INTERIM TAGMOKITUG CLINICAL DATA – WEBCAST - COHERUS ONCOLOGY INC

Explicit Guidance:

• CasDozo-Ketog Data Disclosure: Anticipated data release scheduled for January 2027.
• First-Line Esophageal Squamous Cell Carcinoma (ESCC) Cohort Expansion: Plans to expand enrollment from current 10–12 patients to a target of 30–40 patients.
• Second-Line ESCC Cohort Expansion: Plans to complete enrollment of the target 20 patients (300mg/700mg doses) and initiate expansion pending durability data.
• Regulatory Meeting Timing: FDA alignment meetings regarding go-forward dose and development plan targeted for the first quarter of next year.
• Expansion Timeline: Potential initiation of expanded cohorts estimated for the second or third quarter of next year, pending FDA discussion and sufficient durability data.
• New Combination Study: Initiation of a metastatic prostate cancer study in collaboration with J&J expected shortly, with data updates anticipated in early Q2 (implied 2026 based on "first quarter" mention for other meetings).

Business-Segment Outlook:

• Esophageal Cancer (Primary Focus):
  • First-Line: Moving to larger cohort to validate 75%–89% ORR (100% in PD-L1 positive) and durability; potential to leverage FDA "Project FrontRunner" for accelerated approval via ORR/DOR surrogate endpoints.
  • Second-Line: Aiming to establish TAGMO-Tori (700mg) as a chemo-free regimen with a confirmed ORR of 16.7% and CBR of 33.3%; seeking to convert to OS endpoint in registrational trials.
  • Market Opportunity: U.S. addressable population estimated at 5,000–7,000 patients across lines of therapy; projected economic opportunity of $1.5 billion for the dual-approval scenario.
  • Commercial Strategy: Leveraging existing rare-disease commercial infrastructure (similar to Nasopharyngeal Cancer footprint); exploring partnerships in Asia (China, Japan) and Europe due to high disease burden and existing Toripalimab approvals.
• Head and Neck Cancer:
  • Focus: Enrichment in HPV-positive population (approx. 30% of recurrent metastatic disease); currently a "white space" compared to competitors targeting HPV-negative.
  • Data Trend: Encouraging durability with one patient on treatment >1 year; exploring TIRI biomarker enrichment to improve ORR/CBR.
• Upper GI Adenocarcinoma:
  • Dose Differentiation: Clear signal at 700mg (23.5% ORR) vs. limited activity at 300mg; targeting chemo-free doublet option in second-line to displace Ramucirumab/Paclitaxel.
• Colorectal Cancer (CRC):
  • Strategic Pivot: Current fourth-line data (6% ORR) supports moving into earlier lines of therapy (e.g., second-line) where immunotherapy activity is historically higher.

Market and Competitive Outlook:

• Differentiation:
  • First-Line: Targeting PD-L1 negative/unselected populations (75% ORR) where current U.S. standards (Chemo + PD-1) show 44–59% ORR in PD-L1 positive and limited efficacy in PD-L1 negative.
  • Second-Line: Offering a chemo-free option in a setting dominated by single-agent chemotherapy with median OS <1 year.
• Competitive Landscape:
  • Head & Neck: Most registrational pathways focus on HPV-negative; minimal development in HPV-positive space represents a structural gap.
  • Combination Strategy: Plans to evaluate combinations with ADCs (Antibody-Drug Conjugates) and VEGF inhibitors to enhance efficacy in Gastric and ESCC settings.
  • Global Standards: Leveraging Toripalimab's existing approval in Europe and China to facilitate global development and potential partnerships.

Macro / Industry Outlook:

• Regulatory Environment:
  • Accelerated Approval Path: Intent to utilize FDA designations including Orphan Drug, Breakthrough Therapy, Fast Track, and Project Orbis (concurrent submission to FDA, EMA, Japan, etc.).
  • Endpoints: Pursuing ORR/DOR as surrogates for accelerated approval with intent to confirm via Overall Survival (OS) later, similar to the Pfizer Breakwater study model.
• Market Dynamics:
  • Unmet Need: ESCC characterized by poor prognosis (median survival 15–17 months) and lack of effective options beyond first-line; strong commercial imperative in Asia (high incidence of gastric/esophageal cancer).
  • U.S. Practice: Moving toward utilizing U.S.-standard-of-care chemotherapy (5-FU/Cisplatin) in trials to ensure FDA acceptability, addressing the limitation of the Jupiter-6 study (non-U.S. chemo regimen).

Strategic Initiatives:

• Dose Optimization: Confirming 700mg of TAGMO-Ketog as the go-forward dose based on clear dose-response differentiation in Esophageal and Upper GI cohorts; 300mg deemed insufficient for ESCC/GI but active in HPV+ Head & Neck.
• CMC & Manufacturing: Completion of manufacturing relocation to the U.S. to facilitate FDA inspections and support a robust BLA package (50% risk/spend on CMC).
• Regulatory Strategy: Engaging FDA to design randomized controlled trials (RCTs) for both first-line (with chemo) and second-line (chemo-free) indications; potential for single-study design to capture both indications.
• Partnership & Licensing: Exploring commercial partnerships in Asia and Europe for Toripalimab/TAGMO-Tori combination; leveraging existing global rights.
• Pipeline Expansion: Launching new study for J&J prostate cancer combination; ongoing biomarker analysis (TIRI, CCR8 scores) to refine patient selection.

Risks and Headwinds to Outlook:

• Data Immaturity: Current data is interim; durability and Median PFS are not yet mature. Significant risk of attrition in ORR as follow-up extends.
• Regulatory Uncertainty: Accelerated approval thresholds (specific ORR benchmarks) not yet confirmed by FDA; need for robust Phase 3 OS confirmation.
• Safety/Tolerability:
  • First-Line: Discontinuation rate ~40% attributed primarily to chemotherapy toxicity (cisplatin-induced renal toxicity, rash) rather than TAGMO-Tori doublet.
  • Management: Mitigation strategies include potential carboplatin substitution to reduce renal toxicity.
• Small Sample Sizes: Current cohorts are small (e.g., 8 evaluable in 1st line), leading to wide confidence intervals; expansion is critical to validate signals.
• Competitive Landscape: Rapid evolution in GI oncology with emerging ADCs and VEGF inhibitors; current gastric data does not yet exceed standard of care benchmarks.

Management Tone on the Future:

• Confidence Level: High confidence in the 700mg dose and the biological mechanism (Treg depletion) driving the activity.
• Tone: Optimistic and aggressive regarding the development path, citing "compelling," "exceeding benchmarks," and "clear dose response."
• Strategic Pivot: Willing to shift focus to earlier lines of therapy based on early signals (e.g., CRC) and to pivot to chemo-free regimens in second-line settings.
• Hedges: Repeated emphasis on the need for "more mature follow-up" and "expanded patient sets" before definitive regulatory conclusions; acknowledges current data limitations while framing them as a "foundation for rapid development."

Miscellaneous:

• Timeline Context: Call references "2025" for prior data presentation (AACR), indicating the current call takes place in late 2025 or early 2026 (based on "next year" FDA meetings and "Jan 2027" CasDozo data).
• Key Personnel: CEO Danny Lancer, CMO Dr. Rosh Dias, CSO Dr. Teresa LaValley, and external KOLs Dr. Doug Atkins (WashU) and Dr. Dan Feng (Mount Sinai).
• Biomarkers: Tumor Immune Regulatory Index (TIRI) and CCR8 scores identified as potential enrichment tools, particularly for HPV+ head and neck.