We are a late stage clinical pharmaceutical company dedicated to the discovery,
development and commercialization of novel oral therapies that address the
neurobiology of sleep-related breathing diseases. Our sole clinical product
candidate, AD109 (Oxnimbi), is an investigational, fixed-dose, anti-apneic
neuromuscular modulator, combining a novel anti-muscarinic and a selective
norepinephrine reuptake inhibitor (NRI) for the treatment of obstructive sleep
apnea (OSA). Oxnimbi is designed to target the neuromuscular defect of OSA by
improving upper airway muscle activity to help maintain airway patency and
prevent airway collapse during sleep. Based on results from two registrational
trials, we submitted a New Drug Application (NDA) for Oxnimbi to the U.S. Food
and Drug Administration (FDA) in April 2026. The registrational trials were
Phase 3, randomized, double-blind, placebo-controlled, parallel-arm trials in
adults with mild to severe OSA, LunAIRo and SynAIRgy, which together enrolled
approximately 1,300 patients and represent one of the largest and most diverse
cohorts ever studied in an OSA pharmacologic trial. LunAIRo was conducted in the
United States and SynAIRgy was conducted in the United States and Canada. In
this prospectus, we also refer to AD109 by its proposed future brand name,
βOxnimbi.β This brand name was conditionally approved by the FDA in May 2025,
which was reconfirmed in June 2026, and is pending approval of the NDA in its
totality. All previous trials of Oxnimbi were conducted in the United States.
Oxnimbi met its primary endpoint and several key secondary endpoints in both
Phase 3 trials, SynAIRgy and LunAIRo. Under the treatment policy estimand, mean
apnea hypopnea index (AHI) reductions at week 26 (≥4% (desaturation criterion
for hypopneas) were 44.1% in SynAIRgy and 33.7% in LunAIRo versus (vs) 17.6% and
7.3% with placebo, respectively (p<0.0001). Under the on-treatment estimand,
reductions were 55.6% and 46.8% from baseline (p<0.0001 vs placebo). Under the
treatment policy estimand, hypoxic burden (HB), a metric associated with
cardiovascular risk and all-cause mortality, was reduced by 44.7% and 37.4% from
baseline (p<0.001 vs placebo), and under the on-treatment estimand by 60.5% and
58.2% (p<0.0001 vs placebo), in SynAIRgy and LunAIRo, respectively. P-values are
statistical measures that help determine whether the results of a trial are
significant. Typically, p-values less than 0.05, like those described here,
suggest that a comparison between two groups is statistically significant.
Oxnimbi was generally well-tolerated, with adverse events (AEs) predominantly
mild across both trials, with no drug-related serious adverse events (SAEs) in
the Oxnimbi group reported in either LunAIRo or SynAIRgy. Clinical trial results
are preliminary in nature, and such results may not be replicated in subsequent
clinical trials. We believe the FDA review cycle will be 10-months from our NDA
submission in April 2026 although the duration of the review may vary based on
various factors.
In connection with the FDAβs review of our top-line Phase 3 data, at the pre-NDA
meeting, the FDA provided feedback about the clinical meaningfulness of certain
endpoint results, including the primary endpoint and the limitations of the
patient-reported outcomes (PROs). The FDA indicated that additional analyses and
justification may be needed to support that the data demonstrates a clinically
meaningful benefit for the treatment of OSA. We believe that we have addressed
this feedback in our NDA submission and plan to continue to address it if raised
as part of the FDA review process. While we believe the totality of the data
supports the potential clinical benefit of AD109, the FDA may have a different
interpretation of whether the data represent clinically meaningful differences,
which could impact the outcome or timing of the regulatory review process and,
in turn, our future operating results.
OSA is a serious chronic disease that can lead to severe and potentially
life-threatening complications and cause debilitating symptoms. Disease severity
of OSA is typically measured by the AHI, which represents the number of times
per hour that the airway fully or partially collapses during sleep and is
considered the standard objective measure of OSA severity in clinical practice.
The AHI may be calculated using different scoring criteria, that vary based on
the minimum oxygen-desaturation threshold required to classify a hypopnea. For
our Phase 3 program, our primary endpoints for both trials are measured by a
change from baseline in AHI, based on hypopneas defined by at least a four
percent reduction in oxygen saturation (SpO2). In addition to the AHI, measures
of nocturnal oxygenation, such as the sleep apnea specific HB, are increasingly
recognized as important complementary metrics to characterize OSA severity.
While AHI is a simple frequency metric, HB captures the depth and duration of
oxygen desaturation associated with airway obstructions and has been shown in
third-party epidemiologic studies to correlate closely with cardiovascular and
neurocognitive consequences of OSA. HB reduction was a secondary endpoint in
both of our Phase 3 trials.
OSA is a highly prevalent condition, estimated to be affecting approximately 80
million people in the United States between the ages of 30-69, according to a
study we commissioned from Clarivate Plc. (Clarivate). We believe many people
with OSA remain undiagnosed in part due to lack of awareness, but also because
they seek to avoid current treatment options that they anticipate will be
uncomfortable or unacceptable. OSA generally affects middle-aged and older
adults of varying ages, weights, sexes, and ethnicities but can also occur in
young adults. A third party study, supported by certain company personnel and a
grant from us in the community setting, estimates that more than 60% of
middle-aged and older adults living with OSA are not obese. We believe Oxnimbi,
if approved, can be prescribed for most adults diagnosed with mild, moderate or
severe OSA, including obese and non-obese patients. In the future, we may seek
approval for Oxnimbi for adolescent and child patients as well. However, our
current focus is on the treatment of the adult OSA population.
The current standard of care is positive airway pressure (PAP), which uses a
bedside machine to deliver pressurized air via a mask to keep the airway open
during use; however, despite its effectiveness, many patients refuse PAP or
discontinue it due to issues such as discomfort, pressure intolerance and
lifestyle disruption, resulting in persistently low patient compliance. There is
no FDA approved pharmacologic therapy to treat the crucial underlying cause of
OSA, neuromuscular dysfunction during sleep. Prescription drug development in
the field of OSA is relatively novel, and until the approval of tirzepatide in
2024 for moderate to severe OSA in obese adults in combination with a
reduced-calorie diet and increased physical activity, the FDA historically did
not have well-established therapeutic endpoints for this indication. We believe
the OSA market is ripe for disruption, similar to other disease markets that
were transformed by the introduction of an effective oral therapy such as
osteoporosis, erectile dysfunction, rheumatoid arthritis, multiple sclerosis,
hepatitis C and others.
We believe a novel, oral and convenient treatment option that targets the
underlying cause of OSA is well positioned to address significant unmet need. A
pharmacological option could unlock latent demand for treatment and expand
overall awareness, screening, diagnosis and treatment of OSA. Therefore, we
designed Oxnimbi as an oral, once-daily, rapid-onset therapy to improve upper
airway muscle activity during sleep, a crucial underlying cause of all OSA. If
approved, we believe Oxnimbi has the potential to become a standard of care for
the treatment of OSA.
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While Oxnimbi currently is our sole clinical product candidate, we are currently
pursuing preclinical-stage programs focused on sleep-related breathing disorders
and related comorbidities. These programs include exploratory
combination-therapy approaches that remain at an early stage of development. For
each of these programs, we would need to complete significant additional
development activities before we would be in a position to seek regulatory
approval, which may include, as applicable, completion of preclinical studies,
identification and optimization of a development candidate, submission and
clearance of an IND or comparable regulatory filing, initiation and completion
of Phase 1, Phase 2 and Phase 3 clinical trials, development of a commercial
manufacturing process, completion of chemistry, manufacturing, and controls
(CMC) activities and submission of an NDA or other applicable marketing
application. These programs remain at an early stage, and we may not
successfully advance any of them into or through clinical development.
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We were incorporated under the laws of the State of Delaware in June 2017. Our
principal executive offices are located at 39 John F. Kennedy Street, 4th Floor,
Cambridge, Massachusetts 02138 and our telephone number is (617) 500-8880. Our
website address is www.apnimed.com.
