Slides
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Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors Francis Worden,1 Cristina Rodriguez,2 Amita Patnaik,3 Justin Call,4 A. Dimitrios Colevas,5 Ammar Sukari,6 Trisha Wise-Draper,7 Nabil F. Saba,8 Koho Iizuka,9 Hong Tang,9 Varun N Kapoor,9 Douglas Adkins10 Abstract Presentation #CT038 AACR 2025 1University of Michigan, Ann Arbor, MI, USA; 2Fred Hutch Cancer Center, Seattle, WA, USA; 3START Center for Cancer Research, San Antonio, TX, USA; 4START Center for Cancer Research, Salt Lake City, UT, USA; 5Stanford Cancer Institute, Stanford, CA, USA; 6Barbara Ann Karmanos Cancer Institute, Farmington Hills, MI, USA; 7University of Cincinnati, Cincinnati, OH, USA; 8Emory University, Atlanta, GA, USA; 9Coherus BioSciences, Redwood City, CA, USA; 10Washington University, St. Louis, MO, USA
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Forward Looking Statements Forward Looking Statements - Except for the historical information contained herein, the matters set forth in this presentation are forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding anti-tumor immunity; statements about the ability of Coherus’ product candidates to meet needs in multiple indications; statements about further clinical evaluation of CHS-114; and statements about clinical evaluation of CHS-114 in combination with other drugs; and the assumptions underlying such statements. Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance or achievements to differ significantly from any future results, performance or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent with clinical research and commercialization; the risks and uncertainties of the clinical development and regulatory approval process, including the timing of Coherus’ regulatory filings; the risks of Coherus’ reliance on third parties; the risks and uncertainties of obtaining financing in the future; and the risks and uncertainties related to manufacturing and supply of Coherus’ products. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Coherus undertakes no obligation to update or revise any forward- looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Annual Report on Form 10-K for the fiscal year ended December 31, 2024, filed with the Securities and Exchange Commission on March 17, 2025, including the section therein captioned “Risk Factors,” and in other documents Coherus files with the Securities and Exchange Commission. LOQTORZI®, whether or not appearing in large print or with the trademark symbol, is a trademark of Coherus, its affiliates, related companies or its licensors or joint venture partners, unless otherwise noted. Trademarks and trade names of other companies appearing in this presentation are, to the knowledge of Coherus, the property of their respective owners. ©2025 Coherus BioSciences, Inc. All rights reserved. © 2025 Coherus BioSciences. 2
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Today’s Speakers © 2025 Coherus BioSciences. 3 Douglas Adkins, M.D. Professor of Medicine Director, Section of Head and Neck and Thyroid Medical Oncology Division of Medical Oncology Washington University School of Medicine Theresa LaVallee, Ph.D. Chief Development Officer Coherus Rosh Dias, M.D. Chief Medical Officer Coherus
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Agenda CHS-114 Introduction & Preclinical Development Theresa LaVallee, Ph.D., Chief Development Officer, Coherus CHS-114 Phase 1 Clinical Development Rosh Dias, M.D., Chief Medical Officer, Coherus Phase 1 Study Results in HNSCC Douglas Adams, M.D., Study Investigator Professor of Medicine Director, Section of Head and Neck and Thyroid Medical Oncology Washington University School of Medicine Biomarker Data & Conclusions Theresa LaVallee, Ph.D., Chief Development Officer, Coherus Q&A Session © 2025 Coherus BioSciences. 4
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Agenda Introduction & CHS-114 Preclinical Development Theresa LaVallee, Ph.D. Chief Development Officer, Coherus © 2025 Coherus BioSciences. 5
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High unmet need in multiple indications including CRC (I-O has not worked historically) and HNSCC (low survival with approved PD-1s) Overcoming Treg immune suppression by recruiting T cells to turn “cold” tumors “hot,” with no added toxicity Specifically binds and preferentially depletes CCR8+ tumor Tregs, with no off-target binding CHS-114: Phase 1 Clinical Stage Program 6 CHS-114 is a Highly Selective Anti-CCR8 mAb with the Potential to Augment I-O Therapy Via Depletion of Treg Mediated Tumor Immune Suppression 6©2025 Coherus BioSciences Head & Neck Strong line-of-sight for additional target indications Gastric Colorectal (I-O Desert) Esophageal
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CHS-114 Targets Immunosuppressive Intratumoral Tregs By Selectively Depleting CCR8+ Tregs Via "Bind and Kill” Mechanism 7©2025 Coherus BioSciences Solution Problem • Intratumoral Tregs suppress antitumor immune responses and promote an immunosuppressive TME • Targeting Tregs is a challenge o Broad targeting may lead to autoimmunity o Strategies for selective Treg depletion have failed due to non-specificity of target markers • CCR8 is enriched and preferentially expressed on intratumoral Tregs1,2 • CCR8+ Treg depletion in preclinical studies3,4 o Selective CCR8+ Treg depletion, no decrease in CD4/CD8 T cells o No autoimmunity (CCR8 antibody treatment or genetic deletion) o Significant antitumor activity in ICI resistant tumor models • Phase 1 clinical data reported to date: no autoimmunity, antitumor activity, marked CCR8 Treg depletion and CD8 T cell infiltration in tumors 1) Simone et al. Immunity, 2016 2) Plitas et al. Immunity, 2016 3) Kidani et al. Immunology and Inflammation, 2022 4) Haruna et al, Scientific Reports, 2022 "Bind and Kill" via anti-CCR8 to Deplete Intratumoral Tregs X CCR8+Treg CHS-114
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CHS-114 Binds Only to CCR8, and is the Only Selective mAb Known To-Date 8© 2025 Coherus BioSciences. mAb selectivity is a challenge with GPCR targets Antibody Lead Identification: One and Only One Selective • Limited extracellular surface • Conformational heterogeneity. • High degree of sequence homology with similar receptors 1) Zhao et al, JITC, 2024 DOI: https://doi.org/10.1136/jitc-2024-SITC2024.1498 CCR8 Cell microarray for off target binding: evaluates 5,528 human proteins
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Anti-CCR8 With Anti-PD-1 Treatment Shows Antitumor Activity and a Significant Increase in Tumoral CD8 T Cells 0 5 10 15 20 25 0 1000 2000 3000 Days of Study Tumor Volume (mm3) Control Anti-PD1 Anti-CCR8 Combo *** *** 0 10 20 30 40 50 0 20 40 60 80 100 Days of Study % Survival Control Anti-PD1 Anti-CCR8 Combo *** **** 1/10 CR 0 500 1000 1500 2000 CD8+ T cells/mm2 ✱ ✱ Anti-PD1 Anti-CCR8 - + - + - - + + ✱ Control Anti-PD1 Anti-CCR8 Combo Antitumor activity in a PD-1R model (B16F10 subcu model) Combination treatment significantly increases CD8+ T cells in tumors 1x105 B16F10 cells were injected to the flank of C57BL/6 mice subcutaneously. Mice were randomized to four groups and dosing with isotype control antibodies, anti-CCR8 (50 µg/mouse), anti-PD-1 (200 µg/mouse), or combo treatments on day 6 post tumor implantation (n=10/group) 9© 2025 Coherus BioSciences. Combination treatment of CHS-114 (anti-CCR8) with toripalimab (anti-PD-1) has the potential for improved anti-tumor immunity
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CCR8+ Tregs Are Broadly Expressed In Several Solid Tumors, Reflecting Significant Opportunity TMA dataset from US Biomax 10© 2025 Coherus BioSciences. CCR8+ Tregs (density vs frequency) Signifies clinical benefits observed in CHS-114 Phase 1 and other clinical stage anti-CCR8 mAbs CHS-114 Has Broad Market Potential, Including Indications That Are I/O Treatment Deserts * * * No approved anti-PD(L1) IO desert Summary of available clinical data including CHS-114 • HNSCC (PD-1i combo): PR and SD in PD-(L1) refractory patients • GC (PD-1i combo): PR, CR with 36% ORR in heavily pre- treated PD-(L1) refractory patients; 1 anti-CCR8 alone PR1 • CRC: SD > 11m (CHS-114 and others)2 • NSCLC: 1 PR (anti-CCR8 alone)3 • Endometrial: SD > 14m in heavily pre-treated patients 1. Gong et al. J Clin Oncol. 2024;42(suppl 16): 2504. 2. Patnaik et al. J Clin Oncol. 2024;42(suppl 16):2664. 3. Starodub et al. Ann Oncol. 2023;20(suppl 1):100589.
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CHS-114 Demonstrates In Vitro Dose-Dependent Treg Depletion and Activation of NK And Myeloid Cells (Cytolytic Cells) NK Activation (ADCC)CHS-114 Dose Dependent Treg Depletion 11 Myeloid Activation (ADCP) PBMCs were treated with increasing concentrations of CHS-114 or isotype control at 37°C for 16 hours. The number of Tregs (CD4+ FOXP3+) per million of CD45+ cells was determined by flow cytometry PBMCs were treated with increasing concentrations of CHS-114 or isotype control at 37°C for 16 hours. The frequency of NK cells expressing 4-1BB was determined by flow cytometry. The percent increase in frequency of 4-1BB (normalized to isotope control) was calculated. EC50 values of CHS-114 were calculated based on 4-1BB induction on NK cells PBMCs were treated with increasing concentrations of CHS-114 at 37°C for 16 hours. The frequency of B7-H3 and CD83 expressing monocytes was determined by flow cytometry. EC50 values of CHS- 114 were calculated based on B7-H3 frequency Isotype control CHS-114 Preclinical in vitro pharmacology data used to support CHS-114 target trough levels in Phase 1 for dose expansion Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL © 2025 Coherus BioSciences.
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Background: CHS-114–Mediated Peripheral Immune Activation During Dose Escalation Supports Biologically Active Dose and RDE Selection 12 Phase 1 dose escalation study shows administration of CHS-114 ≥ DL5 results in Th1 immune activation over the dosing interval Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL © 2025 Coherus BioSciences.
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Agenda Phase 1 Clinical Development Rosh Dias, M.D. Chief Medical Officer, Coherus © 2025 Coherus BioSciences. 13
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CHS-114 Phase 1/1b Study Design Open-label single-agent and combination dose trial to evaluate CHS-114 in patients with advanced solid tumors and HNSCC Primary endpoint • Safety and tolerability Key secondary endpoints • Pharmacokinetics (PK) • Objective Response Rate† (ORR) • Additional measures of efficacy including: • Duration of response † (DoR) • Disease control rate † (DCR) • Progression-free survival† (PFS) • Biomarker endpoints • Treg depletion in tumor • CD8 T cell number Arm 1a: CHS-114 Dose Escalation in Advanced/Refractory Solid Tumor Patients* Arm 1b: Limited CHS-114 Dose Expansion in 2L+ HNSCC DL6 CHS-114 Expansion/Biopsy DL5 CHS-114 Expansion/Biopsy ClinicalTrials.gov ID: NCT05635643† Per RECIST 1.1 based on investigator assessment DL5 CHS-114 + Toripalimab Safety/Biopsy DL6 CHS-114 + Toripalimab Safety/Biopsy CHS-114 Dose Level 1 N=1 CHS-114 Dose Level 2 N=3 CHS-114 Dose Level 3 N=4 CHS-114 Dose Level 4 N=3 CHS-114 Dose Level 5 N=3 CHS-114 Dose Level 6 N=3 CHS-114 Dose Level 7 N=3 Arm 2: Combination Dose Escalation in 2L+ HNSCC (Paired Tumor Biopsy) Monotherapy Dose Escalation BOIN Design CHS-114 + Toripalimab Dose Escalation 3+3 Design *Doses evaluated ranging from 5mg to 1200 mg; Tumor types include HNSCC (n=2), colorectal (n=4), endometrial (n=2), kidney (n=1), melanoma (n=1), non-small cell lung cancer (n=2), pancreatic (n=3), biliary tract (n=1), esthesioneuroblastoma (n=1), ovarian (n=3), and rectal (n=1). HNSCC, Head and Neck Squamous Cell Carcinoma 14© 2025 Coherus BioSciences.
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Monotherapy dose escalation (Stage 1a) enrolled 20 patients with advanced solid tumors and evaluated seven dose levels (5 mg – 1200 mg) of CHS-114 • CHS-114 demonstrated an acceptable safety profile in heavily pre-treated patients with advanced solid tumors, with no DLTs reported to date and generally low-grade treatment-emergent adverse events • 47.4% of patients had stable disease (SD); one patient with SD of ~1 year remains on study • PK exposure increased with dose, was approximately dose proportional, and the elimination appeared linear with a half-life of about 10 days (range 9-17 days) • Depletion of peripheral CCR8+ Tregs was observed (>85% in the periphery) and depletion was maintained over the dosing interval, establishing proof of mechanism; CHS-114 did not deplete non- CCR8+ Tregs and effector CD4 T cells (proof of specificity) Two doses were selected for dose optimization based on safety, peripheral CCR8+ Treg depletion, PK and biomarker data CHS-114 Phase 1 Monotherapy Dose Escalation Results © 2025 Coherus BioSciences. 15 1. Patnaik A, et al. J Clin Oncol. 2024;42(suppl 16):2664.
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CHS-114 Phase 1/1b Study Design Current Status: Combo Dose Expansion: 2L HNSCC (CHS-114 with Toripalimab) Enrolling Primary endpoint • Safety and tolerability Key secondary endpoints • Pharmacokinetics (PK) • Objective Response Rate† (ORR) • Additional measures of efficacy including: • Duration of response † (DoR) • Disease control rate † (DCR) • Progression-free survival† (PFS) • Biomarker endpoints • Treg depletion in tumor • CD8 T cell number CHS-114 Monotherapy Dose Escalation (7 Dose Levels, DL1-DL7) Arm 1a: CHS-114 Dose Escalation in Advanced/Refractory Solid Tumor Patients Arm 1b: Limited CHS-114 Dose Expansion Arm 2: Combination Dose Escalation in 2L+ HNSCC (Paired Tumor Biopsy) DL6 CHS-114 Expansion/Biopsy DL5 CHS-114 Expansion/Biopsy ClinicalTrials.gov ID: NCT05635643† Per RECIST 1.1 based on investigator assessment Arm 3: CHS-114 Dose Optimization with Toripalimab in 2L HNSCC DL5 CHS-114 + Toripalimab DL6 CHS-114 + Toripalimab Select RP2D Phase 2 Enrollment Completed Enrollment Completed Enrolling R 1:1 N=40 2L HNSCC Should have been treated with anti-PD-1 therapy and only one prior systemic therapy allowed for advanced/metastatic condition DL5 CHS-114 + Toripalimab Safety/Biopsy DL6 CHS-114 + Toripalimab Safety/Biopsy Patnaik A, et al. J Clin Oncol. 2024;42(suppl 16):2664. Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL 16© 2025 Coherus BioSciences.
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CHS-114 + Toripalimab Phase 1b Study Design 2L Gastric Cancer (CHS-114 in combination with toripalimab) Open for Enrollment Primary endpoint • Safety and tolerability Key secondary endpoints • Pharmacokinetics (PK) • Objective Response Rate† (ORR) • Additional measures of efficacy including: • Duration of response † (DoR) • Disease control rate † (DCR) • Progression-free survival† (PFS) • Biomarker endpoints • Treg depletion in tumor • CD8 T cell number ClinicalTrials.gov ID: NCT06657144 © 2025 Coherus BioSciences. 17 † Per RECIST 1.1 based on investigator assessment Arm A1 DL 5 CHS-114 + Toripalimab Arm A2 DL6 CHS-114 + Toripalimab 2L Gastric Cancer/ Gastro-esophageal- Junction (GEJ)/Esophageal Adenocarcinoma (EAC) N=40 • Unresectable, advanced or metastatic • HER-2-negative, MSS R 1:1 N=40
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Agenda CHS-114 Phase 1 Study Results in Head and Neck Squamous Cell Carcinoma: Arms 1 and 2 Douglas Adkins, M.D. Professor of Medicine Director, Section of Head and Neck and Thyroid Medical Oncology Washington University School of Medicine © 2025 Coherus BioSciences. 18
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CHS-114 Phase 1/1b Study Design Open-label single-agent and combination dose trial to evaluate CHS-114 in patients with advanced solid tumors and 2L+ HNSCC Primary endpoint • Safety and tolerability Key secondary endpoints • Pharmacokinetics (PK) • Objective Response Rate† (ORR) • Additional measures of efficacy including: • Duration of response † (DoR) • Disease control rate † (DCR) • Progression-free survival† (PFS) • Biomarker endpoints • Treg depletion in tumor • CD8 T cell number Arm 1a: CHS-114 Dose Escalation in Advanced/Refractory Solid Tumor Patients* Arm 1b: Limited CHS-114 Dose Expansion in 2L+ HNSCC DL6 CHS-114 Expansion/Biopsy DL5 CHS-114 Expansion/Biopsy ClinicalTrials.gov ID: NCT05635643† Per RECIST 1.1 based on investigator assessment DL5 CHS-114 + Toripalimab Safety/Biopsy DL6 CHS-114 + Toripalimab Safety/Biopsy CHS-114 Dose Level 1 N=1 CHS-114 Dose Level 2 N=3 CHS-114 Dose Level 3 N=4 CHS-114 Dose Level 4 N=3 CHS-114 Dose Level 5 N=3 CHS-114 Dose Level 6 N=3 CHS-114 Dose Level 7 N=3 Arm 2: Combination Dose Escalation in 2L+ HNSCC (Paired Tumor Biopsy) Monotherapy Dose Escalation BOIN Design CHS-114 + Toripalimab Dose Escalation 3+3 Design *Doses evaluated ranging from 5mg to 1200 mg; Tumor types include HNSCC (n=2), colorectal (n=4), endometrial (n=2), kidney (n=1), melanoma (n=1), non-small cell lung cancer (n=2), pancreatic (n=3), biliary tract (n=1), esthesioneuroblastoma (n=1), ovarian (n=3), and rectal (n=1). HNSCC, Head and Neck Squamous Cell Carcinoma © 2025 Coherus BioSciences. 19
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CHS-114 Phase 1 Study Demographics and Baseline Characteristics for Patients with HNSCC 20 CHS-114 CHS-114 + Monotherapy Toripalimab (n=14†) (n=7) Age, median years (range) 67 (42, 88) 67 (49, 79) Gender, n (%) Female 3 (21.4) 2 (28.6) Male 11 (78.6) 5 (71.4) Race, n (%) American Indian or Alaska Native 0 0 Asian 0 0 Black or African American 2 (14.3) 0 Native Hawaiian or Other Pacific Islander 0 0 White 12 (85.7) 7 (100.0) Unknown 0 0 Other 0 0 Not Reported 0 0 ECOG, n (%) 0 4 (28.6) 5 (71.4) 1 10 (71.4) 2 (28.6) Median time since initial diagnosis, months (range) 25.5 (11, 184) 21 (15, 84) Lines of prior systemic therapy, n (%) 0 1 (7.1) 0 1-2 7 (50.0) 5 (71.4) 3-4 5 (35.7) 2 (28.6) ≥5 1 (7.1) 0 PD-L1 expression*, n (%) Positive 13 (92.9) 7 (100.0) Negative 1 (7.1) 0 Not Done 0 0 †Patients with HNSCC from stage 1a (n=2) and stage 1b (n=12) *PD-L1 expression measured by combined positive score (CPS) or tumor proportion score (TPS) © 2025 Coherus BioSciences.
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CHS-114 Phase 1 Study in Patients with HNSCC Summary of Adverse Events 21 AE Summary CHS-114 Monotherapy (n=14) CHS-114 + Toripalimab (n=7) Treatment-emergent adverse event (TEAE), n (%) 12 (85.7) 7 (100.0) Treatment-related† AE, n (%) 7 (50.0) 7 (100.0) Grade ≥3 TEAE, n (%) 4 (28.6) 5 (71.4) Grade ≥3 treatment-related† AE, n (%) 1 (7.1) 4 (57.1) Serious treatment-emergent adverse event (TESAE), n (%) 3 (21.4) 3 (42.9) Treatment-related† SAE, n (%) 0 0 TEAE leading to study drug(s) discontinuation*, n (%) 0 4 (57.1) Treatment-related† AE leading to study drug(s)* 0 2 (28.6) discontinuation, n (%) TEAE leading to death, n (%) 0 0 Treatment-related† AE leading to death, n (%) 0 0 †For monotherapy with HNSCC, treatment-related AEs are CHS-114–related AE; For stage 2 subjects, treatment-related AEs are CHS-114 and/or toripalimab related AEs. *For stage 2 subjects, treatment discontinuation are CHS-114 and/or toripalimab discontinuation. Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL © 2025 Coherus BioSciences.
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© 2025 Coherus BioSciences. 22 CHS-114 Phase 1 Study in Patients with HNSCC Summary of Responses: Investigator Assessment per RECIST v1.1 Confirmed Partial Response in Heavily Pretreated PD-1 Refractory Patient with HNSCC Treated with CHS-114 + Toripalimab Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL CHS-114 Monotherapy 70 60 50 40 30 20 10 0 -10 -20 -30 -40 Percent Change from Baseline 70 60 50 40 30 20 10 0 -10 -20 -30 -40 Percent Change from Baseline DL4, n=1 DL5, n=4 DL6, n=3 Best Percent Change from Baseline in Sum of Target Lesions* (n=8) DL4, n=1 DL5, n=4 DL6, n=3 Target Lesion Change Over Time (n=8) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 Weeks Patients Response Evaluable DL6 (n=3) Response Evaluable DL5 (n=5) Response Evaluable DL4 (n=1)Best Overall Response, n (%) 0 2 (66.7) 1 (33.3) 0 2 (40.0) 3 (60.0) 0 0 1 (100.0) *as of the January 24, 2025, data cutoff date CHS-114 + Toripalimab Percent Change from Baseline Percent Change from Baseline Best Percent Change from Baseline in Target Lesion Change Over Time (n=6) Sum of Target Lesions* (n=6) Patients Response Evaluable DL6 + Tori (n=3) Response Evaluable DL5 + Tori (n=4)Best Overall Response, n (%) 1 (33.3) 1 (33.3) 1 (33.3) 0 1 (25.0) 2 (50.0) Partial response (confirmed) *as of the January 24, 2025, data cutoff date Stable disease Progressive disease DL5 + Tori, n=3 DL6 + Tori, n=3 DL5 + Tori, n=3 DL6 + Tori, n=3 140 120 100 80 60 40 20 0 -20 -40 -60 -60 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 Weeks 140 120 100 80 60 40 20 0 -20 -40 Partial response (confirmed) Stable disease Progressive disease Not evaluable 1 (25.0) 0Not evaluable 0 00
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© 2025 Coherus BioSciences. 23 CHS-114 Phase 1 Study in Patients with HNSCC Summary of Responses: Time on Treatment Confirmed Partial Response in Heavily Pretreated PD-1 Refractory Patient with HNSCC Treated with CHS-114 + Toripalimab Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL CHS-114 + Toripalimab (n=7)CHS-114 Monotherapy (n=14) Confirmed Partial Response (cPR) Unconfirmed Partial Response Progressive Disease Death Patient Continuing Positive PD-L1 Expression Negative PD-L1 Expression DL4, n=1 DL5, n=9 DL6, n=4 Timeon treatment= daysfrom first doseto end of treatment Median Time on Treatment, weeks (range) = 6 (2-22) Patients 0 2 4 6 8 10 12 14 16 18 20 22 24 0 2 4 6 8 10 12 14 16 18 20 Weeks Weeks Confirmed Partial Response (cPR) Unconfirmed Partial Response Progressive Disease Death Patient Continuing Positive PD-L1 Expression Negative PD-L1 Expression DL5 + Tori, n=4 DL6 + Tori, n=3 Median Time on Treatment, weeks (range) = 8 (5-19) Patients
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Patient Demographics and Cancer History 65-year-old Caucasian male, non-smoker In April 2023, chief complaint of right neck mass Diagnosed at Stage IV (cT1N1M1) right base of tongue • HPV genotype 16 positive (PCR) OPSCC Biopsy-proven lung metastasis. No liver metastasis. Low immunogenicity features: • PD-L1 CPS 3-5% • TMB 8 mut/Mb • Microsatellite stable (MSS) Case Study: Confirmed Partial Response in PD-1 Refractory HNSCC Patient Treated with CHS-114 (DL6) + Toripalimab © 2025 Coherus BioSciences. 24 HPV: Human papillomavirus; OPSCC: oropharyngeal squamous cell carcinoma; TMB: tumor mutational burden
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Treatment History Prior to Study Enrollment Case Study: Confirmed Partial Response in PD-1 Refractory HNSCC Patient Treated with CHS-114 (DL6) + Toripalimab © 2025 Coherus BioSciences. 25 APR2023 Right neck mass HPV type 16 SCC Right glossotonsillar sulcus lesion, enlarged neck nodes, and lung nodules MAY-AUG2023 1L treatment Carboplatin, 5-fluouracil & pembrolizumab BOR: Progressive disease SEP-DEC2023 2L treatment Afatinib BOR: Progressive disease JAN-MAR2024 3L treatment Docetaxel (3 cycles) [Apr-24] CT HNCAP: PD (large R>L neck nodes, right BOT mass and lung nodules): syncopal events d/t carotid bulb involvement USG biopsy of the right neck mass showed NKT SCC JUN2024 Palliative RT to the neck: 5000 cGy over 4 weeks. [Aug-24] CT NCAP: BOT mass (3.6 → 2.8 cm) BL neck nodes (right: 5.8 → 2.8 cm) Increased left hilar node Stable lung nodules AUG2024 4L treatment CHS-114 + Toripalimab L: line; BOR: best overall response; PD: progressive disease; BOT: base of tongue; USG: ultrasound-guided; NKT SCC: non-keratinizing squamous cell carcinoma; CT (H)NCAP: (head) neck, chest, abdomen-pelvis ClinicalTrials.gov ID: NCT05635643
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Case Study: Confirmed Partial Response in PD-1 Refractory HNSCC Patient Treated with CHS-114 (DL6) + Toripalimab © 2025 Coherus BioSciences. 26 Baseline (02 AUG2024) Follow-up 3 (10DEC2024)
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Case Study: Confirmed Partial Response in PD-1 Refractory HNSCC Patient Treated with CHS-114 (DL6) + Toripalimab © 2025 Coherus BioSciences. 2727 Baseline (02 AUG2024) Follow-up 3 (10DEC2024)
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PD-1 Refractory HNSCC Patient Treated with CHS-114 (DL6) + Toripalimab: Confirmed Partial Response in Target Lesions © 2025 Coherus BioSciences. 2828 RECIST Assessment 40% Reduction in Target Lesions at time of Confirmed PR at follow-up 3 Non-target Lesions: 2 out of 4 non-target lesions disappeared after 2 treatment cycles
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PD-1 Refractory HNSCC Patient Treated with CHS-114 (DL6) + Toripalimab: Response in Irradiated Lesion to Improve QOL © 2025 Coherus BioSciences. 2929 Baseline (02 AUG2024) Follow-up 3 (10DEC2024)
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Agenda Biomarker Data and Conclusions Theresa LaVallee, Ph.D. Chief Development Officer, Coherus © 2025 Coherus BioSciences. 30
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Validated mIF Assay to Evaluate Tumor Tissue for Treg and CD8 T Cells: CCR8, FOXP3 and CD8 © 2025 Coherus BioSciences. 3131 Panel Markers: • CCR8 (enriched on itTregs): Target receptor • FOXP3 (Tregs): Defines Treg cell • CD8 (effector T cells): Monitor immune activation • DAPI: nuclear stain – to identify cells Staining Opal mIF/IHC LEICA autostainer Imaging Akoya PhenoImager Analysis Quantitative analysis HALO software (pathologist assisted) CCR8 FOXP3 CD8 DAPI Green/White: CCR8+ Tregs White only: Treg w/o CCR8 Magenta: CD8 only HNSCC Hypothesis: Depleting highly immunosuppressive CCR8+ Tregs will promote CD8+T cell expansion
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Results: CHS-114 Alone Depletes CCR8+ Tregs and Remodels the TME in Favor of Anti-Tumor Immunity © 2025 Coherus BioSciences. 32 Hypothesis: Depleting highly immunosuppressive CCR8+ Tregs will promote CD8+T cell expansion – The data: yes turns the tumor ”hot” Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL
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Results: CHS-114 Monotherapy Treatment Promotes an Inflamed TME (HNSCC) – “Hot Tumor” © 2025 Coherus BioSciences. 33 Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL
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Conclusions Two doses were selected for dose optimization based on safety, peripheral CCR8+ Treg depletion, PK and biomarker data; these two doses are supported by the observed immune activation in blood and CCR8+ Treg depletion in tumor CHS-114 with and without toripalimab had a manageable safety profile in HNSCC patients CHS-114 with toripalimab had promising antitumor activity in HNSCC that warrants continued exploration In on-treatment tumor biopsies, CHS-114 depleted CCR8+ Tregs and increased CD8+ T cells in the TME indicating favorable TME remodeling and establishing proof of mechanism CHS-114 administration leads to a substantial increase in CD8+ T cells in the TME providing a strong rationale for combining with other drugs such as T cell engagers and bispecifics All together, these data support further evaluation of CHS-114 in combination with other drugs including toripalimab; a second-line (2L) HNSCC CHS-114 with toripalimab dose optimization study is ongoing CHS-114 Phase 1 Study in Patients with HNSCC © 2025 Coherus BioSciences. 34 Worden, F., et al., Phase 1 study of anti-CCR8 antibody CHS-114 with and without anti-PD-1 antibody toripalimab in patients with advanced solid tumors [abstract CT038]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL
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CHS-114 Summary: A Highly Selective Anti-CCR8 mAb Targeting Advancing in Clinical Development © 2025 Coherus BioSciences. 35 Strong line-of-sight for target indications and patient populations Preferentially depletes CCR8+ tumor Tregs with no off-target binding Potential to address high unmet need in multiple indications including NSCLC and CRC Recruits T cells to turn “cold” tumors “hot,” with no added toxicity
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Agenda Q&A Session © 2025 Coherus BioSciences. 36
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