CY-101 / Cytovation - LARVOL DELTA

Cytovation Raises US$6m to Advance Phase 2 Development of CY-101 in Adrenocortical Carcinoma to First Clinical Readouts (GlobeNewswire) - "Cytovation ASA...announces that it has raised NOK62 million (US$6m) largely from existing investors, led by Sandwater. These funds will be used to advance CY-101 into a multi-national Phase 2 clinical trial in patients with adrenocortical carcinoma due to start in late 2025 and with first clinical readouts expected in 2026. The trial will be conducted through a partnership between Cytovation, Cancer Research UK and the Norwegian Cancer Society under an agreement announced in January 2025....New preclinical data being presented at the American Association of Cancer Research (AACR) annual meeting...provide further insights into the mechanistic basis of CY-101’s activity. The studies, conducted in in vivo immune-refractory models of ACC, colorectal carcinoma (CRC) and melanoma, demonstrated that CY-101 eliminates ACC and CRC tumors, enhances the efficacy of anti-PD-1 activity and triggers a systemic antitumor immune response."

Commercial • New P2 trial • Preclinical • Adrenal Cortex Carcinoma • Colorectal Cancer • Melanoma

CY-101 inhibits the tumor growth and improves anti-PD-1 immunotherapy in beta-catenin-driven tumors (AACR 2025) - "Mechanistically, CY-101-treated tumors exhibited downregulation of Wnt/beta-catenin downstream target genes, emphasizing its role as a potent Wnt/beta-catenin inhibitor.These preclinical findings support the observations seen in the first in human CICILIA Phase 1/2a trial, which reported clinical activity in ACC and melanoma patients. Collectively, our study demonstrates the therapeutic potential of CY-101 in beta-catenin-driven tumors, both as monotherapy and in combination with anti-PD1 checkpoint inhibitors."

IO biomarker • Adrenal Cortex Carcinoma • Colorectal Cancer • Genito-urinary Cancer • Melanoma • Oncology • Solid Tumor • CD8 • CTNNB1

Cancer Research UK, Cytovation and the Norwegian Cancer Society collaborate to advance treatment for rare cancer (GlobeNewswire) - "Cancer Research UK, Cytovation and the Norwegian Cancer Society have signed an agreement to bring Cytovation’s lead asset, CY-101, into a multi-national Phase 2 clinical trial for patients with adrenocortical carcinoma...Under the agreement, Cancer Research UK’s Centre for Drug Development (CDD) will sponsor, design and deliver the Phase 2 trial and Cytovation will be responsible for providing CY-101 for the clinical trial."

Commercial • Adrenal Cortex Carcinoma

Catalyst: A Study to Evaluate the Safety and Efficacy of CyPep-1 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic Cancers (clinicaltrials.gov) - P1/2 | N=6 | Completed | Sponsor: Cytovation AS | Active, not recruiting ➔ Completed | N=90 ➔ 6 | Trial completion date: Feb 2025 ➔ Sep 2024

Combination therapy • Enrollment change • Metastases • Trial completion • Trial completion date • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF

Safety and activity of CY-101 in patients with advanced solid tumors: The phase I/IIa CICILIA trial (ESMO 2024) - P1/2 | "Here, we report findings from a phase I/IIa trial evaluating intratumoral (IT) administration of CY-101 monotherapy and in combination with pembrolizumab in patients (pts) with heavily pretreated advanced solid tumors. Eligible pts received biweekly (Q2W) IT injections with CY-101 into 1-3 accessible metastatic lesion(s). CY-101 is well tolerated at the RP2D of 20 mg and demonstrated early signs of antitumor activity, especially in tumors with dysregulated Wnt/β-catenin signaling."

Clinical • Metastases • P1/2 data • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Cytovation to present full safety and efficacy data from the CICILIA Phase I/IIa trial evaluating CY-101 in solid tumors at ESMO 2024 (GlobeNewswire) - P1/2a | N=60 | CICILIA (NCT04260529) | Sponsor: Cytovation AS | "Data from the ESMO poster show that no dose-limiting toxicities were observed in the dose- escalation part of the study with the RP2D defined at 20 mg. Analyses of paired tumor biopsies demonstrated induction of cancer cell death in >70% across tumor types at the RP2D, translating to a clinical benefit in several different cancer types. Notably, among six patients with adrenocortical carcinoma (ACC) receiving CY-101 monotherapy, a disease control rate of 50% (n = 3/6) was observed, with durable responses (> 6 months) in two patients. Both patients expressed β-catenin and had somatic mutations in the Wnt/β-catenin pathway. Separately, the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to CY-101 monotherapy for the treatment of ACC...'We look forward to advancing towards our planned Phase 2 trial in ACC with registrational intent.'"

Orphan drug • P1/2 data • Adrenal Cortex Carcinoma • Endocrine Cancer • Oncology • Solid Tumor

CICILIA: CyPep-1 Injections in Cancer Inducing Lymphocyte Infiltrate Accumulations (clinicaltrials.gov) - P1/2 | N=60 | Completed | Sponsor: Cytovation AS | Active, not recruiting ➔ Completed | Trial primary completion date: Mar 2024 ➔ Jul 2024

Combination therapy • Metastases • Monotherapy • Trial completion • Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Melanoma • Oncology • Solid Tumor • BRAF

Catalyst: A Study to Evaluate the Safety and Efficacy of CyPep-1 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic Cancers (clinicaltrials.gov) - P1/2 | N=90 | Active, not recruiting | Sponsor: Cytovation AS

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF

Catalyst: A Study to Evaluate the Safety and Efficacy of CyPep-1 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic Cancers (clinicaltrials.gov) - P1/2 | N=90 | Active, not recruiting | Sponsor: Cytovation AS | Recruiting ➔ Active, not recruiting | Phase classification: P1b/2a ➔ P1/2

Combination therapy • Enrollment closed • Metastases • Phase classification • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF

CyPep-1 reprograms the tumor microenvironment and enhances the efficacy of immune checkpoint inhibitors (ESMO 2023) - P1b/2a | "This process results in a systemic immune response, transforming immunological "cold" tumors into "hot" ones. A clinical trial based on these findings has been initiated (NCT05383170)."

Biomarker • Checkpoint inhibition • Clinical • Tumor microenvironment • Oncology

Cytovation Reports Promising Interim Results from Phase 1/2a CICILIA Study with CyPep-1 in Solid Tumors (GlobeNewswire) - P1/2a | N=75 | CICILIA (NCT04260529) | Sponsor: Cytovation AS | "Cytovation ASA...announces positive initial data from Part 2 of its Phase 1/2a CICILIA basket trial with all trial endpoints met. In this heavily pretreated, advanced and metastatic patient group CyPep-1 exhibits an excellent safety profile with no dose-limiting toxicities and has shown strong early signs of efficacy across solid tumor types....The early signals of efficacy from CICILIA confirm the importance of CyPep-1’s unique dual mechanism of action with the most promising responses seen in patients with tumor types characterized by aberrant Wnt/β-catenin pathway signaling and with liver metastases....Cytovation is planning to start a Phase 2 trial in ACC in 2024 with registrational intent."

New P2 trial • P1/2 data • Adrenal Cortex Carcinoma • Endocrine Cancer • Oncology • Solid Tumor

CICILIA: CyPep-1 Injections in Cancer Inducing Lymphocyte Infiltrate Accumulations (clinicaltrials.gov) - P1/2 | N=75 | Active, not recruiting | Sponsor: Cytovation AS | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Aug 2023 ➔ Mar 2024

Combination therapy • Enrollment closed • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Melanoma • Oncology • Solid Tumor • BRAF

Cytovation raises $8 million in Series A extension financing round for clinical advancement of CyPep-1, a first-in-class targeted tumor membrane immunotherapy (GlobeNewswire) - "Cytovation ASA...announces the successful closing of its $8 million (NOK 85 million) Series A extension financing round. This new investment will support the progress of Cytovation’s lead asset, CyPep-1, into a full Phase 2 program for the treatment of solid tumors....Cytovation’s 57-patient Phase 1/2 CICILIA solid tumor basket trial is now well advanced, with top line results due in H2 2023."

Financing • P1/2 data • Oncology • Solid Tumor

Catalyst: A Study to Evaluate the Safety and Efficacy of CyPep-1 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic Cancers (clinicaltrials.gov) - P1b/2a | N=90 | Recruiting | Sponsor: Cytovation AS | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF

Cytovation announces first patient dosed in Phase 2a study investigating CyPep-1 monotherapy in advanced melanoma refractory to checkpoint inhibitors (GlobeNewswire) - "Cytovation ASA...announces that the first patient has been dosed in its Phase 2a study investigating CyPep-1 monotherapy in patients with advanced melanoma refractory to checkpoint inhibitors (CPIs)....The study is an expansion arm of its ongoing Phase 1/2 CICILIA trial in solid tumors, which is being conducted in The Netherlands, France, and Spain. The Phase 2a study builds on encouraging data from the first phase of the trial, which has demonstrated a favorable safety profile for CyPep-1 monotherapy along with strong early signals of efficacy in several tumor types....Cytovation has an ongoing clinical research collaboration with MSD to explore CyPep-1 in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), and melanoma."

Trial status • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Catalyst: A Study to Evaluate the Safety and Efficacy of CyPep-1 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic Cancers (clinicaltrials.gov) - P1b/2a | N=90 | Not yet recruiting | Sponsor: Cytovation AS | Initiation date: Aug 2022 ➔ Jan 2023

Combination therapy • Trial initiation date • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

First-in-human, dose-escalation phase I trial of intratumoral (IT) CyPep-1 in patients (pts) with advanced solid tumors (ESMO 2022) - P1/2 | "PK data showed minimal systemic exposure with IT injection. Histopathologic examination showed local oncolytic effect, and TCR clonal changes were consistent with systemic immune activation."

Clinical • P1 data • Oncology • Solid Tumor

A study to evaluate the safety and efficacy of CyPep-1 in combination with Pembrolizumab for the treatment of advanced or metastatic cancers. (clinicaltrialsregister.eu) - P1/2 | N=90 | Ongoing | Sponsor: Cytovation ASA

Combination therapy • New P1/2 trial • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • PD-L1

CICILIA: CyPep-1 Injections in Cancer Inducing Lymphocyte Infiltrate Accumulations (clinicaltrials.gov) - P1/2 | N=75 | Recruiting | Sponsor: Cytovation AS | N=45 ➔ 75 | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Aug 2022 ➔ Aug 2023

Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Melanoma • Oncology • Solid Tumor • BRAF

US FDA accepts Cytovation’s IND application for Phase II combination studies of CyPep-1, a first-in-class targeted tumor membrane immunotherapy (PRNewswire) - "Cytovation ASA...announces that its investigational new drug (IND) application for CyPep-1 has been accepted by the U.S. FDA, allowing the drug to proceed into Phase II studies in combination with...KEYTRUDA® (pembrolizumab) in advanced solid tumors....'We look forward to reporting further data from the early clinical program later in 2022 and initiating in the U.S. the series of studies of CyPep-1 in combination with KEYTRUDA in collaboration with MSD, as enabled by this IND'....In the U.S., Cytovation will conduct Phase II studies investigating CyPep-1 in combination with KEYTRUDA® in melanoma, head and neck squamous cell carcinoma (HNSCC) and triple-negative breast cancer (TNBC)."

IND • P2 data • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Cytovation collaborates with Recurrent Respiratory Papillomatosis Foundation to expand its clinical investigations of CyPep-1 into rare neoplastic disease (PRNewswire) - "Cytovation AS...announces that it is has entered into a collaboration with the Recurrent Respiratory Papillomatosis Foundation (RRPF) to advance the development of CyPep-1 for the treatment of this orphan disease alongside the Company's cancer development program....The collaboration will enable Cytovation to draw upon RRPF's extensive knowledge and network in preparation for a Phase I/II study to be initiated in 2H 2022."

Licensing / partnership • New P1/2 trial • Oncology • Solid Tumor

Cytovation raises $20 million in Series A financing round to advance clinical development of CyPep-1, a first-in-class targeted tumor membrane immunotherapy (PRNewswire) - "Cytovation AS...announces the successful closing of its Series A financing round, raising a total of NOK 180 million ($20 million)...'we have begun patient dosing of CyPep-1 in combination with Keytruda in patients with a range of solid tumors. These new proceeds will enable us to further advance and expand our clinical development plans in cancer, and we look forward to reporting further data from this clinical program in 2022.'"

Financing • P1/2 data • Breast Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

First Patient Dosed with CyPep-1 in Combination with KEYTRUDA in Cytovation's Ph I/IIa CICILIA Clinical Trial (PRNewswire) - “Cytovation AS…announces that the first patient has been dosed in the expansion phase of its Phase I/IIa CICILIA clinical trial. In this phase of the trial, CyPep-1 is being administered in combination with KEYTRUDA® (pembrolizumab) in patients with a range of solid tumors….Initial results from Phase 1 of the combination arm safety study are expected early in 2022 with the Phase II combination trial scheduled to start shortly thereafter.”

P1 data • Trial status • Oncology • Solid Tumor

CICILIA: CyPep-1 Injections in Cancer Inducing Lymphocyte Infiltrate Accumulations (clinicaltrials.gov) - P1/2; N=45; Recruiting; Sponsor: Cytovation AS; N=21 ➔ 45; Trial completion date: Jun 2021 ➔ Dec 2022; Trial primary completion date: Jan 2021 ➔ Aug 2022

Clinical • Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • MRI

CyPep-1 Shows Preliminary Safety, Tolerability and Early Signs of Efficacy in Part 1 of its Ph I/IIa CICILIA Trial Which Now Moves to Expansion Phase (PRNewswire) - "Cytovation...announced that it has successfully completed Part 1 of its Ph I/IIa CICILIA study having reached the planned target dose of CyPep-1 while maintaining a favorable safety profile. To date the trial has recruited 12 patients with a range of solid tumors, each patient having received a minimum of three intra-tumoral injections of CyPep-1. Safety and tolerability in this first part of the study have been encouraging with no serious adverse events or dose-limiting toxicities, while early efficacy signals are positive and remain consistent with the preclinical proof-of-concept data previously generated....Based on these results, Cytovation plans to advance and expand the study to include a combination arm with KEYTRUDA® (pembrolizumab)..."

Trial status • Oncology • Solid Tumor