Topline combination data for zelenectide
pevedotin plus pembrolizumab in first-line metastatic urothelial
cancer demonstrated a 60% overall response rate, in line with
existing therapies
Dose selection and topline data from Phase 2/3
Duravelo-2 trial planned for 2H 2025
Heavily pretreated breast cancer and non-small
cell lung cancer patients with NECTIN4 gene amplification and/or
polysomy demonstrated an enhanced response to zelenectide
pevedotin
Company to advance development strategy
leveraging NECTIN4 gene amplification, with Phase 1/2 trials in
breast cancer, lung cancer and multi-tumor planned for 2025
Bicycle Therapeutics to host conference call
and webcast with management and oncology experts on Friday, Dec.
13, at 8 a.m. ET
Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical
company pioneering a new and differentiated class of therapeutics
based on its proprietary bicyclic peptide (Bicycle®) technology,
today announced the presentation of data showing the enhanced
anti-tumor activity of zelenectide pevedotin monotherapy in breast
cancer patients with NECTIN4 gene amplification at the 2024 San
Antonio Breast Conference Symposium (SABCS) in San Antonio, Texas.
The company also announced topline combination data for zelenectide
pevedotin plus pembrolizumab in previously untreated (first-line)
cisplatin-ineligible patients with metastatic urothelial cancer
(mUC), provided an enrollment and timeline update for the company’s
Phase 2/3 Duravelo-2 trial and shared topline monotherapy data for
zelenectide pevedotin in non-small cell lung cancer (NSCLC)
patients with NECTIN4 gene amplification. Bicycle Therapeutics will
host a conference call and webcast tomorrow, Dec. 13, at 8 a.m. ET
to review the data updates for zelenectide pevedotin and discuss
its development strategy leveraging NECTIN4 gene amplification.
Management will be joined by oncology experts Sherene Loi, M.D.,
Ph.D., from the Peter MacCallum Cancer Centre in Melbourne,
Australia, and Niklas Klümper, M.D., from the University Hospital
Bonn in Germany.
“The totality of the data shared today builds on the breadth of
previously reported data for zelenectide pevedotin that we believe,
when combined with our ambitious development strategy leveraging
NECTIN4 gene amplification, position Bicycle as a leader in
addressing Nectin-4 associated cancers,” said Bicycle Therapeutics
CEO Kevin Lee, Ph.D. “We are encouraged by the topline zelenectide
pevedotin data in combination with pembrolizumab in first-line mUC
patients, which demonstrate zelenectide pevedotin’s response data
are in line with other drug conjugates used to treat mUC while its
safety and tolerability profile continues to be differentiated.
Additionally, we are very pleased with our progress in enrolling
our Duravelo-2 registrational trial for zelenectide pevedotin in
mUC and look forward to providing dose selection and topline data
in the second half of next year.”
Dr. Lee continued: “While early, the zelenectide pevedotin
monotherapy data in breast cancer and NSCLC patients with NECTIN4
gene amplification underscore its promising anti-tumor activity and
solidify our next steps for the therapy’s development. By
leveraging NECTIN4 gene amplification, we expect to be able to
identify the patients who may most benefit from zelenectide
pevedotin and accelerate development for solid tumor indications
beyond bladder cancer. Over the course of 2025, we plan to initiate
Phase 1/2 trials evaluating zelenectide pevedotin in NECTIN4
gene-amplified breast cancer, lung cancer and multiple other
cancers.”
Topline Zelenectide Pevedotin Plus Pembrolizumab Combination
Data in First-line mUC Highlights Zelenectide pevedotin is a
Bicycle® Toxin Conjugate (BTC®) targeting Nectin-4, a
well-validated tumor antigen. Topline results from the ongoing
Phase 1/2 Duravelo-1 trial evaluating zelenectide pevedotin 5 mg/m2
weekly plus pembrolizumab 200 mg once every three weeks in 22
first-line cisplatin-ineligible patients with mUC showed:
- 60% overall response rate (ORR) (12/20) among
efficacy-evaluable patients. Of the responses, 5 were confirmed and
7 were unconfirmed at the time of the data cut. Fifteen patients
remained on treatment at the time of the data cut.
- Safety and tolerability profile was broadly consistent with
late-line Duravelo-1 monotherapy and combination cohorts.
- Adverse events of clinical interest such as peripheral
neuropathy, skin reactions and eye disorders were primarily low
grade. There was one report of Grade 3 sensory peripheral
neuropathy and one report of Grade 3 rash, both of which were
transient and reverted to Grade 1 upon dose interruption.
More detailed data from this study will be presented at a future
medical meeting.
Bicycle Therapeutics is currently conducting the Phase 2/3
Duravelo-2 trial evaluating zelenectide pevedotin plus
pembrolizumab versus chemotherapy in first-line mUC (Cohort 1), and
zelenectide pevedotin monotherapy and in combination with
pembrolizumab in late-line mUC (Cohort 2). In each cohort, two
doses of zelenectide pevedotin – 5 mg/m2 weekly and 6 mg/m2 two
weeks on, one week off – are being initially assessed. Based on
enrollment progress, the company plans to report dose selection and
topline data for both cohorts in the second half of 2025.
Zelenectide Pevedotin Monotherapy Data in Breast Cancer
Patients with NECTIN4 Gene Amplification Highlights (Presented at
2024 SABCS) Gene amplification is a common mechanism by which
cancer cells gain function. Bicycle Therapeutics identified that
the NECTIN4 gene sits on a commonly amplified chromosomal site in
cancer, creating more copies of the gene and often translating to
more protein expression. Since zelenectide pevedotin binds to
Nectin-4, it was hypothesized that NECTIN4 gene amplification may
predict response and could serve as a biomarker for therapy
stratification.
The company conducted a post-hoc analysis of 38 heavily
pretreated breast cancer patients enrolled in Duravelo-1, of which
32 were confirmed to have triple-negative breast cancer (TNBC). The
majority of patients were treated with zelenectide pevedotin 5
mg/m2 weekly.
Of the 38 breast cancer patients enrolled, 35 patients were
efficacy evaluable. Additionally, 23 breast cancer patient samples
were available for NECTIN4 testing, of which 8 demonstrated NECTIN4
gene amplification or harbored NECTIN4 polysomy. Results
showed:
- 62.5% ORR (5/8) among breast cancer patients with NECTIN4 gene
amplification or polysomy, compared to 14.3% ORR (5/35) among all
efficacy-evaluable breast cancer patients.
- Of the 5 partial responses, 4 were confirmed and 1 was
unconfirmed.
- No responses in non-amplified or non-polysomy patients.
Of the 32 TNBC patients enrolled, 30 patients were efficacy
evaluable. Additionally, 19 TNBC patient samples were available for
NECTIN4 testing, of which 7 demonstrated NECTIN4 gene amplification
or harbored a NECTIN4 polysomy. Results showed:
- 57.1% ORR (4/7) among TNBC patients with NECTIN4 gene
amplification or polysomy, compared to 13.3% ORR (4/30) among all
efficacy-evaluable TNBC patients.
- Of the 4 partial responses, 3 were confirmed and 1 was
unconfirmed.
- All 3 TNBC patients with NECTIN4 gene amplification who
responded to zelenectide pevedotin had prior treatment with
sacituzumab govitecan.
- No responses in non-amplified or non-polysomy patients.
In this study of heavily pretreated breast cancer patients,
zelenectide pevedotin was generally well tolerated, and its safety
and tolerability profile was consistent with data from other
Duravelo-1 cohorts. Low rates of Grade ≥3 treatment-related adverse
events (TRAEs) (34.2%) and Grade ≥3 treatment-related serious
adverse events (TRSAEs) (10.5%) occurred. The most common TRAEs
were fever (pyrexia), nausea and diarrhea. TRAEs of clinical
interest, including peripheral neuropathy (any kind) and skin
reactions, were low grade.
“Although the sample size was limited, this post-hoc analysis
highlights the encouraging anti-tumor activity of zelenectide
pevedotin in breast cancer patients with NECTIN4 gene
amplification, particularly among those with TNBC who urgently need
new treatment options,” said Professor Sherene Loi, M.D., Ph.D.,
consultant medical oncologist in the Breast Unit and group leader
at the Peter MacCallum Cancer Centre in Melbourne, Australia. “As
innovative and genomically targeted therapies for breast cancer
continue to emerge, these findings position zelenectide pevedotin
as a promising potential new therapy and NECTIN4 gene amplification
as a novel target for breast cancer drug development.”
The poster presentation, “Enhanced anti-tumor activity of
zelenectide pevedotin in triple-negative breast cancer (TNBC)
patients with NECTIN4 gene amplification” is available in the
Publications section of the Bicycle Therapeutics website.
Topline Zelenectide Pevedotin Monotherapy Data in NSCLC
Patients with NECTIN4 Gene Amplification Highlights The company
conducted a post-hoc analysis of 40 pretreated patients with NSCLC
enrolled in Duravelo-1. The majority of patients received
zelenectide pevedotin 5 mg/m2 weekly.
Of the 40 patients enrolled, 34 patients were efficacy
evaluable. Additionally, 19 patient samples were available for
NECTIN4 testing, of which 6 demonstrated NECTIN4 gene
amplification. Five out of 6 patients with NECTIN4 gene
amplification were efficacy evaluable. Results showed:
- 40.0% ORR (2/5) among patients with NECTIN4 gene amplification,
compared to 8.8% ORR (3/34) among all efficacy-evaluable
patients.
- Of the 3 partial responses, 2 were confirmed and 1 was
unconfirmed.
- Out of 19 patients tested for NECTIN4 gene amplification, none
of the non-amplified patients responded.
The safety and tolerability profile of zelenectide pevedotin was
broadly consistent with data from other Duravelo-1 monotherapy
cohorts.
More detailed data from this study will be presented at a future
medical meeting.
Overview of Development Strategy Leveraging NECTIN4 Gene
Amplification Bicycle Therapeutics plans to advance development
of zelenectide pevedotin in broader indications outside of mUC
utilizing a NECTIN4 gene amplification strategy to target patients
who have the potential for significantly deeper responses.
Over the course of 2025, Bicycle Therapeutics plans to initiate
several additional Phase 1/2 trials to assess zelenectide pevedotin
in NECTIN4 gene-amplified breast cancer, lung cancer and multiple
other cancers. Through this strategy, the company believes it has
the opportunity to become the leader in addressing Nectin-4
associated cancers and potentially transform the treatment
landscape for thousands of patients in the United States.
Conference Call Details Bicycle Therapeutics will host a
conference call and webcast on Friday, Dec. 13, at 8 a.m. ET to
review the data updates for zelenectide pevedotin. The company’s
management team will be joined by Sherene Loi, M.D., Ph.D., Peter
MacCallum Cancer Centre, and Niklas Klümper, M.D., University
Hospital Bonn.
To access the call, please dial +1-833-816-1408 (U.S.) or
+1-412-317-0501 (international) and ask to join the Bicycle
Therapeutics call. A live webcast and replay of the conference call
will be accessible in the Investor section of the Company’s website
at www.bicycletherapeutics.com.
About Bicycle Therapeutics Bicycle Therapeutics is a
clinical-stage pharmaceutical company developing a novel class of
medicines, referred to as Bicycle® molecules, 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 zelenectide pevedotin
(formerly BT8009), a Bicycle® Toxin Conjugate (BTC®) targeting
Nectin-4, a well-validated tumor antigen; BT5528, a BTC molecule
targeting EphA2, a historically undruggable target; and BT7480, a
Bicycle Tumor-Targeted Immune Cell Agonist® (Bicycle TICA®)
targeting Nectin-4 and agonizing CD137, in company-sponsored
clinical trials. Additionally, the company is developing Bicycle
Radionuclide Conjugates (BRC®) for radiopharmaceutical use and,
through various partnerships, is exploring the use of Bicycle®
technology to develop therapies for diseases beyond oncology.
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
www.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
development of zelenectide pevedotin, BT5528 and BT7480 as well as
potential radiopharmaceutical product candidates; the company’s
plans to utilize a NECTIN4 gene amplification strategy in the
clinical development of zelenectide pevedotin; expectations with
respect to Bicycle’s ability to identify the patients who may most
benefit from zelenectide pevedotin, to advance or accelerate
development of this product candidate for broader indications,
including solid tumor cancers beyond bladder cancer, and to become
a leader in addressing Nectin-4 associated cancers; the planned
initiation of clinical trials of zelenectide pevedotin in breast
cancer, lung cancer, and other cancers; the timing and manner of
announcement of data and program updates from clinical trials for
zelenectide pevedotin, including reporting of dose selection and
topline data from the Duravelo-2 trial; and the use of Bicycle’s
technology through various partnerships to develop potential
therapies in diseases beyond oncology. 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 research and
development and in the initiation, progress and completion of
clinical trials and clinical development of Bicycle’s product
candidates; the risk that Bicycle may not realize the intended
benefits of its technology, partnerships or NECTIN4 gene
amplification strategy; timing of results from clinical trials;
whether the outcomes of preclinical studies and prior clinical
trials will be predictive of future clinical trial results; the
risk that trials may have unsatisfactory outcomes; potential
adverse effects arising from the testing or use of Bicycle’s
product candidates; 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 October 31, 2024, 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/20241212212246/en/
Investors: Stephanie Yao SVP, Investor Relations and
Corporate Communications stephanie.yao@bicycletx.com
857-523-8544
Matthew DeYoung Argot Partners ir@bicycletx.com 212-600-1902
Media: Jim O’Connell Weber Shandwick media@bicycletx.com
312-988-2343
Grafico Azioni Bicycle Therapeutics (NASDAQ:BCYC)
Storico
Da Dic 2024 a Gen 2025
Grafico Azioni Bicycle Therapeutics (NASDAQ:BCYC)
Storico
Da Gen 2024 a Gen 2025
