Cytovation to present full CICILIA trial data on CY-101 in solid tumors at ESMO 2024

Cytovation ASA, an oncology-focused clinical-stage company, has announced the presentation of data from its Phase I/IIa CICILIA trial at ESMO 2024. The study evaluates the safety and efficacy of CY-101 (CyPep-1), a bifunctional immunotherapy, in patients with advanced solid tumors. CY-101, administered intratumorally alone and in combination with MSD's anti-PD-1 therapy KEYTRUDA® (pembrolizumab), has shown promise in heavily pretreated patients. The recommended Phase 2 dose (RP2D) is set at 20 mg, with impressive early signs of antitumor activity, particularly in tumors exhibiting dysregulated Wnt/β-catenin signaling.

CY-101 is a synthetic peptide functioning through a dual mechanism. It inhibits the Wnt/β-catenin oncogenic pathway by activating Axin2, and it also induces a pore-forming membranolytic effect on cancer cells. This dual action exposes cancer cell antigens, prompting a tumor-specific immune response. In 2023, interim results from the CICILIA trial indicated that all endpoints were met. CY-101 showed a consistent safety profile across different tumor types, along with strong early efficacy signals.

The ESMO poster reveals that no dose-limiting toxicities were observed during the dose-escalation phase, confirming the RP2D at 20 mg. Significant cancer cell death was noted in over 70% of tumor cases at this dose, leading to clinical benefits in various cancers. Notably, in six patients with adrenocortical carcinoma (ACC) treated with CY-101 monotherapy, a disease control rate of 50% was observed, with two patients showing durable responses exceeding six months. These patients had β-catenin expression and somatic mutations in the Wnt/β-catenin pathway.

CY-101 has also been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of ACC. This designation is given to treatments for rare diseases affecting fewer than 200,000 people in the U.S. It provides benefits such as development cost advantages, increased FDA interaction, and eligibility for seven-year market exclusivity post-approval.

Lars Prestergarden, CEO of Cytovation, emphasized the potential of CY-101 as a new treatment option for Wnt/β-catenin driven cancers, which are implicated in over 20% of all cancers. He highlighted the promising early data and expressed confidence in further investigating CY-101 in larger studies. The company is planning a Phase 2 trial with registrational intent for ACC.

ACC, or adrenal cancer, is a rare and aggressive cancer with limited treatment options. Currently, there is no approved treatment after the first line in metastatic settings. Cytovation ASA is dedicated to developing CY-101, focusing on its unique ability to target cancer cells by both attacking the cell membrane and inhibiting the Wnt/β-catenin pathway. This dual action not only limits tumor growth but also reverses immune exclusion associated with β-catenin expression. The dysregulation of the Wnt/β-catenin pathway is linked to various cancers, including those of the colon, liver, uterus, lung, and ovary, among others. The dual mechanism of CY-101 induces a systemic, tumor-specific immune response, representing a potential breakthrough in cancer treatment.