CDH6: Can It Support the Next $10.1 Billion Valuation?

The pharmaceutical industry is constantly seeking better treatment options for platinum-resistant ovarian cancer. In a recent announcement, AbbVie acquired ADC company ImmunoGen for nearly $10.1 billion, primarily to gain access to the FRαADC pipeline and its novel drug, Elahere. Elahere, developed by ImmunoGen, is an antibody-drug conjugate (ADC) targeting the FR-α receptor for the treatment of platinum-resistant ovarian cancer. The drug received accelerated approval from the FDA in November 2022 for FRa-positive platinum-resistant ovarian cancer, and subsequent clinical trials demonstrated significant benefits in terms of overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). This acquisition highlights the high demand for improved therapies in the field of platinum-resistant ovarian cancer.

The Need for Better Treatment Options:

Ovarian cancer has seen limited advancements in treatment options. While poly (ADP-ribose) polymerase inhibitors (PARPi) have shown efficacy in maintaining HRD or BRCA-mutated ovarian cancer, they have not yielded satisfactory results in platinum-resistant cases. The current standard of care for advanced ovarian cancer remains the combination of platinum-based chemotherapy and taxanes. It is evident that there is a significant unmet need for better treatment options in platinum-resistant ovarian cancer.

MSD's Acquisition and CDH6:

In October 2023, MSD made a significant acquisition, investing a total of $22 billion to obtain three assets: U3 (HER-3ADC), DS-7300 (B7H3ADC), and DS-6000 (CDH6ADC). While the HER-3ADC pipeline garnered the most attention, the CDH6ADC pipeline holds promise for the treatment of platinum-resistant ovarian cancer. DS-6000, also known as raludotatugderuxtecan, is an ADC developed by Daiichi Sankyo, targeting CDH6. It utilizes a humanized anti-CDH6 IgG1 monoclonal antibody with a GGFG cleavable linker and a Dxd payload, achieving a drug-antibody ratio (DAR) of 8. DS-6000 is being investigated for the treatment of renal cell carcinoma and ovarian cancer in phase I clinical trials in the United States and Japan.

Encouraging Results and Clinical Trials:

DS-6000's potential for ovarian cancer stems from promising phase I study results. The ongoing study, conducted across multiple centers in Japan and the United States, aims to evaluate the efficacy and safety of DS-6000 in patients with renal cell carcinoma and ovarian cancer. The study consists of two parts: Part A focuses on safety, maximum tolerated dose (MTD), and dose expansion, while Part B assesses the safety, tolerability, and efficacy of DS-6000. Key endpoints include dose-limiting toxicities (DLTs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), and adverse events of special interest (AESIs). Secondary endpoints include pharmacokinetics/pharmacodynamics (PK/PD), overall response rate (ORR), duration of response (DoR), and median progression-free survival (mPFS).

Preliminary results from the study showed promising outcomes. Among the 22 evaluable patients (7 with renal cell carcinoma and 15 with ovarian cancer), the majority being platinum-resistant ovarian cancer patients, DS-6000 demonstrated acceptable safety and tolerability profiles. Adverse events were mainly fatigue, nausea, and vomiting. Encouragingly, two patients achieved partial responses, and nine patients experienced disease stabilization. In addition, CA-125 responses were observed in patients with platinum-resistant ovarian cancer, indicating potential efficacy in this difficult-to-treat population.

The acquisition of ImmunoGen by AbbVie and MSD's investment in the CDH6ADC pipeline indicate the growing interest in finding effective treatments for platinum-resistant ovarian cancer. DS-6000, with its promising early-stage results, offers hope for patients in need of better therapeutic options. As clinical trials progress, further evaluation will determine its efficacy and safety profile. If successful, CDH6ADC could potentially support a valuation of $10.1 billion, contributing to the ongoing transformation of ovarian cancer treatment.