Coherus Bets Esophageal Focus Against Cash Burn and Crowded Second-Line Standards

Coherus Oncology Cuts Workforce, Narrows Pipeline Focus

Coherus Oncology is implementing a significant reorganization, resulting in a 30% workforce reduction, impacting approximately 44 roles. This strategic move aims to streamline its pipeline by deprioritizing the broad development of an investigational combination treatment across various cancers to focus primarily on esophageal cancer. The company anticipates that these efforts will lower its quarterly core cash burn by $6 million, with benefits realized over the next two quarters. This marks the second 30% layoff for Coherus in less than two years, following a previous reduction in March 2025 after the divestment of its Udenyca franchise.

• Coherus Oncology is undergoing a major reorganization, leading to a 30% reduction in its workforce, affecting around 44 employees. This strategic pivot involves narrowing its pipeline focus, specifically deprioritizing the development of its investigational combination treatment across multiple cancer indications to concentrate on esophageal cancer as its lead program. This aims to optimize resource allocation and enhance operational efficiency.
• The current workforce reduction is expected to generate substantial financial benefits, reducing Coherus's quarterly core cash burn by $6 million over the next two quarters. This follows a similar 30% layoff in March 2025, which occurred after the divestment of the Udenyca franchise to Intas Pharmaceuticals’ Accord BioPharma for an upfront payment of $483 million, used to repay existing convertible notes.
• The decision to prioritize esophageal cancer is underpinned by compelling interim Phase 1b results for the cytolytic CCR8 antibody tagmokitug, combined with toripalimab. The duo demonstrated a confirmed overall response rate of 75% among patients with esophageal squamous cell carcinoma in a front-line setting, irrespective of PD-L1 status, validating the strategic shift towards this specific and promising indication.

The Evolving Treatment Landscape for Esophageal Squamous Cell Carcinoma

In first-line advanced esophageal squamous cell carcinoma (ESCC), PD-1/PD-L1 inhibitors combined with chemotherapy have significantly improved outcomes compared to non-combination therapy. A meta-analysis including eight phase 3 RCTs encompassing 4,479 participants showed improved overall survival (OS) (HR: 0.68, 95% CI: 0.63-0.74) and progression-free survival (PFS) (HR: 0.62, 95% CI: 0.58-0.67). Patients with higher PD-L1 expression (CPS>1 or TPS>1) demonstrated superior responses, with CPS identified as a stronger predictor of therapeutic benefit, particularly at a threshold of CPS =10. Subgroup analysis revealed that male, Asian, smoking, and liver metastasis patients exhibited a greater trend toward improved disease control, while there was no significant difference in treatment efficacy between immune therapy combined with TP (taxol [paclitaxel] + cisplatin) and FP (5-fluorouracil [5-FU] + cisplatin) regimens (P =0.51, P =0.11). PD-1/PD-L1 inhibition was associated with a higher incidence of grade ≥3 adverse events compared to chemotherapy alone (HR: 1.21, 95% CI: 1.07-1.37). Reconstructed patient-level data from seven randomized controlled trials including 4,162 patients showed PD-1 inhibitors prolonged median OS from 11.3 months (95% CI 10.7-11.7) to 15.6 months (95% CI 14.7-16.3), with the toripalimab, tislelizumab, and sintilimab group achieving the longest OS.

In previously treated advanced ESCC, immune checkpoint inhibitors have demonstrated long-term benefit over chemotherapy. In ATTRACTION-3, 210 received nivolumab and 209 received chemotherapy, with a minimum follow-up of 36.0 months, OS was longer in the nivolumab versus the chemotherapy group (median, 10.9 vs. 8.5 months; HR, 0.79; P = 0.0264), with 3-year OS rates of 15.3% and 8.7%, respectively. Grade 3 or higher treatment-related adverse events were reported in 40 patients (19.1%) in the nivolumab group and 133 patients (63.9%) in the chemotherapy group. In RATIONALE-302, 512 patients were randomly assigned to tislelizumab 200 mg every 3 weeks or chemotherapy, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6 v 6.3 months; hazard ratio [HR], 0.70 [95% CI, 0.57 to 0.85]; one-sided P = .0001), and in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10% (median, 10.3 months v 6.8 months; HR, 0.54 [95% CI, 0.36 to 0.79]; one-sided P = .0006). Treatment with tislelizumab was associated with higher objective response rate (20.3% v 9.8%) and a more durable antitumor response (median, 7.1 months v 4.0 months), with fewer ≥ grade 3 treatment-related adverse events (18.8% v 55.8%).

In resectable locally advanced ESCC, neoadjuvant chemoimmunotherapy (NCIT) has emerged as an alternative to neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (nCT). A meta-analysis of 34 studies (1275 NCIT, 1045 NCRT patients) showed NCIT significantly improved OS (HR 0.63, 95% CI 0.47-0.84) and PFS (HR 0.69, 95% CI 0.51-0.93), with 3-year OS rates of 74.7% (NCIT) versus 63.2% (NCRT) and 3-year PFS rates of 65.7% versus 54.6%, while pCR (31% versus 39%) and MPR (55% versus 64%) were lower with NCIT (P < 0.05). In a retrospective cohort of 50 eligible participants, pCR rates were 7.1% and 22.2% (χ=0.699; P=0.40) and MPR rates were 7.1% and 38.9% (χ=4.837; P=0.03) in the nCT and nICT groups, respectively, and following neoadjuvant therapy, the expression rates of PD-L1, CD3 T cells, and CD8 T cells in the tumor tissue was higher in the nICT group compared to the nCT group (P<0.05). An interim analysis of a phase III randomized trial of perioperative toripalimab plus neoadjuvant chemotherapy in 252 ESCC patients showed the 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05), the 1-year OS rates were 94.1% and 83.0% (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037), and pCR rate was higher (18.6% vs. 4.6%; P = 0.001), with no significant difference in postoperative Clavien-Dindo grade IIIb or higher morbidity (9.8% and 6.8%; P = 0.460) or grade 3 or 4 treatment-related AEs (12.5% versus 12.4%).

Gyre's Acquisition: Expanding into Novel Therapeutic Targets

Recent research in esophageal squamous cell carcinoma (ESCC) is expanding beyond cytotoxic chemotherapy toward immune checkpoints, cell-surface antigens for antibody-drug conjugates and cellular therapy, and receptor tyrosine kinase pathways. Immune checkpoint inhibitors have shown therapeutic efficacy and have been approved as monotherapy or combination therapy for advanced ESCC, while novel antibody-drug conjugates hold promise for advanced disease.

• Co-inhibitory T-cell checkpoints including PD-1, TIM-3, BTLA, TIGIT, CTLA-4, LAG-3 and A2AR: In a follow-up study of 161 patients undergoing resection, levels of PD-1, TIM-3 and BTLA can be used as independent prognostic factors for overall survival, and co-expression of PD-1 and TIM-3, PD-1 and BTLA, and TIM-3 and BTLA significantly reduced survival (P<0.05). Higher TIGIT expression correlated with shorter DFS and OS, with median DFS of 17.4 months and OS of 26.8 months in 69 resected patients, and TIGIT knockdown reduced ESCC cell migration, invasion, and proliferation with S-phase accumulation, implicating cytokine-receptor interactions and the JAK-STAT signaling axis.

• TROP2 as ADC target with AUNIP as sensitivity determinant: Through single-cell transcriptomic analysis, TROP2 was identified as a consistently and highly overexpressed cell-surface antigen in HNSCC and ESCA, and DS-1062a, a TROP2-directed ADC delivering deruxtecan (Dxd), demonstrated marked tumor regression in HNSCC and ESCA xenografts. Genome-wide CRISPR/Cas9 knockout screening identified AUNIP as a determinant of chemosensitivity, where AUNIP loss profoundly enhanced DS-1062a cytotoxicity and multiple SSB-inducing chemotherapies via impaired DNA repair, attenuated stress response signaling, and heightened apoptotic susceptibility.

• B7-H3-directed microenvironment-regulated CAR-T: B7-H3 was selected as the target antigen for a tumor microenvironment regulated system chimeric antigen receptor T (MRS.CAR-T) incorporating a human serum albumin binding peptide and matrix metalloproteases cleavage site between the 5' terminal signal peptide and single chain fragment variable. MRS.B7-H3.CAR-T was not cytotoxic in normal tissues expressing B7-H3, recovered anti-tumor function once cleaved by MMPs in the TME, showed improved anti-tumor efficacy compared to classic B7-H3.CAR-T in vitro with less IFN-γ release, and had strong anti-tumor activity and safety in vivo.

• c-Met / HGF signaling and imaging-guided targeting: Positive c-Met staining was observed in 97.64% (124/127) of eSCC samples and 91.67% (55/60) of lymph node metastases, with increased expression in metastases versus normal lymph nodes (P<0.0001), and c-Met overexpression was significantly associated with shorter OS (HR: 2.04, 95% CI: 1.66-2.52, P<0.001) and DSS (HR: 3.03, 95% CI: 2.04-4.48, P<0.001). Coptisine inhibited c-Met phosphorylation and proliferation in ESCC cells, inhibited expression of downstream proteins of the HGF/c-Met signaling pathway, induced ROS generation, and effectively inhibited tumor growth in xenografts by reducing levels of pyroptosis-associated proteins.

• EGFR, FGFR, PI3K, CDK4/6, EpCAM and microenvironment-associated genes: Targeted therapies including EGFR, FGFR, PI3K, or CDK4/6, despite showing preliminary efficacy signals, have not yet received regulatory approval, and PD-L1 expression is the only clinically applicable biomarker for first-line therapy with ICIs. Median TIS of EGFR in squamous cell carcinoma was 12, vs. 4 in healthy mucosa (p<0.001), with neoadjuvant therapy not affecting marker expression, while YY2 upregulation was significantly associated with poor prognosis and elevated levels of M2 macrophages, NK cells, Tregs, CTLA4, TIGIT, and Siglec-15, and AIF1 was negatively associated with prognosis and correlated with TIGIT expression.