Innovent Receives Fast Track Designation from the U.S. FDA for IBI343 (TOPO1i anti-CLDN18.2 ADC) as Monotherapy for Advanced Pancreatic Cancer

Rhea-AI Summary

Innovent Biologics announced that its drug IBI343, designed for advanced pancreatic ductal adenocarcinoma (PDAC), received Fast Track Designation (FTD) from the U.S. FDA. IBI343 is a TOPO1i anti-CLDN18.2 ADC, aimed at patients with relapsed or refractory PDAC after one prior line of therapy. Preliminary Phase 1 results showed a 40% overall response rate (ORR) in a 6 mg/kg dose group among 10 evaluable PDAC patients with specific biomarkers. Pancreatic cancer remains hard to treat, with second-line options and poor survival rates. Innovent plans to further investigate IBI343's efficacy and safety in combination therapies and other solid tumors.

Positive

• IBI343 received Fast Track Designation from the FDA, facilitating its faster clinical development and approval process.
• Preliminary Phase 1 results showed a 40% overall response rate (ORR) for IBI343 in a specific patient group.
• IBI343 is the first CLDN18.2 ADC to receive FTD for advanced pancreatic cancer, indicating its potential in a hard-to-treat disease.
• Innovent plans to explore IBI343 in combination therapies and for other solid tumors, broadening its potential application.

Negative

• sample size in Phase 1 results (only 10 evaluable patients), which may not be representative.
• Current treatment options for advanced pancreatic cancer have very low response rates and short survival periods (3-6 months), indicating a high-risk area.
• The efficacy and safety of IBI343 are still to be confirmed in subsequent clinical trials, indicating uncertainty.

SAN FRANCISCO and SUZHOU, China, June 12, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to its TOPO1i anti-CLDN18.2 ADC (R&D code: IBI343), for the treatment of advanced unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) that has relapsed and/or is refractory to one prior line of therapy. Previously, IBI343 has already received FDA approval of its IND application for the treatment of PDAC.

At the ASCO 2024 Annual Meeting, Innovent reported the preliminary Phase 1 results of IBI343 in advanced PDAC patients who have received at least one prior line of treatment. In the 6 mg/kg dose group, among the 10 evaluable PDAC patients with CLDN18.2 1/2/3+≥60%, the overall response rate (ORR) was 40% (link).

Dr. Hui Zhou, Senior Vice President of Innovent, said, "Pancreatic cancer is highly malignant and difficult to diagnose early. At present, the treatment of advanced pancreatic cancer is still based on systemic chemotherapy. The clinical options for the second-line treatment are particularly limited, with response rate of only 6%-16%, and median survival period of only about 3-6 months. There are urgent clinical needs to be met. As the world's first CLDN18.2 ADC to obtain FTD certification in this difficult-to-treat cancer, IBI343 single-agent therapy shows encouraging efficacy and tolerable safety in the late-line treatment of patients with advanced pancreatic cancer. We will continue to confirm its efficacy and safety in this disease in subsequent clinical trials, and also explore IBI343 in combination therapy and other solid tumors including gastric cancer."

Fast Track Designation (FTD) is a rapid review process designed to facilitate the clinical development of a drug that may treat serious conditions and fulfill an unmet medical need. According to regulations, drug candidates that obtain FTD qualifications will have more opportunities to communicate with the FDA during subsequent drug development and review processes, which will help speed up the clinical development and approval of the drug.

About Pancreatic Ductal Adenocarcinoma

Pancreatic cancer is one of the most malignant tumors of the digestive system, with a 5-year survival rate of about 10% ^[i]. In recent years, the incidence of pancreatic cancer has increased, but the early diagnosis rate is still low, seriously endangering human life and health. At present, the treatment of advanced pancreatic cancer is still based on systemic chemotherapy. Currently, the first-line treatment options mostly use fluorouracil (5-FU) or gemcitabine-based chemotherapy. In the second-line treatment, clinical options are very limited, mainly alternatives to the first-line regimen, and the median survival period is only about 3 to 4 months^{[ii], [iii]}. Claudin, a member of the tight junction molecule family, is a key structural and functional component of epithelial tight junctions. Among them, CLDN18.2 is normally buried in the gastric mucosa, but the development of malignancy leads to disruption of tight junctions and exposure of CLDN18.2 epitopes on the membrane of tumor cells^[iv]. CLDN18.2 is present in 50% to 70% of pancreatic cancer patients, making it a highly scrutinized target^[v].

About IBI343 (Claudin18.2 ADC)

IBI343 is a recombinant human anti-Claudin 18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the Claudin 18.2-expressing tumor cells, which causes the Claudin 18.2-dependent ADC internalization to occur. Following lysosomal processing of the ADC, the active drug (TOP1i) is liberated, which results in DNA damage and eventually apoptosis of the tumor cells. The free drug can also diffuse through the plasma membrane and effectively eliminate neighboring cells, leading to a "bystander killing effect". As an innovative TOPO1i ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in Phase 1 clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric cancer and pancreatic cancer.

In May 2024, The National Medical Products Administration (NMPA) of China granted breakthrough therapy designation (BTD) to IBI343 for use as a single agent in patients with claudin 18.2–positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who experienced disease progression following 2 prior lines of systemic treatment. The multi-center Phase 3 trial of IBI343 for this indication is in preparation.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 4 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

 

References:

[i]  Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7-33. doi: 10.3322/caac.21708.

[ii] Vaccaro V, Sperduti I, Vari S, et al. Metastatic pancreatic cancer: Is there a light at the end of the tunnel?. World J Gastroenterol. 2015;21(16):4788-4801.

[iii] Wang-Gillam A,Li CP,Bodoky G,et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial.Lancet 2016;387:545-557.

[iv] Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008;14(23):7624-7634.

[v] Wu YY, Fan L, Liao XH, et al. Claudin 18.2 is a potential therapeutic target for zolbetuximab in pancreatic ductal adenocarcinoma. World J Gastrointest Oncol. 2022 Jul 15;14(7):1252-1264.

 

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SOURCE Innovent Biologics

FAQ

What is the significance of Innovent's IBI343 receiving Fast Track Designation from the FDA?

The Fast Track Designation (FTD) will expedite the clinical development and review process of IBI343, potentially leading to faster approval.

What are the preliminary results of Innovent’s IBI343 for advanced pancreatic cancer?

Preliminary Phase 1 results showed a 40% overall response rate (ORR) in a 6 mg/kg dose group among 10 evaluable patients with specific biomarkers.

What is the current state of treatment for advanced pancreatic cancer?

Treatment options for advanced pancreatic cancer are , with second-line therapies showing response rates of only 6%-16% and a median survival period of 3-6 months.

What future plans does Innovent have for IBI343?

Innovent plans to confirm the efficacy and safety of IBI343 in further clinical trials and explore its use in combination therapies and other solid tumors.