Ultimovacs Announces Protocol Amendment in UV1 Phase II Study INITIUM in Malignant Melanoma, Enabling Data Readout in First Half of 2024

• Patients in the INITIUM study are taking longer than expected to experience cancer progression. Reaching the number of progressing patients required for readout may take several months or even years, which has justified an amendment of the study protocol.
  
  
• The amended protocol in INITIUM enables the data analysis to start mid-January 2024 after the last enrolled patient has been followed up for 18 months. The topline results from the randomized Phase II study are expected to be announced approximately two to three months later.
  
  
• INITIUM completed enrollment of 156 patients in July 2022. The results from the randomized trial will provide comparative data on efficacy and safety for UV1 treatment in malignant melanoma added to standard-of-care immunotherapy, ipilimumab and nivolumab.
  
  

Oslo, October 31, 2023: Ultimovacs ASA ("Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines, today announced that the analysis of the INITIUM data will be initiated in mid-January 2024, following an amendment of the clinical trial protocol. The INITIUM protocol has been amended to allow data readout based on a minimum of 18-month follow-up of all evaluable patients, at which time the patients have a mean follow-up time of 24 months. The amendment will maintain the integrity of the study statistics.

The protocol amendment was submitted to the regulatory authorities in the countries where the INITIUM trial is conducted: The U.S. Food and Drug Administration (FDA) and regulatory bodies in Belgium, Norway, and the U.K. The FDA has not issued any objections to the amendment and the Regulatory Authorities in two European countries have approved the amendment with one pending.

The INITIUM study (NCT04382664) evaluates Ultimovacs’ universal cancer vaccine, UV1, as first-line treatment in unresectable or metastatic malignant melanoma in combination with PD-1 checkpoint inhibitor nivolumab and CTLA-4 checkpoint inhibitor ipilimumab. The first patient was enrolled in June 2020, and the trial completed enrollment of 156 patients in July 2022. Per the original trial protocol, data analysis would be conducted after cancer progression or death has been verified in 70 patients.

Based on published historical references, progression was estimated to occur in 70 patients by the first half of 2023. With the current development in patient progression, reaching these 70 events could take many months or even years, justifying the decision to implement the protocol amendment. Based on the recent acceptance from the regulators, the data can now be analyzed in early 2024, enabling Ultimovacs to maintain its guidance on reporting the outcome of the study two to three months later in the first half of 2024.

"We are pleased for the patients in the INITIUM study that it takes longer than anticipated to experience progression of the disease. With positive survival results from the first randomized Phase II study in malignant mesothelioma, a very hard-to-treat cancer, we are increasingly optimistic about UV1’s potential to benefit cancer patients. As we seek to bring UV1 to the patients as quickly as possible, it is important to advance the INITIUM trial towards a data readout,” said Carlos de Sousa, CEO of Ultimovacs. "We appreciate the support from regulatory authorities, and we now look forward to sharing the results in the first half of 2024.”

The primary endpoint of the Phase II study INITIUM is progression-free survival (PFS) as per RECIST 1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety of UV1 vaccination in combination with nivolumab and ipilimumab.

Ultimovacs has received a dual Fast Track designation from the FDA, granted in October 2021, for UV1 in combination with checkpoint inhibitors in the treatment of unresectable or metastatic melanoma – either as add-on therapy to pembrolizumab or as add-on therapy to ipilimumab. In December 2021, UV1 was granted Orphan Drug designation from the FDA for treatment of stage IIB-IV melanoma.

UV1 is a therapeutic cancer vaccine used to generate an immune response against the enzyme human telomerase (hTERT).  The enzyme is essential for the ability of cancer cells to proliferate. Telomerase is present in 85-90% of all cancers, across the stages of the disease. The vaccine is manufactured as an off-the-shelf product with a long shelf life. UV1 is easy to use and does not require sophisticated hospital infrastructure, enabling patient access to therapy also in community centers, and rural and underserved communities.

Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical development program across various cancer indications with different biology and disease stages, combined with different checkpoint inhibitors. The topline data from INITIUM will be 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, 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 second half of 2024.

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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 was 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 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 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’ adjuvant platform, based on the proprietary Tetanus-Epitope-Targeting (TET) technology, combines tumor-specific antigens and adjuvant in the same molecule and is in Phase I clinical development.
The Company is listed on the Euronext Oslo Stock Exchange (ULTI.OL).

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. As of the Q2 2023 report, 70 events were not reached. Expected readout H1 2024. 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 an add-on to ipilimumab and nivolumab, demonstrated a statistically significant and clinically meaningful improvement in overall survival versus ipilimumab and nivolumab alone. 31% of the patients receiving the 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 H2 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. >20% of 184 patients enrolled as of Q2 2023 reporting, expected readout H2 2024. 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. <10% of 138 patients enrolled as of Q2 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 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 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 Investor Relations at Ultimovacs ASA, on October 31, 2023 at 07:00 CET.