Bicycle Therapeutics Reports First Quarter 2022 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline, including interim BT8009 Phase I clinical data - Cash and cash equivalents of

Bicycle Therapeutics Reports First Quarter 2022

Financial Results and Provides Corporate Update

clinical progress across pipeline, including interim BT8009 Phase I clinical data

and cash equivalents of $407.4 million as of March 31, 2022 expected to provide

financial runway through 2024

CAMBRIDGE, England, & BOSTON, May 5,

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 first quarter ended March 31, 2022 and provided recent corporate updates.

"We have made significant progress recently

across our oncology pipeline," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "We reported

interim data for the Phase I portion of the Phase I/II trial in BT8009, showing an overall response rate, or ORR, of 50% in the 5mg/m2

weekly cohort in patients with urothelial cancer and an encouraging tolerability profile. We believe BT8009 has the potential to offer

clinically meaningful differentiation compared to currently available therapies and we look forward to advancing the program once the

dose escalation phase is complete. We also look forward to initiating the BT5528 Phase II expansion cohorts soon."

Dr. Lee continued: "Beyond our Bicycle

Toxin Conjugates , or BTCs, we continue to be encouraged as we progress our Bicycle TICA programs forward, including

BT7480, which is advancing in the dose escalation portion of the Phase I clinical trial. Underscoring our efforts is a strong balance

sheet and we anticipate our cash and cash equivalents will provide financial runway through 2024."

First Quarter 2022 and Recent Highlights

of additional doses and frequencies continues, and Bicycle intends to provide further updates this year.

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, Massachusetts. 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 BT8009, BT5528

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;

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, and Bicycle's ability 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 such as 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 not have satisfactory outcomes,

and potential adverse effects arising from the testing or use of Bicycle's product candidates; the risk that Bicycle may not realize

the intended benefits of its technology; the risk that Bicycle's projections regarding its expected financial 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, and which are described in greater detail in the section

entitled "Risk Factors" in Bicycle's Annual Report on Form 10-K filed with the Securities and Exchange Commission

(SEC) on March 1, 2022, 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

Bicycle Therapeutics plc

Condensed Consolidated Statements of Operations

and Comprehensive Loss

(In thousands, except share and per share data)

VP, Capital Markets & Investor Relations