Company Overview
June 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-Q filed by Tempest Therapeutics with the Securities and Exchange Commission on May 9, 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 | Phase 3 |
Status
Clinical Programs | ||
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 & Combination PD-1 |
Dual EP2/4 | Endometrial | Combination PD-1 |
Antagonist | FAP | |
Monotherapy |
Discovery & Research Programs
Novel Targets | Solid Tumors & |
Hematologic Malignancies |
ASCO
Oral
Presentation
ASCO Presentation
Completed ü
Completed ü
Full Data ü
Completed ü
Ongoing
FPI 2H'242
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. 2 Initial approval by NCI received; awaiting final approval. |
TPST-1120
First-in-Class PPAR Antagonist
5
TPST-1120:First-in-Class1 PPARα Antagonist
Targets both tumor cells and immune suppressive cells
TPST-1120
Tumor cell
PPARα RXR | FAO |
(>100 genes) |
Immune
Target tumor or immune suppressive cell
Targets FAO-dependent tumors (on-tumoractivity)
Targets angiogenesis distinct from VEGF inhibitors (combination opportunity)
Targets FAO-dependent immune suppressor cells (ICI combination opportunity)
PPARα: Peroxisome Proliferator-Activated Receptor alpha
1First-in-Class status is dependent on FDA approval | 6 |
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 | 8 |
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
- 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. | 9 |
Preclinical HCC Data Support Clinical Development Strategy
β-catenin pathway frequently activated in HCC: Potential Biomarker
- 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
Efficacy in syngeneic β-Catenin-driven
hepatocellular carcinoma model*
3) | Vehicle |
(mm | TPST-1120 |
VolumeTumor | 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 | |
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Tempest Therapeutics Inc. published this content on 30 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 30 May 2024 19:21:03 UTC.