Ultimovacs provides update on Phase II NIPU trial evaluating UV1 in second-line patients with malignant pleural mesothelioma

• The central independent review concluded that the NIPU study did not meet the primary endpoint of progression-free survival (PFS). However, a statistically significant improvement in PFS for patients receiving UV1 was measured in a separate pre-defined local assessment at the participating hospitals
• The trial investigators also observed an improvement in overall survival in the UV1 arm over the control arm, although the data need to mature before a conclusion can be reached
• Safety profile was similar in both arms of the trial, confirming good safety profile for UV1
• Detailed, updated results will be shared at an upcoming medical conference
• Two additional ongoing UV1 Phase II trials in malignant melanoma and head and neck cancer expected to report within a year

Webcast to take place tomorrow, 8 June 2023 at 10:00 am (CET). Webcast link

Oslo, 7 June 2023: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines, today announced the topline results of  NIPU, an investigator-initiated Phase II trial in patients indicated for second-line treatment of malignant pleural mesothelioma (MPM). Based on central review, the study did not meet the primary endpoint of PFS. Investigator assessment of the primary endpoint, a pre-defined supportive analysis, showed a statistically significant positive PFS benefit for the patients in the UV1 arm. The central review was performed by a blinded, independent clinical research organization, whereas the investigator assessment was performed by specialized radiologists at the study hospitals.

Current data indicates improvement in overall survival in the UV1 arm over the control arm, but the data need to mature before a conclusion can be reached. The safety profile of the combination of UV1 plus ipilimumab and nivolumab (treatment arm) observed in the trial was consistent with the safety profile of ipilimumab and nivolumab alone (control arm), confirming the good safety profile for UV1. Further results from the study will be presented by the sponsor at an upcoming medical conference. The patients will continue to be monitored for efficacy and safety endpoints over the next years.

“The results showed that the NIPU trial did not meet the primary endpoint of PFS based on blinded independent central review. Based on investigator assessment, a pre-defined supportive analysis of PFS, the study showed a statistically significant improvement in PFS for patients receiving UV1,” said Åslaug Helland, Principal Investigator in the NIPU trial and Professor at Oslo University Hospital. “Further, the data show a positive trend towards improvement in overall survival in the UV1 arm over the control arm, although it is still early, and the data need to mature before we can reach a conclusion. Overall survival is the most important efficacy measure in cancer treatment. We are encouraged by the results and look forward to further understanding the vaccine’s role in improving survival in this hard-to-treat patient group. Detailed, updated results will be shared at an upcoming medical conference. We wish to thank the patients and investigators for their participation and important contributions to the NIPU study.”

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 Scandinavia, Spain, and Australia 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 pleural mesothelioma as a second-line treatment, 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 randomized in January 2023.

“NIPU was a tough challenge because mesothelioma is known as a very hard-to-treat form of cancer particularly in second-line treatment where there is no established standard of care. Despite not meeting the primary endpoint of PFS based on central review, we are encouraged by the overall results including safety, PFS based on investigator assessment, and preliminary overall survival. We are looking forward to learning more about the data and especially the overall survival, when the data have matured,” said Carlos de Sousa, Chief Executive Officer, Ultimovacs. “We are now even more optimistic about the ongoing Phase II clinical development program, which will report data from two additional studies in different cancer indications within a year.”

MPM is considered an aggressive, complicated 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 MPM. There is currently no established standard of care in second-line treatment. The biological characteristics of pleural mesothelioma set it apart from other cancer types being investigated in the UV1 clinical program. 

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.

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 currently five randomized trials in the UV1 Phase II clinical program. In addition to malignant pleural mesothelioma, Phase II studies are ongoing in patients with MPM, 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 within a year. UV1 is a patented, proprietary technology owned by Ultimovacs.

A webcast will be hosted by Ultimovacs management team tomorrow 8 June 2023 at 10:00 CET (link). The presentation will be held in English and questions can be submitted throughout the event. Link to the webcasts will also be available on Ultimovacs’ website.

==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 pleural 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 progression-free survival (PFS) benefit in patients with malignant pleural 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.

About Mesothelioma

Malignant pleural 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). Pleural 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 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 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 UV1 Phase II program’s diversity puts Ultimovacs in an advantageous position to capture  the cancer vaccine’s potential broad applicability when combined with checkpoint inhibitors, for further clinical development:

• 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 H2 2023. 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. Topline results announced June 2023. Investigator-initiated study led by Oslo University Hospital, supported by Bristol-Myers Squibbs and Ultimovacs.
• FOCUS: Evaluating UV1 in combination with pembrolizumab as first-line treatment for patients with head and neck cancer. >80% of 75 patients recruited as of Q1 2023 reporting, expected readout H1 2024. Investigator-initiated study 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 recruited as of Q1 2023 reporting, expected readout H2 2024. Investigator-initiated study led by NSGO-CTU, supported by ENGOT, AstraZeneca and Ultimovacs.
• LUNGVAC: Evaluating UV1 in combination with cemiplimab as first-line treatment of patients with non-small cell lung cancer. <10% of 138 patients recruited as of Q1 2023 reporting, expected readout H2 2025. Investigator-initiated study led by Vestre Viken (Drammen Hospital), supported by Ultimovacs.

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 that 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’ 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.

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 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 Investor Relations at Ultimovacs ASA, on 7 June, 2023 at 19:00 CET.