UV1 Cancer Vaccine Receives FDA Fast Track for Mesothelioma

The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to UV1, a therapeutic cancer vaccine developed by Ultimovacs, for the treatment of malignant pleural mesothelioma. This regulatory milestone accelerates the development pathway for a novel immunotherapy approach that trains the immune system to attack cancer cells expressing telomerase.

UV1 represents a fundamentally different approach to cancer immunotherapy. Unlike checkpoint inhibitors that release the brakes on immune cells, UV1 actively educates the immune system to recognize and target a specific protein called telomerase, which is expressed by the vast majority of mesothelioma tumors but not by normal adult cells.

What Is UV1?

UV1 is a peptide-based therapeutic cancer vaccine consisting of three synthetic peptides derived from human telomerase reverse transcriptase (hTERT). When injected, these peptides stimulate the patient’s immune system to generate T cells that specifically recognize and kill cancer cells expressing telomerase.

Key characteristics:

• Peptide vaccine: Three short protein fragments from telomerase
• Intradermal injection: Administered as injections into the skin
• Adjuvant required: Given with GM-CSF to enhance immune response
• Universal target: Telomerase is expressed in >85% of cancers, including mesothelioma
• Combination approach: Most effective when combined with checkpoint inhibitors

Why Telomerase?

Telomerase is an enzyme that maintains telomeres, the protective caps at the ends of chromosomes. In normal adult cells, telomerase is largely inactive, allowing cells to age and eventually stop dividing. Cancer cells, however, reactivate telomerase to achieve immortality and divide indefinitely.

Telomerase as a target:

• Present in over 85% of all cancers, including mesothelioma
• Rarely expressed in normal adult tissues (except stem cells)
• Essential for cancer cell survival: tumors cannot simply downregulate it
• Universal antigen: same target across different cancer types

This makes telomerase an ideal target for vaccination: it’s broadly expressed in cancer, absent from most normal cells, and critical for tumor survival.

The FDA Fast Track Designation

The FDA’s Fast Track program facilitates the development of drugs addressing serious conditions with unmet medical needs. For UV1, the designation means:

Expedited development: More frequent FDA interactions and guidance during clinical trials

Rolling review: The company can submit completed sections of its application as they’re ready, rather than waiting until the entire submission is complete

Priority review potential: If the drug meets additional criteria, it may qualify for priority review, shortening the review period from 10 months to 6 months

Breakthrough designation possibility: Strong clinical data could lead to additional breakthrough therapy designation

Clinical Trial Results

UV1 has been studied in multiple cancer types. The data supporting the mesothelioma Fast Track designation comes from a Phase 2 study combining UV1 with pembrolizumab (Keytruda), a PD-1 checkpoint inhibitor.

INITIO Trial (Mesothelioma Cohort):

• Patient population: Previously untreated malignant pleural mesothelioma
• Treatment: UV1 vaccine plus pembrolizumab
• Primary endpoint: Objective response rate (ORR)

Results:

• Overall response rate: 64% (complete + partial responses)
• Disease control rate: Over 90%
• Median progression-free survival: Approximately 12 months
• Durable responses: Many responses lasting beyond 6-12 months

These response rates compare favorably to pembrolizumab alone in mesothelioma, suggesting the vaccine provides meaningful benefit when added to checkpoint inhibition.

Safety:

• UV1 was well-tolerated with primarily local injection site reactions
• Systemic immune-related adverse events were manageable
• No new safety signals beyond what’s expected with pembrolizumab

How UV1 Works with Checkpoint Inhibitors

The combination of UV1 with checkpoint inhibitors creates a synergistic anti-cancer immune response:

Step 1: Vaccination (UV1)

• UV1 peptides are injected into the skin with GM-CSF adjuvant
• Dendritic cells pick up the peptides and present them to T cells
• T cells that recognize telomerase are activated and multiply
• These T cells enter the bloodstream seeking telomerase-expressing cells

Step 2: Checkpoint Inhibition (Pembrolizumab)

• Tumor cells often express PD-L1 to “hide” from the immune system
• PD-1 inhibitors block this “hiding” mechanism
• The telomerase-specific T cells generated by UV1 can now attack tumor cells effectively
• The combination amplifies anti-tumor immunity

The synergy: UV1 creates an army of cancer-specific T cells, while pembrolizumab removes the barriers preventing those T cells from killing tumors. Neither approach alone is as effective as both together.

Comparison to Other Immunotherapies

UV1 vs. Checkpoint Inhibitors Alone:

• Checkpoint inhibitors release immune brakes but don’t direct the immune response
• UV1 specifically trains T cells to recognize cancer, then checkpoint inhibitors allow them to attack
• Combination may produce deeper, more durable responses

UV1 vs. Nivolumab/Ipilimumab:

• Nivo/Ipi is the current standard first-line immunotherapy for mesothelioma
• UV1 + pembrolizumab may offer an alternative with different toxicity profile
• Head-to-head comparison needed to determine relative efficacy

UV1 vs. CAR-T:

• CAR-T requires extracting and engineering patient’s own cells
• UV1 is an off-the-shelf vaccine administered in clinic
• CAR-T is more intensive but potentially more powerful for individual patients

What This Means for Patients

Current access:

• UV1 is not yet approved; access is limited to clinical trials
• Ultimovacs is planning pivotal Phase 3 studies
• Ask your oncologist about trial eligibility

Future potential:

• If Phase 3 trials succeed, UV1 could become a standard component of first-line therapy
• May provide option for patients who don’t respond to current immunotherapies
• Could extend benefits of immunotherapy to more patients

Questions to ask your doctor:

• Am I eligible for UV1 clinical trials?
• How does UV1 compare to current standard immunotherapy?
• What is my tumor’s telomerase expression status?
• Would adding a cancer vaccine make sense for my treatment plan?

The Development Path Forward

Planned studies:

• Randomized Phase 3 trial comparing UV1 + checkpoint inhibitor vs. checkpoint inhibitor alone
• Studies in second-line mesothelioma after progression on initial therapy
• Combination studies with other immunotherapy agents

Regulatory timeline:

• Pivotal Phase 3 trials expected to read out in 2027-2028
• If successful, FDA approval possible by 2028-2029
• Fast Track designation may accelerate this timeline

Market context:

• Mesothelioma has limited treatment options
• Immunotherapy has improved outcomes but not for all patients
• Novel approaches like UV1 could address this unmet need

The Broader Picture: Cancer Vaccines

UV1’s progress in mesothelioma comes amid renewed interest in therapeutic cancer vaccines across oncology:

Recent developments:

• mRNA cancer vaccines showing promise (Moderna, BioNTech)
• Personalized neoantigen vaccines advancing in melanoma
• Shared antigen vaccines like UV1 offering off-the-shelf convenience

Why mesothelioma is a good fit:

• Limited treatment options create urgent need
• High telomerase expression makes it a strong target
• Immunotherapy-responsive nature of the disease
• Regulatory willingness to accelerate development

Related Articles

• Immunotherapy for Mesothelioma
• Current Clinical Trials
• Mesothelioma Treatment Options
• Understanding PD-1/PD-L1 Inhibitors