- BHV-1300 achieved deep lowering of targeted IgG, with
reductions > 60% in the lowest subcutaneous dose tested in the
MAD.
- Subcutaneous BHV-1300 achieved rapid and progressive lowering
of IgG within hours of each weekly dose administration, and
pharmacodynamic effects were sustained relative to baseline over
the four-week period. The optimized subcutaneous formulation also
showed substantially less inter-patient variability in the MAD
compared to the previously reported intravenously administered
BHV-1300.
- BHV-1300 has been safe and well tolerated across the ongoing
Phase 1 without any dose limiting toxicity to date. All AEs
have been mild, with no SAEs or discontinuations related to study
drug. Dose escalation continues with the optimized subcutaneous
formulation to explore the full range of IgG reductions possible
with BHV-1300. Additional Phase 1 data will be presented upon
completion of the remaining subcutaneous cohorts in 1Q25.
- Laboratory data from the MAD confirm a differentiated safety
profile compared to competitor agents as BHV-1300 has had no
clinically significant reductions in albumin, liver function test
abnormalities or increases in cholesterol at week 4 relative to
baseline. Further enhancing the competitive safety profile,
BHV-1300 was rationally designed to spare IgG3 with plasma IgG3
levels over the course of the MAD preserved through the end of
study week 4 to allow for healthy immune effector
functioning.
- Submitted new drug application (NDA) to US FDA for troriluzole
in spinocerebellar ataxia (SCA), following completion of pre-NDA
meeting in 4Q 2024. Troriluzole has Orphan Drug and Fast-Track
designations and qualifies for potential Priority Review.
- Announced completion of enrollment during 4Q 2024 in the
BHV-7000 pivotal 3-week, Phase 2/3 bipolar trial, several months
ahead of timelines.
- Expanded and advanced the molecular degraders of extracellular
proteins (MoDE) clinical program to include next-generation
autoantibody specific degraders that selectively remove pathogenic
antibodies while preserving healthy immune functioning, with
regulatory acceptance of 3 novel drug candidate INDs and/or CTAs in
4Q24:
- IgA nephropathy: Initiated Phase 1 dosing with BHV-1400, a
novel IgAN investigational therapy designed to selectively degrade
pathogenic galactose deficient IgA1 (Gd-IgA1) while sparing normal
IgA. In addition to rapid and sustained lowering of Gd-IgA1,
BHV-1400 is expected to result in less potential for respiratory,
mucosal or central nervous system infections compared to broader
IgA lowering or immunosuppressive strategies in development by
competitors.
- Autoimmune cardiomyopathy: Initiated Phase 1 dosing with
BHV-1600, a novel investigational therapy designed to selectively
degrade b1 adrenergic receptor (b1AR) autoantibodies. Biohaven also
completed an INTERACT meeting with FDA regarding BHV-1600 in 4Q
2024 and gained alignment for the study design to pursue an
accelerated approval pathway in peripartum cardiomyopathy (PPCM), a
rare autoimmune life-threatening disease with no approved
therapy.
- IgG mediated diseases: IND opened for BHV-1310, an optimized
and selective IgG1, IgG2, and IgG4 degrader in 4Q 2024 with first
dosing planned for 1Q 2025.
- Entered into an agreement with Ypsomed to develop and
manufacture BHV-1300 in an easy-to-use, autoinjector for
self-administration. Ypsomed is a leading provider of autoinjector
technology used in commercialized products for convenient patient
use.
- The Ypsomed device is expected to be used across all MoDE
programs through development and commercial use, derisking this
aspect of the development program as well as providing seamless
transitions and allowing for significant data generation on the
device in advance of future NDA filings.
NEW
HAVEN, Conn., Dec. 16,
2024 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN)
("Biohaven"), a global clinical-stage biopharmaceutical company
focused on the discovery, development, and commercialization of
life-changing therapies to treat a broad range of rare and common
diseases, today highlighted the achievement of several clinical and
regulatory milestones across its proprietary Molecular Degrader of
Extracellular Proteins (MoDE™) platform as well as its glutamate
modulation and ion channel programs.
Subcutaneously administered BHV-1300 achieved deep lowering of
targeted IgG, with reductions > 60% in the lowest subcutaneous
dose tested in the ongoing multiple ascending dose (MAD) study.
Subcutaneous BHV-1300 achieved progressive reduction in IgG within
hours of each weekly dose administration in the MAD, and
pharmacodynamic effects were sustained relative to baseline over
the four-week study period. BHV-1300 has been safe and
well-tolerated across the Phase 1 study. There were no clinically
significant effects on albumin or liver function, and no increases
in cholesterol were noted. Further enhancing the competitive safety
profile and as intentionally designed, plasma IgG3 levels were
preserved through the end of study week 4 to allow for healthy
immune effector functioning. All AEs were mild, any drug-related AE
resolved, and there were no discontinuations due to study drug
related AEs. The optimized subcutaneous formulation in the MAD also
showed substantially less inter-patient variability compared to
previously reported intravenous BHV-1300. Escalating dose level
cohorts of subcutaneous BHV-1300 are ongoing to explore the full
range of IgG reductions possible with BHV-1300 for a wide range of
future disease indications.
Tova Gardin MD, MPP, Biohaven's
Chief Translational Officer, commented, "The results of
subcutaneously delivered BHV-1300 from the first and lowest MAD
dose cohort represent a monumental step forward for our MoDE
platform with deep and rapid reduction in targeted IgG. Our
results highlight the selectivity and precision of BHV-1300 in
potentially treating IgG mediated immune diseases while the
regulatory acceptance of three next generation degraders showcases
the future of the MoDE technology in autoantibody disease.
With speed, selectivity, and depth of lowering, BHV-1300
has the potential to transform the treatment of autoimmune disease
and has paved the way for rapid innovation across the degrader
platform. With the mechanistic validation of BHV-1300 and
performance of the optimized subcutaneous formulation in Phase 1,
we have begun the manufacturing of a convenient autoinjector that
will further differentiate our approach in the clinic. The early
autoinjector development to ensure a commercial ready,
patient-administered device for BHV-1300 was important to derisking
this aspect of our MoDE development program."
Biohaven licensed the MoDE technology from Yale University with high potential differentiation
for the treatment of autoimmune diseases, including rapid
degradation of targets within hours, deep reductions that can be
titrated by dose level and frequency, simple-to-use patient
administration, excellent tolerability without deleterious effects
on albumin or cholesterol, and the flexibility to be used in
conjunction with Fc-containing biologics (unlike other IgG lowering
agents). Additionally, BHV-1300 is unique with its selective
removal of targeted IgG (IgG1, IgG2 and IgG4 over IgG3). IgG3 plays
a critical role in the immune response and in activating effector
functions crucial for combating bacteria, parasites, and viruses.
BHV-1300 was designed to spare IgG3 to avoid the broad
immunosuppression associated with other IgG lowering approaches and
to allow for an immune response to combat potential infections
while delivering therapeutic actions in autoimmune disease.
Results of the ongoing Phase 1 trial validate the selectivity of
BHV-1300 and the adaptability of the platform to engage targets of
interest with precision.
In addition to the new Phase 1 data with BHV-1300, Biohaven also
announced regulatory acceptance of three INDs and/or CTAs for its
next-generation MoDE molecules to target other immune mediated
diseases. Two of these novel MoDEs, BHV-1400 and BHV-1600,
represent the platform's first autoantibody specific degraders,
sparing the body's healthy antibodies (IgG, IgA, etc.) to function
normally while clearing disease-causing antibodies.
Dosing in humans has been initiated for BHV-1400, a novel IgA
nephropathy (IgAN) investigational therapy designed to selectively
degrade galactose deficient IgA1 (Gd-IgA1) without
immunosuppression. IgAN is a rare disease affecting approximately
60,000 individuals in the United
States. It is often diagnosed in the second or third decade
of life, progresses over decades, and can result in kidney failure
leading to the need for hemodialysis. Approved therapies broadly
suppress the immune system or target the downstream consequences of
immune damage without targeting the autoimmune cause of disease.
For a disease which is diagnosed in young adults and treatment may
be required over the lifespan, BHV-1400 is highly differentiated,
engineered to clear the pathogenic nidus of disease, Gd-IgA1, and
preserve the individual's immunoglobulins (IgG, IgA, IgE, IgM),
immune cells, and complement system (Figure 2). Thus, BHV-1400 is
expected to result in less potential for respiratory, mucosal or
central nervous system infections compared to broader IgA lowering
or immunosuppressive strategies in development. Additionally,
IgAN clinical trials have a well-established pathway for
accelerated approval.
Biohaven also initiated dosing in humans with BHV-1600 in 4Q
2024. BHV-1600 is a MoDE engineered to rapidly degrade pathogenic
autoantibodies to the b1-adrenergic receptor (b1AR). BHV-1600 is
the first rationally designed investigative treatment in
development for peripartum cardiomyopathy (PPCM), a rare type of
heart failure that occurs during pregnancy or soon after birth that
has no currently approved therapy. In b1AR autoantibody-driven
cardiomyopathy, autoantibodies bind b1AR and induce
cardiomyocyte toxicity and heart failure (Figure
3).1 PPCM affects mothers at an incredibly
vulnerable period: previously healthy, individuals with PPCM
develop profound heart failure, struggling with new symptoms as
their child experiences its first days and often first years of
life. Without disease-specific therapies, women with PPCM can
develop heart failure and may emergently require left ventricular
assistive devices or heart transplant. Given PPCM is a
life-threatening disease with no current treatment and the
potential for BHV-1600 to rapidly degrade pathogenic b1AR
autoantibodies, Biohaven completed an INTERACT meeting with the FDA
in 4Q 2024 and gained alignment on a clinical development program
to pursue an accelerated approval pathway for BHV-1600 in
PPCM.
An IND has also been accepted for BHV-1310, an optimized and
selective IgG1, IgG2, and IgG4 degrader. Dosing is expected in
humans in 1Q 2025.
In addition to key updates in the MoDE clinical development
program, Biohaven also announced critically important advances
related to its late-stage glutamate and ion channel platforms. A
new drug application (NDA) was submitted to the US FDA for
troriluzole in the treatment of all genotypes of spinocerebellar
ataxia (SCA), following the completion of a pre-NDA meeting in 4Q
2024. Troriluzole was previously granted Orphan Drug and Fast-Track
designations by FDA, and qualifies for potential Priority Review.
Biohaven recently reported positive topline pivotal results in SCA
in September 2024, demonstrating that
troriluzole slowed disease progression by 50-70% over the 3-year
study period. SCA is a rare, life-threatening, progressively
debilitating neurodegenerative disease that affects approximately
15,000 people in the US, and 24,000
in Europe and the United Kingdom. Troriluzole has
been safe and well-tolerated in over 8 years of clinical trial
experience. There are no FDA approved treatments for SCA and
troriluzole is the first investigational agent to show disease
slowing in its clinical development program.
Biohaven further announced the completion of enrollment in a
pivotal BHV-7000 Phase 2/3 trial in bipolar disorder in 4Q 2024.
BHV-7000 is a selective activator of Kv7 potassium channels that
offers a novel and compelling mechanism of action for the treatment
of bipolar disorder and an excellent tolerability at all doses
evaluated in previous studies without the central nervous system
adverse effects, such as somnolence and other CNS-related effects,
that typically limit the use of other mood stabilizing medications.
The trial completed enrollment several months ahead of anticipated
timelines, reflecting the high unmet need for new treatments in
bipolar disorder. The Phase 2/3 double-blind,
placebo-controlled study enrolled approximately 256 patients.
Patients were randomized to receive BHV-7000 75 mg once daily or
placebo over a 3-week treatment period. The primary outcome measure
of the study is the change from baseline to week 3 in mania symptom
severity, as measured by the Young Mania Rating Scale (YMRS).
Secondary objectives include response and remission rates, early
onset of efficacy, depression symptom severity as measured by the
Montgomery-Åsberg Depression Rating Scale (MADRS), and safety.
Irfan Qureshi MD, Chief Medical
Officer of Biohaven, commented, "Biohaven continues to propel
cutting edge science into reality in the clinic. Biohaven's
proprietary MoDE degrader platform is a technology that has the
potential to revolutionize precision treatment of a spectrum of
common and rare autoimmune diseases. Targeted removal of IgG, b1AR
autoantibodies and galactose deficient IgA1 has the potential to
transform the treatment of rheumatoid arthritis, myasthenia gravis,
autoimmune cardiomyopathy, IgAN, and many other immune mediated
disorders. While advancing new compounds in immunology and
inflammation, our R&D teams have also delivered important
milestones for our ion channel and glutamate modulating agents. We
are proud to have completed enrollment in the pivotal bipolar study
with BHV-7000, months ahead of timelines and eagerly await topline
results. And, our NDA submission for spinocerebellar ataxia
represents the culmination of over 8 years of innovation, research,
and commitment to patients with this devastating neurodegenerative
disease. We believe troriluzole is a transformative breakthrough
that offers new hope to individuals and families suffering from SCA
who currently have no therapeutic options to alter the course of
this relentless disease." Dr. Qureshi added, "We are extremely
excited about the rapid progress across the portfolio and
optimistic about the opportunities we have to make a positive
impact on patients' lives and create value in 2025 and beyond."
About Biohaven
Biohaven is a biopharmaceutical
company focused on the discovery, development, and
commercialization of life-changing treatments in key therapeutic
areas, including immunology, neuroscience, and oncology. Biohaven
is advancing its innovative portfolio of therapeutics, leveraging
its proven drug development experience and multiple proprietary
drug development platforms. Biohaven's extensive clinical and
nonclinical programs include Kv7 ion channel modulation for
epilepsy and mood disorders; extracellular protein degradation for
immunological diseases; TRPM3 antagonism for migraine and
neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory
disorders; glutamate modulation for OCD and SCA (spinocerebellar
ataxia); myostatin inhibition for neuromuscular and metabolic
diseases, including SMA and obesity; antibody recruiting bispecific
molecules and antibody drug conjugates for cancer. For more
information, visit www.biohaven.com.
Forward-looking Statements
This news release includes
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. The use of certain words,
including "continue", "plan", "will", "believe", "may", "expect",
"anticipate" and similar expressions, is intended to identify
forward-looking statements. Investors are cautioned that any
forward-looking statements, including statements regarding the
future development, timing and potential marketing approval and
commercialization of development candidates, are not guarantees of
future performance or results and involve substantial risks and
uncertainties. Actual results, developments and events may differ
materially from those in the forward-looking statements as a result
of various factors including: the expected timing, commencement and
outcomes of Biohaven's planned and ongoing clinical trials; the
timing of planned interactions and filings with the FDA; the timing
and outcome of expected regulatory filings; complying with
applicable U.S. regulatory requirements; the potential
commercialization of Biohaven's product candidates; and the
effectiveness and safety of Biohaven's product candidates.
Additional important factors to be considered in connection with
forward-looking statements are described in Biohaven's filings with
the Securities and Exchange Commission, including within the
sections titled "Risk Factors" and "Management's Discussion and
Analysis of Financial Condition and Results of Operations". The
forward-looking statements are made as of the date of this news
release, and Biohaven does not undertake any obligation to update
any forward-looking statements, whether as a result of new
information, future events or otherwise, except as required by
law.
MoDE is a trademark of Biohaven Therapeutics Ltd.
Investor Contact:
Jennifer
Porcelli
Vice President, Investor Relations
jennifer.porcelli@biohavenpharma.com
+1 (201) 248-0741
Media Contact:
Mike
Beyer
Sam Brown Inc.
mikebeyer@sambrown.com
+1 (312) 961-2502
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