PLYMOUTH
MEETING, Pa., Oct. 1, 2024
/PRNewswire/ -- Harmony Biosciences Holdings, Inc. (Nasdaq:
HRMY), will be providing a comprehensive pipeline update at its
Investor Day event today, showcasing new data from its orexin-2
receptor agonist, next-generation pitolisant programs, and
long-term extension data from its pitolisant program in idiopathic
hypersomnia. The company will also provide program updates from its
strategic acquisitions in Fragile X syndrome (FXS) and rare
epilepsies, which have strengthened its late-stage development
pipeline.
"Harmony Biosciences has transformed into an innovative,
catalyst-rich, self-funding biotech company focused on patient
impact and long-term value creation," said Jeffrey M. Dayno, M.D., President and Chief Executive Officer of
Harmony Biosciences. "We strategically expanded and advanced our
pipeline, with near-term catalysts positioned to deliver one or
more new product or indication launches each year over the next
five years, positioning Harmony to generate over $3 billion in potential annual revenue. Our
expertise in CNS and proven track record of success, combined with
our unique commercial model, provide a strong foundation to
efficiently scale beyond sleep/wake. I am extremely proud of what
the Harmony team has accomplished over the past year, and we are
just getting started in our growth story."
The event will feature presentations from Harmony's executive
leadership team and experts in the fields of sleep disorders,
Fragile X syndrome and developmental epileptic encephalopathies,
highlighting Harmony's expansion and diversification of its
pipeline, continued commitment to innovation, and focus on driving
value for patients and shareholders.
Key Highlights:
- Orexin-2 agonist program: New data show BP1.15205
(formerly TPM-1116) is based on a novel chemical scaffold and has
demonstrated greater potency compared to all publicly disclosed
data on orexin-2 agonists, with the potential to be
best-in-class.
- Pitolisant in Idiopathic Hypersomnia: New data show
robust and sustained efficacy of pitolisant in patients with
idiopathic hypersomnia in the Long-Term Extension study; mean
improvement in Epworth Sleepiness Scale (ESS) was ~9 points from
baseline out beyond one year, with the majority of patients
achieving normal levels of wakefulness.
- Pitolisant-HD program: Preliminary data confirm
safety up to five times the highest labeled dose of WAKIX,
establishing the safety margins for the pitolisant-HD development
program. Market research indicates healthcare professionals view HD
as a superior product profile and anticipate high uptake of
pitolisant-HD for all patients, including patients on WAKIX. Payers
also see value in the HD profile and anticipate broad access to
pitolisant-HD both pre- and post-WAKIX LOE.
- Fragile X syndrome program (ZYN-002): A
prespecified ad hoc analysis from the Phase 2 CONNECT-FX in Fragile
X syndrome study (published in 2022) showed that patients with
complete methylation of FMR1 gene showed a 40% median improvement
in socially avoidant behaviors (p=0.027) on the Aberrant
Behavior Checklist-Community FXS Specific (ABC-CFXS)
Social Avoidance subscale; this and other learnings from this trial
have informed the design and selection of the primary endpoint for
the Phase 3 RECONNECT study, which is on track for topline data in
mid-2025.
- EPX-100 development program: New safety and
tolerability data on EPX-100, a potent, oral, centrally acting
serotonin (5HT2) agonist currently in a pivotal registrational
trial (ARGUS) for Dravet syndrome (DS), shows a favorable
risk/benefit profile for EPX-100 compared to select approved drugs
for DS and Lennox-Gastaut syndrome (LGS); topline data in DS is
expected in 2026, and a pivotal Phase 3 trial for LGS is on track
to initiate later this year.
The replay webcast and presentation slides from this event will
be available on Harmony Biosciences' investor relations
at https://ir.harmonybiosciences.com/.
About WAKIX® (pitolisant)
Tablets
WAKIX, a first-in-class medication, is approved by
the U.S. Food and Drug Administration for the treatment
of excessive daytime sleepiness (EDS) or cataplexy in adult
patients with narcolepsy and for the treatment of EDS in pediatric
patients 6 years of age and older with narcolepsy. It was granted
orphan drug designation for the treatment of narcolepsy in 2010,
and breakthrough therapy designation for the treatment of cataplexy
in 2018. WAKIX is a selective histamine 3 (H₃) receptor
antagonist/inverse agonist. The mechanism of action of WAKIX is
unclear; however, its efficacy could be mediated through its
activity at H₃ receptors, thereby increasing the synthesis and
release of histamine, a wake promoting neurotransmitter. WAKIX was
designed and developed by Bioprojet (France). Harmony has an exclusive license
from Bioprojet to develop, manufacture and commercialize
pitolisant in the United States.
INDICATIONS AND USAGE
WAKIX is indicated for the
treatment of excessive daytime sleepiness (EDS) or cataplexy in
adult patients with narcolepsy and for the treatment of excessive
daytime sleepiness (EDS) in pediatric patients 6 years of age and
older with narcolepsy.
IMPORTANT SAFETY INFORMATION
Contraindications
WAKIX is contraindicated in patients
with known hypersensitivity to pitolisant or any component of the
formulation. Anaphylaxis has been reported. WAKIX is also
contraindicated in patients with severe hepatic impairment.
Warnings and Precautions
WAKIX prolongs the QT
interval. Avoid use of WAKIX in patients with known QT prolongation
or in combination with other drugs known to prolong the QT
interval. Avoid use in patients with a history of cardiac
arrhythmias, as well as other circumstances that may increase the
risk of the occurrence of torsade de pointes or sudden death,
including symptomatic bradycardia, hypokalemia or hypomagnesemia,
and the presence of congenital prolongation of the QT interval.
The risk of QT prolongation may be greater in patients with
hepatic or renal impairment due to higher concentrations of
pitolisant; monitor these patients for increased QTc. Dosage
modification is recommended in patients with moderate hepatic
impairment and moderate or severe renal impairment. WAKIX is
contraindicated in patients with severe hepatic impairment and not
recommended in patients with end-stage renal disease (ESRD).
Adverse Reactions
In the placebo-controlled clinical
trials conducted in adult patients with narcolepsy with or without
cataplexy, the most common adverse reactions (≥5% and at least
twice placebo) for WAKIX were insomnia (6%), nausea (6%), and
anxiety (5%). Other adverse reactions that occurred at ≥2% and more
frequently than in patients treated with placebo included headache,
upper respiratory tract infection, musculoskeletal pain, heart rate
increased, hallucinations, irritability, abdominal pain, sleep
disturbance, decreased appetite, cataplexy, dry mouth, and
rash.
In the placebo-controlled phase of the clinical trial conducted
in pediatric patients 6 years and older with narcolepsy with or
without cataplexy, the most common adverse reactions (≥5% and
greater than placebo) for WAKIX were headache (19%) and insomnia
(7%). The overall adverse reaction profile of WAKIX in the
pediatric clinical trial was similar to that seen in the adult
clinical trial program.
Drug Interactions
Concomitant administration of WAKIX
with strong CYP2D6 inhibitors increases pitolisant exposure by
2.2-fold. Reduce the dose of WAKIX by half.
Concomitant use of WAKIX with strong CYP3A4 inducers decreases
exposure of pitolisant by 50%. Dosage adjustments may be
required.
H1 receptor antagonists that cross the blood-brain barrier may
reduce the effectiveness of WAKIX. Patients should avoid centrally
acting H1 receptor antagonists.
WAKIX is a borderline/weak inducer of CYP3A4. WAKIX may reduce
the effectiveness of sensitive CYP3A4 substrates, including
hormonal contraceptives. Patients using hormonal contraception
should be advised to use an alternative non-hormonal contraceptive
method during treatment with WAKIX and for at least 21 days after
discontinuing treatment.
Use in Specific Populations
There is a pregnancy
exposure registry that monitors pregnancy outcomes in women who are
exposed to WAKIX during pregnancy. Patients should be encouraged to
enroll in the WAKIX pregnancy registry if they become pregnant. To
enroll or obtain information from the registry, patients can call
1-800-833-7460.
The safety and effectiveness of WAKIX have not been established
for treatment of excessive daytime sleepiness in pediatric patients
less than 6 years of age with narcolepsy.
The safety and effectiveness of WAKIX have not been established
for treatment of cataplexy in pediatric patients with
narcolepsy.
WAKIX is extensively metabolized by the liver. WAKIX is
contraindicated in patients with severe hepatic impairment. Dosage
adjustment is recommended in patients with moderate hepatic
impairment.
WAKIX is not recommended in patients with end-stage renal
disease. Dosage adjustment of WAKIX is recommended in patients with
eGFR <60 mL/minute/1.73
m2.
Dosage reduction is recommended in patients known to be poor
CYP2D6 metabolizers; these patients have higher concentrations of
WAKIX than normal CYP2D6 metabolizers.
Please see the Full Prescribing Information for
WAKIX for more information.
To report suspected adverse reactions, contact Harmony
Biosciences at 1-800-833-7460 or the FDA at 1-800-FDA-1088
or www.fda.gov/medwatch.
About Narcolepsy
Narcolepsy is a rare, chronic, debilitating neurological disease of
sleep-wake state instability that impacts approximately 170,000
Americans and is primarily characterized by excessive daytime
sleepiness (EDS) and cataplexy – its two cardinal symptoms – along
with other manifestations of REM sleep dysregulation
(hallucinations and sleep paralysis), which intrude into
wakefulness. EDS is the inability to stay awake and alert during
the day and is the symptom that is present in all people living
with narcolepsy. In most patients, narcolepsy is caused by the loss
of hypocretin/orexin, a neuropeptide in the brain that supports
sleep-wake state stability. This disease affects men and women
equally, with typical symptom onset in adolescence or young
adulthood; however, it can take up to a decade to be properly
diagnosed.
About Idiopathic Hypersomnia
Idiopathic Hypersomnia (IH) is a rare and chronic neurological
disease that is characterized by excessive daytime sleepiness
(EDS) despite sufficient or even long sleep time. EDS in IH cannot
be alleviated by naps, longer sleep or more efficient sleep. People
living with IH experience significant EDS along with the symptoms
of sleep inertia (prolonged difficulty waking up from sleep) and
'brain fog' (impaired cognition, attention, and alertness). The
cause of IH is unknown, but it is likely due to alterations in
areas of the brain that stabilize states of sleep and
wakefulness. IH is one of the central disorders of hypersomnolence
and, like narcolepsy, is a debilitating sleep disorder that can
result in significant disruption in daily functioning.
About ZYN-002
ZYN-002 is the first-and-only pharmaceutically manufactured
synthetic cannabidiol devoid of THC and formulated as a
patent-protected permeation-enhanced gel for transdermal delivery
through the skin and into the circulatory system. The product is
manufactured through a synthetic process in a cGMP facility and is
not extracted from the cannabis plant. ZYN-002 does not contain
THC, the compound that causes the euphoric effect of cannabis, and
has the potential to be a nonscheduled product if approved.
Cannabidiol, the active ingredient in ZYN-002, has been granted
orphan drug designation by the United States Food and Drug
Administration (FDA) and the European Medicines
Agency (EMA) for the treatment of FXS and for the treatment of
22q. Additionally, ZYN-002 has received FDA Fast Track designation
for the treatment of behavioral symptoms in patients with FXS.
About Fragile X Syndrome
Fragile X syndrome (FXS) is a rare genetic disorder that is the
leading known cause of both inherited intellectual disability and
autism spectrum disorder. The disorder negatively affects synaptic
function, plasticity and neuronal connections, and results in a
spectrum of intellectual disabilities and behavioral symptoms, such
as social avoidance and irritability. While the exact prevalence is
unknown, upwards of 80,000 patients in the U.S. and
121,000 patients in the European Union and
the UK are believed to have FXS, based on FXS prevalence
estimates of approximately 1 in 4,000 to 7,000 in males and
approximately 1 in 8,000 to 11,000 in females. There is a
significant unmet medical need in patients living with FXS as there
are currently no FDA approved treatments for this disorder.
FXS is caused by a mutation in FMR1, a gene which modulates a
number of systems, including the endocannabinoid system, and most
critically, codes for a protein called FMRP. The FMR1 mutation
manifests as multiple repeats of a DNA segment, known as the CGG
triplet repeat, resulting in deficiency or lack of FMRP. FMRP helps
regulate the production of other proteins and plays a role in the
development of synapses, which are critical for relaying nerve
impulses, and in regulating synaptic plasticity. In people with
full mutation of the FMR1 gene, the CGG segment is repeated more
than 200 times, and in most cases causes the gene to not function.
Methylation of the FMR1 gene also plays a role in determining
functionality of the gene. In approximately 60% of patients with
FXS, who have complete methylation of the FMR1 gene, no FMRP is
produced, resulting in dysregulation of the systems modulated by
FMRP.
About Clemizole Hydrochloride (EPX-100)
EPX-100, clemizole hydrochloride, is under development for the
treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome
(LGS). EPX-100 acts by targeting central 5-hydroxytryptamine
receptors to modulate serotonin signaling. The drug candidate is
administered orally twice a day in a liquid formulation and has
been developed based on a proprietary phenotype-based zebrafish
drug screening platform. DS is caused by a loss of function
mutation in the SCN1A gene, and scn1 mutant zebrafish replicate the
genetic etiology and phenotype observed in the majority of DS
patients. The scn1Lab mutant zebrafish model that expresses voltage
gated sodium channels has been used for high-throughput screening
of compounds that modulate Nav1.1 in the central nervous
system.
About Dravet Syndrome
Dravet syndrome (DS) is a severe and progressive epileptic
encephalopathy that begins in infancy and causes significant impact
on patient functioning. DS begins in the first year of life and is
characterized by high seizure frequency and severity, intellectual
disability, and a risk of sudden unexpected death in epilepsy.
Approximately 85% of Dravet Syndrome cases are caused by de novo
loss-of-function (LOF) mutations in a voltage-gated sodium channel
gene, SCN1A1. DS has an estimated incidence rate of
1:15,700.
About Lennox-Gastaut Syndrome
Lennox-Gastaut syndrome (LGS) is a rare and drug-resistant
epileptic encephalopathy characterized by onset in children between
3-5 years of age. The underlying cause of LGS is unknown and can be
related to a wide range of factors including genetic differences
and structural differences in the brain. As a result, patients
experience multiple seizure types, including atonic seizures, and
developmental, cognitive, and behavioral issues. LGS affects
approximately 48,000 patients in the U.S.
About Harmony Biosciences
Harmony Biosciences is a pharmaceutical company dedicated to
developing and commercializing innovative therapies for patients
with rare neurological diseases who have unmet medical needs.
Driven by novel science, visionary thinking, and a commitment to
those who feel overlooked, Harmony Biosciences is nurturing a
future full of therapeutic possibilities that may enable patients
with rare neurological diseases to truly thrive. Established by
Paragon Biosciences, LLC, in 2017 and headquartered in Plymouth Meeting, PA, we believe that when
empathy and innovation meet, a better future can begin; a vision
evident in the therapeutic innovations we advance, the culture we
cultivate, and the community programs we foster. For more
information, please visit www.harmonybiosciences.com.
Forward Looking Statement:
This presentation
includes forward‐looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995. All statements
other than statements of historical facts contained in these
materials or elsewhere, including statements regarding Harmony
Biosciences Holdings, Inc.'s (the "Company") future financial
position, business strategy and plans and objectives of management
for future operations, should be considered forward-looking
statements. Forward-looking statements use words like "believes,"
"plans," "expects," "intends," "will," "would," "anticipates,"
"estimates," "may," "could," "might," "continue," "potential," and
similar words or expressions in discussions of the Company's future
operations, financial performance or the Company's strategies, but
the absence of these words does not mean that a statement is not
forward-looking. These statements are based on current expectations
or objectives that are inherently uncertain. These forward-looking
statements involve significant risks and uncertainties that could
cause the actual results to differ materially from the expressed or
implied forwarding-looking statements, including, but not limited
to the risk factors discussed under the caption "Risk Factors" in
the Company's Annual Report on Form 10-K filed with the U.S.
Securities and Exchange Commission (the "SEC") on February 22, 2024 and its other filings with the
SEC. While the Company may elect to update such forward-looking
statements at some point in the future, it disclaims any obligation
to do so, even if subsequent events cause its views to
change.
This presentation includes information related to market
opportunity as well as cost and other estimates obtained from
internal analyses and external sources. The internal analyses are
based upon management's understanding of market and industry
conditions and have not been verified by independent sources.
Similarly, the externally sourced information has been obtained
from sources the Company believes to be reliable, but the accuracy
and completeness of such information cannot be assured. Neither the
Company, nor any of its respective officers, directors, managers,
employees, agents, or representatives, (i) make any representations
or warranties, express or implied, with respect to any of the
information contained herein, including the accuracy or
completeness of this presentation or any other written or oral
information made available to any interested party or its advisor
(and any liability therefore is expressly disclaimed), (ii) have
any liability from the use of the information, including with
respect to any forward-looking statements, or (iii) undertake to
update any of the information contained herein or provide
additional information as a result of new information or future
events or developments.
Harmony Biosciences Investor Contact:
Brennan Doyle
484-539-9700
bdoyle@harmonybiosciences.com
Harmony Biosciences Media Contact:
Cate McCanless
202-641-6086
cmccanless@harmonybiosciences.com
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