exlinkibart (LVGN6051) / Lyvgen - LARVOL DELTA

Study of LVGN3616 and LVGN6051±LVGN7409 in Combination With Nab-Paclitaxel or Bevacizumab and Cyclophosphamide in Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=352 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Esophageal Cancer • Eye Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Uveal Melanoma • CD40

KEYNOTE-A31: Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Keytruda (Pembrolizumab) in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1 | N=276 | Active, not recruiting | Sponsor: Lyvgen Biopharma Holdings Limited | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Dec 2025

Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Oncology

Phase 1 Trial of LVGN7409 (CD40 Agonist Antibody) as Single Agent and Combination Therapies in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1 | N=126 | Active, not recruiting | Sponsor: Lyvgen Biopharma Holdings Limited | Recruiting ➔ Active, not recruiting | Phase classification: P1a/1b ➔ P1 | Trial completion date: Jun 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2024 ➔ Dec 2025

Combination therapy • Enrollment closed • Metastases • Phase classification • Trial completion date • Trial primary completion date • Oncology

A Study of LVGN6051 Combination Therapy in Patient With Head and Neck Squamous Cell Carcinoma (HNSCC) (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: Lyvgen Biopharma Holdings Limited | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Efficacy, safety, and PK/PD of LVGN6051, 4-1BB agonistic antibody, with pembrolizumab in a phase Ib dose expansion in resistant NSCLC, melanoma, and GI malignancy. (ASCO 2024) - P1 | "Targeting 4-1BB and PD-1 with the combination of LVGN6051 and pembrolizumab appears to be well tolerated at this dose and schedule and shows predictable PK/PD parameters. In patients with ICI resistant Melanoma and NSCLC, durable objective responses were achieved with clinical benefits in patients resistant to prior ICI treatment. Further development of LVGN6051 is warranted."

Clinical • P1 data • PK/PD data • Gastrointestinal Cancer • Hematological Disorders • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • PD-1

An open label, phase 1b/2 trial of LVGN6051 (4-1BB agonistic antibody) combined with anlotinib for refractory soft tissue sarcoma (STS). (ASCO 2024) - P1/2 | "LVGN6051 plus anlotinib was well tolerated, and the RP2D is LVGN6051 3 mg/kg plus a standard dose of anlotinib. The combination showed preliminary and encouraging efficacy for refractory STS. As the study is ongoing, additional data will further validate the safety and efficacy of such combination therapy for refractory STS."

Clinical • P1/2 data • Alveolar Soft Tissue Sarcoma • Hematological Disorders • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Thrombocytopenia • Undifferentiated Pleomorphic Sarcoma

A Study of LVGN6051 Combination Therapy in Patient With Head and Neck Squamous Cell Carcinoma (HNSCC) (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: Lyvgen Biopharma Holdings Limited

Combination therapy • Metastases • New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Study of LVGN6051 (CD137 Agonist Antibody) in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Lyvgen Biopharma Holdings Limited | Terminated ➔ Completed

Combination therapy • Metastases • Trial completion • Oncology

Study of LVGN6051 (CD137 Agonist Antibody) in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1 | N=18 | Terminated | Sponsor: Lyvgen Biopharma Holdings Limited | N=50 ➔ 18 | Trial completion date: Jul 2024 ➔ Oct 2023 | Recruiting ➔ Terminated | Trial primary completion date: Apr 2024 ➔ Oct 2023; The study was terminated due to product development strategy adjustment,there were no safety concerns.

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Oncology

Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Keytruda (MK-3475-A31/KEYNOTE-A31) in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1 | N=276 | Recruiting | Sponsor: Lyvgen Biopharma Holdings Limited | Trial completion date: Mar 2024 ➔ Dec 2024 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology

Study of LVGN3616 and LVGN6051±LVGN7409 in Combination With Nab-Paclitaxel or Bevacizumab and Cyclophosphamide in Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=352 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jul 2023 ➔ Feb 2027 | Trial primary completion date: Jul 2023 ➔ Feb 2027

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Uveal Melanoma • CD40

Phase 1 Trial of LVGN7409 (CD40 Agonist Antibody) as Single Agent and Combination Therapies in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1a/1b | N=126 | Recruiting | Sponsor: Lyvgen Biopharma Holdings Limited | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology

First-in-human, phase 1a dose finding of LVGN6051 CD137/4-1BB agonistic antibody with or without pembrolizumab in patients with advanced solid tumors. (ASCO 2023) - P1 | "We established the RP2Ds of LVGN6051 alone and in combination with pembrolizumab in this FIH phase 1a study. These regimens were well tolerated. Preliminary efficacy data showed encouraging anti-tumor activity in heavily pretreated pts who had progressed on ICI."

Clinical • IO biomarker • Metastases • P1 data • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Immune Modulation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Thrombocytopenia • TNFRSF9

Study of LVGN6051 (CD137 Agonist Antibody) in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Lyvgen Biopharma Holdings Limited | Trial completion date: Jul 2023 ➔ Jul 2024 | Trial primary completion date: Apr 2023 ➔ Apr 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology

Early safety and efficacy from a phase I open-label clinical study of LVGN7409 (CD40 agonist antibody) in patients with advanced or metastatic malignancies. (ASCO 2022) - P1a/1b | "An open-label, first in human phase 1 study of LVGN7409 as a single agent, combined with LVGN3616 (anti-PD-1 antibody), and combined with LVGN3616 and LVGN6051 (CD137 agonist antibody) is ongoing. Preliminary evidence showed LVGN7409 monotherapy was well tolerated up to 2mg/kg. Approximately 44% of stable diseases were observed in these heavily treated patients. The favorable safety profile and preliminary antitumor activity warrant further evaluation of LVGN7409 as a single agent and in combination with other cancer therapeutics in patients with advanced malignancies."

Clinical • IO biomarker • P1 data • Immune Modulation • Inflammation • Oncology • CD40

[VIRTUAL] Bifunctional agonist antibody LVGN6051 activates CD137/4-1BB selectively in tumor microenvironment for cancer immunotherapy (AACR-II 2020) - P1 | "In addition, LVGN6051 showed no noticeable activity in inducing cytokine release in tested bloods or PBMCs. These preclinical data demonstrated that LVGN6051 represents a well differentiated 2nd generation CD137 agonist antibody supporting the ongoing clinical study of LVGN6051 in advanced or metastatic malignancies (ClinicalTrials.gov Identifier: NCT04130542)."

Biomarker • Tumor microenvironment • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • CD8

Phase 1 Trial of LVGN7409 (CD40 Agonist Antibody) as Single Agent and Combination Therapies in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1a/1b | N=126 | Recruiting | Sponsor: Lyvgen Biopharma Holdings Limited | Trial completion date: Apr 2023 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology

A Study of LVGN6051 Combined With Anlotinib in Patient With Soft Tissue Sarcoma (clinicaltrials.gov) - P1/2 | N=65 | Recruiting | Sponsor: Lyvgen Biopharma Holdings Limited | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • IFNG • IL12A • IL6 • TMB • TNFA • TNFRSF9

A Study of LVGN6051 Combined With Anlotinib in Patient With Soft Tissue Sarcoma (clinicaltrials.gov) - P1/2 | N=65 | Not yet recruiting | Sponsor: Lyvgen Biopharma Holdings Limited

IO biomarker • New P1/2 trial • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • IFNG • IL12A • IL6 • TMB • TNFA • TNFRSF9

Study of LVGN6051 (CD137 Agonist Antibody) in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Lyvgen Biopharma Holdings Limited; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Oncology

Study of LVGN3616 and LVGN6501±LVGN7409 in Combination With Nab-Paclitaxel or Bevacizumab and Cyclophosphamide in Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=352; Recruiting; Sponsor: M.D. Anderson Cancer Center; Not yet recruiting ➔ Recruiting; Initiation date: Mar 2022 ➔ Nov 2021

Combination therapy • Enrollment open • Trial initiation date • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Uveal Melanoma • CD40

Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Keytruda (MK-3475-A31/KEYNOTE-A31) in Advanced or Metastatic Malignancy (clinicaltrials.gov) - P1; N=276; Recruiting; Sponsor: Lyvgen Biopharma Holdings Limited; Trial completion date: Feb 2022 ➔ Mar 2024; Trial primary completion date: Oct 2021 ➔ Oct 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Oncology

Study of LVGN3616 and LVGN6501±LVGN7409 in Combination With Nab-Paclitaxel or Bevacizumab and Cyclophosphamide in Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=352; Not yet recruiting; Sponsor: M.D. Anderson Cancer Center

Combination therapy • New P1 trial • Esophageal Cancer • Eye Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Uveal Melanoma • CD40

[VIRTUAL] Early safety and efficacy from a phase I open-label clinical trial of CD137(4-1BB) agonistic antibody LVGN6051 as monotherapy and in combination with pembrolizumab. (ASCO 2021) - P1 | "Preliminary evidence showed that LVGN6051 was well tolerated and tumor shrinkages were observed . While we continue assessing its safety profile, antitumor activity was observed in the LVGN6051 and pembrolizumab cohort . The favorable safety profile and preliminary antitumor activity warrant further evaluation in patients with advanced malignancies."

Clinical • Combination therapy • Monotherapy • P1 data • Endocrine Cancer • Fatigue • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Disorders • Hepatocellular Cancer • Hepatology • Melanoma • Neuroendocrine Tumor • Neutropenia • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • TNFRSF9

Lyvgen Biopharma Presents Clinical Trial Data of CD137/4-1BB Agonistic Antibody LVGN6051 at the 2021 ASCO Annual Meeting (Businesswire) - P1, N=276; KEYNOTE-A31 (NCT04130542); Sponsor: Lyvgen Biopharma Holdings Limited; "The trial is evaluating LVGN6051, a second generation 4-1BB (CD137) agonist antibody based on Lyvgen proprietary xLinkAb platform, as monotherapy or in combination with KEYTRUDA® (pembrolizumab), MSD’s anti-PD-1 therapy, in adult patients with advanced malignancies. No MTD was reached at 7 mg/kg monotherapy and 4 mg/kg q3w monotherapy was determined as RP2D. Preliminary antitumor activity in late stage cancer patients was observed. Combination with pembrolizumab induced rapid antitumor responses in advanced cancer patients with immune-cold tumor or relapsed from prior immunotherapies."

P1 data • Oncology