Bicycle Therapeutics : EuroTIDES – November 2021

Bicycles, bi-cyclic peptides, novel small molecule delivery systems for RNA therapeutics

EuroTIDES - November 2021

Forward-looking statements

This presentation 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. All statements other than statements of historical facts contained in this presentation are forward-looking statements, including statements regarding our future financial or business performance, conditions, plans, prospects, trends or strategies and other financial and business matters; our current and prospective product candidates, planned clinical trials and preclinical activities, current and prospective collaborations and the timing and success of our development of our anticipated product candidates.

Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development plans, our preclinical and clinical results, our plans to initiate clinical trials and the designs of the planned trials and other future conditions, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward- looking statements. These risks and uncertainties include, but are not limited to, risks related to the ongoing COVID-19 pandemic, the risk that any one or more of our product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials, the risk that we may not realize the intended benefits of our technology, including that we may not identify and develop additional product candidates for our pipeline, the risk that we may not maintain our current collaborations or enter into new collaborations in the future, or that we may not realize the intended benefits of these collaborations, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results will not be replicated or will not continue in ongoing or future studies or trials, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-parties and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Quarterly Report on Form 10-Q, filed with the Securities and Exchange Commission (SEC) on November 4, 2021 as well as in other filings Bicycle may make with the SEC in the future, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings with the Securities and Exchange Commission. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

• I am an employee of Bicycle Therapeutics

2	EuroTIDES Nov 2021

Bicycle Therapeutics

• Bicycle Therapeutics - drug discovery and development Biopharma
• Unique therapeutic modality conceived by Nobel Prize winner Sir Greg Winter & Christian Heinis
  - platform applicable across many therapeutic areas
• Five molecules in clinic

3	EuroTIDES Nov 2021

Bicycle® a unique & disruptive therapeutic modality

Linear peptide

Bicycle

		Scaffold
	X	Loop	Loop
	COOH	1	2
NH2	Chemical modification	NH2	COOH
	with scaffold

Form biologically

relevant 3D structures

Unique and attractive drug-like attributes	Our platform enables conjugation
Constraint	pM affinity, absolute selectivity to target	Target	~1.5-2 kDa	~1-2 MDa
Large binding	Protein-protein "hard to drug" targets"
footprint
Fully synthetic	NCEs, scalable mass production
Readily	Come off platform conjugation ready -
conjugated	payload enabled
Routes of admin	Multiple : IV, SQ, inhalation
Rapid platform	Rapid timelines to tools & drug like molecules

4	EuroTIDES Nov 2021

Bicycle platform - a marriage of phage display and peptide /medicinal chemistry creating novel potential medicines

Bicycle Phage Display -	Peptide & Medicinal
Discovery	Chemistry

Optimize	Build and Optimize
Bicycle monomers	Therapeutic Bicycle

Diverse Bicycle phage	Target binding
libraries (>1017)	Bicycles

Natural Amino Acids	Non-natural
Amino Acids

Bicycle

Medicines

Monomeric	In the clinic ✓
Bicycles

Targeted Drug	In the clinic ✓
Conjugates

In the clinic ✓

Multi-valent

Bicycles

Targeted delivery

5	EuroTIDES Nov 2021