Ultimovacs Announces NIPU Results Presented at ESMO 2023: Significant and Clinically Meaningful Improvement in Overall Survival for Patients Receiving UV1 Cancer Vaccine in Phase II NIPU Trial in Mali

• UV1, in combination with the checkpoint inhibitors ipilimumab and nivolumab from Bristol-Myers Squibb, demonstrated a clinically meaningful overall survival benefit with no added toxicities, compared to ipilimumab and nivolumab alone, in the second-line treatment of patients with malignant mesothelioma
• The UV1 cancer vaccination combined with ipilimumab and nivolumab reduced the risk of death by 27%, meeting the protocol predefined threshold for statistical significance, in a hard-to-treat patient group with currently no standard-of-care treatment options
• First demonstration of universal cancer vaccine efficacy and therapeutic impact in a randomized Phase II clinical trial, supporting further clinical development
• NIPU results to be presented by the Principal Investigator Professor Åslaug Helland, MD, Ph.D., at the ESMO Congress 2023 happening this week in Madrid
  
  
• The full dataset will be shared in a separate press release and at the Company website after the Principal Investigator’s oral presentation, Saturday October 21, 2023 at 15:15 (CET)
• Webcast with the Principal Investigator and Ultimovacs management to take place
  on Mon, Oct 23 2023 at 14:30 (CET) <Link to webcast>
  
  

Oslo, October 17, 2023: Ultimovacs ASA ("Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines, today announced the results from the NIPU clinical trial (NCT04300244), an investigator-initiated, randomized, multi-center, open-label Phase II clinical trial for second-line treatment in patients with malignant mesothelioma. The data presented as a late-breaking abstract at the ESMO Congress, shows that Ultimovacs’ cancer vaccine UV1, in combination with ipilimumab and nivolumab, demonstrated a statistically significant and clinically meaningful improvement of overall survival versus ipilimumab and nivolumab alone, a key secondary endpoint. No additional safety concerns were reported from the UV1 treatment. The late-breaking abstract is accessible at the ESMO website.

Malignant mesothelioma is considered an aggressive, complex form of cancer with a high mortality rate and few therapeutic options. Patients affected have often been occupationally or environmentally exposed to asbestos. Several efforts have been made in the last decades to improve the survival outcomes of patients with mesothelioma. There is currently no established standard of care in second-line treatment.

"For patients with malignant mesothelioma, few treatment options are available after first-line chemotherapy. The NIPU study showed that patients receiving UV1 vaccination as add-on to nivolumab and ipilimumab experienced an increased objective response rate and a clinically meaningful prolonged survival. These encouraging results provide a foundation for advancing further clinical development with UV1 vaccination in mesothelioma patients,” said Principal Investigator of the NIPU clinical trial, Professor Åslaug Helland, MD Ph.D. "We want to extend our gratitude to the patients and their families, as well as the dedicated investigators and all our supporters whose invaluable contributions made this study possible.”

The results showed that UV1 plus ipilimumab and nivolumab improved overall survival (OS), reducing the risk of death by 27% (HR=0.73 [80% CI, 0.53-1.00]). The median OS was 15.4 months (95% CI, 11.1-22.6) for UV1 plus ipilimumab and nivolumab (treatment arm) versus 11.1 months (95% CI, 8.8-18.1) for ipilimumab and nivolumab alone (control arm), with a median observation time of 17.3 months. This degree of improvement met protocol predefined threshold for statistical significance.

The data further demonstrated a benefit in terms of objective response rate, as determined by a blinded independent central review. In the UV1 arm, 31% of the patients experienced an objective response, as compared to 16% in the control arm (odds ratio 2.44 [80% CI, 1.35-4.49]).

The safety profile of the combination of UV1 plus ipilimumab and nivolumab observed in the trial was consistent with the safety profile of ipilimumab and nivolumab alone, confirming the good safety profile for UV1. The patients will continue to be monitored for efficacy and safety endpoints over the next years.

The title of the late-breaking ESMO abstract is "LBA99 First survival data from the NIPU trial; A randomized, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma.”

"We are thrilled to announce the highly advantageous results from the first randomized UV1 Phase II trial, marking a major milestone for Ultimovacs. Overall survival is the ‘gold standard’ in cancer treatment. We believe these data supports further development in mesothelioma, and we are looking forward to discussing the results with the regulatory authorities,” said Carlos de Sousa, CEO of Ultimovacs. "UV1, by demonstrating significant survival improvement in a hard-to-treat indication as malignant mesothelioma, shows that universal cancer vaccines are a treatment modality with the potential to improve the current treatment regime for cancer patients globally. The encouraging NIPU results heighten our optimism and raise our expectations for favorable results in the four additional ongoing UV1 Phase II trials. I would like to thank everyone who has contributed, especially Professor Åslaug Helland, who invited us to participate in the study, and Bristol-Meyers Squibb for their valuable contribution.”

The NIPU study is sponsored by Oslo University Hospital with support from Bristol-Myers Squibb and Ultimovacs. The randomized, open-label, multi-center trial with 118 patients conducted in Australia, Denmark, Norway, Spain, and Sweden, was designed to investigate if combining UV1 with checkpoint inhibitors ipilimumab and nivolumab would provide a benefit compared to ipilimumab and nivolumab alone, in patients with malignant mesothelioma after first-line treatment with platinum-based chemotherapy. The first patient in the NIPU trial was enrolled in June 2020, and the last patient was enrolled in January 2023.

The NIPU study announced topline results in June 2023. Based on blinded independent central review (BICR), the study did not meet the primary endpoint of PFS. Investigator assessment, a pre-defined supportive analysis of the primary endpoint performed by specialized radiologists at the study hospitals, showed a statistically significant positive PFS benefit for the patients in the UV1 arm. The HR per BICR was 1.01 (80% CI 0.75-1.36), with a median PFS of 4.2 months (95% CI 2.9-9.8) for UV1 plus ipilimumab and nivolumab, and 4.7 months (95% CI 3.9-7.0) for ipilimumab and nivolumab alone. The HR per investigator assessment was 0.60 (80% CI 0.45-0.81), with a median PFS of 4.3 months (95% CI 3.0-6.8) for UV1 plus ipilimumab and nivolumab and 2.9 months (95% CI 2.4-5.5) for ipilimumab and nivolumab alone.

The data from June 2023 showed a positive trend of improvement in overall survival in the UV1 arm over the control arm, but the data needed to mature before a conclusion could be reached. As of August, with a median observation time of 17.3 months, the data presented at ESMO demonstrates survival benefit for patients receiving the UV1 vaccine in the NIPU study.  

In October 2023, Ultimovacs announced that FDA had granted Orphan Drug Designation for UV1 in the treatment of mesothelioma (based on the NIPU data from June 2023).

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 in rural and underserved communities.

Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical development program across various cancer indications with different biologies and disease stages, in combination with different checkpoint inhibitors. The topline data from NIPU are the first results among the five randomized trials in the UV1 Phase II clinical program. In addition to malignant mesothelioma, Phase II studies are ongoing in patients with malignant melanoma, head and neck cancer, ovarian cancer, and non-small cell lung cancer. The topline data from the malignant melanoma and head and neck cancer trials are expected during the first and second half of 2024. UV1 is a patented, proprietary technology owned by Ultimovacs.

==ENDS==

About NIPU
NIPU (Nivolumab and Ipilimumab Plus/minus UV1 vaccination) is a randomized, multi-center phase II trial in which Ultimovacs’ universal cancer vaccine, UV1, is evaluated in combination with Bristol-Myers Squibb’s checkpoint inhibitors, nivolumab and ipilimumab, as second-line treatment of malignant mesothelioma. The trial sponsor is Oslo University Hospital, supported in the preparation and execution of the trial by Ultimovacs and Bristol-Myers Squibb.

The 118 patients are randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomized to the experimental arm received 8 intradermal injections of UV1 vaccine during the first three months of treatment. The objective of the study is to achieve a clinically meaningful benefit in patients with malignant mesothelioma (MPM) after progression on first-line standard platinum doublet chemotherapy. Subsequent events emerging in patients in both arms of the NIPU study will continue to be monitored beyond read-out of the primary endpoint. The ipilimumab and nivolumab combination has recently been approved as first-line treatment for patients with malignant pleural mesothelioma in Europe and the U.S.

The trial was sized to detect a target PFS HR of 0.6, with 80% power and a 1-sided alpha of 0.1. Overall survival was calculated using the same method as for PFS.

About Mesothelioma

Malignant mesothelioma is a rare and aggressive type of cancer that occurs in the thin layer of tissue that surrounds the lungs and inside of the chest. Mesothelioma accounted for 30 870 new cancer cases and 26 278 cancer deaths worldwide in 2020, according to International Agency for Research on Cancer (Globocan 2020). Mesothelioma is a disease with a high unmet medical need, especially in industrialized countries. The median overall survival is approximately 1 year.  Occupational asbestos exposure is the No. 1 cause of the disease, and several occupations like firefighters, military veterans, construction, and industry workers, are at risk. This cancer usually takes several decades to develop after a person’s first exposure to asbestos. Most patients are diagnosed after age 70 because of the long latency period. Even though the use of asbestos to a large extent is banned in new constructions in many countries today, new incidences of mesothelioma will continue to be a medical and public health challenge because of the long latency period typical of the illness. For patients with inoperable disease, few treatment options are available after first-line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond, and improvements are called for. Telomerase is expressed in mesothelioma cells and is therefore a relevant target for therapeutic vaccination.

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 Euronext Oslo Stock Exchange (ULTI).

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. 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; results will be presented at the ESMO Congress in October 2023. 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, 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.

A link to the webcast and the comprehensive results from the NIPU study may be accessed from the Company website www.ultimovacs.com. 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 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 Investor Relations at Ultimovacs ASA, on October 17, 2023 at 18:05 CET.