UV1 / Zelluna - LARVOL DELTA

The telomerase vaccine UV1 combined with ipilimumab and nivolumab versus ipilimumab and nivolumab in advanced melanoma (INITIUM): A randomized open-label phase 2 study. (PubMed, Eur J Cancer) - "For patients with treatment naïve advanced melanoma, the addition of UV1 to ipilimumab-nivolumab did not result in improved efficacy compared with ipilimumab-nivolumab alone."

Journal • P2 data • Melanoma • Oncology • Solid Tumor

Blood-based biomarkers associated with response to immune checkpoint inhibition in pleural mesothelioma (ESMO 2025) - P2 | "Patients were randomized to ipilimumab and nivolumab with or without the UV1 vaccine. Baseline eotaxin and longitudinal changes in cytokines such as HuMIF, IL2ra, and IL-6 may serve as non-invasive biomarkers to guide ICI therapy. Further details will be presented."

Biomarker • Checkpoint inhibition • IO biomarker • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • CCL11 • IL16 • IL18 • IL2RA • IL6

Dual-time-point [18F] FDG PET/CT and tumour microenvironment features in pleural mesothelioma patients receiving immunotherapy (ESMO 2025) - P2 | "Methods 118 patients with PM were enrolled in the NIPU trial (NCT04300244) and randomised 1:1 to Ipilimumab and Nivolumab ± UV1 telomerase vaccine. Immune score was associated with treatment response but not directly correlated with metabolic PET features. These findings suggest potential for DTP PET/CT as a non-invasive surrogate of stromal TME features."

Clinical • FDG PET • IO biomarker • Tumor microenvironment • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor

When UV1 cancer vaccine meets immune checkpoint blockade: Positive immune response but negative clinical outcome. (PubMed, Med) - "present findings from the phase 2 FOCUS trial evaluating UV1 vaccine combined with pembrolizumab in PD-L1-positive recurrent/metastatic head and neck squamous cell carcinoma. While UV1 elicited human telomerase reverse transcriptase-specific T cell responses in 86% of patients, clinical outcomes showed no improvement over pembrolizumab monotherapy.1 This discordance between immune activation and therapeutic efficacy underscores the necessity for further disease understanding and vaccine design in the future."

Checkpoint inhibition • Clinical data • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1 • TERT

Multiomics profiling for prediction of immunotherapy response in advanced pleural mesothelioma: Sub-study of the NIPU trial. (ASCO 2025) - P2 | "Funded by Bristol Myers Squibb, South-Eastern Norway Regional Health Authority, Ultimovacs Clinical Trial Registration Number: NCT04300244 Background: The combination of ipilimumab and nivolumab (IPI/NIVO) is a standard treatment for unresectable pleural mesothelioma... In the NIPU trial, 118 patients progressing after first-line chemotherapy were included in the study and were randomly assigned to IPI/NIVO alone or in combination with the telomerase UV1 vaccine... High/positive levels of tumoral CD66b+ neutrophils show promise as predictive biomarkers for immunotherapy efficacy in advanced pleural mesothelioma. Larger, independent studies are needed to confirm these findings and validate their clinical utility."

IO biomarker • Metastases • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • CD20 • CD4 • CD8 • CEACAM8 • FOXP3 • GZMB • IFNG

Zelluna Q1 2025 slides highlight TCR-NK manufacturing breakthrough post-merger (Investing.com) - "The first quarter of 2025 was transformative for Zelluna, marked by the completion of its business combination with Ultimovacs ASA on March 3, 2025, accompanied by a private placement of MNOK 51.7...Zelluna’s pipeline consists of three main programs: ZI-MA4-1 targeting MAGE-A4, ZI-KL1-1 targeting KK-LC-1, and ZI-PR-1 targeting PRAME...Zelluna provided an update on the MultiClick Technology and UV1 Program inherited from Ultimovacs....two remaining trials, LUNGVAC and DOVACC, have completed enrollment with topline results expected during 2025....Zelluna outlined several key upcoming milestones that could serve as value inflection points. In the second half of 2025, the company expects to complete preclinical work, begin GMP manufacturing, and submit IND/CTA applications. Initial clinical readouts are anticipated in the first half of 2026."

Clinical data • M&A • Cervical Cancer • Gastric Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Synovial Sarcoma

UV1 vaccination in pembrolizumab-treated patients with recurrent or metastatic head and neck cancer: A randomized multicenter phase 2 trial. (PubMed, Med) - P2 | "The addition of UV1 to pembrolizumab was safe but did not show an efficacy signal in this study population."

Journal • P2 data • Allergy • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1 • TERT

DOVACC: Olaparib, Durvalumab and UV1 in Relapsed Ovarian Cancer (clinicaltrials.gov) - P2 | N=184 | Recruiting | Sponsor: Nordic Society of Gynaecological Oncology - Clinical Trials Unit | Trial completion date: Dec 2026 ➔ Dec 2030 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

Telomerase-based vaccines: a promising frontier in cancer immunotherapy. (PubMed, Cancer Cell Int) - "While DNA vaccines demonstrate promising immunogenicity, peptide vaccines, such as UV1, UCPVax, and Vx-001, have shown clinical efficacy in certain cancer types. Accordingly, we discuss the mechanisms of action, preclinical and clinical data, and the potential of these vaccines to elicit robust and durable anti-tumor immune responses. This review highlights the potential of telomerase-based vaccines as a promising strategy for cancer treatment and identifies areas for future research."

Journal • Review • Gene Therapies • Oncology • TERT

Safety of UV1 Vaccination in Combination With Ipilimumab in Patients With Unresectable or Metastatic Malignant Melanoma (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: Ultimovacs ASA | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Melanoma • Oncology • Solid Tumor

Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma. (PubMed, Front Immunol) - "Patients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Elevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES."

Biomarker • Checkpoint inhibition • IO biomarker • Journal • Dermatitis • Dermatology • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pneumonia • Solid Tumor • CCL11 • CCL4 • IL16 • IL2RA • IL4 • TNFA

A Phase I/IIa Study of UV1 Vaccination in Patients With Non Small Cell Lung Cancer. (clinicaltrials.gov) - P1/2 | N=18 | Completed | Sponsor: Ultimovacs ASA | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Phase I/IIa Study of UV1 Vaccine in Patients With Prostate Cancer (clinicaltrials.gov) - P1/2 | N=22 | Completed | Sponsor: Ultimovacs ASA | Active, not recruiting ➔ Completed

Metastases • Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[PREPRINT] UV1 cancer vaccine in pembrolizumab-treated patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma: results from the randomized phase 2 FOCUS trial (medRxiv) - P2 | N=75 | FOCUS (NCT05075122) | "The PFSR@6 was 30% in the UV1 arm. No specific safety signals were observed in the UV1 arm apart from a reversible allergic reaction that appeared in one patient. At a median follow-up of almost one year (11.3 months), median overall survival was 13.1 months in the calibration arm A and 12.6 months in the UV1 arm B."

P2 data • Preprint • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Updated survival and vaccine response from the NIPU trial: A randomised, phase II study evaluating nivolumab and ipilimumab with or without UV1 vaccination in patients with pleural mesothelioma (ESMO 2024) - P2 | "There is no significant difference in OS between the treatment arms. UV1-specific response is detected in some patients receiving UV1 vaccine, and will be further explored. Translational analyses will investigate whether some patients with epithelioid histology benefit more from UV1, warranting further clinical studies."

Clinical • P2 data • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

Ultimovacs Announces Patient Recruitment Discontinuation in LUNGVAC Trial Investigating UV1 Combined with Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer (GlobeNewswire) - "Ultimovacs ASA...announced that the company has agreed with the investigators conducting the LUNGVAC trial (NCT05344209) to discontinue patient recruitment. LUNGVAC is an investigator-initiated, randomized Phase II trial designed to assess the impact of UV1 in combination with the checkpoint inhibitor cemiplimab or pembrolizumab as first-line treatment in patients with inoperable advanced or metastatic non-small cell lung cancer (NSCLC). The decision is driven by very slow recruitment in the study, which is primarily due to new treatment options available to NSCLC patients. All 31 patients that have been enrolled in the LUNGVAC study since 2022 will be treated and followed up as per the trial protocol. Topline data from these patients is expected in the first half of 2025."

P2 data • Trial status • Non Small Cell Lung Cancer

Ultimovacs Announces Updated Data Analysis on UV1 Phase II NIPU Trial in Mesothelioma at ESMO 2024 (GlobeNewswire) - P2 | N=118 | NIPU (NIPU) | "Ultimovacs ASA...announces the presentation of updated data analysis from the UV1 Phase II NIPU trial (NCT04300244), at the 2024 ESMO Congress.....The ESMO 2024 poster presentation highlights an increased clinical benefit observed for the epithelioid subgroup, demonstrating an improvement in median PFS of 5.5 months for UV1 in combination with ipilimumab and nivolumab, versus a median PFS of 2.9 months for immunotherapy alone. The epithelioid subtype represents approximately 70% of all patients with mesothelioma. In addition, the ESMO 2024 data presentation demonstrates a positive difference in overall survival (OS) for UV1 treatment at the latest patient follow-up, although the degree of benefit is less than previously reported. The full results will be presented in a poster at the congress..."

P2 data • Malignant Pleural Mesothelioma • Mesothelioma

UV1-103: UV1 Vaccine With Pembrolizumab for Patients With Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Ultimovacs ASA | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Jun 2024

Metastases • Trial completion • Trial completion date • Melanoma • Oncology • Solid Tumor • BRAF

Ultimovacs ASA Reports Second Quarter 2024 Financial Results and Provides General Business Update (GlobeNewswire) - "UV1 randomized controlled Phase II trials: INITIUM Supplementary Study: Evaluating ipilimumab and nivolumab + UV1...The results are expected to be submitted for publication in a peer-reviewed medical journal by the end of this year; DOVACC (ovarian cancer)...The readout is expected in the first half of 2025; LUNGVAC (non-small cell lung cancer)...The readout is expected in the first half of 2026."

P2 data • Gynecologic Cancers • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Skin Cancer • Solid Tumor

Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine. (PubMed, Eur J Nucl Med Mol Imaging) - P2 | "MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response."

FDG PET • Journal • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

Ultimovacs Announces Topline Data from FOCUS Phase II Trial of UV1 Combined with Pembrolizumab in Patients with Metastatic or Recurrent Head and Neck Cancer (GlobeNewswire) - P2 | N=72 | FOCUS (NCT05075122) | "Ultimovacs ASA...announced the topline results from the Phase II FOCUS trial (NCT05075122). The topline data readout demonstrated that adding UV1 to the standard of care pembrolizumab did not lead to clinical benefits in progression free survival or overall survival in those late-stage HNSCC patients, therefore, the study did not meet its primary and secondary endpoints....Ultimovacs is also investigating UV1 in ovarian cancer in the ongoing Phase II DOVACC trial...for patients with high-grade BRCA negative ovarian cancer. Topline results are expected in the first half of 2025 well within the current financial runway which reaches to the fourth quarter of 2025."

P2 data • Ovarian Cancer • Squamous Cell Carcinoma of Head and Neck

Ultimovacs Announces Poster Presentation of NIPU Phase II Trial Update at Upcoming ESMO Congress 2024 (GlobeNewswire) - "Ultimovacs ASA...announced that an update from the Phase II NIPU trial (NCT04300244) in patients with malignant mesothelioma will be presented in a poster presentation at the 2024 ESMO Congress. The conference will be held in Barcelona, Spain from September 13-17, 2024."

P2 data • Mesothelioma

Ipilimumab and nivolumab plus UV1, an anticancer vaccination against telomerase, in advanced melanoma. (ASCO 2024) - P2 | "In a Phase I trial in melanoma (N = 30), UV1 plus pembrolizumab demonstrated a tolerable safety profile, a complete response rate of 33%, median PFS of 18.9 months, and 2-year OS rate of 73.3%... UV1 did not improve on outcomes of IPI-NIVO, in terms of PFS. Longer follow-up is required for the accurate assessment of OS. No significant toxicity increases were observed with the addition of UV1."

Late-breaking abstract • Metastases • Melanoma • Mesothelioma • Oncology • Solid Tumor • BRAF • CSF2

UV1 Cancer Vaccine as a Pembrolizumab Add-On Continues to Strengthen OS in Melanoma (OncLive) - P1 | N=30 | UV1-103 (NCT03538314) | Sponsor: Ultimovacs ASA | "At a median follow-up of 53.0 months and a minimum follow-up of 4 years, among the 30 patients enrolled in the trial, all patients who were alive at 3 years (69.5%) remained alive at 4 years....UV1-301 enrolled 30 patients in the United States across 2 cohorts, which are distinguishable by the concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) used as a vaccine adjuvant. Patients in cohort 1 (n = 20) received a 37.5 µg adjuvant dose of GN-CSF per UV1 vaccination. Patients in cohort 2 (n = 10) received the standard 75 µg adjuvant dose of GM-CSF per UV1 vaccination....UV1-103 has met its primary end point of the safety and tolerability of UV1 added to pembrolizumab. Previously reported data from this trial showed a 33% complete response rate, a 57% objective response rate, and a median progression-free survival of 18.9 months per iRECIST criteria."

P1 data • Melanoma

Ultimovacs provides update from Phase I study in malignant melanoma: Continued strong overall survival in patients treated with UV1 cancer vaccine and pembrolizumab (GlobeNewswire) - P1 | N=30 | NCT03538314 | Sponsor: Ultimovacs ASA | "Ultimovacs ASA...announced encouraging overall survival (OS) data from both cohorts in the UV1-103 Phase I clinical trial in malignant melanoma....The study enrolled 30 patients in the U.S. in two cohorts that differed only in the concentration of GM-CSF used as vaccine adjuvant. With a minimum follow-up of 4 years (median 53.0 months), the updated OS results show that all patients who were alive at the 3-year mark remain alive at 4 years, with an OS rate of 69.5%....The expected next key milestone for UV1 is the readout of the FOCUS trial during Q3 2024, in which the treatment combination is the same as in the UV1-103 trial."

P1 data • P2 data • Melanoma • Squamous Cell Carcinoma of Head and Neck