Tempest Therapeutics : Corporate Presentation - March 2024

Company Overview

March 2024

Forward-Looking Statements

This presentation contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended (the "Securities Act") concerning Tempest Therapeutics, Inc. ("Tempest Therapeutics"). These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Tempest Therapeutics, as well as assumptions made by, and information currently available to, management of Tempest Therapeutics. Forward-looking statements generally include statements that are predictive in nature

and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "could", "expect," "anticipate," "plan," "likely," "believe," "estimate," "project," "intend," and other similar expressions. All statements that are not historical facts are forward-looking statements, including any statements regarding the design, initiation, progress, timing, scope and results of clinical trials, the ability of Tempest Therapeutics to advance discussions with potential partners to explore the development of TPST-1120, the anticipated therapeutic benefit, opportunity to improve patient care, and regulatory development of Tempest Therapeutic's product candidates, Tempest Therapeutic's ability to deliver on potential value-creating milestones, the potential use of Tempest Therapeutic's product candidates to treat additional indications, Tempest Therapeutic's ability to achieve its operational plans, and the sufficiency of Tempest Therapeutic's cash and cash

equivalents. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: our strategies, prospects, plans, expectations or objectives for future operations; the progress, scope or timing of the development of our product candidates; the benefits that may be derived from any future products or the commercial or market opportunity with respect to any of our future products; our ability to protect our intellectual property rights; our anticipated operations, financial position, ability to raise capital to fund operations, revenues, costs or expenses; statements regarding future economic conditions or performance; statements of belief and any statement of assumptions underlying any of the foregoing. Many of these risks are described in greater detail in the Form 10-K filed by Tempest Therapeutics with the Securities and Exchange Commission on November 19, 2024. Except as required by applicable law, Tempest Therapeutics undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

2

TPST-1120 Data Support Pivotal Study in First-Line Liver Cancer

Emerging as a Potential Franchise

Programs

Randomized 1L HCC data are superior

to standard of care

• ORR of 1120 arm is independent of PD-L1 or inflamed tumor status
• OS HR favors 1120 and median not reached
• Biomarker data further support dual MOA of TPST-1120
• Beyond HCC: positive data in RCC & CCA
• Three additional programs - diversified portfolio

Strategy

Focused on indications

with potential for substantial impact

Programs fully owned;

BD optionality

Team

Experienced in novel

drug discovery,

development, and

delivering value

Catalysts

Multiple potential value-

creating milestones

through 2024

3

First First-in-Class Oncology Pipeline with Broad Potential

Spanning early-stage novel targets to late-stage, pivotal development

Indication(s)

STAGE OF DEVELOPMENT

Research

IND-Enabling

Phase 1

Phase 2

Clinical Programs

Phase 3

Status

TPST-1120		Multiple Solid Tumors		Monotherapy dose & schedule finding
PPARα		HCC/RCC/CCA		Combination PD-1 dose and schedule finding
Antagonist
	HCC		First-line triplet	combination	(randomized)1
TPST-1495		Multiple Solid Tumors		Monotherapy dose & schedule finding
Dual EP2/4		Multiple Solid Tumors		Combo PD-1 dose & schedule finding
Antagonist
	Endometrial		Combination PD-1

Discovery & Research Programs

Novel Targets		Solid Tumors &
	Hematologic Malignancies

ASCO

Oral

Presentation

	Completed	✓
		✓
	Completed
		✓
	Full Data
		✓
	Completed
		✓
	Completed

Ongoing

Ongoing

"HCC" hepatocellular carcinoma, "RCC" renal cell carcinoma, "CCA" cholangiocarcinoma	4
First in class if approved by FDA. 1 Pursuant to a collaboration with Roche; TPST retains all product rights.

TPST-1120

First-in-Class PPAR Antagonist

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TPST-1120:First-in-Class1 PPARα Antagonist

Targets both tumor cells and immune suppressive cells

TPST-1120

Tumor cell

Targets FAO-dependent tumors

(on-tumor activity)

Targets angiogenesis distinct

PPARα

RXR

FAO

(>100 genes)

Immune suppression

from VEGF inhibitors

(combination opportunity)

Targets FAO-dependent immune suppressor cells

Target tumor or immune suppressive cell

(ICI combination opportunity)

PPARα: Peroxisome Proliferator-Activated Receptor alpha

1First-in-Class status is dependent on FDA approval

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FAO-Dependent Tumors Inform Clinical Strategy

TCGA-based analysis of tumor metabolic gene expression profiles

Increasing FAO usage

High

Expression

PPARα + 30

FAO Genes

Low

Expression

Focus on FAO-dependent tumors: HCC, RCC, prostate, cholangiocarcinoma, pancreas, NSCLC, CRC

Positive data in HCC, RCC & CCA

7

Durable Responses in Combination with α-PD-1

MC38 colorectal cancer tumor model, C57BL/6 immunocompetent mice

TPST-1120 + anti-PD1 treatment	Tumor re-challenge

Tumor

Re-challenge

C57BL/6 mice bearing 150 mm3 MC38 flank tumors treated with TPST-1120 30 mg/kg BID and 200 μg α-PD-1 Q3D

Source: Dipak Panigrahy, Harvard

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Activated β-Catenin Pathway Induces PPARα Expression and Reliance on FAO

Identifying cancers with increased sensitivity to TPST-1120

Activated β-catenin pathway

Enhanced PPARα expression in mutated CTNNB1 HCC

NT: Normal liver tissue

1. Mt CTNNB1 HCC

NM: Non-mtCTNNB1 HCC

PPARA

Increased FAO in β-catenin-activated mouse hepatocytes

Increased FAO in β-catenin-activated mouse liver is PPARα-dependent

Refs: Senni (2019) Gut, 68:322.

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Preclinical HCC Data Support Clinical Development Strategy

β-catenin pathway frequently activated in HCC: Potential Biomarker

Efficacy in syngeneic β-Catenin-driven

• Wnt/β-cateninpathway is critical for stem cell regeneration, and tumorigenesis (i.e., EMT)
• Activation of WNT/β-catenin pathway occurs frequently in HCC: 40-70%1,2,3
• PPARα expression is higher in
  CTNNB1-mutated human HCC
• β-cateninactivated HCC confers dependence on FAO for metabolism
• Available genetic tests for CTNNB1, APC and modulators of β-catenin pathway

Tumor Volume (mm3)

hepatocellular carcinoma model*

Vehicle

TPST-1120

Anti-PD-1 mAb

TPST-1120 + Anti-PD-1 mAb

*Hepa 1-6 tumor cells are β-catenin driven (Pandit et al. BMC Cancer (2018) 18:783)	10
Source: Dipak Panigrahy collaboration; Rx initiated 12d post implantation; TPST-1120 30 MGPK BID; α-PD-1 200 ug Q3d