Bicycle Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline of Bicycle Toxin Conjugates (BTCs) and Bicycle tumor-targeted i

Bicycle Therapeutics Reports Fourth Quarter

and Full Year 2021 Financial Results and Provides Corporate Update

clinical progress across pipeline of Bicycle Toxin Conjugates (BTCs) and Bicycle tumor-targeted immune cell agonists

of $438.7 million at December 31, 2021 expected to provide financial runway through 2024

CAMBRIDGE, England, & BOSTON, March 1,

2022 - Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology 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, 2021, and provided recent corporate

"We are encouraged by the progress we continue

to make across our oncology pipeline," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "As we previously

reported, BT8009 and BT5528 have demonstrated anti-tumor activity in two tumor types, and we look forward to presenting interim results

from our Phase I trial of BT8009 at a medical meeting and initiating the expansion cohorts in our clinical trial of BT5528 this year.

We also are moving our Bicycle TICA programs forward, including BT7480, which entered the clinic in the fourth quarter

of 2021. Our plans to advance our clinical programs, as well as to expand our discovery efforts and early development pipeline, are on

track and are supported by a strong balance sheet, with sufficient cash to fund these initiatives and support operations through 2024."

Fourth Quarter 2021 and Recent Highlights

The Phase I/II trial of BT5528,

Bicycle's second-generation BTC targeting EphA2, is also ongoing, with initiation of expansion cohorts planned for this year, with

an expected recommended Phase II dose of 6.5mg/m2 every-other-week.

Bicycle also initiated a Phase I

clinical trial of BT7480, a novel, fully synthetic Bicycle TICA targeting Nectin-4 and agonizing CD137, in the fourth

quarter of 2021, and dose escalation in that trial remains ongoing.

About Bicycle Therapeutics

Bicycle Therapeutics (NASDAQ: BCYC) is a clinical-stage

biopharmaceutical company developing a novel class of medicines, referred to as Bicycles, for diseases that are underserved by

existing therapeutics. Bicycles 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 Bicycles

attractive candidates for drug development. Bicycle is evaluating BT5528, a second-generation Bicycle Toxin Conjugate (BTC )

targeting EphA2; BT8009, a second-generation BTC targeting Nectin-4, a well-validated tumor antigen; and BT7480, a Bicycle TICA

targeting Nectin-4 and agonizing CD137, in company-sponsored Phase I/II

trials. In addition, BT1718, a BTC that targets MT1-MMP, is being investigated in an ongoing Phase I/IIa clinical trial sponsored by

the Cancer Research UK Centre for Drug Development. Bicycle is headquartered in Cambridge, UK, with many key functions and members of

its leadership team located in Lexington, MA. 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 product candidates, including BT5528, BT8009

and BT7480; the anticipated design of, initiation of expansion cohorts in, dosing in and progression of Bicycle's clinical trials;

the availability of data from clinical trials; the therapeutic potential for Bicycles in oncology and other applications;

Bicycle's plans to expand its discovery efforts and early development pipeline; and Bicycle's expected cash runway. 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: risks to clinical trial site initiation, patient

enrollment and follow-up, as well as to Bicycle's abilities to meet other anticipated deadlines and milestones, presented by the

ongoing COVID-19 pandemic; uncertainties inherent in the initiation 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; 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 be delayed and may not have satisfactory outcomes; 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; 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 4, 2021,

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.

Bicycle Therapeutics plc

Condensed Consolidated Statements of Operations

(In thousands, except share and per share data)

VP, Capital Markets & Investor Relations

Consilium Strategic Communications

Sukaina Virji or Mary-Jane Elliott