April 4, 2019

Lee Kalowski
Chief Financial Officer
Bicycle Therapeutics Ltd.
4 Hartwell Place
Lexington, Massachusetts 02421

       Re: Bicycle Therapeutics Ltd.
           Amendment No. 1 to Draft Registration Statement on Form S-1
           Submitted March 22, 2019
           CIK 0001761612

Dear Mr. Kalowski:

      We have reviewed your amended draft registration statement and have the
comments. In some of our comments, we may ask you to provide us with
information so we
may better understand your disclosure.

       Please respond to this letter by providing the requested information and
either submitting
an amended draft registration statement or publicly filing your registration
statement on
EDGAR. If you do not believe our comments apply to your facts and circumstances
or do not
believe an amendment is appropriate, please tell us why in your response.

      After reviewing the information you provide in response to these comments
and your
amended draft registration statement or filed registration statement, we may
have additional

Amendment No. 1 to Draft Registration Statement on Form S-1 submitted March 22,

Prospectus Summary
Beyond Oncology, page 5

1.     We note your response to prior comment 4. Please also revise your
prospectus summary
       to describe the ongoing Phase I clinical trial of THR-149.
 Lee Kalowski
Bicycle Therapeutics Ltd.
April 4, 2019
Page 2
Our Collaborations
Our Other Collaborators
AstraZeneca, page 144

2.    We note your statement that, pursuant to your collaboration agreement
      AstraZenaca, you could receive more than $1 billion in milestone payments
and royalties.
      We also note your disclosure that, pursuant to the collaboration
      agreement, AstraZeneca owes you milestone fee of $8 million for the first
drug candidate
      selected from each research program, and you are eligible to receive up
to an additional
      $162 million in development, regulatory and commercial milestones on a
      program by research program basis, as well as tiered royalty payments of
mid-single digits
      based on a percentage of net sales. Please provide further details
regarding how these
      amounts could total over $1 billion.
Executive Officers, page 168

3.    We note your updated disclosure regarding your Chief Business Officer,
Peter Leone.
      Please clarify Mr. Leone's activities between April 2016 and 2012. Please
see Item
      401(e)(1) of Regulation S-K.
       You may contact Jim Dunn at 202-551-3724 or Isaac Esquivel at
202-551-3395 if you
have questions regarding comments on the financial statements and related
matters. Please
contact Liz Walsh at 202-551-3696 or Christopher Edwards at 202-551-6761 with
any other

FirstName LastNameLee Kalowski
                                                          Division of
Corporation Finance
Comapany NameBicycle Therapeutics Ltd.
                                                          Office of Healthcare
& Insurance
April 4, 2019 Page 2
cc:       Jonathan Schur
FirstName LastName