Bi-XDC makes debut at the 14th World ADC Conference

[San Diego, CA, USA] On October 18, 2023, Dr. Robert Huang, Founder, Chairman, and CEO of Coherent Biopharma, unveiled the latest clinical data on the company’s leading pipeline product, CBP-1008, at the 14th World ADC Conference. These data highlighted the significant advantages of the Bi-XDC technology-based conjugated drug in providing broad clinical benefits across diverse patient populations.

At the 14th World ADC Conference in San Diego, USA, Coherent Biopharma once again showcased its remarkable clinical data. Dr. Robert Huang delivered a keynote speech entitled “Bispecific-XDC: Novel First-in-Class Cancer Therapies from Concept to Clinical” in the “Clinical Lessons”. His presentation emphasized the advantages of Bi-XDC technology, pipeline strategy, and clinical achievements. The promising data on the company’s first product, CBP-1008, demonstrated its significant potential for clinical development.

CBP-1008 is a dual-targeted drug conjugate developed by Coherent Biopharma using its first-generation Bi-XDC technology platform. It targets folate receptor alpha (FRα) and TRPV6 receptor, utilizing MMAE as the payload. FRα is highly expressed in tumor types such as ovarian cancer, breast cancer, and lung cancer, while TRPV6 exhibits high expression in breast cancer, ovarian cancer, and pancreatic cancer.

As of September 25, 2023, a total of 206 patients have been treated with varying doses of CBP-1008, showing favorable efficacy and tolerability in ovarian cancer and breast cancer. In the 0.15 mg/kg dose group, 56 patients with platinum-resistant ovarian cancer (PROC) were evaluated for efficacy, achieving an objective response rate (ORR) of 25% and a disease control rate (DCR) of 66%. These results surpass the outcomes typically observed with conventional treatments for PROC in clinical practice. When considering patients who received CBP-1008 as a third-line treatment, 25 eligible patients with PROC exhibited an ORR of 36%, a DCR of 84%, and a median duration of response (mDOR) of 5.3 months. These efficacy data are comparable to approved ADCs targeting FRα, but CBP-1008 demonstrates the potential to cover the entire patient population without restricting treatment based on FRα expression levels. This provides significant clinical benefits to ovarian cancer patients with low FRα expression. The synergistic effect of the Bi-XDC dual-targeted structure and its excellent tumor penetration enable CBP-1008 to overcome the dependency on target expression levels observed with FRα antibody ADCs, thus addressing the unmet treatment needs for patients with low FRα expression and effectively benefiting a broad patient population.

Moreover, ovarian clear cell carcinoma (OCCC) represents a pathological subtype of epithelial ovarian cancer, accounting for 5%-25% of all ovarian cancers. It is rather resistant to chemotherapy, and the ORR for platinum-resistant OCCC in later lines of treatment is typically below 10%. However, CBP-1008 has demonstrated excellent clinical performance in OCCC patients. As of October 6, 2023, a total of 12 OCCC patients have been enrolled, achieving an ORR of 33.3%, a DCR of 58.3%, and a median duration of response (mDOR) of 7.3 months. Translational medicine research has revealed that OCCC patients exhibit lower levels of FRα expression, yet higher and more widespread expression of TRPV6, which allows the dual-targeted conjugated drug to exhibit potent therapeutic efficacy against refractory tumors. This highlights that the dual-targeted structure of Bi-XDC endows CBP-1008 with the potential for development in multiple indications, covering a broader range of rare tumors and subtypes.

In terms of safety, the majority of adverse events associated with CBP-1008 are classified as low-grade events, such as fever, falling under Grade 1-2 adverse events (AE). These events are predictable and can be effectively managed in clinical practice.

Furthermore, CBP-1018, the world’s first PSMA/FRα dual-targeted ligand drug conjugate, has demonstrated efficacy and a favorable safety profile in patients with advanced prostate cancer. This evidences the broad applicability of the Bi-XDC technology. Detailed data will be presented at the upcoming ESMO conference.

With the successful therapeutic application of DS-8201 in patients with HER2-low-expressing breast cancer, the development of ADC drugs is progressing towards populations with low expression levels. However, the efficacy of FRα antibody ADC drugs still depends on high target expression levels. The introduction of CBP-1008’s existing clinical data at the conference, showcases its therapeutic advantages in populations with low FRα expression, which are not addressed by other ADC products. Additionally, it demonstrates efficacy in rare subtypes such as clear cell carcinoma. CBP-1008 effectively covers the entire population and shows promising potential for clinical development in multiple indications.

Currently, the clinical development of CBP-1008 in various indications of ovarian cancer is progressing rapidly. More data will be revealed at international conferences, so stay tuned for updates!