G1 Therapeutics : June 2023 Corporate Presentation

Advancing our Mission to Improve the Lives of Those Affected by Cancer

June 2023

Forward-Looking Statements

This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," "intend" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this presentation include, but are not limited to, those relating to expectations for the commercial success of COSELA® (trilaciclib), our ability to accelerate adoption of COSELA in the treatment of small cell lung cancer, the therapeutic potential of trilaciclib in the treatment triple negative breast cancer, and other cancers, our ability to generate data to maximize trilaciclib's applicability to future treatment paradigms, our reliance on partners to globally develop and commercial licensed products, our financial position and need for additional capital, our ability to extend our cash through the readouts from our ongoing clinical trials. the association between gene expression profiles demonstrated by the Phase 2 Mechanism of Action Trial results and the improved clinical outcome, that trilaciclib's greatest effect is on longer term endpoints including OS rather than earlier efficacy measures, and that the reason why trilaciclib's greatest effect on longer term endpoints is because of its immune-mediated mechanism of action. In addition, COSELA may fail to achieve the degree of market acceptance for commercial success, and the impact of pandemics such as COVID-19 (coronavirus), are based on our expectations and assumptions as of the date of this presentation. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause our actual results to differ from those expressed or implied in the forward-looking statements in this presentation are discussed in our filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein and include, but are not limited to, our ability to successfully commercialize COSELA; our ability to complete clinical trials for, obtain approvals for and commercialize additional indications of COSELA and any of our product candidates other than COSELA; our initial success in clinical trials may not be indicative of results obtained when these trials are completed or in later stage trials; the inherent uncertainties associated with developing new products or technologies and operating as a commercial-stage company; and market conditions. Lerociclib is not approved by the FDA. Except as required by law, we assume no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

G1Therapeutics® and G1Therapeutics logo and COSELA® and COSELA logo are trademarks of G1 Therapeutics, Inc. ©2023 G1 Therapeutics, Inc.

For Investor Use Only 2

Evolution of G1: Building Upon Unique Product - Trilaciclib

Original Premise

HSPCs

Unique Product		Initial Indication		Robust OS in TNBC

Dual Benefits

Potential to improve

Transient arrest

in G1 Phase

To protect HSPCs from

damage caused by chemo through transient G1 arrest

Rationally designed and optimized a unique IV transient CDK4/6 inhibitor

Demonstrated robust

myeloprotection across three randomized SCLC studies

OS hazard ratios in Ph2:

0.31 - 0.40

Improved survival in

randomized trial consistent with immune-modulation

overall survival through:

1. Protect immune system from damage
2. Enhancedimmunity anti-tumor

Aggressively investigating dual benefit impact across multiple tumor types

Maximizing the dual benefits of trilaciclib with the potential to improve overall survival

For Investor Use Only 3

Myeloprotection: Protecting Bone Marrow from Cytotoxic Damage

Bone Marrow

Myeloid	Lymphoid
progenitor cell	progenitor cell
	Hematopoietic
	stem cells

			Myeloblast		Lymphoblast
Erythrocytes	Platelets
			Granulocytes
					T lymphocyte	Natural
	Eosinophil	Basophil
						killer cell
			Neutrophil		B lymphocyte

Potential Benefits of Myeloprotection

• Improves patients' QoL
• Decreases rescue interventions, hospitalizations, associated costs
• Protects immune system function from damage by cytotoxic therapy
• Enables patients to tolerate greater exposure to cytotoxic therapy

Trilaciclib helps protect HSPCs and myeloid and lymphoid cell lineages

from damage caused by cytotoxic therapy - providing multiple potential benefits

Hematopoietic tree adapted from 'Hematopoietic Tree, Plasma Cell', National Cancer Institute Visuals Online: https://visualsonline.cancer.gov/details.cfm?imageid=7177
1. Weiss J, et al. Ann Oncol. 2019 Oct; 30(10): 1613-1621. 2. He S, et al. Sci Transl Med. 2017;9:eaal3986. 3. Bisi JE, et al. Mol Cancer Ther. 2016;15:783-93.	For Investor Use Only	4

Potential to Enhance Anti-Tumor Immunity

3 Improves Long-Term Immune Surveillance

Cancer Immune Cycle

Mechanistic Roles of Trilaciclib

		1	Release of Cancer
			Cell Antigens		MHC-1
Killing of				Upregulation1
7
Cancer Cells		2	Cancer Antigen	1	Enhances T Cell
			Presentation	Activation
Memory T Cells5					IL-2 & IFN-γ
					Secretion2
Recognition of Cancer				3	Priming and
Cells by T Cells	6				Activation

Infiltration of T Cells	5	4	Trafficking of
Immunosuppressive Cell	into Tumors	T Cells to Tumors
Populations2,4 (Tregs and MDSCs)		Favorably Alters Tumor	CCL5/CXCL9/CXCL10
		2	Chemokines2,3
			Microenvironment

Trilaciclib enhances multiple immunological processes - providing synergistic benefit in combination with chemotherapy, ADCs and checkpoint inhibitors

Cancer immunity cycle graphic adapted from Chen & Mellman. Oncology Meets Immunology: The Cancer-Immunity Cycle. Immunity. 2013;39(1):1-10. doi:10.1016/j.immune.2013.07.012.

1. Goel S, DeCristo MJ, et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature. 2017. 2. Deng J, Wang ES, Jenkins RW, et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation. Cancer Discov. 2018;8(2):216-233.doi:10.1158/2159-8290.CD-17-0915.

1. Uzhachenko R, et al. Metabolic modulation by CDK4/6 inhibitor promotes chemokine-mediated recruitment of T cells into mammary tumors. Cell Rep. 2021;35(1):108944/j.celrep.2021.108944. 4. Lai AY, et al. CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy. Journal for ImmunoTherapy of Cancer. 2020; 8:e000847. doi:10.1136/ jitc-2020-000847. 5. Lelliott EJ, et al.

CDK4/6 Inhibition Promotes Antitumor Immunity through the Induction of T-cell Memory. Cancer Discov. 2021 Oct;11(10):2582-2601. DOI: 10.1158/2159-8290.CD-20-1554; and Heckler M, Ali LR, et al. Inhibition of CDK4/6 promotes CD8 T-cell	For Investor Use Only	5
memory formation. Cancer Discov. 2021 Oct;11(10):2564-2582. doi: 10.1158/2159-8290.CD-20-1540