2025-04-29-Jefferies-AACR_25观点IDYA（与管理层沟通情况）_ORIC_ERAS_ELVN_TNGX和PYXS_11页_489kb

报告摘要

Biotech Equity Research Summary: Jefferies April 28, 2025

IDYA/GSK vs Roche on WRN Inhibitors for MSI-H Cancers

AACR'25 Highlights: Roche presented dose escalation data for oral WRN inhibitor RO7589831, showing ~14% ORR in dMMR/MSI-H solid tumors (80% ORR in endometrial/ovarian). IDYA/GSK's oral WRN inhibitor (IDE275/GSK959) is 65-380x more potent than Roche's drug and binds to a different conformation; it demonstrates broader efficacy against resistance mutations and cleaner safety (no GI issues).
Mechanism & Potency: IDYA/GSK drug binds to the D1-D2 helicase domain without C727 (common resistance site); potent, cell-line inducing strong DNA damage; vs Roche: lower binding affinity, higher C727-targeting. Safety clean, tolerability slightly worse at higher doses.
Durability: Data suggests responses may lack durability; potential to add further biomarkers (MLH1, (TA)n repeats) for better prediction.

Key Companies Mentioned

IDYA/GSK

Key Message: Differentiated WRN inhibitor candidate, >65x more potent than Roche; could bypass mechanism & resistance issues. Maintains strong activity in F730S/L, S709P (mutations increasing in MSI-H tumors).

Roche

Program: Optimizing oral WRN inhibitor (RO7589831) dose with dose escalation data showing modest 14% ORR (4 PR, 1 uPR) in 35 pts; >80% ORR in endometrial/ovarian (3 cPR, 1 uPR). Clean safety profile (no heme-related toxicities). RP2D determination in progress.

ORIC (Prostate, EGFR/HER2)

Program: '944 (PRC2i) combo with DaroTeno (APSL); dose escalation data expected H1 25. Data showed enhanced survival in xenografts vs each agent alone.
EGFR/HER2 '114 NSCLC: Preclin only update; competitive data (Roche's zongertinib) discussed, ORIC plans 2H25 comprehensive update from 4 cohorts.

ELVN

Program: Partner with Roche for drug synergy in CML (Scemblix combo). '001 (TKI for CML/HER2) aiming to treat resistance mutations; FRM synergistic effects in xenograft models. CML Phase I data mid '25 (EHA). '002 (HER2 TKI) to potentially enhance ADC efficiency.

TNGX

Program: Preclin data on PRMT5 inhibitor (GSK232655 HX) boosting efficacy with various targeted agents (e.g., partnership with Roche's KRAS inh, via co supply agreement). Phase I recruitment for GBM focus.

PYXS

Program: Preclin data on MICVO '201 (TSA ADC); combo with Pembro in syngeneic mouse model; R/M HNSCC clinical data 2/3L platinum starting 2H25; 1/2L+ combo PEM data planned 2H25.

Analyst Notes & Disclaimers (Key Points):

Analyst Certifications: Multi-signature, statement of independence.
Investment Recommendations: Various "Buy", "Hold", "Underperform", etc., referenced for key companies.
Conflicts & Disclosures: Jefferies institutional interest in multiple companies discussed programs mentioned.

* Clinical trial data presented at AACR'25, focusing on IDYA/GSK, Roche, ORIC, ELVN, TNGX, PYXS.
* Company summaries include Phase I status, synergy with partners, and potential data readouts.

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