Akeso, a biopharmaceutical company based in Hong Kong, has recently received clearance for clinical trials in China for a next-generation antibody-drug conjugate (ADC) aimed at the B7-H3 protein. This marks a significant step forward as the company prepares for a Phase I study involving patients with advanced solid tumors.
This new candidate, designated AK157D1, is the third next-generation ADC from Akeso to enter clinical development. It follows the earlier candidates AK146D1, which targets TROP2/Nectin-4, and AK138D1, which focuses on HER3. Akeso plans to explore the use of AK157D1 in combination with its bispecific antibodies, ivonescimab and cadonilimab, as part of its innovative strategy termed “IO2.0 + ADC2.0.”
Targeting B7-H3 in Cancer Therapy
B7-H3 is an immune checkpoint protein present in various solid tumors, such as non-small cell lung cancer, small cell lung cancer, prostate, colorectal, and breast cancers. While its expression in normal tissues is limited, it is significantly elevated on the surface of cancer cells, making it an attractive target for antibody-based therapies. This characteristic makes drug development focused on B7-H3 a promising avenue for delivering treatments directly to tumors.
AK157D1 consists of a humanized IgG1 antibody linked to Dxd, a topoisomerase I inhibitor derived from camptothecin. The innovative design employs a site-specific approach and a proprietary linker, allowing the drug to utilize the B7-H3 protein as a “Trojan horse.” This mechanism effectively bypasses the defenses of the tumor, enabling the delivery of the therapeutic payload directly into the cancer cell.
Promising Preclinical Results
In preclinical evaluations, AK157D1 exhibited notable antitumor activity coupled with what Akeso describes as a favorable safety profile. The company claims that the findings suggest potential solutions to toxicity challenges associated with existing ADCs, specifically addressing issues like hematological toxicities and interstitial lung disease. These claims are now set to undergo rigorous testing in human trials, as Akeso gears up for the Phase I study.
Additionally, Akeso is actively developing a broader portfolio of next-generation ADCs in tandem with its bispecific antibody initiatives. Among its upcoming candidates is AK158D1, a bispecific ADC anticipated to enter clinical development soon.
CStone Advances Bispecific ADC Trials
In a related development, CStone Pharmaceuticals has received approval for an investigational new drug application for CS5007, a bispecific ADC targeting both EGFR and HER3. The approval was granted swiftly, with the review completed in just 23 working days via the innovative drug clinical trial pathway established by the National Medical Products Administration.
CStone began a global Phase I study of CS5007 in Australia in June, where the first patient has already been enrolled. The company aims to initiate parallel trials in China to expedite the development of this candidate across multiple regions.
Mechanism of Action for CS5007
CS5007 is designed to target EGFR and HER3 simultaneously, addressing the co-expression of these receptors in epithelial solid tumors. The development of this candidate aims to counter resistance mechanisms that may arise following EGFR-targeted therapies, particularly those related to HER3-mediated signaling.
The Phase I program will evaluate the safety and tolerability of CS5007, while also investigating its pharmacokinetic and pharmacodynamic properties and early indicators of antitumor activity.
Conclusion
The advancements made by Akeso and CStone in the realm of next-generation ADCs highlight the dynamic landscape of oncology therapeutics in China. As these companies progress toward clinical trials, they may pave the way for more effective treatments that address current challenges in cancer therapy. This progress not only showcases the innovation within the biopharma sector but also reflects a growing commitment to improving patient outcomes in oncology.
- Akeso’s AK157D1 targets B7-H3, showing promise in preclinical trials.
- CStone’s CS5007 aims to address resistance in solid tumors by targeting EGFR and HER3.
- Both companies are pioneering next-generation ADCs to enhance cancer treatment efficacy.
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