Bicycle Therapeutics Announces First Patient Dosed in BT8009 Phase II Expansion Cohorts and Provides Program Update The Phase II multi-center, open label trial will evaluate BT8009 administered at the recommended Phase I

Bicycle Therapeutics Announces First Patient

Dosed in BT8009 Phase II Expansion Cohorts and Provides Program Update

The Phase II multi-center, open label trial

will evaluate BT8009 administered at the recommended Phase II doses of 5mg/m2 and 7.5mg/m2

Phase I dose escalation cohorts complete; results

to be presented at a medical conference in 1H 2023

Confirmed RECIST response in a non-small cell

CAMBRIDGE, England, & BOSTON, November 8, 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 announced

updates from the Phase I/II trial of BT8009 in patients with numerous cancer types where Nectin-4 is expressed. BT8009

is a potential first in class Bicycle Toxin Conjugate (BTC ) targeting Nectin-4, a protein located on the surface of cells

that is highly expressed in urothelial cancer (UC) and other solid tumors.

"Dosing our first patient in the Phase II expansion portion of

the BT8009 trial is a key development milestone for Bicycle," said Kevin Lee, Ph.D., Chief Executive Officer. "Based on the

data presented to date, we believe we are making an important step towards hopefully providing a clinically meaningful, differentiated

therapy compared to what is currently available for UC as well as for other tumors that express Nectin-4, such as non-small cell lung

"The results from the Phase I dose escalation portion of the

BT8009 Phase I/II trial are very encouraging and we are excited to move rapidly forward with the dose expansion portion of the trial,"

said Dominic Smethurst, MRCP, Chief Medical Officer of Bicycle Therapeutics. "BT8009 continues to exhibit potential best-in-class

anti-tumor activity and a favorable tolerability profile, with a confirmed overall response rate from the latest cohorts consistent with

previous findings from the trial, and we are pleased to see UC patients at the 5mg/m2 dose remaining on therapy and continuing

to respond. We are also pleased to report a confirmed partial response in an NSCLC patient and look forward to providing additional data

from the Phase I escalation cohorts at a medical meeting in the first half of 2023."

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: the potential of BT8009 to target and kill cancer tumor cells; the initiation, progress,

and timing of clinical trials of BT8009; and pursuit of additional indications for and further clinical development of this product candidate.

Bicycle may not actually achieve the 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 intentions and expectations

disclosed in these forward-looking statements as a result of various factors, including: whether the outcomes of preclinical studies will

be predictive of clinical trial results; the risk that trials and studies may be delayed and may not have satisfactory outcomes; 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 3, 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 by law.

VP, Capital Markets & Investor Relations