Ultimovacs Provides Complete Phase II NIPU Results Presented at ESMO 2023: Significant and Clinically Meaningful Improvement in Overall Survival for Patients with Malignant Mesothelioma Receiving UV1

• UV1, in combination with the checkpoint inhibitors ipilimumab and nivolumab from Bristol-Myers Squibb, met the study protocol’s predefined threshold for statistical significance and 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
  
  
• First demonstration of universal cancer vaccine efficacy in randomized Phase II clinical trial; Proof of Concept supporting further clinical development
  
  
• Webcast presentation by Principal Investigator Professor Åslaug Helland, MD, PhD, and Ultimovacs management will take place today, Mon, Oct 23, 2023, at 14:30 am (CET). The slide presentation is attached to this announcement. The webcast can be accessed live or as a replay (link). Company presentation, incl. NIPU data is available on the Ultimovacs website.  

Oslo, October 23, 2023: Ultimovacs ASA ("Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines, today announced the full dataset from the NIPU clinical trial (NCT04300244) presented at the ESMO Congress 2023 in Madrid. NIPU is an investigator-initiated, randomized, multi-center, open-label Phase II clinical trial for second-line treatment in patients with malignant mesothelioma (MPM).

The data from the study was published initially in a late-breaking abstract at ESMO. Further details have now been provided in an oral presentation by the Principal Investigator at the ESMO Congress. The results showed that Ultimovacs’ cancer vaccine UV1, in combination with ipilimumab and nivolumab, demonstrated a statistically significant and clinically meaningful improvement in overall survival versus ipilimumab and nivolumab alone, a key secondary endpoint. No additional safety concerns were reported from the UV1 treatment.

UV1 plus ipilimumab and nivolumab improved overall survival (OS), reducing the risk of death by 27% (hazard ratio (HR)=0.73 [80% CI, 0.53-1.00], 1-sided p value = 0.0985, 2-sided p value = 0.197). 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 the protocol's predefined threshold for statistical significance.

The data further demonstrated a benefit in terms of objective response rate (tumor reduction by at least 30%), as determined by blinded independent central review (BICR). In the UV1 arm, 31% of the patients experienced an objective response, compared to 16% in the control arm (odds ratio 2.44 [80% CI, 1.35-4.49], 1-sided p value = 0.028).

The baseline patient characteristics were well balanced between the two treatment arms. The epithelioid subtype of MPM comprised 77.1% of the study population, in line with the frequency of this subtype among the general MPM population. Notably, the trial enrolled a relatively high fraction of patients with PD-L1 negative tumor biopsies (53.4%), a characteristic for patients typically less responsive to checkpoint inhibitors alone.

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 results from the first randomized UV1 Phase II trial, NIPU presented by the Principal Investigator Professor Åslaug Helland at ESMO 2023, is a proof of concept for UV1. These data reaffirm our unwavering commitment to developing UV1 as an effective add-on treatment to checkpoint inhibitors for a range of cancers. We eagerly anticipate the forthcoming results from our other ongoing Phase II trials and how these data will move us forward in our mission to improve outcomes for cancer patients worldwide,” said Carlos de Sousa, CEO of Ultimovacs.

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 was conducted in Australia, Denmark, Norway, Spain, and Sweden. The trial enrolled 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 trial was designed to detect a clinically meaningful difference between the two treatment groups and includes a statistical analysis plan typical for randomized phase 2 trials where the aim is to assess efficacy without recruiting a large number of patients. Both the study protocol and the statistical plan were approved by the regulatory authorities. It was set up with 80% statistical power and a 1-sided alpha of 0.1. This means we can be 80% confident that we've accurately measured the effects of UV1. According to the trial protocol and the number of patients included, the trial results are presented with 80% confidence intervals and are considered statistically significant if the one-sided p-value is below 0.1.

Ultimovacs announced topline NIPU study results in June 2023. Based on 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, 1-sided p value = 0.4895, 2-sided p value = 0.979), 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, 1-sided p value = 0.0125, 2-sided p value = 0.025), 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.

In October 2023, Ultimovacs announced that the U.S. Food and Drug Administration (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 that generates an immune response against the human telomerase (hTERT) enzyme.  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 biology 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 were randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every two weeks) and ipilimumab (1 mg/kg every six weeks) until disease progression, unacceptable toxicity, or for a maximum of 2 years. Patients randomized to the experimental arm received eight 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 the 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 surrounding 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 the 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 one 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. Few treatment options are available after first-line chemotherapy for patients with inoperable disease. 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.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, 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, the results were 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 with eight intradermal injections and 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 23, 2023 at 07:00 CET.

Attachment

• 20231023_Ultimovacs_webcast_NIPU_ESMO