UbiVac is a Clinical Stage Immunotherapy & Cancer Target Discovery Company, with First-in-Human Combination Immunotherapies that Include Cancer’s Dark Matter - the Newly Discovered Non-Mutated Shared Cancer Neoantigens 

UbiVac has unique and disruptive immune educating and activating vaccine technology. UbiVac’s lead agent, DPV-001, contains the newly discovered cancer’s “Dark Matter”, non-mutated shared cancer neoantigens, and more than 300 antigens for the majority of patients with adenocarcinoma or squamous cell cancers. Due to its unique platform vaccine technology, novel targets are being discovered that might be used for ADC, CAR-T/NK, and TCR gene therapy. UbiVac postulates that by applying machine learning, artificial intelligence, and generative adversarial networks to the analysis of the extensive monitoring data from these ongoing first-in-human trials, new insights will allow future trials to tailor treatment regimens and further improve outcomes of patients with cancer.

UbiVac was co-founded and is led by Dr. Bernard A. Fox, an internationally recognized expert in cancer immunotherapy, and was spun-out and is closely aligned with a world class immunotherapy center of excellence, the Earle A. Chiles Research Institute. UbiVac has their own GMP capable facility with in-house manufacturing capability for its off-the-shelf cancer immunotherapies.

The Problem for Patients with Advanced Cancer: 

Many or most patients with advanced cancer are thought to lack immunity to their cancer. This is the reason that many experts believe that both standard cancer therapies (chemotherapy and radiation) or immunotherapy (checkpoint blockade) fail to provide extended benefit to patients with currently “incurable” cancers. 

2021 - A Breakthrough in Our Understanding

In 2021 several high impact publications identified a previously unknown class of shared non-mutated cancer neoantigens that make up as much as 25% of the antigens on cancer cells (PMID: 33740418; PMID: 33691108; PMID: 34663921). These remarkable studies have opened up a new area of investigation and raised the possibility of off-the-shelf Universal Cancer Vaccines (PMID: 33852826). The identified non-mutated shared cancer neoantigens are short-lived proteins, the majority of which are expected to be contained in UbiVac’s DPV-001, and UbiVac has studies underway to characterize their numbers in DPV-001. Importantly, these findings help explain why UbiVac’s immunotherapy strategy provided cross-protective cancer immunity in preclinical models, something that had not been observed in 50 years of study (PMID: 21810919). 

2023 – Critical Insight Into Cancer’s Dark Matter and Relevance to Cancer Vaccines

In June 2023, in further support of the relevance of using short-lived non-mutated shared neoantigens in vaccine strategies, a breakthrough paper appeared reporting that tumor-infiltrating lymphocytes (TIL) did not recognize these short-lived non-mutated shared neoantigens . This is consistent with the nature of short-lived proteins, they are degraded so quickly and transported to HLA and the surface of cancer cells that they are not available to be cross-presented and don’t induce an endogenous immune response. Importantly, immunizing the patient’s peripheral blood cells with short-lived non-mutated shared neoantigens led to immunity to these antigens and to recognition of autologous tumor cells. This suggests that short-lived non-mutated shared neoantigens represent a treasure trove of untapped targets for the immune system to recognize. Additional data documents that a single TCR recognizing a short-lived non-mutated neoantigens could recognize 12 of 22 cancer cell lines tested (Gynecologic cancer, melanoma and GI cancer cell lines). This is an AMAZING finding! It provides evidence that a single “Dark Matter” epitope is shared by three very different cancer types and underscores the potential for universal cancer vaccines. UbiVac co-founder and CEO, Bernard A. Fox, together with colleagues, penned the commentary that accompanied the Clinical Cancer Research publication and provided additional insights into the importance of the work from Dr. Gros’ lab. As DPV-001 contains these short-lived proteins it underscores both the relevance of UbiVac’s vaccine as well as UbiVac’s potential to mine immune response data and discover new cancer targets. An early report of efforts to characterize Cancer’s Dark Matter contained in the DPV-001 vaccine was presented in November 2023 at the annual SITC meeting.

Potential Solution to Improve Outcomes of Patients with Cancer:

Given the nature of these newly described non-mutated cancer neoantigens, UbiVac believes that DPV-001 is the only vaccine containing these antigens in a formulation that can stimulate an immune response. This has engendered additional interest in UbiVac’s platform technology.  Further, UbiVac has shown that patients receiving DPV-001, an “off-the-shelf” immune activator and cancer vaccine, develop strong immune responses to numerous cancer antigens. By inducing anti-cancer immunity in patients, UbiVac believes that DPV-001 and other UbiVac DPV and UPV platform vaccines, in combination with other therapies, provides the possibility of increasing response rates and cures of patients with cancer. 

UbiVac’s DPV-001 in the Clinic

UbiVac has patented immune activating and vaccine technologies that, when used in combination with other immunotherapies, have proven highly effective at improving survival and apparent cure in difficult to treat animal cancers (PMID: 27874054; PMID: 31747946; PMID: 22068657; PMID: 21810919).  UbiVac has completed a National Cancer Institute (NCI)-funded phase I/II adjuvant clinical trial of its lead agent, DPV-001, in patients at high risk of their non-small cell lung cancer (NSCLC) recurring. This trial met its endpoints, determined safety, identified drug formulation, and demonstrated proof-of-concept. 

Based on these data UbiVac has partnered with the Providence Cancer Institute and Incyte on a first-in-human immunotherapy trio clinical trial of UbiVac’s immune activator and cancer vaccine – DPV-001, anti-GITR and anti-PD-1 for advanced or metastatic head and neck squamous cell cancer (HNSCC). The first patients were treated in Q4 2021, and immunological monitoring data was presented at AACR in April 2023 and at the Society for Immunotherapy of Cancer (SITC) annual meeting in November 2023. UbiVac will present initial clinical efficacy data at the American Association for Cancer Research (AACR) on April 8th 2024.

Monitoring Data Leads to New 1st-in-Human Quad Immunotherapy Trial

The data noted above, reported that by 2 weeks of treatment all evaluated tumor biopsies contained a significant increase in tumor-reactive CD39/CD103 double positive T cells that expressed the LAG-3 checkpoint molecule. These CD39/CD103 double positive are recognized as tumor-reactive cancer killer cells. Since the only treatment half of these patients had received was UbiVac’s DPV-001 vaccine, it demonstrates that the vaccine is activating the tumor-reactive tumor infiltrating lymphocytes (TIL) to destroy cancer cells. However, the up regulation of the LAG-3 checkpoint molecule on these activated tumor-killer cells, likely limits their anti-cancer function. UbiVac postulates that adding anti-LAG-3 to these patient’s treatment will further increase response rates. This has led Incyte to support addition of a third arm to the current trial. This arm will include UbiVac’s DPV-001, + anti-LAG-3 and anti-TIM3, + delayed anti-PD-1. This trial is expected to open in early 2024.

Additional New Trial in 2024

UbiVac is also expected to launch at least one additional trial of DPV-001 in 2024. This trial will be for neoadjuvant treatment of locally advanced breast cancer. The trial, which already has FDA approval to start, will combine UbiVac’s vaccine with standard of care chemotherapy. There are several other trial possibilities under discussion with potential partners.