uliledlimab (TJD5) / I-Mab, Tracon Pharma, PT Kalbe Farma - LARVOL DELTA

A Study to Compare Uliledlimab Combined With Toripalimab, Toripalimab Monotherapy, and Pembrolizumab Monotherapy in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1- and CD73- Selected Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2/3 | N=450 | Recruiting | Sponsor: TJ Biopharma Co., Ltd.

Monotherapy • New P2/3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • PD-L1

A Phase I/II Study of TJ004309 for Advanced Solid Tumor (clinicaltrials.gov) - P1/2 | N=376 | Active, not recruiting | Sponsor: TJ Biopharma Co., Ltd. | Trial completion date: Apr 2025 ➔ Dec 2025 | Trial primary completion date: Apr 2025 ➔ Dec 2025

IO biomarker • Trial completion date • Trial primary completion date • Solid Tumor

I-Mab Reports First Quarter 2025 Financial Results and Provides Business Update (I-Mab Biopharma) - "Presentation of new givastomig dose escalation combination data on U.S. patients at the European Society of Medical Oncology ('ESMO') Gastrointestinal ('GI') Cancers Congress 2025, being held July 2-5 in Barcelona, Spain; 1H 2026: Presentation of data from givastomig dose expansion cohorts (n=40); Enrollment in the ongoing dose expansion study for givastomig is progressing ahead of schedule. In addition, the Company anticipates updates in 2026 for two programs being developed with its partners: uliledlimab (monoclonal antibody targeting CD73); and ragistomig (PD-L1 x 4-1BB bispecific)...As of March 31, 2025, the Company had cash and cash equivalents, and short-term investments of $168.6 million. The Company’s current cash position is expected to fund the givastomig Phase 1b study through anticipated dose expansion data readouts and further development initiatives into 2027."

Clinical • Commercial • Enrollment status • P1 data • Gastroesophageal Cancer

ROLE AND MECHANISM OF ADENOSINERGIC AXIS INVOLVED IN THE FORMATION OF MYELOSUPPRESSIVE IMMUNE MICROENVIRONMENT IN MDS PATIENTS (EHA 2025) - "Blockade of all targets of the adenosinergic axis restored the bone marrow immune microenvironment of MDS patients to varying degrees, and blockade of A2aR had the most significant effect."

Clinical • Acute Myelogenous Leukemia • Aplastic Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD34 • CD73 • ENTPD1

A Phase I/II Study of TJ004309 for Advanced Solid Tumor (clinicaltrials.gov) - P1/2 | N=376 | Active, not recruiting | Sponsor: TJ Biopharma Co., Ltd. | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

IO biomarker • Trial completion date • Trial primary completion date • Solid Tumor

I-Mab Announces Portfolio Prioritization of Givastomig (CLDN18.2 x 4-1BB Bispecific Antibody) as Lead Clinical Program (PRNewswire) - "The development of uliledlimab is being paused to allow the Company to focus resources toward advancing its lead clinical program, givastomig, and to allow data to mature from an ongoing China-only randomized study conducted by its partner TJ Biopharma evaluating uliledlimab in combination with a CPI (toripalimab) in CD73-high NSCLC patients. As a result, further clinical investment in uliledlimab will be put on hold....Ragistomig: ABL Bio is continuing the Phase 1b study to increase the therapeutic index by altering the dosing level and/or frequency, and to identify the appropriate tumor types for further development....The Company has completed enrollment of a dose escalation study of givastomig in combination with nivolumab plus chemotherapy, and data is expected in the early second half of 2025; a 40-patient dose expansion study is now underway with data expected in early 2026."

Discontinued • P1 data • Pipeline update • Esophageal Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Solid Tumor

I-Mab Reports Third Quarter 2024 Results (PRNewswire) - "Pipeline Overview and Potential Upcoming Milestones:...(i) The Company is on track to dose the first patient in the randomized Phase 2 study in patients with first-line mNSCLC testing multiple doses of uliledlimab in combination with pembrolizumab plus chemotherapy versus standard of care in 1H 2025...; (ii) Topline data from the on-going Phase 1b study evaluating givastomig in combination with nivolumab plus chemotherapy are expected in 2H 2025 in patients with treatment-naïve CLDN 18.2-positive metastatic gastric cancer."

New P2 trial • P1 data • Gastric Cancer • Non Small Cell Lung Cancer

I-Mab and Sanofi Enter into Strategic Collaboration for Uliledlimab [Google translation] (Sina Corp) - "...On September 25, Tianjin Jiancheng Biopharma announced that it has reached a strategic cooperation with Sanofi on the development, production and commercialization of the company's independently developed innovative CD73 antibody uliledlimab in China...Under the terms of the agreement, Sanofi will pay Tianjin Jianke Biopharma approximately 32 million euros (approximately 250 million yuan) in down payments and near-term milestone payments, as well as subsequent milestone payments; the potential total amount will not exceed 213 million euros (approximately 1.7 billion yuan). Tianjin Jianke Biopharma will also receive tiered royalties based on sales and additional milestone payments for new indications....In addition, Sanofi will obtain exclusive rights to develop, produce and commercialize uliledlimab in China."

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Integrated PK/PD Modeling for Uliledlimab, an Anti-CD73 Monoclonal Antibody, In Non-Small Cell Lung Cancer Patients (IASLC-WCLC 2024) - "PK data from three previous clinical studies with uliledlimab monotherapy or in combination with atezolizumab or toripalimab were used to construct the popPK model. The K-M analysis indicated that the uliledlimab C trough threshold of 80 μg/mL may be associated with PFS benefit and is likely clinically meaningful. The non-traditional integrated PK/PD coupled with modeling & simulation and exposure-response analyses and findings support and inform further uliledlimab development in NSCLC patients."

Clinical • IO biomarker • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD73

I-Mab Presents Positive Uliledlimab Pharmacokinetics Data at 2024 World Conference on Lung Cancer (PRNewswire) - "Randomized Phase 2 study of uliledlimab in combination with pembrolizumab plus chemotherapy expected to begin in 1H 2025...I-Mab...announced a poster presentation of PK/PD modeling data for uliledlimab at the International Association for the Study of Lung Disease (IASLD)'s 2024 World Conference on Lung Cancer (WCLC 2024) held September 7-10, 2024 in San Diego, CA....Most of the simulated population (95%) could achieve the target threshold with 30 mg/kg of uliledlimab; Integrated PK/PD modeling and pharmacometrics analyses indicate there is a positive relationship between the probability of overall response and uliledlimab trough concentration in NSCLC patients; CD73 receptor occupancy (RO) in peripheral B cells achieved 90% or above and maintained at high levels until the end of treatment."

New P2 trial • PK/PD data • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

I-Mab Reports 1H 2024 Financial Results, Pipeline Progress, and Business Updates (PRNewswire) - "Uliledlimab is also being evaluated in an ongoing, randomized Phase 2 study conducted by I-Mab's collaborator, TJ Biopharma, comparing uliledlimab plus toripalimab to pembrolizumab alone and toripalimab alone. The primary endpoint is progression free survival ('PFS'), and data are expected in the 2H 2025; I-Mab has received IND clearance to proceed with a randomized Phase 2 study testing multiple doses of uliledlimab plus pembrolizumab/chemotherapy vs. pembrolizumab/chemotherapy alone. Patient enrollment is expected to begin in the 1H 2025; R&D costs for the six months ended June 30, 2024 were $1.8 million higher than the comparable period in 2023, driven by higher clinical trial costs associated with the preparation of enrollment for the uliledlimab Phase 2 combination study and ongoing givastomig Phase 1b dose expansion study."

Commercial • IND • New P2 trial • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

I-Mab’s management team undergoes another major reshuffle: only three innovative pipelines remain, and the shadow of CD47 target failure remains [Google translation] (Sina Corp) - "After announcing the divestment of its assets in China, the official website of listed company I-Mab currently only has three innovative pipelines left, namely uliledlimab (CD73 antibody), givastomig (Claudin 18.2 x 4-1BB bispecific antibody) and ragistomig (PD-L1 x 4-1BB bispecific antibody)....I-Mab said it will launch a Phase III clinical trial of uliledlimab combined with chemotherapy and immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) in the second half of 2024."

New P3 trial • Pipeline update • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Phase I/II Study of TJ004309 for Advanced Solid Tumor (clinicaltrials.gov) - P1/2 | N=376 | Active, not recruiting | Sponsor: TJ Biopharma Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Metastases • Oncology • Solid Tumor

I-Mab Reports Full Year 2023 Financial Results and Business Update (PRNewswire) - "Pipeline Overview and Upcoming Milestones:...(i) Upon the receipt of the investigational new drug (IND) approval, the Company plans to initiate the triplet study for uliledlimab in combination with chemotherapy and checkpoint inhibitors in newly diagnosed patients with advanced NSCLC in the second half of 2024; (ii) Ragistomig (PD-L1 x 4-1BB bispecific antibody):...Top-line Phase 1 dose escalation and dose expansion results are expected to be presented at a major medical conference in the first half of 2024."

New trial • P1 data • Non Small Cell Lung Cancer

I-Mab's CD73 monoclonal antibody launches phase 2/3 clinical trial for first-line treatment of non-small cell lung cancer! [Google translation] (163.com) - "The official website of the China Drug Clinical Trial Registration and Information Disclosure Platform announced that I-Mab has launched a Phase 2/3 clinical study of TJ004309 injection for the first-line treatment of advanced non-small cell lung cancer....I-Mab is launching phase 2/3 trial, multicentre, open-label study targeting patients with previously untreated locally advanced, unresectable or metastatic PD-L1 and CD73-selective non- small cell lung cancer patients. The primary purpose of the phase 2 study is to evaluate the effectiveness of uliledlimab in combination with the anti-PD-1 monoclonal antibody toripalimab in prolonging progression free survival (PFS) compared with pembrolizumab monotherapy. Benefit; the main purpose of the phase 3 study is to confirm the superiority of uliledlimab combined with toripalimab in prolonging PFS compared with pembrolizumab treatment."

New P2/3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

I-Mab Signs Agreement to Divest its Assets and Business Operations in China (PRNewswire) - "I-Mab...announced that as part of its strategy to become a U.S.-based biotech, its Chinese subsidiaries have entered into definitive agreements with I-Mab Biopharma (Hangzhou) Co., Ltd. (the 'Hangzhou Company'), an unconsolidated affiliate of the Company, and a group of China-based investors to divest the Company's assets and business operations in China....Once the transaction is completed, the Hangzhou Company will acquire I-Mab drug assets in China, including the Greater China rights for...uliledlimab, givastomig, and lemzoparlimab; bear all future development costs of these assets; and be responsible for the operations of the research & development (R&D) center of I-Mab Shanghai and the manufacturing facility of the Hangzhou Company."

Licensing / partnership • Oncology

A Clinical Study of TJ004309 With Atezolizumab (TECENTRIQ®) in Patients With Ovarian Cancer and Selected Solid Tumors (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: I-Mab Biopharma US Limited | Active, not recruiting ➔ Completed | Trial completion date: Jun 2023 ➔ Feb 2023 | Trial primary completion date: Jun 2023 ➔ Feb 2023

Combination therapy • Metastases • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Head and Neck Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PD-L1 • PGR

I-Mab Provides Mid-Year 2023 Financial Results, Business and Corporate Updates (PRNewswire) - "In the US, I-Mab plans to submit an IND for uliledlimab in combination with chemotherapy and checkpoint inhibitors in newly diagnosed patients with advanced NSCLC in H1 2024."

IND • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Uliledlimab and toripalimab combination therapy in treatment naive advanced NSCLC: Phase 1b/2 clinical trial results using CD73 as a potential predictive biomarker. (ASCO 2023) - P1/2 | "Uliledlimab and toripalimab combination therapy was well-tolerated in treatment naïve advanced NSCLC pts. Clinical response of the therapy seems to correlate with high tumor CD73 expression, indicating a potential value of CD73 as a predictive biomarker. The study warrants a biomarker-guided randomized clinical trial that is currently in preparation."

Biomarker • Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • NT5E

I-Mab Announces Encouraging Phase 1b/2 Study Results of Patients with Advanced NSCLC Receiving Uliledlimab and Toripalimab Combination Therapy at ASCO 2023 (PRNewswire) - P1b/2 | N=376 | NCT04322006 | Sponsor: I-Mab Biopharma Co. Ltd | "I-Mab...announced encouraging results from the Phase 1b/2 study...evaluating uliledlimab...in combination with toripalimab (TUOYI®), a PD-1 antibody, in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC), and exploring the potential value of CD73 expression as a predictive biomarker. The results will be reported in a poster presentation on June 3 at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting....As of April 14, 2023, a total of 70 patients were enrolled in the study. Uliledlimab demonstrated a favorable safety profile up to 30mg/kg Q3W in combination with toripalimab with most treatment-related adverse events (TRAEs) being Grade 1 or Grade 2 in severity. In the efficacy evaluable population (n=67), the objective response rate (ORR) was 31.3% regardless of PD-L1 and CD73 expression."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

I-Mab Announces Encouraging Phase 1b/2 Study Results of Patients with Advanced NSCLC Receiving Uliledlimab and Toripalimab Combination Therapy at ASCO 2023 (I-Mab Biopharma) - "'The new results are compelling for uliledlimab as a new treatment for NSCLC and its potential to make a meaningful impact on patients' lives. We're particularly excited by the strong correlation between high CD73 expression and clinical response. With this finding, we are in a unique position to apply CD73 as a predictive biomarker to raise the probability of treatment success for NSCLC,' said Dr. Andrew Zhu...'Building on encouraging results from this study, we intend to commence a biomarker-guided pivotal trial with the aim of providing these promising new treatment options to patients as quickly as we can.'"

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I-Mab (NASDAQ:IMAB) Q4 2022 Earnings Call Transcript (Insider Monkey) - "Andrew Zhu...I want to take this opportunity to discuss our key business update and major progress in core asset development for the year ended December 31st, 2022. Since the start of 2022, the company faced multiple challenges, including, but not limited to geopolitical issues such as ADR delisting risks, macroeconomic factors, including interest rate hikes and COVID-19 pandemic. In response to these challenges, the company made several strategic efforts to reposition the overall business and prioritize its pipeline. These measures resulted in a streamlined corporate structure and workforce as well as focused development of five key assets, leading to a significant reduction in the cash burn rate in 2022 and beyond."

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I-Mab Announces Positive Outcome in Arbitration Relating to Agreements with Tracon (PRNewswire) - "'This is an important victory for I-Mab and its shareholders on multiple levels, both from a legal and business standpoint, as I-Mab successfully protected and preserved its shareholder's value and I-Mab's rights of its proprietary CD73 antibody, uliledlimab, and bi-specific antibody assets,' said Dr. Andrew Zhu, President and Acting CEO of I-Mab."

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I-Mab Announces Poster Presentation of Proprietary CD73 Antibody Uliledlimab at ASCO 2023 (PRNewswire) - "I-Mab...today announced that a poster featuring the latest clinical data of uliledlimab, the Company's proprietary and highly differentiated CD73 antibody, in combination with PD-1 therapy in non-small-cell lung cancer (NSCLC), will be presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place June 2-6 in Chicago, Illinois."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

I-Mab Provides Business and Corporate Updates and Reports Financial Results for the Year Ended December 31, 2022 (PRNewswire) - "'Going into 2023, we are now in a strong position to deliver on our innovative pipeline and corporate milestones, as well as to make expected progress in global partnerships and commercial partnerships given that business development remains a key strategic priority of the Company. We will stay laser-focused on creating value for our shareholders while extending the cash runway to support key business operations in the coming years,' Dr. Zhu concluded."

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