Tempest Therapeutics, Inc. · NASDAQ:TPST
Tempest Therapeutics — Technical Presentation (June 2022)
17 slides from Tempest Therapeutics's technical presentation, June 2022
Slide 1: A Phase 1 Study of TPST-1120 as a Single Agent and in Combination with Nivolumab
Abstract # 3005 A Phase 1 Study of TPST-1120 as a Single Agent and in Combination with Nivolumab in Subjects with Advanced Solid Tumors Mark Yarchoan1, John Powderly2, Bruno Bastos3, Thomas Karasic4, Oxana Crysler5, Pamela Munster6, Meredith McKean7, Leisha Emens8, Yvonne Saenger9, Yasser Ged1, Robe
Slide 2: Fatty Acid Oxidation Supports Cancer Progression
Fatty Acid Oxidation Supports Cancer Progression • FAO is a key cancer metabolic adaptation that supports tumor growth and metastasis Tumor cell proliferation PPARα • FAO is a principal metabolic pathway for immune suppressive cell types and FAO induces angiogenesis Angiogenesis • PPARα is a transcr
Slide 3: TPST-1120 – First-in-Class PPARα Antagonist
TPST-1120 – First-in-Class PPARα Antagonist Tumor cell proliferation PPAR Inhibition* IC50 (µM) PPARα Isoform Species TPST-1120 PPAR- Human Mouse Angiogenesis α 0.052 0.42 β/δ 13 29 FAO (100+ genes) γ 33 30 Immune suppression *Luciferase Reporter PRESENTED BY: Mark Yarchoan, MD
Slide 4: Genetic Validation for Targeting PPARα
Genetic Validation for Targeting PPARα PPARα and FAO Are Required to Sustain Tumor Growth PPARα KO Prevents Tumor Growth PPARα Inhibition in Immune Cells Enhances Antitumor Immunity Bone Marrow Transplantation Confers Transplant Phenotype Kaipainen et al., PLoS ONE 2007, 2(2): e260 PRESENTED BY: Mar
Slide 5: TPST-1120 and anti-PD-1 Synergize and Confer Durable Immunity
TPST-1120 and anti-PD-1 Synergize and Confer Durable Immunity MC38 colorectal cancer tumor model, C57BL/6 immunocompetent mice Splenocyte adoptive transfer TPST-1120 + anti-PD1 treatment Tumor re-challenge followed by tumor cell challenge Tumor Re-challenge C57BL/6 mice bearing 150 mm3 MC38 flank tu
Slide 6: TPST-1120-001 Phase 1 Study Design
TPST-1120-001 Phase 1 Study Design NCT03829436 Key Eligibility Criteria Part 1: TPST-1120 Monotherapy Dose Escalation Endpoints • Safety Inclusion: • MTD and/or OBD of TPST-1120 • Advanced/metastatic solid Solid Tumors • Pharmacokinetics tumor 3+3 Design • Preliminary efficacy • ECOG PS 0-1 TPST-112
Slide 7: Demographics and Patient Characteristics
Demographics and Patient Characteristics TPST-1120 Monotherapy TPST-1120 + Nivolumab Baseline Characteristics (N=20) (N=18) Age [median (range)] 65 (41-78) 64 (43-84) Female [n (%)] 10 (50) 9 (50) 100 mg BID 3 (15) - 200 mg BID 4 (20) 3 (17) TPST-1120 Dose [n (%)] 300 mg BID 3 (15) 3 (17) 400 mg BID
Slide 8: TPST-1120 Pharmacokinetics
TPST-1120 Pharmacokinetics Exposure Increases Linearly With Dose Dose-Exposure Relationship Steady-State Profile (Combination) Dotted lines represent 95% CI PPARα IC50 adjusted for protein binding PRESENTED BY: Mark Yarchoan, MD
Slide 9: Safety Summary
Safety Summary TPST-1120 Monotherapy and Combination with Nivolumab Treatment-related adverse events occurring in ≥ 2 patients TPST-1120 + Nivolumab TPST-1120 Monotherapy (N=20) AE, n (%) AE, n (%) (N=18) Any Grade Grade 3 Any Grade Grade 3 Any AE 10 (50.0) 1 (5.0)† Any AE* 15 (83.3) 3 (16.7)^ Nause
Slide 10: TPST-1120 Monotherapy: Prolonged Disease Control and Tumor Shrinkage
TPST-1120 Monotherapy Prolonged Disease Control and Tumor Shrinkage in Late Line Patients 20 Enrolled TPST-1120 Monotherapy (N=19a): 53% DCR Tumor Type Discontinuation for other than disease progression: ^Clinical Deterioration, §Consent withdrawn aResponse-evaluable patients include pts with a post
Slide 11: Monotherapy Tumor Control in Late-Line Cholangiocarcinoma
Monotherapy Tumor Control in Late-Line Cholangiocarcinoma 11-004 • 4 prior systemic therapies ̵ Carboplatin/taxol ̵ Gemcitabine ̵ Oxaliplatin/5-FU ̵ IDOi/investigational anti-PD-1 discontinued due to progression • IDH1 mutation 11-006 • 3 prior systemic therapies ̵ Cisplatin/gemcitabine ̵ Investigat
Slide 12: Combination with Nivolumab: RECIST Responses in RCC and Cholangiocarcinoma
TPST-1120 Combination with Nivolumab RECIST Responses in RCC and Cholangiocarcinoma 18 Enrolled Best %Change in TL RCC SD CCA 40 * CCA SD CCA * * HCC UNK 20 CCA * * (Target Lesions) HCC PR Best %Change PD ^ * * * * Tumor Type (0) (0) HCC PD PD 0 CCA RCC PD PD 200 mg BID HCC PD PD 300 mg BID -20 400
Slide 13: Case Study 1: PR in 53 yo F with Metastatic ccRCC
Case Study 1: PR in 53 yo F with Metastatic ccRCC Change in Measurable Disease Over Time Baseline 8 weeks %Change from Baseline Time on Study (Mo) Baseline SLD: 108 mm Treatment History Sites of baseline metastatic disease: IPI/NIVO CABO EVEROLIMUS • Large volume pulmonary • Multiple soft tissue (ch
Slide 14: Case Study 2: PR in 84 yo M with Extrahepatic CCA
Case Study 2: PR in 84 yo M with Extrahepatic CCA Change in Measurable Disease Over Time Baseline 31 weeks %Change from Baseline Time on Study (Mo) Major response in liver lesion Baseline SLD: 76 mm Target lesion sites: liver, lymph node, peritoneum Treatment History Prior Regimen Reason for Discont
Slide 15: TPST-1120 Development: Next Step
TPST-1120 Development: Next Step Morpheus Liver Study Randomized Phase 1b/2 (NCT04524871) n = 40-60 pts TPST-1120* + atezolizumab + Primary Endpoint: ORR bevacizumab Secondary Endpoints (include): PFS, OS Global study: US, EU, Asia 1L HCC Enrolling Operationalized by Roche atezolizumab + bevacizumab
Slide 16: Conclusions
Conclusions • TPST-1120 is a first-in-class antagonist of the FAO regulator PPARα • TPST-1120 demonstrated a tolerable safety profile in patients as monotherapy and in combination with nivolumab • TPST-1120 demonstrated disease control as monotherapy and promising responses in combination with nivol
Slide 17: Acknowledgements
Acknowledgements • We humbly thank all of the patients and their families who supported this research • We thank our fellow investigators and their dedicated site staff Marina Gelman, PhD, provided editorial support for this presentation PRESENTED BY: Mark Yarchoan, MD
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