27 September
2024
PureTech Health plc
PureTech-Invented KarXT
Receives U.S. Food and Drug Administration
Approval for the
Treatment of Schizophrenia in Adults
Milestone triggers payments
to PureTech totaling $29 million under agreements with Royalty
Pharma and PureTech's Founded Entity, Karuna Therapeutics, which
was acquired by Bristol Myers Squibb in March 2024, and unlocks
potential future payments related to additional milestones and
royalties
Bristol Myers Squibb to
market KarXT as CobenfyTM[1]
Cobenfy is the first new
drug mechanism approved in over 50 years for the treatment of
schizophrenia in adults
PureTech Health plc
(Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company dedicated to changing
the lives of patients with devastating diseases, today announced
that KarXT (xanomeline and trospium chloride), which was initially
invented and advanced by PureTech, has received U.S. Food and Drug
Administration ("FDA") approval for the treatment of schizophrenia
in adults. The FDA approval triggers
two separate milestone payments to PureTech totaling $29 million
under agreements with
Royalty Pharma and PureTech's Founded
Entity, Karuna Therapeutics, which was
acquired by Bristol
Myers Squibb (NYSE: BMY) ("BMS") in
March of 2024. Under these agreements,
PureTech is also entitled to potential future payments related to
additional milestones as well as approximately 2% royalties on net
annual sales over $2 billion. Following the acquisition of Karuna,
KarXT is now under the stewardship of BMS and will be marketed as Cobenfy.
Cobenfy was invented at
PureTech by combining two biologically active molecules -
xanomeline and trospium chloride - to address a tolerability challenge that had held back a potential
new class of medicines for the treatment of neuropsychiatric conditions, such as
schizophrenia. Consistent with its unique model of
drug development, PureTech advanced Cobenfy by founding Karuna Therapeutics, which later became a publicly
traded company on Nasdaq.
Eric Elenko, PhD, Co-founder and
President of PureTech said: "The FDA approval of
Cobenfy is a significant
milestone in our mission to transform the lives of patients with
devastating diseases. Our initial hypothesis was that we could
overcome the tolerability issues that had hindered the development
of an otherwise promising drug, xanomeline, and we were able to
test and validate this concept early on. We are immensely proud
that our dedication to this program has led to the first major
innovation in decades for those living with schizophrenia, and I am
equally pleased that our unique approach to R&D has delivered
yet another novel therapeutic to patients. Congratulations to the
teams at Karuna and BMS on this historic
accomplishment."
The FDA approval of Cobenfy is
further validation of PureTech's model and a hallmark of how it
creates value both clinically and financially. PureTech's
monetization of equity holdings in Karuna, including gross proceeds
from the BMS acquisition of Karuna, and a strategic royalty
agreement with Royalty Pharma have enabled PureTech to generate
approximately $1.1 billion to date after directing $18.5 million
toward Karuna's founding and Cobenfy's development. PureTech's
business model is designed to repeat and scale this type of
outcome, and proceeds from the success of Cobenfy have enabled
PureTech to self-fund the advancement of several programs -
including LYT-100 (deupirfenidone), LYT-200 (anti-galectin-9 mAb),
and the GlyphTM platform supporting the pipeline of
Seaport Therapeutics.
Bharatt Chowrira, PhD, JD, Chief
Executive Officer of PureTech said: "Congratulations to the Karuna
and BMS teams for delivering a groundbreaking treatment to people
with schizophrenia. The FDA approval of Cobenfy is a testament to our unique R&D
engine, which has now produced three FDA approved therapeutics.
We've applied this approach across our portfolio, from our
late-stage Internal Program LYT-100 (deupirfenidone) to our newly
launched Founded Entity, Seaport Therapeutics, and we will continue
to leverage this successful drug development model as we enter our
next phase of innovation."
PureTech's next wave of innovation
continues to focus on validated biologic and small molecule
modalities with human clinical data in diseases with significant
unmet need. LYT-100 (deupirfenidone) is PureTech's wholly-owned
program in development for the treatment of idiopathic pulmonary
fibrosis (IPF), a rare progressive lung disease with no cure. The
LYT-100 program leverages extensive prior clinical data and follows
the same blueprint used with Cobenfy to unlock the full therapeutic
potential of an efficacious but poorly tolerated medicine. PureTech
anticipates topline data from the Phase 2b clinical trial of
LYT-100 in patients with IPF by the end of the year, as well as
additional readouts from its oncology program, LYT-200
(anti-galectin-9 monoclonal antibody).
Important Safety Information
CONTRAINDICATIONS
COBENFY is contraindicated in
patients with:
- urinary retention
- moderate (Child-Pugh Class
B) or severe (Child-Pugh Class C) hepatic impairment
- gastric retention
- history of hypersensitivity
to COBENFY or trospium chloride. Angioedema has been reported with
COBENFY and trospium chloride.
- untreated narrow-angle
glaucoma
WARNINGS AND PRECAUTIONS
Risk of Urinary Retention: COBENFY can cause urinary retention. Geriatric patients
and patients with clinically significant bladder outlet obstruction
and incomplete bladder emptying (e.g., patients with benign
prostatic hyperplasia (BPH), diabetic cystopathy) may be at
increased risk of urinary retention.
COBENFY is contraindicated in
patients with pre-existing urinary retention and is not recommended
in patients with moderate or severe renal impairment.
In patients taking COBENFY, monitor
for symptoms of urinary retention, including urinary hesitancy,
weak stream, incomplete bladder emptying, and dysuria. Instruct
patients to be aware of the risk and promptly report symptoms of
urinary retention to their healthcare provider. Urinary retention
is a known risk factor for urinary tract infections. In patients
with symptoms of urinary retention, consider reducing the dose of
COBENFY, discontinuing COBENFY, or referring patients for urologic
evaluation as clinically indicated.
Risk of Use in Patients with Hepatic
Impairment: Patients with
hepatic impairment have higher systemic exposures of xanomeline, a
component of COBENFY, compared to patients with normal hepatic
function, which may result in increased incidence of
COBENFY-related adverse reactions.
COBENFY is contraindicated in
patients with moderate or severe hepatic impairment. COBENFY is not
recommended in patients with mild hepatic impairment.
Assess liver enzymes prior to
initiating COBENFY and as clinically indicated during
treatment.
Risk of Use in Patients with Biliary
Disease: In clinical studies
with COBENFY, transient increases in liver enzymes with rapid
decline occurred, consistent with transient biliary obstruction due
to biliary contraction and possible gallstone passage.
COBENFY is not recommended for
patients with active biliary disease such as symptomatic
gallstones. Assess liver enzymes and bilirubin prior to initiating
COBENFY and as clinically indicated during treatment. The
occurrence of symptoms such as dyspepsia, nausea, vomiting, or
upper abdominal pain should prompt assessment for gallbladder
disorders, biliary disorders, and pancreatitis, as clinically
indicated.
Discontinue COBENFY in the presence
of signs or symptoms of substantial liver injury such as jaundice,
pruritus, or alanine aminotransferase levels more than five times
the upper limit of normal or five times baseline values.
Decreased Gastrointestinal Motility: COBENFY contains trospium chloride. Trospium chloride,
like other antimuscarinic agents, may decrease gastrointestinal
motility. Administer COBENFY with caution in patients with
gastrointestinal obstructive disorders because of the risk of
gastric retention. Use COBENFY with caution in patients with
conditions such as ulcerative colitis, intestinal atony, and
myasthenia gravis.
Risk of Angioedema: Angioedema of the face, lips, tongue, and/or larynx has
been reported with COBENFY and trospium chloride, a component of
COBENFY. In one case, angioedema occurred after the first dose of
trospium chloride. Angioedema associated with upper airway swelling
may be life-threatening. If involvement of the tongue, hypopharynx,
or larynx occurs, discontinue COBENFY and initiate appropriate
therapy and/or measures necessary to ensure a patent airway.
COBENFY is contraindicated in patients with a history of
hypersensitivity to trospium chloride.
Risk of Use in Patients with Narrow-angle
Glaucoma: Pupillary dilation
may occur due to the anticholinergic effects of COBENFY. This may
trigger an acute angle closure attack in patients with anatomically
narrow angles. In patients known to have anatomically narrow
angles, COBENFY should only be used if the potential benefits
outweigh the risks and with careful monitoring.
Increases in Heart Rate: COBENFY can increase heart rate. Assess heart rate at
baseline and as clinically indicated during treatment with
COBENFY.
Anticholinergic Adverse Reactions in Patients with Renal
Impairment: Trospium chloride,
a component of COBENFY, is substantially excreted by the kidney.
COBENFY is not recommended in patients with moderate or severe
renal impairment (estimated glomerular filtration rate (eGFR)
<60 mL/min). Systemic exposure of trospium chloride is higher in
patients with moderate and severe renal impairment. Therefore,
anticholinergic adverse reactions (including dry mouth,
constipation, dyspepsia, urinary tract infection, and urinary
retention) are expected to be greater in patients with moderate and
severe renal impairment.
Central Nervous System Effects: Trospium chloride, a component of COBENFY, is associated
with anticholinergic central nervous system (CNS) effects. A
variety of CNS anticholinergic effects have been reported with
trospium chloride, including dizziness, confusion, hallucinations,
and somnolence. Monitor patients for signs of anticholinergic CNS
effects, particularly after beginning treatment or increasing the
dose. Advise patients not to drive or operate heavy machinery until
they know how COBENFY affects them. If a patient experiences
anticholinergic CNS effects, consider dose reduction or drug
discontinuation.
Most Common Adverse Reactions (³5% and at least twice
placebo): nausea, dyspepsia,
constipation, vomiting, hypertension, abdominal pain, diarrhea,
tachycardia, dizziness, and gastroesophageal reflux
disease.
Use
in Specific Populations:
- Moderate or Severe Renal
Impairment: Not recommended
- Mild Hepatic Impairment:
Not recommended
COBENFY (xanomeline and trospium
chloride) is available in 50mg/20mg, 100mg/20mg, and 125mg/30mg
capsules.
Please see U.S.
Full Prescribing Information ,
including Patient
Information .
About PureTech Health
PureTech is a clinical-stage
biotherapeutics company dedicated to giving life to new classes of
medicine to change the lives of patients with devastating diseases.
The Company has created a broad and deep pipeline through its
experienced research and development team and its extensive network
of scientists, clinicians and industry leaders that is being
advanced both internally and through its Founded Entities.
PureTech's R&D engine has resulted in the development of 29
therapeutics and therapeutic candidates, including three that have
been approved by the U.S. Food and Drug Administration. A number of
these programs are being advanced by PureTech or its Founded
Entities in various indications and stages of clinical development,
including registration enabling studies. All of the underlying
programs and platforms that resulted in this pipeline of
therapeutic candidates were initially identified or discovered and
then advanced by the PureTech team through key validation
points.
For more information, visit
www.puretechhealth.com
or connect with us on X (formerly Twitter)
@puretechh.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains
statements that are or may be forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995.
All statements contained in this press release that do not relate
to matters of historical fact should be considered forward-looking
statements, including without limitation those related to
additional milestones or royalties potentially due to PureTech in
relation to KarXT/Cobenfy, PureTechÕs development plans and the
timing of data readouts, including as related to LYT-100 and
LYT-200, and our future prospects, developments and strategies. The
forward-looking statements are based on current expectations and
are subject to known and unknown risks, uncertainties and other
important factors that could cause actual results, performance and
achievements to differ materially from current expectations,
including, but not limited to, those risks, uncertainties and other
important factors described under the caption "Risk Factors" in our
Annual Report on Form 20-F for the year ended December 31, 2023,
filed with the SEC and in our other regulatory filings. These
forward-looking statements are based on assumptions regarding the
present and future business strategies of the Company and the
environment in which it will operate in the future. Each
forward-looking statement speaks only as at the date of this press
release. Except as required by law and regulatory requirements, we
disclaim any obligation to update or revise these forward-looking
statements, whether as a result of new information, future events
or otherwise.
Contact:
PureTech
Public Relations
publicrelations@puretechhealth.com
Investor Relations
UK/EU Media
Ben Atwell, Rob Winder
+44 (0) 20 3727 1000
puretech@fticonsulting.com
US
Media
Nichole Bobbyn
+1 774 278 8273
nichole@tenbridgecommunications.com