Innovent to Present Anti-CLDN18.2 ADC Data at ESMO GI Cancers Congress 2024

SAN FRANCISCO and SUZHOU, China, July 1, 2024 -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), an eminent biopharmaceutical company specializing in developing, manufacturing, and commercializing high-quality medicines for oncology, cardiovascular and metabolic disorders, autoimmune diseases, ophthalmology, and other significant illnesses, unveiled the latest Phase 1 clinical data of their innovative anti-CLDN18.2 ADC (IBI343). This new drug is intended for advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJ AC) and the results were showcased at the ESMO Gastrointestinal Cancers (ESMO GI) Congress 2024 (NCT05458219). The data indicates promising efficacy and a satisfactory safety profile for IBI343 in gastric cancer patients with tumors expressing CLDN18.2.

Gastric cancer remains one of the most frequent and lethal malignancies globally. GLOBOCAN 2022 statistics reveal that it ranks as the 5th most common malignant tumor and the 5th leading cause of cancer death worldwide, accounting for approximately 970,000 cases and 660,000 deaths annually. China alone reports 359,000 new cases and 260,000 deaths each year, representing 37.0% and 39.4% of the global totals, respectively, underscoring a substantial unmet medical need.

The Phase 1 study data presented at the conference, conducted in China and Australia, includes the following key findings for IBI343:

For participants with high CLDN18.2 expression (≥75% tumor cells with membranous staining intensity ≥2+ by IHC) at the 6 mg/kg dose (N=30), the Objective Response Rate (ORR) and Disease Control Rate (DCR) were 36.7% and 93.3%, respectively. At the 8 mg/kg dose (N=17), the ORR was 47.1% and the DCR was 88.2%.

With a median follow-up duration of 7.2 months in the 6 mg/kg dose group, the median progression-free survival (mPFS) of participants with high CLDN18.2 expression reached up to 6.8 months.

Most treatment emergent adverse events (TEAEs) were graded 1-2. In the 6 mg/kg dose group, 31.6% of patients experienced ≥ Grade 3 treatment-related adverse events (TRAEs), with gastrointestinal toxicities of Grade 3 or higher being notably low (<5%). No cases of interstitial lung disease (ILD) were observed.

Dr. Jia (Jenny) Liu, translational lead of early-phase clinical trials at The Kinghorn Cancer Centre, St. Vincent's Hospital Sydney, commented, "IBI343, as a next-generation anti-CLDN18.2 antibody-drug conjugate that is Fc silenced, has shown encouraging tolerability and clinical benefits in patients with advanced gastric and gastroesophageal junction adenocarcinomas with moderate to high CLDN18.2 expression. Notably, the gastrointestinal toxicity observed in this Phase 1 trial appears lower than that seen with other CLDN18.2 targeting drugs, and no cases of interstitial lung disease were reported. We anticipate the results of the ongoing Phase 3 trials comparing IBI343’s efficacy and tolerability with standard-of-care treatments."

Dr. Hui Zhou, Senior Vice President of Innovent Biologics, remarked, "IBI343’s unique ADC platform is designed to deliver effective and more tolerable therapeutics, and the data from gastric cancer trials attest to its molecular design. We aim to explore IBI343 in combination with other treatments, including immunotherapies, across various tumor types to benefit cancer patients globally. Innovent is dedicated to advancing global innovation to develop and commercialize high-quality biopharmaceuticals that are affordable for ordinary people."

Beyond gastric cancer, Innovent is also examining IBI343’s therapeutic potential in solid tumors like pancreatic cancer. Earlier this month, data from the Phase 1 clinical study of IBI343 in treating pancreatic cancer patients were presented at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting, showing encouraging efficacy and a favorable safety profile.

Gastric cancer stands as a prominent malignant tumor worldwide and a leading cause of cancer-related deaths. The 5-year survival rate for patients with metastatic gastric cancer remains below 5%. China and Japan exhibit the highest incidence rates of this cancer. Current standard treatments for advanced metastatic gastric cancer include chemotherapy combinations and immune checkpoint inhibitors, but these have limited efficacy, especially in third-line or higher treatments, leaving patients with poor prognoses and limited options.

Claudin is a crucial component of epithelial tight junctions, and among them, CLDN18.2 is typically buried in the gastric mucosa. However, malignancy disrupts these tight junctions, exposing CLDN18.2 epitopes on tumor cell membranes. CLDN18.2 expression is found in up to 80% of gastric cancer patients.

IBI343, developed by Innovent Biologics, is a recombinant human anti-CLDN18.2 monoclonal antibody-drug conjugate. It binds to CLDN18.2-expressing tumor cells, leading to ADC internalization and drug release, causing DNA damage and apoptosis of tumor cells. The released drug can also affect neighboring cells, resulting in a "bystander killing effect." IBI343 has shown tolerable safety and promising efficacy signals in Phase 1 clinical studies, and its therapeutic potential is being explored for gastric and pancreatic cancers.

In May 2024, China's National Medical Products Administration (NMPA) granted breakthrough therapy designation to IBI343 for treating CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma after two prior lines of systemic treatment. A multi-center Phase 3 trial for this indication is in preparation. In June 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to IBI343 for advanced unresectable or metastatic pancreatic ductal adenocarcinoma that has relapsed or is refractory to one prior line of therapy.

Innovent Biologics, established in 2011, is a leading biopharmaceutical company committed to providing affordable, high-quality biopharmaceuticals globally. Innovent focuses on innovative medicines for cancer, cardiovascular and metabolic disorders, autoimmune diseases, and eye diseases, with multiple products launched and new drug applications under review. The company collaborates with over 30 global healthcare companies to make top-tier pharmaceuticals widely accessible.

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