The company’s universal cancer vaccine, UV1, in combination with the checkpoint inhibitor pembrolizumab, has recently demonstrated a 60% objective response rate in metastatic malignant melanoma.

Nordic Life Science asked the Chief Medical Officer (CMO) of Ultimovacs, Jens Bjørheim, about the new findings and the company’s further development of UV1.

Describe your reactions to these new, very encouraging, findings and what this data means for the company’s further development of UV1?

“We presented 18 months landmark data from 20 patients with advanced malignant melanoma at the ASCO annual meeting in June 2021. The safety profile of combined treatment with pembrolizumab and UV1 was as expected for pembrolizumab monotherapy treatment alone, apart from injection site reactions. The safety profile of the UV1 vaccine in this study opens for combination treatment with little risk that UV1 adds much to safety events.”

“The results from that study, together with the results from the current study, give us confidence moving forward within this indication.”

“On the efficacy side the objective response rate was high compared with results reported for pembrolizumab alone. The most surprising was 6 complete responders among the 30 patients, corresponding to a complete response rate of 30%. We have previously conducted a phase 1 trial with 12 patients where we combined ipilimumab and the vaccine. The results from that study, together with the results from the current study, give us confidence moving forward within this indication.”

[August 12, Ultimovacs also announced positive results from the second cohort of 10 patients after one year of the ongoing trial. Tumor shrinkage was evident in six of the 10 patients, a 60% objective response rate. In three of the patients, the tumors were reduced to undetectable levels, a 30% complete response rate.]

Describe the advantages of the design of your vaccine?

“The UV1 vaccine is a peptide-based therapeutic cancer vaccine. The antigen we vaccinate towards is the enzyme telomerase (hTERT). This is a highly relevant target because 80-90% of all cancer indications express this antigen, so the vaccine might become relevant for a very large number of cancer patients. The telomerase expression in these cancer patients is mainly due to mutations that appear early in the development of the cancer. Therefore, the vaccine might be relevant in different stages of cancer and in all parts of the cancer.”

“Further, within the vaccine peptides there are several sequences or epitopes that can be recognized by T-cells, so we do not need to perform tissue typing (HLA-analysis) of the patients prior to inclusion in studies.”

UV1-vaksinen injiseres i huden på pasientens mage og innholdet i vaksinen (telomerasepeptidene) tas opp av såkalte antigen-presenterende celler Disse cellene transporterer peptidene til lymfeknuten der de aktiverer T celler rettet mot telomerase. Sjekkpunkthemmere «slipper opp bremsen» slik at flere T celler lages. T cellene går over i blodbanen og infiltrerer pasientens kreftsvulst T cellene gjenkjenner telomerase i svulsten og dreper kreftcellene. Her vil sjekkpunkthemmere føre til økt effektivitet av T cellene og drap av kreftceller. Credit: Ultimovacs / BioRender

 

“The production of the vaccine is pretty much straight-forward. It consists of synthetic peptides in powder form, has a long shelf life and is “off-the-shelf” – one vaccine fits all (80-90% of patients).”

What’s next for your development of UV1 and what results can we expect this fall and during 2022?

“The data presented at ASCO was from one of two cohorts in that study. Over the next half year data from the second cohort will also be presented. A phase 2 study in malignant melanoma is also initiated. In that randomized study, all patients receive ipilimumab and nivolumab, whereas half the patients receive the UV1 vaccine on top. A total number of 154 patients will be included in US, UK, Belgium and Norway and inclusion of patients started in June 2020. Topline results are expected late 2022.”

“UV1 is also part of three other randomized phase 2 studies where external collaborators are sponsors of the trials. The NIPU study is testing UV1 in combination with the checkpoint inhibitors ipilimumab and nivolumab as second-line treatment in 118 patients with advanced malignant pleural mesothelioma, a rare lung cancer. The study started to recruit patients in June 2020 and is expected to report topline results late in 2022. In the DOVACC study, 184 patients with high-grade ovarian cancer will be enrolled to evaluate UV1 in combination with durvalumab and olaparib. This study will start to include patients over the next few months. The third study, the FOCUS study, is an investigator-sponsored, randomized trial enrolling 75 patients with metastatic head and neck cancer receiving pembrolizumab as standard of care. This study will evaluate the impact of adding UV1 to this regimen and will also start to include patients over the next few months.”

“Unfortunately, it seems that not all patients have a T-cell repertoire that can kill off the cancer when treated with CPIs. For these patients we believe that a telomerase-based cancer vaccine could be of benefit to complement a suboptimal T-cell pool in the patient.”

Many say we are in the beginning of a new era in cancer treatment. What are your hopes for the future of treating cancer using your cancer vaccine?

“The immune system has proved to be a highly relevant tool in the fight against cancer. With the approved check point inhibitors (CPIs) several patients have a better prognosis now as compared to only 10 years back. CPIs are however dependent on a pre-existing pool of T-cells in the patient for the treatment to be effective. In some patients this has led to long-term survival, for example in non-small cell lung cancer and malignant melanoma. Unfortunately, it seems that not all patients have a T-cell repertoire that can kill off the cancer when treated with CPIs. For these patients we believe that a telomerase-based cancer vaccine could be of benefit to complement a suboptimal T-cell pool in the patient.”

Photo of Jens Bjørheim: Anton Soggiu. This interview was originally published in No 03 2021 of Nordic Life Science magazine