February 12, 2019

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

       Re: Bicycle Therapeutics Ltd.
           Draft Registration Statement on Form S-1
           Filed December 21, 2018
           CIK 0001761612

Dear Mr. Kalowski:

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

DRS Form S-1

Prospectus Summary
Overview, page 1

1.     Please provide the expected timing for reporting preliminary data for
the Phase I part of
       the clinical trial of BT1718.
Introduction to Bicycles, page 2

2.     We note your disclosure that the Bicycle's "renal route of elimination"
minimizes liver
       exposure. Please provide further details as to the benefits of this
route of elimination and
       why it does not result in increased renal exposure.
 Lee Kalowski
FirstName LastNameLee Kalowski
Bicycle Therapeutics Ltd.
Comapany NameBicycle Therapeutics Ltd.
February 12, 2019
February 12, 2019 Page 2
Page 2
FirstName LastName
Our Pipeline, page 4

3.       Please revise you pipeline table to include columns for each stage of
further development
         and provide more specific details regarding each type of oncology
indicator. In addition,
         we note your disclosure that BT1718 is undergoing a Phase I/IIa
clinical trial; however,
         your table seems to indicate that BT1718 is currently undergoing a
Phase I clinical trial
         only. Please revise or explain.
4.       Your pipeline table shows that THR-149, the subject of your
collaboration agreement with
         Oxurion, is currently undergoing a Phase I clinical trial. Please
describe the Phase I trial
         in the Business section.
5.       Please revise your pipeline table to remove the programs that are in
the discovery phase.
         Because you have not identified a product candidate for these
programs, it is premature to
         include them in a product pipeline table.
Implications of Being an Emerging Growth Company, page 9

6.       Please supplementally provide us with copies of all written
communications, as defined in
         Rule 405 under the Securities Act, that you, or anyone authorized to
do so on your behalf,
         present to potential investors in reliance on Section 5(d) of the
Securities Act, whether or
         not they retain copies of the communications.
Risk Factors
Risks Related to the Discovery, Development and Regulatory Approval of Our
Candidates, page 19

7.       Here or elsewhere in your Risk Factors section, please disclose that
upon the completion
         of the Phase I/IIa clinical trial for BT1718, you have the right to
obtain a license to the
         results of the clinical trial from CRUK upon the payment of a
milestone, in cash and
         ordinary shares, and any related risks or impact on your ability to
continue to develop
         and/or commercialize BT1718. We note your related disclosure on page
Our current or future product candidates may cause undesirable side effects or
have other
properties when used alone... , page 24

8.       We note your statement that your current and future product candidates
have undergone
         [...] safety testing. Please revise your disclosure, if true, to state
that certain of your
         products are currently undergoing safety testing in the form of Phase
I and Phase I/IIa
         clinical trials, as appropriate, and none of your products have
completed this testing to
 Lee Kalowski
FirstName LastNameLee Kalowski
Bicycle Therapeutics Ltd.
Comapany NameBicycle Therapeutics Ltd.
February 12, 2019
February 12, 2019 Page 3
Page 3
FirstName LastName
Risks Related to Our Dependence on Third Parties
If conflicts arise with our development and commercialization collaborators or
licensors, they
may act in their own self-interest..., page 48

9.       We note your disclosure on page 162 regarding the notices of
opposition filed by Pepscan
         in respect of each of European patents 2 257 624 and 2 474 613. If
material, please revise
         your Risk Factor disclosure to describe such notices of opposition, as
well as any potential
         material consequences on your business or operations.
Risks Related to Our Intellectual Property
Cyber-attacks or other failures in telecommunications or information technology
systems could
result in information theft..., page 62

10.      Please provide further details regarding the cyber-attack you
experienced in 2018,
         including any material impact of the attack on your business or
financial condition.
Capitalization, page 86

11.      We note that your pro forma adjustments will give effect to the
conversion of all
         outstanding preferred shares as of September 30, 2018 into ordinary
shares and the
         effectiveness of your amended and restated memorandum and articles of
association upon
         the closing of this offering. We also note from your disclosure on
page 85 (Share Capital
         Reorganization...) that, pursuant to Part 17 of the Companies Act, you
will reduce your
         share capital and that amount will be reclassified to reserves
available for distribution.
         Please tell us if the reclassification of share capital will be
disclosed in these pro forma
         adjustments, and if so, revise your filing to indicate that such
disclosure will be made. If
         not, please tell us why the reclassification of share capital is not
applicable to these pro
         forma adjustments.
Overview, page 92

12.      We note that BT1718 is being developed to treat tumors with high
MT1-MMP. Here or
         elsewhere in your prospectus, please provide further details about the
percentage or
         volume of tumors with high MT1-MMP, and any resulting impact on the
         potential commercialization opportunities for BT1718. Please also
provide similar details
         for EphA2 and Nectin-4.
13.      To the extent material, please disclose the Materials Transfer
Agreement into which you
         entered in October 2018, along with the material terms and conditions
of such
         Agreement. In this regard, we note your disclosure in Note 17 to your
         Financial Statements on page F-59.
 Lee Kalowski
FirstName LastNameLee Kalowski
Bicycle Therapeutics Ltd.
Comapany NameBicycle Therapeutics Ltd.
February 12, 2019
February 12, 2019 Page 4
Page 4
FirstName LastName
Financial Overview, page 93

14.      Please clarify the breakdown of revenues produced by each of your
         agreements. In addition, please clarify whether or not the $20.5
million in revenue
         cumulatively earned from your collaboration agreements includes the
$5.0 million to be
         paid in January 2019 pursuant to the terms of your collaboration
agreement with
Management's Discussion and Analysis of Financial Condition and Results of
Components of Our Results of Operations
Expenses, page 95

15.      We note your disclosure regarding your Clinical Trial and License
Agreement with CRTL
         and CRUK pursuant to which you are entitled to receive revenue sharing
of a "mid to high
         double digit percentage of the net revenue." Please revise your
disclosure to present a
         range of not more than 10 percentage points. Please similarly revise
your disclosure
         regarding your potential tiered royalty payments pursuant to the terms
of the Bioverativ
         collaboration agreement on page 139 and the Oxurion collaboration
agreement on page
Results of Operations
Research and Development Expenses, page 102

16.      We note from your disclosure here that you have incurred research and
development costs
         for several product candidates (i.e. BT1718 (MT1), BT5528 (EphA2) and
         (Nectin-4)), and your lead product candidate, BT1718 (MT1), has
incurred these costs
         since at least 2016. Please revise your filing to disclose research
and development costs
         for each of your product candidates incurred from inception to date.
Properties of Bicycles as Therapeutic Agents, page 121

17.      Please clarify whether you can always identify a compound for
development in only six to
         12 months after a target has been selected, or if this is an average
amount of time.
Our Oncology Programs, page 124

18.      To the extent not disclosed, please provide the endpoint for each of
your clinical trials and
         preclinical studies.
Preclinical Experience, page 127

19.      We note your disclosure that, in the docetaxel resistant model, BT1718
at both doses
         tested was associated with significant responses. Please clarify
whether this response was
         statistically significant, and if so, please indicate the p-value by
which you measured
 Lee Kalowski
FirstName LastNameLee Kalowski
Bicycle Therapeutics Ltd.
Comapany NameBicycle Therapeutics Ltd.
February 12, 2019
February 12, 2019 Page 5
Page 5
FirstName LastName
         statistical significance. Please also explain how "p-value" is used to
measure statistical
Founder Royalty Arrangements, page 142

20.      Please provide further details about each of your founder royalty
agreements, including
         the parties to each agreement and any other material terms. In this
regard, we note your
         disclosure in Note 12 to your Consolidated Financial Statements on
page F-55.
Intellectual Property, page 142

21.      Please expand your disclosure regarding your patent portfolio to
disclose the type of
         patent protection provided by the patents or patent applications
(e.g., composition of
         matter, method of use).
Executive Compensation
Employment Agreements with Our Named Executive Officers, page 172

22.      We note that pursuant to the terms of their respective employment
agreements, each of
         Kevin Lee, Lee Kalowski and Maria Koehler are entitled to annual
discretionary cash
         bonuses if certain performance targets are met. Please provide further
details regarding
         such performance targets.
Note 2 - Summary of Significant Accounting Policies
Share-based Compensation, page F-20

23.      You disclose at the top of page F-21 four factors used to determine
the fair value of your
         ordinary shares at each grant date. Once you have an estimated
offering price or range,
         please explain to us in further detail how you determined the fair
value of the common
         stock underlying your equity issuances and the reasons for any
differences between the
         recent valuations of your common stock leading up to the initial
public offering and the
         estimated offering price. This information will help facilitate our
review of your
         accounting for equity issuances of stock compensation.
Note 7 - Warranty Liability, page F-29

24.      We note that your warrants are remeasured to fair value at each
reporting date. We also
         note that your warrants are classified within Level 3 of the fair
value hierarchy. Please
         revise your filing to disclose the following:
           Quantitative information about the significant unobservable inputs
used in the fair
             value measurement of these warrants (e.g. risk-adjusted discount
rate, present value
             periods, equity values calculated under the OPM, et al); and
           A narrative description of the sensitivity of the fair value
measurement to changes in
             the unobservable inputs.
         Refer to ASC 820-10-50-2(bbb)(2) and 50-2(g), respectively.
 Lee Kalowski
Bicycle Therapeutics Ltd.
February 12, 2019
Page 6

25.   Please provide us proofs of all graphics, visual, or photographic
information you
      will provide in the printed prospectus prior to its use, for example in a
      prospectus. Please note that we may have comments regarding this
       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 Chris Edwards at (202) 551-6761 with any

FirstName LastNameLee Kalowski
                                                             Division of
Corporation Finance
Comapany NameBicycle Therapeutics Ltd.
                                                             Office of
Healthcare & Insurance
February 12, 2019 Page 6
cc:       Jonathan Schur
FirstName LastName