BOXR1030 / Cogent Biosci, Sotio - LARVOL DELTA

DUET-1: BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors (clinicaltrials.gov) - P1/2 | N=7 | Active, not recruiting | Sponsor: Sotio Biotech Inc. | Trial primary completion date: Oct 2027 ➔ Oct 2025

First-in-human • Trial primary completion date • Breast Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Oncology • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • ALK • BRCA • EGFR • GPC3

DUET-1: BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors (clinicaltrials.gov) - P1/2 | N=7 | Active, not recruiting | Sponsor: Sotio Biotech Inc. | Recruiting ➔ Active, not recruiting | N=110 ➔ 7

Enrollment change • Enrollment closed • Breast Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Oncology • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • ALK • BRCA • EGFR • GPC3

DUET-1: BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors (clinicaltrials.gov) - P1/2 | N=110 | Recruiting | Sponsor: Sotio Biotech Inc. | Trial completion date: Dec 2041 ➔ Dec 2042 | Trial primary completion date: Apr 2026 ➔ Oct 2027

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Oncology • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • ALK • BRCA • EGFR • GPC3

DUET-01: A first-in-human, phase 1/2 study of BOXR1030 in patients with advanced glypican-3-positive solid tumors. (ASCO 2024) - P1/2 | "Eligible subjects will undergo leukapheresis to obtain T cells for BOXR1030 manufacturing and will receive 3 days of lymphodepleting chemotherapy with fludarabine and cyclophosphamide within 5 days prior to BOXR1030 administration. Key secondary endpoints include efficacy parameters such as objective response rate, BOXR1030 T-cell expansion and persistence, and levels of inflammatory markers and cytokines. The first patient was treated with BOXR1030 in December 2022."

Clinical • Metastases • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • GPC3

SOTIO Presents Overview of DUET-01 Phase 1/2 Study at ASCO Annual Meeting (Businesswire) - "SOTIO Biotech...will present on June 1, 2024 (Developmental Therapeutics—Immunotherapy session) a Trial-in-Progress poster on the first-in-human DUET-01 Phase 1/2 study at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The study is evaluating the use of BOXR1030, a metabolically enhanced CAR T-cell therapy, for the treatment of patients with solid tumors....Patient enrollment and dosing in the DUET-01 clinical trial...are ongoing at three leading cancer care centers across the U.S., with additional sites expected to be imminently initiated in the U.K....The trial will enroll up to 98 patients with advanced, unresectable hepatocellular carcinoma, squamous cell lung cancer, myxoid/round cell liposarcoma, and Merkel cell carcinoma."

Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Oncology • Solid Tumor

SOTIO to Present Poster on DUET-01 Clinical Trial at 2024 ASCO Annual Meeting (Businesswire) - "SOTIO Biotech...today announced it will present a Trial-in-Progress poster on the DUET-01 Phase 1/2 study of BOXR1030 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 31 – June 4, 2024, in Chicago, IL....The trial will enroll up to 98 patients with advanced, unresectable hepatocellular carcinoma, squamous cell lung cancer, myxoid/round cell liposarcoma, and Merkel cell carcinoma."

Trial status • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Oncology • Solid Tumor

BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors (clinicaltrials.gov) - P1/2 | N=110 | Recruiting | Sponsor: Sotio Biotech Inc. | Trial completion date: Jul 2039 ➔ Dec 2041 | Trial primary completion date: Jul 2024 ➔ Apr 2026

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Oncology • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • ALK • BRCA • EGFR • GPC3

Exogenous GOT2 in CAR-T cells improves metabolic function and preserves early memory T cell subsets (SITC 2022) - P1/2 | "These data suggest potentially increased fitness of BOXR1030 T cells enabling enhanced in vivo T cell persistence and antitumor activity. BOXR1030 is currently in Phase 1 trials to assess safety and preliminary efficacy ( NCT05120271 )."

CAR T-Cell Therapy • Oncology • Solid Tumor • CCR7 • CD27 • CD8 • FAS • GZMB

SOTIO Presents Preclinical Data from BOXR CAR-T Program and Trial Design of Phase 2 AURELIO-04 Study at SITC Annual Meeting - "SOTIO Biotech...presented preclinical data evaluating the mechanism of action and metabolic function of its BOXR T cell platform in a poster presentation at the...(SITC) 37th Annual Meeting...An analysis of the BOXR1030 T cell data show that the BOXR CAR-T cells co-expressing the metabolic gene GOT2 have a higher frequency of less differentiated stem cell memory T cell (TSCM) populations and more CD27+ cells in all memory T cell subsets, suggesting fewer terminally differentiated cells compared to control CAR-T cells lacking the GOT2 transgene. When BOXR1030 T cells were exposed to stressful conditions characteristic of difficult-to-penetrate tumor microenvironments such as low glucose and chronic stimulation, the cells exhibited improved metabolic fitness, increased cell survival and proliferative capacity, multiple characteristics of less differentiated or early memory T cell populations, and retention of effector functions relative to control CAR-T cells."

Preclinical • Oncology

BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors (clinicaltrials.gov) - P1/2 | N=98 | Recruiting | Sponsor: SOTIO, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • ALK • BRCA • EGFR • GPC3

BOXR1030, an anti-GPC3 CAR with exogenous GOT2 expression, shows enhanced T cell metabolism and improved anti-cell line derived tumor xenograft activity. (PubMed, PLoS One) - P1/2 | "Together, these results demonstrated that co-expression of GOT2 can substantially improve the overall antitumor activity of CAR T cells by inducing broad changes in cellular function and phenotype. These data show that BOXR1030 is an attractive approach to targeting select solid tumors. To this end, BOXR1030 will be explored in the clinic to assess safety, dose-finding, and preliminary efficacy (NCT05120271)."

IO biomarker • Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • GPC3

BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors (clinicaltrials.gov) - P1/2 | N=98 | Not yet recruiting | Sponsor: SOTIO, LLC | Initiation date: Jan 2022 ➔ Apr 2022

Trial initiation date • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • ALK • BRCA • EGFR • GPC3

SOTIO Announces Oral and Multiple Poster Presentations on Key Clinical Programs at the American Association of Cancer Research Annual Meeting (AACR) 2022 (GlobeNewswire) - "SOTIO Biotech...announced today that it will deliver an oral presentation featuring interim safety and efficacy data from its Phase 1/1b AURELIO-03 study with its IL-15 superagonist, SOT101, in combination with pembrolizumab, as well as two poster presentations at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2022, taking place in New Orleans, Louisiana, April 8-13, 2022....Poster presentations will focus on preclinical results obtained with SOTIO’s clinical stage, GPC-3 targeting, CAR-T cell therapy candidate, BOXR1030 and lead immunocytokine candidate, SOT201."

P1 data • Preclinical • Oncology • Solid Tumor

SOTIO Secures €280m of Funding to Expand and Advance Clinical Pipeline (GlobeNewswire) - "The funding will be used to advance SOT101 through two multi-indication phase 2 clinical trials: The phase 2 AURELIO-03 study tests SOT101 as monotherapy in patients with melanoma, squamous skin carcinoma and kidney cancer, and a planned phase 2 AURELIO-04 study will evaluate the combination of SOT101 with a checkpoint inhibitor...This funding will also be used to advance three novel programs through phase 1: BOXR1030 is the company’s lead CAR-T program for the treatment of various solid tumors expressing GPC3...The study is scheduled to start early 2022; SOT102...A phase 1 dose escalation in patients with gastric and pancreatic cancer shall start in March 2022; SOTIO plans to initiate a phase 1 study with our first IL-15 based immunocytokine using a PD-1 inhibitor as the targeting arm by the end of 2022."

Commercial • New P1 trial • New P2 trial • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Kidney Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Skin Cancer • Squamous Cell Skin Cancer

BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors (clinicaltrials.gov) - P1/2; N=98; Not yet recruiting; Sponsor: SOTIO, LLC

Clinical • New P1/2 trial • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • ALK • BRCA • EGFR • GPC3

SOTIO Acquires Rights to BOXR CAR-T Platform and Products from Unum Therapeutics (GlobeNewswire) - "SOTIO…announced that it has acquired the rights to Unum Therapeutics’…BOXR cell therapy platform and BOXR lead programs to develop novel T cell therapies for the treatment of solid tumors. The proprietary Bolt-on Chimeric Receptor technology incorporates novel transgenes to enhance T cell function in the solid tumor microenvironment…SOTIO aims to develop multiple enhanced Chimeric Antigen Receptor (CAR)-T cell therapies for the treatment of solid tumors based on the BOXR technology. The lead program, BOXR1030 for the treatment of hepatocellular carcinoma and other solid tumors, is expected to initiate first clinical studies in 2021….Under the terms of the agreement, SOTIO will make an upfront payment of $8.1 million for the BOXR technology and success dependent future milestone payments up to $3.4 million."

M&A • New trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

[VIRTUAL] BOXR1030: A first-in-class CAR T-cell therapy co-expressing GOT2 enhances T-cell metabolic function for the treatment of GPC3-positive solid tumors (AACR-II 2020) - "BOXR1030 has potential application in GPC3-positive solid tumor indications with significant unmet medical need. IND-enabling studies are currently in progress to support a future first-in-human trial in subjects with GPC3-positive tumors."

CAR T-Cell Therapy • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • GPC3

Unum Therapeutics reports first quarter financial results and provides corporate updates (GlobeNewswire, Unum Therapeutics Inc.) - "Unum has initiated formal preclinical development activities, including preclinical safety testing and cGMP manufacturing readiness activities, to support filing an investigational new drug (IND) application for BOXR1030 in late 2020."

IND • Oncology • Solid Tumor

Unum Therapeutics reports fourth quarter and full year 2019 financial results and provides corporate updates (GlobeNewswire, Unum Therapeutics Inc.) - “Announced plans to prioritize resources towards advancing its preclinical program, BOXR1030, for the treatment of solid tumor cancers: Unum has initiated formal preclinical development activities, including preclinical safety testing and GMP process development, to support filing an IND application for BOXR1030 in late 2020.”

Preclinical

"#UnumTherapeutics Implements Strategic Restructuring to Prioritize Efforts on #BOXR1030 for the Treatment of #SolidTumor #Cancers $UMRX https://t.co/6oaKYyOh4S" (@1stOncology)

Unum Therapeutics implements strategic restructuring to prioritize efforts on BOXR1030 for the treatment of solid tumor cancers (GlobeNewswire) - "Unum has initiated formal preclinical development activities, including preclinical safety testing and GMP process development, to support filing an IND application for BOXR1030 in late 2020....As part of this effort, and to conserve resources for BOXR1030, Unum is concluding its ACTR707 clinical trials, including the Phase 1 trial (ATTCK-20-03) in combination with rituximab in relapsed/refractory non-Hodgkin lymphoma and the Phase 1 trial (ATTCK-34-01) in combination with trastuzumab to treat advanced HER2+ solid tumor cancers."

IND • Preclinical • Trial status