INTERIM TAGMOKITUG CLINICAL DATA – WEBCAST - COHERUS ONCOLOGY INC

Financial Performance:

• No specific financial metrics (revenue, earnings, cash flow, debt) were disclosed in this interim clinical data call, as the company is in a clinical development stage prior to commercialization.
• Management highlighted a potential economic opportunity of approximately $1.5 billion in the U.S. market for esophageal squamous cell carcinoma (ESCC), driven by an estimated 5,000–7,000 treatable patients across first and second lines.
• Manufacturing for investigational agents has been moved to the U.S. to facilitate FDA inspections and support a potential Blockage License Application (BLA) submission.

Guidance and Future Outlook:

• ESCC Development: Plans to expand first-line and second-line ESCC cohorts to 30–40 patients to generate mature durability data (PFS, OS) by the second or third quarter of next year.
• Regulatory Strategy: Intends to engage the FDA in Q1 of next year to align on dosing (700 mg) and expedited pathways (Breakthrough Therapy, Fast Track, Orphan Drug); exploring Project Orbis for concurrent global review.
• Future Pipeline: Anticipates a data disclosure for the "CasDozo-Ketog" program in January 2027; a new combination study with J&J for metastatic prostate cancer is launching in early 2026.
• Commercialization: Strategy includes U.S. commercialization for rare/ESCC indications and potential partnering opportunities in Europe and Asia (where ESCC incidence is high) due to Toripalimab's existing approvals there.

Business Segments and Product Lines:

• Tagmo-Ketog + Toripalimab (ESCC):
  • First-line: In 8 evaluable patients (12 total enrolled), observed a 75% Confirmed Overall Response Rate (ORR), rising to 89% with post-cutoff data; 100% ORR in PD-L1 positive patients and 75% in PD-L1 negative patients. 50% of patients remain on therapy.
  • Second-line: In 17 of 20 dosed patients, the 700 mg dose showed an ORR of 16.7% (1 confirmed PR) plus unconfirmed PRs; Clinical Benefit Rate (CBR) of 33.3%. Median PFS of 5.5 months observed, with clear dose-dependency (300 mg ineffective).
• Head and Neck (HNSCC): Second-line interim data (23 evaluable patients) showed enrichment in HPV-positive disease with an ORR of ~30% and CBR of 26% in HPV+ patients; durability noted with some patients >1 year on treatment.
• Upper GI Adenocarcinoma: Second-line data (40 patients) showed 23.5% ORR (4 confirmed PRs) and ~30% CBR at the 700 mg dose; activity observed in PD-L1 low/negative and PD-1 refractory populations.
• Colorectal Cancer (CRC): Fourth-line cohort (20 patients) showed 6% ORR and 12% CBR; molecular response (ctDNA/CEA decline) observed, supporting move to earlier lines of therapy.
• CasDozo-Ketog: Demonstrating dose-dependent activity; data disclosure expected January 2027.

Market and Competitive Landscape:

• ESCC: Significant unmet need; current standard of care in first-line yields 44–59% ORR (PD-L1+), while second-line options post-PD-1 failure are limited to chemotherapy with median PFS of 2–4 months. The company positions its chemo-free doublet in second-line and higher-efficacy combo in first-line.
• HNSCC: Focus on HPV-positive, PD-1 refractory space, a "white space" where most current development targets HPV-negative disease; current 4-month PFS for this cohort is ~10%.
• Competitive Positioning: Tagmo-Ketog + Toripalimab aims to rescue PD-1 resistance by depleting Tregs and remodeling the tumor microenvironment, showing activity in PD-L1 negative tumors where standard PD-1 inhibitors fail.
• Global Context: Toripalimab is already approved in Europe/China for ESCC (irrespective of PD-L1), creating a potential pathway for partnership or leveraging existing data for U.S. approval discussions.

Risks and Challenges:

• Sample Size: Current data sets are small (interim), requiring expansion and longer follow-up to confirm durability and PFS/OS benefits before pivotal trials.
• Toxicity Management: First-line regimen involves a 4-drug combo (Tagmo-Ketog + Toripalimab + Chemo); discontinuations (40% in first-line) were partly driven by chemotherapy toxicities (e.g., cisplatin-induced renal toxicity, rash), though Tagmo-Ketog itself showed no new safety signals.
• Regulatory Uncertainty: Accelerated approval will require robust surrogate endpoints (ORR/DOR) and subsequent OS confirmation; FDA alignment on go-forward doses and trial designs is pending.
• Competitive Pressure: Emerging ADCs and other novel combinations in gastric and esophageal cancers could impact the competitive landscape.

Management Commentary and Tone:

• Tone: Highly optimistic and confident regarding the clinical activity, particularly the "clear dose-response" and ability to treat PD-L1 negative patients.
• Strategic Focus: Emphasis on "patient survival" and extending the "tail of the curve" (durability/stable disease) rather than just tumor shrinkage.
• Differentiation: Management stressed the ability to combine with standard U.S. chemotherapy (unlike the China-only Jupiter-6 study for Toripalimab) and the potential to bring immunotherapy to patients ineligible for current IO therapies.

Analyst Questions and Answers:

• Q (Paul Cheng, Guggenheim): Asked about PFS trends and regulatory bar for accelerated approval. A: Too early for median PFS; CBR is the key interim metric. Regulatory bar will be discussed post-expansion; molecular response data will complement clinical data.
• Q (Jay Olson, Oppenheimer): Asked about enrollment timelines and U.S. filing for Toripalimab. A: Expansion to 30–40 patients expected in Q2–Q3 next year; FDA meeting package to be finalized in Q1. Toripalimab U.S. filing for ESCC is under discussion but data from China study (Jupiter-6) is not directly comparable due to chemo regimen differences.
• Q (Mike Nedeljkovic, TD Cowen): Asked about commercial strategy and competitive landscape. A: Global strategy with potential partners in Europe/Asia; U.S. footprint fits rare disease model. Competitive landscape includes ADCs; plans to explore combinations with ADCs and VEGF inhibitors.
• Q (Brian Chang, J.P. Morgan): Asked about data confidence vs. Jupiter-6 and reasons for patient drop-off. A: Confidence derived from second-line activity and dose-dependency. Drop-offs in first-line were primarily due to chemotherapy (cisplatin renal toxicity) and rash, manageable with future regimen adjustments (e.g., carboplatin).
• Q (HC Wainwright): Asked about clinically meaningful benefit metrics (QoL, PFS). A: QoL not measured in this interim trial but expected to improve with tumor reduction; Second-line median PFS of 5.5 months compares favorably to 2–4 months standard of care.

Other Key Points:

• Safety Profile: Across >120 patients treated with Tagmo-Ketog + Toripalimab, no new safety signals beyond known PD-1 inhibitor toxicities; no Grade 5 Tagmo-related events; immune-related AEs were mostly Grade 1–2 and manageable.
• Biomarkers: Tumor Immune Regulatory Index (TIRI) and CCR8 scores show potential enrichment for response, particularly in HPV-positive head and neck and PD-L1 negative esophageal cancers.
• KOL Perspectives: Dr. Dan Feng (Mount Sinai) and Dr. Doug Atkins (WashU) validated the clinical significance of the high response rates, especially in PD-L1 negative populations and the potential for a chemo-free second-line option.
• Dose Selection: 700 mg identified as the optimal go-forward dose for esophageal and upper GI cancers based on clear dose-response; 300 mg showed limited efficacy in these settings but may be sufficient for HPV-positive head and neck.