SecProbe.io

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 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
comments.
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.

 FirstName LastNameLee Kalowski
 Comapany NameBicycle Therapeutics Ltd.
 February 12, 2019 Page 2
 FirstName LastNameLee Kalowski
Bicycle Therapeutics Ltd.
February 12, 2019
Page 2
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 Product
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 95.
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
date.

 FirstName LastNameLee Kalowski
 Comapany NameBicycle Therapeutics Ltd.
 February 12, 2019 Page 3
 FirstName LastNameLee Kalowski
Bicycle Therapeutics Ltd.
February 12, 2019
Page 3
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 Consolidated
Financial Statements on page F-59.

 FirstName LastNameLee Kalowski
 Comapany NameBicycle Therapeutics Ltd.
 February 12, 2019 Page 4
 FirstName LastNameLee Kalowski
Bicycle Therapeutics Ltd.
February 12, 2019
Page 4
Financial Overview, page 93
14.Please clarify the breakdown of revenues produced by each of your collaboration
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
AstraZeneca.
Management's Discussion and Analysis of Financial Condition and Results of Operations
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
141.
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 BT8009
(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.
Business
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

 FirstName LastNameLee Kalowski
 Comapany NameBicycle Therapeutics Ltd.
 February 12, 2019 Page 5
 FirstName LastNameLee Kalowski
Bicycle Therapeutics Ltd.
February 12, 2019
Page 5
statistical significance. Please also explain how "p-value" is used to measure statistical
significance.
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.

 FirstName LastNameLee Kalowski
 Comapany NameBicycle Therapeutics Ltd.
 February 12, 2019 Page 6
 FirstName LastName
Lee Kalowski
Bicycle Therapeutics Ltd.
February 12, 2019
Page 6
General
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 preliminary
prospectus. Please note that we may have comments regarding this material.
            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 other
questions.
Sincerely,
Division of Corporation Finance
Office of Healthcare & Insurance
cc:       Jonathan Schur