RG6440 / Roche - LARVOL DELTA

Progress made in R&D activities during the period from January 1, 2025 to December 31, 2025 was as follows. (Chugai Press Release) - "We made a management decision to discontinue the in-house development of a RAS inhibitor LUNA18, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-CD137 agonistic switch antibody STA551, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-latent TGF-β1 monoclonal antibody SOF10, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-CLDN6/CD3/CD137 trispecific antibody SAIL66, considering obtained data up to date and the portfolio status."

Discontinued • Gastric Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Thoracic Cancer

Selective blockade of latent TGF-β1 activation suppresses tissue fibrosis with good safety. (PubMed, Commun Med (Lond)) - "Selective blockade of latent TGF-β1 activation represents a promising approach for treating a broad range of fibrotic diseases and cancers. By specifically targeting TGF-β1, SOF10 may offer a safer and more effective therapeutic option compared to non-selective TGF-β inhibitors. This strategy has the potential to transform the treatment paradigm for fibrosis-related conditions."

IO biomarker • Journal • Chronic Kidney Disease • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Oncology • Renal Disease • TGFB1

A Study to Evaluate Safety, Pharmacokinetics, & Activity of RO7496353 in Combination With a Checkpoint Inhibitor With or Without Standard-of-care Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors; Urothelial Carcinoma Substudy in Association With RO7496353 Study GO44010 (clinicaltrials.gov) - P1 | N=102 | Active, not recruiting | Sponsor: Genentech, Inc. | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Checkpoint inhibition • Trial completion date • Trial primary completion date • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Urothelial Cancer

SOF10, a novel selective anti-latent TGF-β1 antibody, augments the efficacy of anti-PD-L1 antibody via modulation of the tumor microenvironment (AACR 2025) - P1 | "Our data suggest that SOF10, a selective anti-latent TGF-β1 antibody, can exert antitumor efficacy in combination with anti-PD-L1 antibody by modulating CAF dynamics and overcomes immune exclusion with preferable safety profile. Clinical studies of SOF10 are currently on-going for patients with solid cancer (NCT05867121)"

Biomarker • Clinical • Tumor microenvironment • Breast Cancer • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CAFs • CD8 • TGFB1

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7496353 in Combination With a Checkpoint Inhibitor With or Without Standard-of-Care Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Combination therapy • Enrollment closed • Metastases • Gastric Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

SOF10, selectively blocking latent TGF-β1 activation, potentiates the efficacy of checkpoint blockade therapy by modulating CAF dynamics and T cell infiltration (SITC 2024) - P1 | "Clinical studies of SOF10 are currently underway for patients with solid cancer (NCT05867121). Ethics Approval All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Chugai Pharmaceutical."

Checkpoint block • Checkpoint inhibition • Clinical • Breast Cancer • Oncology • Solid Tumor • CD8 • TGFB1

Phase I study of SOF10 plus atezolizumab in patients with advanced/recurrent solid tumours (ESMO 2024) - "SOF10 + atezolizumab was well tolerated in pts with advanced solid tumours, with no notable safety concerns. SOF10 showed an increase in exposure with dose and addition of atezolizumab did not appear to affect SOF10 PK. The partial responses were durable."

Clinical • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • TGFB1

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7496353 in Combination With a Checkpoint Inhibitor With or Without Standard-of-Care Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Genentech, Inc. | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Combination therapy • Enrollment open • Metastases • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

The plant-unique protein DRIF1 coordinates with SNX1 to regulate membrane protein homeostasis. (PubMed, Plant Cell) - "These mutants, sof10 and sof641, result in a premature stop codon or a missense mutation in AT5G10370, respectively...DRIF1 is a membrane-associated protein that coordinates with retromer component sorting nexin 1 (SNX1) to regulate PIN-FORMED2 (PIN2) recycling to the plasma membrane. Altogether, our data demonstrate that DRIF1 is a unique retromer interactor that orchestrates FREE1-mediated ILV formation of MVBs and vacuolar sorting of membrane proteins for degradation in plants."

Journal • SNX

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7496353 in Combination With a Checkpoint Inhibitor With or Without Standard-of-Care Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=120 | Not yet recruiting | Sponsor: Genentech, Inc.

Checkpoint inhibition • Combination therapy • Metastases • New P1 trial • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor