Nectin-4 portfolio comprised of BT8009 and
BT7480 represents potential opportunity to become leader in
treating Nectin-4-driven cancers, starting with metastatic
urothelial cancer (mUC)
Updated BT8009 clinical data continue to
support promising response and differentiated safety profile in mUC
as well as emerging clinical activity in additional tumor types
beyond bladder
EphA2 portfolio led by BT5528 could be the
first to address a historically undruggable target widely expressed
in many cancers
Additional work in oncology and beyond
highlight the breadth of the Bicycle® platform and its potential to
address a multitude of diseases
Event and webcast today at 8 a.m. ET
Bicycle Therapeutics (Nasdaq: BCYC), a biotechnology company
pioneering a new and differentiated class of therapeutics based on
its proprietary bicyclic peptide (Bicycle®) technology, is today
hosting a Research & Development (R&D) Day for investors
and analysts in New York to provide clinical updates for BT8009,
BT7480 and BT5528, and an overview of the company’s strategy and
pipeline opportunities. The company will also highlight the broad
capabilities of its novel Bicycle® platform technology. The event
begins at 8 a.m. ET and will be available via webcast here.
“During our first R&D Day, we are excited to showcase the
advantages of our Nobel Prize-winning science and our strategy to
discover and develop therapies with greater tolerability that could
provide enhanced benefit to a multitude of patients, starting with
those who have cancer,” said Kevin Lee, Ph.D., CEO of Bicycle
Therapeutics. “Through our Nectin-4 and EphA2 portfolios and the
continued work on our platform, including through partnerships, we
are building a leading precision-guided therapeutics company with
the potential to address a wide range of diseases that affect
millions of people around the world. We believe that our technology
has the potential to not only help patients live longer but also to
live well.”
“Today we are excited to provide clinical updates for our three
lead programs,” said Santiago Arroyo, M.D., Ph.D., Chief
Development Officer of Bicycle Therapeutics. “In totality, the data
support the emerging differentiated profile of our Bicycle®
molecules, paving the way to deliver best-in-class or
first-in-class therapies for many cancers. Based on our clinical
updates, we are taking important next steps with our development
programs, setting up what we expect to be a catalyst-rich
2024.”
Key R&D Day Highlights
Nectin-4 Portfolio
Bicycle Therapeutics is advancing two clinical programs, BT8009
and BT7480, targeting Nectin-4, a well-validated tumor antigen with
elevated levels of expression in multiple tumor types.
BT8009 is a Nectin-4 Bicycle toxin conjugate (BTC®)
designed to overcome the significant toxicity associated with other
toxin conjugate approaches. In the ongoing Phase 1/2 Duravelo-1
study involving heavily pre-treated patients, BT8009 showed:
- A promising response profile with a 38% objective response rate
(ORR) in 26 patients with metastatic urothelial cancer (mUC)
receiving 5 mg/m2 weekly and who had not been treated with
enfortumab vedotin (EV-naïve), and a median duration of response
(mDOR) of 11.1 months in 10 patients with 5 responders still on
therapy. This includes 1 complete response, 7 partial responses and
2 unconfirmed responses.
- Encouraging initial data in other cancers such as ovarian,
triple-negative breast (TNBC) and non-small cell lung (NSCLC) that
support further expansion beyond mUC.
- An emerging differentiated safety profile seen in 113 patients
with various types of cancer receiving 5 mg/m2 weekly, with
treatment-related adverse events being primarily low in frequency
and severity.
- Adverse events of interest such as ocular disorders, peripheral
neuropathy and skin reactions were low in frequency and severity.
Importantly, treatment-related peripheral neuropathy was low-grade
and often reversible, including zero cases of severe (≥Grade 3)
peripheral sensory neuropathy (damage to the nerves that carry
sensations like pain to the brain).
- In 34 EV-naïve mUC patients, treatment-related adverse events
and adverse events of interest were also low, similar to the 5
mg/m2 weekly total safety study population. Notably, there were
zero cases of severe (≥Grade 3) ocular disorders, peripheral
neuropathy or skin reactions.
- In 7 heavily pre-treated mUC patients receiving BT8009 5 mg/m2
weekly in combination with pembrolizumab, an acceptable
tolerability profile was observed with limited severe
treatment-related adverse events, including zero cases of severe
(≥Grade 3) ocular disorders, peripheral neuropathy or skin
reactions.
Bicycle Therapeutics plans to initiate the Phase 2/3 Duravelo-2
registrational trial of BT8009 in patients with mUC in 1Q 2024 and
intends to complete the Phase 1/2 Duravelo-1 open-label study
across multiple cancers.
BT7480 is a Nectin-4 targeted CD137 agonist designed to
overcome immune agonist toxicities and activate the immune system
in Nectin-4 expressing tumors. Clinical development has been guided
by safety considerations observed with first-generation CD137
agonists, the novelty of the Bicycle® platform technology and the
U.S. Food and Drug Administration’s (FDA) Project Optimus
initiative. In a Phase 1 clinical trial, BT7480 showed:
- In 33 patients assigned to receive one of 9 different doses of
BT7480, an emerging differentiated safety and tolerability profile
with a low number of severe adverse events. The majority of the
patients studied had tumors that expressed Nectin-4 and CD137.
- Two unconfirmed partial responses in heavily pre-treated
patients with cervical cancer.
- Three prolonged stable disease (≥7 months) in NSCLC and anal
cancer.
Bicycle Therapeutics will continue to define the recommended
Phase 2 dose (or maximum dose) and dose range for BT7480, with a
view to enroll combination cohorts with checkpoint inhibitors in
2024. These data will inform the design of a Phase 2 trial that
could support potential accelerated approval of BT7480.
Ephrin-A2 (EphA2)
Portfolio
Bicycle Therapeutics is advancing one clinical program, BT5528,
and one preclinical program, BT7455, targeting EphA2, a tumor
antigen that is widely expressed in many cancers and has
historically been difficult to target. BT7455 is an EphA2-targeted
CD137 agonist whose Investigational New Drug-enabling work is
ongoing.
BT5528 is an EphA2 BTC® designed to overcome the
significant toxicity associated with other toxin conjugate
approaches that have been unsuccessful. In an ongoing Phase 1/2
clinical trial enrolling patients with various solid tumors, BT5528
showed:
- In 109 patients, an acceptable emerging tolerability profile
with few severe adverse events. This was also seen in 74 patients
receiving 6.5 mg/m2 every other week, the dose being studied in
various tumors in the expansion cohorts. Importantly, unlike other
EphA2-targeted agents, no bleeding events were observed in patients
treated with BT5528 at any dose.
- Encouraging early activity in mUC with a 39% ORR in 18 patients
receiving 6.5 mg/m2, 8.5 mg/m2 or 10 mg/m2 every other week, and an
mDOR of 4 months in 7 patients with one responder still on therapy.
This includes 6 partial responses and 1 unconfirmed response.
- Encouraging emerging data in other cancers such as ovarian,
gastric/upper gastrointestinal and head and neck that are informing
the dose optimization strategy and further development.
Given the promising tolerability profile of BT5528 at 6.5 mg/m2
every other week and in line with the FDA’s Project Optimus
initiative, Bicycle Therapeutics has now commenced further cohorts
in mUC and ovarian cancer to test 5 mg/m2 weekly, which will inform
decisions about dose optimization, potential drug combinations and
expansion into other tumor types. Data from these cohorts are
expected to be available in the second half of 2024.
Platform Opportunities
The company will highlight its progress in developing its next
generation of Bicycle® conjugates, including:
- Next generation BTCs: Focusing on designing linkers
specifically for BTCs, which may provide enhanced payload release
into the tumor. The company plans to select a BTC® clinical
candidate using next-generation technology in the second half of
2024.
- Bicycle Radio Conjugates (BRC™): Developing a pipeline
of novel binders with optimized properties for radioisotope
delivery. For example, preclinical studies of a BRC targeting
MT1-MMP, a high-value target in cancer treatment, showed potent
anti-tumor activity and a favorable tolerability profile. Over
2024, Bicycle Therapeutics intends to generate early human imaging
data from its wholly owned BRC pipeline.
- Beyond Oncology: Successfully exploring other
therapeutic applications of the Bicycle® platform technology using
non-dilutive funding, demonstrating the platform’s plug-and-play
approach to precision targeting. For example, through partnerships
with Dementia Discovery Fund and Ionis Therapeutics, the company
demonstrated that delivery of therapies to the central nervous
system, including across the blood brain barrier, can be achieved
with Bicycle® molecules. Bicycle Therapeutics will continue to
develop Bicycle® molecules to address disease outside of oncology
through innovative partnerships.
About Bicycle Therapeutics
Bicycle Therapeutics is a clinical-stage biopharmaceutical
company developing a novel class of medicines for diseases that are
underserved by existing therapeutics. Bicycle® molecules are fully
synthetic short peptides constrained with small molecule scaffolds
to form two loops that stabilize their structural geometry. This
constraint facilitates target binding with high affinity and
selectivity, making Bicycle® molecules attractive candidates for
drug development. The company is evaluating BT8009, a Bicycle Toxin
Conjugate (BTC®) targeting Nectin-4, a well-validated tumor
antigen; BT7480, a Bicycle TICA® targeting Nectin-4 and agonizing
CD137; and BT5528, a BTC® targeting EphA2 in company-sponsored
Phase 1/2 trials. In addition, BT1718, a BTC® that targets MT1-MMP,
is being investigated in a Phase 1/2a clinical trial sponsored by
the Cancer Research UK Centre for Drug Development. Bicycle
Therapeutics is headquartered in Cambridge, UK, with many key
functions and members of its leadership team located in Cambridge,
Mass. For more information, visit bicycletherapeutics.com.
Forward Looking Statements
This press release may contain forward-looking statements made
pursuant to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. These statements may be identified
by words such as “aims,” “anticipates,” “believes,” “could,”
“estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,”
“plans,” “possible,” “potential,” “seeks,” “will” and variations of
these words or similar expressions that are intended to identify
forward-looking statements, although not all forward-looking
statements contain these words. Forward-looking statements in this
press release include, but are not limited to, statements regarding
Bicycle’s anticipated advancement of its current and prospective
product candidates, including the timing of initiation and design
of the Duravelo-2 Phase 2/3 clinical trial and potential
accelerated approval of BT8009; the timing of initiation and design
of a potential Phase 2 trial that could support accelerated
approval for BT7480; the timing and conduct of combination cohorts
for BT7480 with checkpoint inhibitors; the timing of initiation and
design of clinical trials for BT5528; the timing of initiation of
IND-enabling work for BT7455; the anticipated progression of
Bicycle’s clinical trials and preclinical studies; the availability
of and timing of updates for clinical candidates BT8009, BT5528 and
BT7480; the therapeutic potential for Bicycle® molecules in bladder
cancer and other oncologic indications, as well as other
indications beyond oncology; and current and prospective
collaborations. Bicycle may not actually achieve the plans,
intentions or expectations disclosed in these forward-looking
statements, and you should not place undue reliance on these
forward-looking statements. Actual results or events could differ
materially from the plans, intentions and expectations disclosed in
these forward-looking statements as a result of various factors,
including: uncertainties inherent in the initiation, progress and
completion of clinical trials and preclinical studies and clinical
and preclinical development of Bicycle’s product candidates;
availability and timing of results from clinical trials; whether
the outcomes of preclinical studies will be predictive of clinical
trial results; whether initial or interim results from a clinical
trial will be predictive of the final results of the trial or the
results of future trials; the risk that trials may have
unsatisfactory outcomes; potential adverse effects arising from the
testing or use of Bicycle’s current or prospective product
candidates; the risk that Bicycle may not maintain its current
collaborations or enter into new collaborations in the future; and
other important factors, any of which could cause Bicycle’s actual
results to differ from those contained in the forward-looking
statements, are described in greater detail in the section entitled
“Risk Factors” in Bicycle’s Quarterly Report on Form 10-Q filed
with the Securities and Exchange Commission (SEC) on November 2,
2023, as well as in other filings Bicycle may make with the SEC in
the future. Any forward-looking statements contained in this press
release speak only as of the date hereof, and Bicycle expressly
disclaims any obligation to update any forward-looking statements
contained herein, whether because of any new information, future
events, changed circumstances or otherwise, except as otherwise
required by law.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231214384646/en/
Investors: Stephanie Yao SVP, Investor Relations and
Corporate Communications ir@bicycletx.com 857-523-8544
Media: Argot Partners Sarah Sutton media@bicycletx.com
212-600-1902
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