Bicycle Therapeutics : May 2024 Corporate Deck

Bicycle Therapeutics Investor Presentation

• May 2024

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, including expected cash runway; 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 current and prospective product candidates; the safety and efficacy profile of our product candidates; and the size and composition of the potential market for any of our product candidates, if approved.

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, 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 or preclinical activities, 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, risks regarding the accuracy of our estimates of expenses and cash runway, risks relating to our capital requirements and needs for additional financing, 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 (the "SEC") on May 2, 2024, as well as in other filings we 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 SEC. 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.

This presentation does not constitute an offer to sell or a solicitation of an offer to buy securities, nor shall there be any sale of any securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

• 2

Bicycle Therapeutics: Pioneering a new, differentiated class of innovative medicines

Unique

Platform

Developing Bicycle® molecules

• a novel synthetic peptide modality that enables the drugging of complex targets

Technology based on Nobel Prize-winning science

Strong intellectual property portfolio

Internal

Programs

Focused on oncology, with multiple clinical assets

Expedited development and regulatory pathway for BT8009 in metastatic urothelial cancer

BT8009, BT5528 and BT7480 have shown signs of anti-tumor activity and emerging differentiated safety profiles

Validating

Partnerships

Extending use of platform into diverse range of therapeutic areas like radiopharmaceuticals and neurology

Ambitious

Company

Deeply experienced team

Located in Cambridge, UK, and Cambridge, MA

NASDAQ: BCYC

Cash and cash equivalents of $457.0M as of March 31, 2024, with expected cash runway into 2026

• 3

Bicycle® molecules are short peptides chemically constrained with a central scaffold that can induce diverse structures

Short linear

peptide

+

Bicycle® molecule

Scaffold

Chemical modification

with scaffold

• 4

Bicycle® platform delivers a toolkit of modular building blocks to create novel precision-guided medicines

Bicycle® Phage Display	Peptide & Medicinal
Discovery		Chemistry
Linear peptide	Bicycle® molecule
				Build and
		Optimize		Optimize
			Therapeutic
		Bicycle®		Bicycle®
		monomers		molecules
		Non-natural		Easy
		Amino Acids		conjugation
				of Linkers
				and Payloads

Diverse Bicycle® phage

libraries (>1020)

Targeting and Effector

Bicycle® molecules

Natural Amino Acids

Potential Bicycle®

Medicines

Monomeric Bicycle® molecules

Targeted Drug

Conjugates

Targeted/ Multi-specific Bicycle® molecules

• 5

The Bicycle® Advantage

Small size for rapid tissue penetration

Tunable PK for optimized target vs. systemic exposure

High affinity and selectivity for precision targeting and tumor retention

• 6

We believe The Bicycle® Advantage will lead to enhanced patient benefits

Precision Guided	Greater Tolerability		Enhanced Patient Benefit
Therapeutics
		Enhanced Patient Benefit
Rapid tumor penetration	Improved adherence to	•	Longer responses
	optimized dosage	Longer responses
Minimized systemic	•	Deeper/broader
exposure	regimen	Deeper/Broader responses
	responses

Minimal off-target activity	Better combinability
Tumor retention

• 7

Turning The Bicycle® Advantage into reality

Execute

Translate our Nobel Prize-winning science into therapies

Expand

Address numerous solid tumors and improve outcomes for patients through our Nectin-4 and EphA2 portfolios and by bringing forward next- generation molecules

Explore

Establish high-value collaborations that enable clinical development beyond oncology

We are building a leading precision-guided therapeutics company

• 8

Broad range of programs supports robust nature of the Bicycle® platform

Target / Product	Partner/Sponsor	Indication	Modality	Preclinical	IND-	Phase I	Phase II/	Phase III
					enabling		Expansion
Internal Programs
BT8009 (Nectin-4)		Oncology	Bicycle® Toxin Conjugate
BT5528 (EphA2)		Oncology	Bicycle® Toxin Conjugate
BT7480 (Nectin-4/CD137)		Immuno-oncology	Bicycle TICA® molecule
BT7455 (EphA2/CD137)		Immuno-oncology	Bicycle TICA® molecule
Undisclosed		Radiopharmaceutical	Bicycle® Radio Conjugate
Partnered Programs
BT1718 (MT1-MMP)		Oncology	Bicycle® Toxin Conjugate
BT7401 (multivalent CD137		Immuno-oncology
system agonist)
Undisclosed		Immuno-oncology
Novel anti-infectives		Anti-infectives
Novel CNS targets		CNS
Novel neuromuscular targets		Neuromuscular
Undisclosed		Radiopharmaceutical	Bicycle® Radio Conjugate
Undisclosed		Radiopharmaceutical	Bicycle® Radio Conjugate
								• 9

Nectin-4 Portfolio