Bicycle Therapeutics Reports Recent Business Progress and Fourth Quarter and Full Year 2023 Financial Results Catalyst-rich 2024 with multiple clinical data readouts and updates expected for pipeline and discovery progra

Bicycle Therapeutics

Reports Recent Business Progress and Fourth Quarter and Full Year 2023 Financial Results

2024 with multiple clinical data readouts and updates expected for pipeline and discovery programs

2/3 Duravelo-2 registrational trial for BT8009 in metastatic urothelial cancer now active and recruiting patients

initial clinical data showed a promising response and differentiated safety profile

Day outlined near-term strategic priorities and highlighted breadth of Bicycle platform technology and ability to develop

highly differentiated precision therapies for cancer and other diseases

Sands appointed to Board of Directors

and cash equivalents of $526.4 million as of December 31, 2023, expected to provide financial runway into 2026

England & BOSTON, February 20, 2024 - Bicycle Therapeutics plc (NASDAQ: BCYC), a biopharmaceutical 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, 2023, and provided recent corporate

was a pivotal year for our company, during which we achieved significant progress across our Nectin-4 and EphA2 clinical oncology portfolios

and our discovery pipeline of next-generation Bicycle molecules, including in radiopharmaceuticals and areas beyond oncology.

We continue to demonstrate our ability to develop highly differentiated, precision-guided therapeutics that may offer greater tolerability

and lead to enhanced benefit for patients," said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics. "With a catalyst-rich 2024

expected, a strong financial position, validating partnerships and a unique platform technology, we enter this year with significant

momentum and focus to advance our mission to help patients not only live longer but also live well."

delighted to welcome Stephen Sands to our Board of Directors," said Pierre Legault, chairman of Bicycle Therapeutics. "He

brings a wealth of experience and knowledge that we believe will provide valuable insight and additional depth to our Board as the company

enters this new stage of growth and seeks to advance its strategic priorities across multiple key areas."

Updates and Recent Events

strategic priorities at the company's first Research & Development (R&D) Day in December:

a BTC targeting Nectin-4 designed to overcome the significant toxicity associated with other toxin conjugate approaches.

2H 2024, the company plans to complete the Phase 1/2 Duravelo-1 open-label study across multiple cancers and report data from the following

a Bicycle TICA targeting Nectin-4 and agonizing CD137 designed to overcome immune agonist toxicities and activate the

immune system in Nectin-4 expressing tumors.

company 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

a BTC targeting EphA2, a historically undruggable target, and is designed to overcome the significant toxicity associated

with other toxin conjugate approaches.

company 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.

Stephen Sands, former chairman of the Global Healthcare Group at Lazard, to the Board of Directors. Mr. Sands has spent more

than 35 years at Lazard providing strategic and financial advice to senior executives and boards of directors at leading healthcare and

life sciences companies across the globe. Prior to joining Lazard, he was a partner in the healthcare practice of McKinsey &

Company. During his career, Mr. Sands has co-founded two life sciences companies: Enzytech (acquired by Alkermes) and Opta Food

Ingredients (acquired by Stake Technology and now SunOpta). Mr. Sands has served as director on the boards of several life sciences

companies and is currently a director on the board of Cytier Therapeutics (NASDAQ: CYT, Oncology Drugs).

Quarter and Year End 2023 Financial Results

Bicycle Therapeutics

is a clinical-stage biopharmaceutical 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 BT8009, a Bicycle

Toxin Conjugate (BTC ) targeting Nectin-4, a well-validated tumor antigen; BT5528, a BTC 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.

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 product candidates, including BT8009, BT5528 and BT7480; the anticipated progression of

Bicycle's clinical trials, including the timing of patient dosing in the Duravelo-2 Phase 2/3 clinical trial; anticipated clinical

and other benefits of Bicycle Therapeutics' participation in the CDRP Program; the availability of and timing of announcement of

data from clinical trials and regulatory updates for clinical candidates the discovery, development and potential commercialization of

potential radiopharmaceutical or other product candidates using Bicycle's technology under the strategic collaboration agreements;

BT8009's potential to be a transformative therapy for patients with metastatic bladder cancer; the therapeutic potential for Bicycles

in oncology and other applications; Bicycle's goal to become a leader in next-generation solid tumor therapeutics and combinations;

Bicycle's expected financial runway; and the potential benefits of appointing Stephen Sands to Bicycle's Board of Directors.

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 clinical development of Bicycle's product candidates; the risk that

Bicycle may not realize the intended benefits of its technology or strategic collaborations; 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; challenges or delays in the development and preparation of the commercial manufacturing readiness of

BT8009; potential adverse effects arising from the testing or use of Bicycle's product candidates; the risk that Bicycle's

projections regarding its expected cash runway are inaccurate or that its conduct of its business requires more cash than anticipated;

the risk that the intended benefits from the appointment of Stephen Sands to Bicycle's Board of Directors may not be realized;

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.

Consolidated Statements of Operations and Comprehensive Loss

thousands, except share and per share data)

Relations and Corporate Communications