• No confirmed patient deaths occurred in cohort 1 between the 3-year and 4-year follow-up.
  
  

Oslo, October 12, 2023: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines, today announced encouraging overall survival (OS) data from cohort 1 in the UV1-103 Phase I clinical trial in malignant melanoma. Among the patients in cohort 1 who were alive at the 3-year follow-up, no further deaths have been reported, reaffirming an encouraging trend of durable overall survival benefit from UV1 vaccination.   

The UV1-103 study evaluates Ultimovacs’ universal cancer vaccine, UV1, in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, as first-line treatment in patients with advanced non-resectable or metastatic malignant melanoma. The study enrolled 30 patients in the U.S. in two cohorts that differed only in the concentration of GM-CSF used as vaccine adjuvant.

Three patients in cohort 1 chose not to be followed up after 2 years. Measured in absolute numbers, the overall survival in cohort 1 after 3-year follow-up was 71% (12 out of 17 patients). Out of the 17 patients included in the 4-year follow-up, one patient could not be reached temporarily, and the status is pending. Employing a conservative approach, 11 out of 16 patients were confirmed alive after 4 years, indicating an overall survival of 69% based on absolute numbers. Overall survival from the trial based on Kaplan-Meier estimates is described below. The 4-year survival across both cohorts is expected to be announced in Q2 2024.

Ultimovacs has previously reported data showing a complete response rate in the UV1-103 study of 33% (complete disappearance of tumors) and an objective response rate of 57% (complete or partial disappearance of tumors). Biomarker analyses reported in October 2022 showed robust clinical responses in patients treated with the combination of UV1 and pembrolizumab, regardless of patients’ PD-L1 status. The safety profile of UV1 in combination with pembrolizumab is comparable to that of pembrolizumab alone.

“We are very encouraged to report a durable and long-term overall survival rate at the 4-year follow-up in the UV1-103 study. The data further strengthen the previously reported results from the study, including good safety for UV1 and the high number of complete responses in patients with metastatic malignant melanoma where surgery is not an option,” said Jens Bjørheim, Chief Medical Officer at Ultimovacs. “The UV1-103 study treats the same patient population as our Phase II study INITIUM. As we await data from the first three randomized UV1 Phase II trials in the near-term, we are increasingly optimistic about UV1’s potential to benefit cancer patients.”

Ultimovacs is investigating UV1 in malignant melanoma in its randomized Phase II INITIUM trial of UV1 in combination with ipilimumab and nivolumab. The trial completed enrollment of 156 patients with advanced non-resectable or metastatic malignant melanoma in July 2022. The top-line results will be disclosed after cancer progression has been verified in 70 patients, which has not yet occurred due to patients taking longer than estimated to experience cancer progression. The outcome of the study is now expected to be announced in the first half of 2024.

==ENDS==

About the UV1-103 phase I trial in Malignant Melanoma

This US-based Phase I clinical trial evaluates the Company’s lead candidate, UV1, combined with the anti-PD-1 checkpoint inhibitor, pembrolizumab, as a first-line treatment in patients with unresectable metastatic malignant melanoma. The trial evaluates safety, tolerability, and initial signs of clinical response. Thirty patients in the U.S. were treated in the study in two cohorts that differed only in the concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) used as vaccine adjuvant.  The 20 patients in the first cohort received a 37.5 mcg GM-CSF adjuvant dose per UV1 vaccination. The 10 patients in the second cohort received the standard 75 mcg GM-CSF adjuvant dose per UV1 vaccination. The study has completed the enrollment of 30 patients, as announced on August 18, 2020. All included patients received the drugs as first-line treatment for advanced and metastatic malignant melanoma.

Compiled clinical results for the 30 patients enrolled are:  

• Objective response rate (ORR): 57%. Complete response rate (CR): 33%
• Median progression-free survival (mPFS): 18.9 months (as measured by iRECIST)
• Out of the 9 deaths, 4 happened during the first year, 4 during the second year, and one during the third year across both cohorts.
  

Patients will continue to be followed up for long-term survival. Three patients in cohort 1 chose not to be followed up further after 24 months. The trial had previously reached its primary endpoint of safety and tolerability, and no unexpected safety issues related to UV1 have been observed in this trial.

Overall survival in UV1-103 based on absolute numbers (conservative approach, only including confirmed surviving patients):

1-year: Cohort 1: 85.0% (n= 17/20)   I   Cohort 2: 90% (n= 9/10)   I   Both cohorts: 86.7% (n= 26/30)
2-year: Cohort 1: 80.0% (n= 16/20)   I   Cohort 2: 60% (n= 6/10)   I   Both cohorts: 73.3% (n= 22/30)
3-year: Cohort 1: 70.6% (n= 12/17)   I   Cohort 2: 60% (n= 6/10)   I   Both cohorts: 66.7% (n= 18/27)
4-year: Cohort 1: 68.8% (n= 11/16)   I   Cohort 2: N.A.  I   Both cohorts: N.A.

The Kaplan-Meier survival curve is defined as the probability of surviving in a given length of time while considering time in many small intervals. Overall survival in UV1-103 based on Kaplan-Meier estimates:

1-year: Cohort 1: 85.0%   I   Cohort 2: 90%   I   Both cohorts: 86.7%
2-year: Cohort 1: 80.0%   I   Cohort 2: 60%   I   Both cohorts: 73.3%
3-year: Cohort 1: 73.8%   I   Cohort 2: 60%   I   Both cohorts: 69.5%
4-year: Cohort 1: 73.8%   I   Cohort 2: N.A.   I   Both cohorts: N.A.

As a historical reference (not a head-to-head comparison since dosing and the patient population differ), the registration study Keynote-006 for pembrolizumab reported a 48-month overall survival rate of 45.7%.

In December 2021, the U.S. Food and Drug Administration (FDA) granted a dual Fast Track designation 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.

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.

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 with eight intradermal injections and 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 October 12, 2023 at 07:00 am CET.