CFT8919 TPD Summit Presentation

Discovery of CFT8919 as an oral, CNS-active,mutant-selective allosteric degrader of EGFR L858R for the treatment of EGFR inhibitor- resistant non-small cell lung cancer

October 27, 2021

4th Annual TPD (Targeted Protein Degradation) Summit

Eunice Park on behalf of the C4T Team

Forward-looking Statements and Intellectual Property

Forward-looking Statements

The following presentation contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to," "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. These forward-looking statements include, but are not limited to, statements regarding the therapeutic potential of C4 Therapeutics, Inc.'s technology and products. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, as well as the fact that the product candidates that we are developing or may develop may not demonstrate success in clinical trials. Prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. C4 Therapeutics, Inc. undertakes no obligation to update or revise the information contained in this presentation, whether as a result of new information, future events or circumstances or otherwise.

Intellectual Property

C4 Therapeutics, Inc. owns various registered and unregistered trademarks in the U.S. and internationally, including, without limitation, C4 THERAPEUTICS, our housemark logo, the name of our TORPEDO platform, and the names of our BIDAC and MONODAC degrader products. All trademarks or trade names referred to in this presentation that we do not own are the property of their respective owners. Solely for convenience, the trademarks and trade names in this prospectus are referred to without the symbols ® and ™, but those references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto.

© 2021 C4 Therapeutics, Inc.

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Mutations in EGFR Drive Oncogenesis in Non-Small Cell Lung Cancer

10-15% of Non-Small Cell	25-45% of mutant EGFR NSCLC is	30-40% of mutant EGFR NSCLC
driven by L858R activating	patients will develop brain
Lung cancer has mutant EGFR
	mutation	metastases

This rises to nearly 40% in Asian	Patients with L858R have inferior	CNS activity desirable to be
population	clinical outcome	competitive

Sources: Zhang, Y.-L. et al. Oncotarget 7, 78985-78993 (2016); Li, K et al. Oncol Rep 37, 1347-1358 (2017); Shin, D.-Y. et al. J Thorac Oncol 9, 195-199 (2014); Rangachari, D. et al. Lung Cancer 88, 108-111 (2015); Soria, J.-C. et al. New Engl J Medicine 378, 113-125 (2018)

© 2021 C4 Therapeutics, Inc.

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Despite Three Generations of Approved EGFR Inhibitors, L858R Patients Have Poorer Prognosis

Median PFS	L858R	Exon 19 Deletion
osimertinib	14.4 months	21.4 months
Standard EGFR TKI	9.5 months	11.0 months

L858R mutation predicts less durable response to EGFR inhibitors

No evidence that L858R is a more aggressive disease

L858R Patients are Underserved by Current EGFR Inhibitor Therapies

Source: Soria, J.-C.et al. New Engl J Medicine 378, 113-125 (2018)

© 2021 C4 Therapeutics, Inc.

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Significant Unmet Need for Patients Who Progress After Current EGFR Inhibitor Therapies

EGFRL858R	Resistance mutations occur
around the ATP binding site
osimertinib	1st-gen EGFR TKIs
PFS: 14.4 mos	PFS: ~9.5 mos
EGFRL858R+C797S	EGFRL858R+T790M

osimertinib PFS: ~9.6 mos

EGFRL858R+T790M+C797S

© 2021 C4 Therapeutics, Inc.

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