “would,” “expect,”
“believe,” “design,” “estimate,” “predict,” “potential,” “develop,”
“plan” or the negative of these terms, and similar expressions, or
statements regarding intent, belief, or current expectations, are
forward-looking statements. While Apogee believes these
forward-looking statements are reasonable, undue reliance should
not be placed on any such forward-looking statements, which are
based on information available to the company on the date of this
release. These forward-looking statements are based upon current
estimates and assumptions and are subject to various risks and
uncertainties (including, without limitation, those set forth in
Apogee’s filings with the U.S. Securities and Exchange Commission
(the SEC)), many of which are beyond the company’s control and
subject to change. Actual results could be materially different.
Risks and uncertainties include: global macroeconomic conditions
and related volatility, expectations regarding the initiation,
progress, and expected results of our preclinical studies, clinical
trials and research and development programs; expectations
regarding the timing, completion and outcome of our clinical
trials; the unpredictable relationship between preclinical study
results and clinical study results; the timing or likelihood of
regulatory filings and approvals; liquidity and capital resources;
and other risks and uncertainties identified in our Quarterly
Report on 10-Q for the quarterly period ended September 30, 2023,
filed with the SEC on November 13, 2023 , and subsequent disclosure
documents we may file with the SEC. Apogee claims the protection of
the Safe Harbor contained in the Private Securities Litigation
Reform Act of 1995 for forward-looking statements. Apogee expressly
disclaims any obligation to update or alter any statements whether
as a result of new information, future events or otherwise, except
as required by law.
Investor Contacts:
Noel KurdiVP, Investor RelationsApogee
TherapeuticsNoel.kurdi@apogeetherapeutics.com
Media Contact:
Dan Budwick1AB dan@1abmedia.com
Apogee Therapeutics (NASDAQ:APGE)
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