Full Press Release Details
Bicycle Therapeutics Presents Updated Clinical
Results Across Oncology Pipeline at ESMO Congress 2024
Updated monotherapy data for Nectin-4 targeting
zelenectide pevedotin in metastatic urothelial cancer (mUC) showed a promising 45% overall response rate (ORR), 11.1 months median duration
of response and a generally well-tolerated safety profile
EphA2-targeting BT5528 demonstrated an emerging
differentiated safety profile and antitumor activity in patients with advanced solid tumors, including a 45% ORR in mUC 6.5 mg/m2
every two weeks dose expansion cohort
Relatively low frequency and severity of treatment-related
peripheral neuropathy following monotherapy with Bicycle Toxin Conjugates zelenectide pevedotin and BT5528, with patients
often able to continue therapy without modification
BT7480 demonstrated a favorable safety profile
and preliminary antitumor activity in advanced Nectin-4-associated solid tumors
BARCELONA, September 14, 2024 - 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 updated Phase 1/2 clinical results for Bicycle Toxin Conjugate (BTC )
zelenectide pevedotin (formerly BT8009) in metastatic urothelial cancer (mUC); BTC molecule BT5528 in advanced solid tumors, such as
mUC and ovarian; and Bicycle Tumor-Targeted Immune Cell Agonist (Bicycle TICA ) BT7480 in advanced solid
tumors. The company also shared an analysis of peripheral neuropathy, a key adverse event of interest associated with monomethyl auristatin
E (MMAE)-based drug conjugates, in patients treated with BTC molecules. These data will be presented during a poster session at the European
Society for Medical Oncology (ESMO) Congress 2024 in Barcelona today.
"We are pleased that the data presented at ESMO continue to support
the promising response and differentiated safety profiles of our Bicycle molecules. Importantly, our lead investigational therapy zelenectide
pevedotin continues to demonstrate an overall response rate that is in line with other drug conjugates used to treat metastatic urothelial
cancer, but with a marked improvement in tolerability. Overall, we believe the data continue to demonstrate the potential of our Bicycle
technology platform to create differentiated medicines designed to help patients not only to live longer but also to live well,"
said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics. "These clinical data are just the first set of updates that we have guided to
delivering this year. In the coming months, we look forward to sharing initial imaging data from our growing radiopharmaceutical pipeline
and additional data for zelenectide pevedotin in bladder, breast and lung cancer."
ESMO 2024 Data Highlights
Zelenectide pevedotin is a BTC molecule targeting
Nectin-4, a well-validated tumor antigen, designed to overcome the significant toxicity associated with other drug conjugate approaches.
Updated results from the ongoing Phase 1/2 Duravelo-1 trial evaluating 5 mg/m2 weekly of zelenectide pevedotin monotherapy
in 45 mUC patients who had not previously been treated with enfortumab vedotin showed:
The global Phase 2/3 Duravelo-2 registrational trial of zelenectide
pevedotin in patients with mUC is currently enrolling. Additional data updates for zelenectide pevedotin in combination with pembrolizumab
in first line mUC and monotherapy in late line triple-negative breast cancer and non-small cell lung cancer (NSCLC) are planned for later
BT5528 is a BTC molecule targeting EphA2, a tumor antigen that
is widely expressed in many cancers and has historically been difficult to target using other drug conjugate approaches. Updated results
from the ongoing Phase 1/2 trial evaluating 6.5 mg/m2 every two weeks and 5 mg/m2 weekly of BT5528 monotherapy in
patients with advanced solid tumors showed:
The company has begun assessing BT5528 at 6.5 mg/m2 every
two weeks in combination with nivolumab. Results from this cohort are expected in 2025.
Low rates of treatment-related peripheral neuropathy (TRPN) following
monotherapy treatment with BTC molecules zelenectide pevedotin or BT5528. In 149 patients treated with zelenectide pevedotin and 74
patients treated with BT5528 from ongoing Phase 1/2 studies, results showed:
The data support the hypothesis that the antibody-drug construct may
be a primary driver of peripheral neuropathy rather than MMAE toxicity as was previously believed.
BT7480 is a Nectin-4 targeted CD137 agonist designed to overcome
immune agonist toxicities and activate the immune system in Nectin-4 expressing tumors. Initial data from the Phase 1/2 dose escalation
trial evaluating BT7480 in patients with advanced solid tumors showed:
As the maximum tolerated dose for BT7480 has not yet been reached,
the company is continuing dose exploration in combination studies, starting with nivolumab.
The posters are available in the Publications section of the
Bicycle Therapeutics website.
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 Radio 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 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 progress across its R&D pipeline
and the advancement of its product candidates, including zelenectide pevedotin, BT5528 and BT7480; the anticipated progression of Bicycle's
clinical trials and the method and timing of announcement of data from clinical trials and program updates for clinical candidates; the
potential of the Bicycle technology platform to create differentiated medicines; the development of potential radiopharmaceutical or other
product candidates using Bicycle's technology through various partnerships; and the therapeutic potential for Bicycles in oncology
and other applications. 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 or partnerships; timing of results from
clinical trials; whether the outcomes of preclinical studies will be predictive of 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 August 6, 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.
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