Bicycle Therapeutics Reports Recent Business Progress and Fourth Quarter and Full Year 2024 Financial Results Updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab continue to show promisi

Bicycle Therapeutics Reports Recent Business

Progress and Fourth Quarter and Full

Year 2024 Financial Results

Updated topline Phase 1 combination data for

zelenectide pevedotin plus pembrolizumab continue to show promising anti-tumor activity and a differentiated safety profile in first-line

metastatic urothelial cancer; Duravelo-2 dose selection data expected in 2H 2025

Enhanced response to zelenectide pevedotin seen

in NECTIN4 gene-amplified late-line breast cancer and non-small cell lung cancer (NSCLC), resulting in U.S. FDA Fast Track designations

for triple-negative breast cancer and NSCLC; several Phase 1/2 trials expected to start in 2025

Advancing radiopharmaceuticals pipeline, with

additional MT1-MMP human imaging data expected in mid-2025 and first EphA2 human imaging data planned for 2H 2025

Cash and cash equivalents of $879.5 million

as of December 31, 2024, expected to provide financial runway into 2H 2027

CAMBRIDGE, England & BOSTON, February 25, 2025 -

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 reported

financial results for the fourth quarter and full year ended December 31, 2024, and provided recent corporate updates.

"In 2024, the significant progress across our pipeline and business

continued to validate our approach to developing next-generation precision-guided therapeutics. We believe that zelenectide pevedotin's

promising anti-tumor activity and differentiated safety profile could transform the treatment landscape not only for patients with metastatic

urothelial cancer but also NECTIN4 gene-amplified solid tumors. Additionally, our encouraging first human imaging data for MT1-MMP demonstrates

the potential of our technology platform to produce radiopharmaceutical medicines to novel targets," said Bicycle Therapeutics

CEO Kevin Lee, Ph.D. "With a clear strategy to build on this foundation and financial runway into the second half of 2027, we are

strongly positioned for another year of execution across our research and development pipeline of oncology, radiopharmaceuticals and

partnered programs as we work to bring innovative therapies to cancer patients."

Fourth Quarter 2024 and Recent Events

Bicycle Therapeutics is currently conducting the Phase

2/3 Duravelo-2 registrational 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 assessed

before a planned final dose selection in 2H 2025.

Zelenectide pevedotin was generally well tolerated, demonstrating

a safety and tolerability profile consistent with data from other Duravelo-1 cohorts, and TRAEs were primarily low grade, further supporting

the potential for NECTIN4 gene amplification to serve as a biomarker for therapy stratification. Based on these data, the U.S. Food and

Drug Administration (FDA) granted Fast Track designation to zelenectide pevedotin for the treatment of adult patients with previously

treated, NECTIN4 gene-amplified, advanced or metastatic TNBC and NSCLC.

Bicycle Therapeutics has continued to build a robust patent

estate related to the use of NECTIN4 gene amplification as a biomarker for patient selection. The company plans to initiate several additional

Phase 1/2 trials evaluating zelenectide pevedotin in NECTIN4 gene-amplified cancer, including breast cancer (Duravelo-3) in 1H 2025 and

lung cancer (Duravelo-4) and multi-tumor (Duravelo-5) in 2H 2025.

Bicycle Therapeutics continues to advance its emerging

BRC pipeline, with additional MT1-MMP human imaging data anticipated in mid-2025 and initial EphA2 human imaging data expected in 2H

2025. The company is targeting clinical trials for its first radiotherapeutic program to begin in 2026.

Participation in Upcoming Investor Conferences

Bicycle Therapeutics management will

participate in a fireside chat at the TD Cowen 45th Annual Health Care Conference on Tuesday, March 4, at 9:50

a.m. ET. A live webcast of the fireside chat will be accessible from the Investor section of the company's website

at www.bicycletherapeutics.com. A replay of the webcast will be archived and available

following the event.

Fourth Quarter and Year End 2024 Financial Results

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 the potential for zelenectide pevedotin to transform the treatment landscape for patients

with mUC and NECTIN4 gene-amplified solid tumors; the potential for Bicycle Therapeutics' technology to produce radiopharmaceutical

medicines; the company's ability to build on its foundation, including with respect to execution across its pipeline; the planned

dose selection for Duravelo-2; the anticipated initiation of clinical trials of zelenectide pevedotin in breast cancer, lung cancer and

multi-tumor types and of the company's first radiotherapeutic program; the timing of announcement of human imaging data for MT1-MMP

and EphA2 targeting BRCs; expectations with respect to Bicycle Therapeutics' financial runway; and the use of Bicycle Therapeutics'

technology through various partnerships to develop potential therapies in diseases beyond oncology. Bicycle Therapeutics 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 Therapeutics' product candidates;

the risk that Bicycle Therapeutics may not realize the intended benefits of its technology, partnerships or NECTIN4 gene-amplification

strategy; the risk that Bicycle Therapeutics may not achieve any of its clinical development strategies; 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 Therapeutics'

product candidates; the risk that Bicycle Therapeutics' projections regarding its expected cash runway are inaccurate or that its

conduct of its business requires more cash than anticipated; and other important factors, any of which could cause Bicycle Therapeutics'

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 Therapeutics' 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 Therapeutics 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 Therapeutics 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.

Bicycle Therapeutics plc

Condensed Consolidated Statements of Operations

and Comprehensive Loss

(In thousands, except share and per share data)

SVP, Investor Relations and Corporate Communications