Ultimovacs Announces Topline Results from INITIUM Study Evaluating UV1 Vaccination Added to Ipilimumab and Nivolumab in Patients with Unresectable or Metastatic Malignant Melanoma

• With the 18-month minimum follow-up of the patients in the INITIUM trial, the trial did not meet the primary endpoint of prolonging progression-free survival (PFS). Median PFS was not reached in either arm. Evaluation of secondary endpoints did not show a difference in overall survival and objective response rate between the treatment and control arms
• UV1 maintained its positive safety profile with similar safety and tolerability as observed in the control arm
• Ultimovacs remains confident in the potential of the UV1 vaccine and its promise in specific therapeutic combinations and indications 
• Upcoming data from the FOCUS Phase II trial and overall survival updates from the NIPU Phase II trial will be the next important data points for the further assessment of UV1
• Cash preservation initiatives will be implemented to ensure that the available financial resources will sustain the company into 2025, enabling the achievement of upcoming key inflection points.
  

Oslo, March 7 2024: Ultimovacs ASA ("Ultimovacs") (OSE ULTI), a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines, today announced topline results from the Phase II clinical trial, INITIUM (NCT04382664), evaluating the company’s therapeutic cancer vaccine candidate UV1 as first-line treatment in unresectable or metastatic malignant melanoma.

The study’s primary endpoint was to investigate progression-free survival (PFS) in the experimental arm (UV1 plus treatment with checkpoint inhibitors (CPIs) ipilimumab and nivolumab) as compared to the control arm (ipilimumab and nivolumab alone). Secondary endpoints included overall survival (OS), objective response rate (ORR) as well as duration of response (DOR) and safety. Topline data demonstrated that the combined treatment of UV1 with ipilimumab and nivolumab showed similar clinical benefits as treatment with ipilimumab and nivolumab alone, meaning the primary and secondary endpoints of the study were not met.

With the 18-month minimum follow-up of the patients in the trial, the median PFS was not reached in either arm, and the Hazard Ratio (HR) between the arms for PFS was 0.95. Evaluation of secondary endpoints did not show a difference in overall survival and objective response rate between the arms. UV1 maintained a positive safety and tolerability profile.

Ultimovacs will further analyze the full data set while continuing to advance its ongoing Phase II trials for UV1.

"Ultimovacs had set a very high bar for UV1 by comparing it to the ipilimumab and nivolumab combination, currently considered the most effective treatment for this patient population. Nevertheless, we are disappointed that UV1 did not add further clinical benefit for these late-stage melanoma patients in the INITIUM trial. Looking forward, our first objective is to complete the analysis of the full data set in depth to gain further insights on UV1’s effects,” said Jens Bjørheim, Chief Medical Officer, Ultimovacs. "We wish to thank the patients for their trust and the investigators for their collaboration with us.”

"We have seen signals in previous trials that UV1 has the ability to show positive effects in cancer patients. We remain committed to UV1, and we look forward to thoroughly examining the INITIUM data, receiving the FOCUS data, and updated NIPU survival data over the next several months. Our objective is to define the best path forward for our development strategy for UV1,” said Carlos de Sousa, Chief Executive Officer, Ultimovacs.

Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical development program across various cancer indications with different biology and disease stages, in combination with different checkpoint inhibitors. The topline data from INITIUM is the second readout among the five randomized trials in the UV1 Phase II clinical program. In October 2023, the UV1 Phase II trial NIPU in malignant mesothelioma reported a clinically meaningful overall survival benefit in the patients receiving UV1 vaccination on top of ipilimumab and nivolumab compared to ipilimumab and nivolumab alone, with no added toxicities. Per protocol, the overall survival results were statistically significant. In addition to the studies in malignant melanoma and malignant mesothelioma, Phase II studies are ongoing in patients with head and neck cancer (FOCUS), ovarian cancer (DOVACC), and non-small cell lung cancer (LUNGVAC). The data from the FOCUS trial is expected in the third quarter of 2024.

The Company will host a webcast presentation and discussion of the results from the INITIUM study on Thursday, March 7 2024 at 08:00 (CET). Link to the webcast here: https://channel.royalcast.com/landingpage/hegnarmedia/20240307_2/

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About Ultimovacs
Ultimovacs is a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines with broad applicability. Ultimovacs’ lead cancer vaccine candidate UV1 is directed against human telomerase (hTERT) an antigen which is present in 85-90% of cancers in all stages of tumor growth. A broad clinical program, with Phase II trials in five cancer indications enrolling more than 670 patients, aims to demonstrate UV1’s impact in combination with other immunotherapies in multiple cancer types expressing telomerase and where patients have unmet medical needs. UV1 is universal, off-the-shelf and easy to use, and is a patented technology owned by Ultimovacs.
In addition, Ultimovacs holds all rights of the proprietary TET technology platform for any possible future use of formulations in various solid tumor indications. The Company is listed on Euronext Oslo Stock Exchange (ULTI.OL). 

About INITIUM
INITIUM is an Ultimovacs-sponsored randomized, comparative, multicenter Phase II trial in which the universal cancer vaccine UV1 will be evaluated in combination with the checkpoint inhibitors ipilimumab and nivolumab for first-line treatment of patients with unresectable or metastatic malignant melanoma. The first patient received treatment in the INITIUM trial in June 2020, and the last patient was enrolled in July 2022. The study is being conducted at 39 hospitals across the U.S., U.K., Belgium, and Norway. The initial study design called for enrollment of 154 patients. Two additional patients were enrolled bringing the total number of patients in the study to 156.

About the UV1 Phase II program

The immunotherapeutic cancer vaccine UV1 is investigated in combination with checkpoint inhibitors in patients with various cancer indications with diverse tumor biology. The diversity of the UV1 Phase II program places Ultimovacs in a favorable position to capture the cancer vaccine’s potential broad applicability when combined with checkpoint inhibitors:

• INITIUM: Evaluating UV1 in combination with ipilimumab and nivolumab as first-line treatment for patients with malignant melanoma. Enrollment of 156 patients completed in July 2022. Sponsored by Ultimovacs.
• NIPU: Evaluating UV1 in combination with ipilimumab and nivolumab as second-line treatment for patients with malignant pleural mesothelioma. Enrollment of 118 patients completed in January 2023. Data presented at the ESMO Congress in October 2023, showed that UV1 as add-on to ipilimumab and nivolumab, demonstrated a statistically significant and clinically meaningful improvement of overall survival versus ipilimumab and nivolumab alone. 31% of the patients receiving UV1 vaccine experienced an objective response, compared to 16% in the control arm. The investigator-initiated study is led by Oslo University Hospital and supported by Bristol-Myers Squibb and Ultimovacs.
• FOCUS: Evaluating UV1 in combination with pembrolizumab as first-line treatment for patients with head and neck cancer. Enrollment of 75 patients completed in August 2023, expected readout Q3 2024. The investigator-initiated study is led by Halle University in Germany, supported by Ultimovacs.
• DOVACC: Evaluating UV1 in combination with olaparib and durvalumab as maintenance therapy in non-BRCA mutated patients with advanced ovarian cancer. 75 of 184 patients enrolled as of Q4 2023 reporting, expected readout H1 2025. The investigator-initiated study is led by NSGO-CTU and supported by ENGOT, AstraZeneca, and Ultimovacs.
• LUNGVAC: Evaluating UV1 combined with cemiplimab as first-line treatment of non-small cell lung cancer patients. 23 of 138 patients enrolled as of Q4 2023 reporting, expected readout H2 2025. The investigator-initiated study is led by Vestre Viken (Drammen Hospital) and supported by Ultimovacs.

About UV1
UV1 is a universal cancer vaccine designed to induce a specific T-cell response against telomerase. UV1 consists of long, synthetic peptides representing a sequence in the reverse transcriptase subunit of telomerase (hTERT), shown to induce CD4+ T-cells. These CD4+ T-cells have the potential to provide inflammatory signals, and T-cell support is believed to be critical for triggering a strong anti-tumor immune response. Following intradermal injection, antigen-presenting cells (APCs) in the skin are exposed to the vaccine peptides. These APCs will process the peptides and present vaccine epitopes on Human Leukocyte Antigen (HLA) molecules to naïve T-cells in the lymph nodes. Activated vaccine-specific T-cells will then enter the circulation and search for cells displaying their cognate antigen in the context of HLA molecules.
The UV1 peptides contain several epitopes, shown to be non-restrictive in terms of (HLA) alleles for presentation. It is, therefore not required to perform HLA pre-screening of patients, which potentially enables broad population utilization of the vaccine. UV1 is administered over three months as eight intradermal injections together with the immune-modulator GM-CSF.

For further information, please see www.ultimovacs.com or contact:

Carlos de Sousa, CEO
Email: carlos.desousa@ultimovacs.com
Phone: +47 908 92507

Anne Worsøe, Head of Investor Relations
Email: anne.worsoe@ultimovacs.com
Phone: +47 90686815

This information is considered to be inside information pursuant to the EU Market Abuse Regulation and is subject to the disclosure requirements pursuant to Section 5-12 in the Norwegian Securities Trading Act. This stock exchange announcement was published by Anne Worsøe, Head of IR at Ultimovacs ASA, on March 7, 2024 at 07:00 CET