Kineta, Inc. (NASDAQ:KA) reported an update to its ongoing VISTA-101 trial completing the first four monotherapy doses and initiating the combination cohort. The company has also recently hosted a key opinion leader (KOL) event, participated in several conferences and published preclinical data for its KVA12123 candidate.
KVA12123 Clinical Study Update
A January 17th press release provided the latest information on the Phase I/II VISTA-101 trial. It has completed the first four monotherapy dose levels for KVA12123 and the first cohort in combination with pembrolizumab. KVA12123 was well tolerated with no dose limiting toxicities or cytokine related adverse events at any dose level. Investigators noted that the candidate demonstrated robust and dose proportional induction of pro-inflammatory biomarkers that are associated with strong anti-tumor activity. This indicates the on-target effects of the drug. The favorable results support moving toward higher doses in both the monotherapy and combination arms. Full enrollment of the Phase I portion of the trial is expected by April 2024.
In terms of progress, 18 patients have been dosed with KVA12123. Of the 18, 15 presented advanced solid tumors and were enrolled in the first four monotherapy dose-escalation cohorts. Three subjects were enrolled in the initial combination cohort. Primary endpoints are safety and tolerability of KVA12123 and identifying the Phase II recommended dose.
KOL Event
In early December, Kineta hosted a key opinion leader (KOL) event featuring Michael Curran, Ph.D. from the M.D. Anderson Cancer Center to present on VISTA and Evan Yu, M.D. of the Fred Hutchinson Cancer Center participating in the fireside chat. Other participants in the event include Kineta’s Chief Scientific Officer, Dr. Thierry Guillaudeaux, Kineta’s VP of Clinical Research, Dr. Vinny Hayreh and Kineta’s CEO, Dr. Shawn Iadonato.
Dr. Curran began with a discussion of VISTA and its place in the checkpoint universe. Despite the success of the CTLA-4, PD-1 and PD-L1 inhibitors, this class of immunotherapy is effective in less than half of all patients, and has an even lower success rate for patients with cold tumors. VISTA has emerged as a multi-functional modulator of the immunosuppressive tumor microenvironment. Blockade of VISTA increases dendritic cell and T cell activity while reversing several immunosuppressive activities. It also appears to work well in combination with the more common CTLA-4, PD-1 and PD-L1 checkpoint inhibitors as it is non-redundant to other checkpoint pathways.
Next, Dr. Guillaudeux grabbed the baton from Dr. Curran and presented Phase I details and preclinical data for KVA12123, Kineta’s anti-VISTA candidate. KVA12123 is an engineered IgG1 monoclonal antibody that binds to a unique epitope on T cells. It is the subject of a Phase I/II clinical trial investigating the drug as both monotherapy and combination therapy with Keytruda in advanced solid tumors. Observations as of early December are that KVA12123 is well tolerated with no dose limiting toxicities, produces a greater than dose-proportional pharmacokinetic profile and induces pro-inflammatory biomarkers and immune cells. No evidence of cytokine release syndrome (CRS) was observed with no detection of TNFα, IL-6 or IL-10.
Preclinical data in mice showed that KVA12123 was able to inhibit tumor growth in a bladder cancer and lymphoma model. Best results, however, were produced when KVA12123 was combined with an anti-PD-1 antibody which inhibited tumor growth by 68% and 85% in a colon and bladder cancer model respectively.
In the last section, CEO Dr. Iadonato spoke with Dr. Yu, a specialist in bladder cancer and solid tumors and lead investigator in the VISTA-101 trial. The first topic of discussion was the evolution of immunotherapy over the last decades and the success of checkpoints in melanoma, which previously had no effective treatment. Dr. Yu sees the improvement in intelligent design of anti-VISTA antibodies as a necessary step to even further improve the successes in immunotherapy as it addresses several mechanisms of resistance and appears to work well in combination with other agents. One of the important efforts that should support the success of the trial is the biomarker work that is being done. The biomarkers will help identify responding patients, avoid side effects, overcome mechanisms of resistance and help understand how the drug works. Dr. Yu also emphasized the importance of combination therapies for success against cancer and provided several historical examples in support. The final ten minutes of the event allowed panel participants to respond to attendee questions.
KVA12123 Preclinical Data
A December 13th missive summarized preclinical data that was published in Frontiers in Immunology under the title “A Highly Potent Anti-VISTA Antibody KVA12123 – A New Immune Checkpoint Inhibitor and a Promising Therapy Against Poorly Immunogenic Tumors.” The article summarized the characterization and selection of Kineta’s clinical candidate and provided data supporting that the anti-VISTA antibody binds to a unique epitope at neutral and acidic pH and has significant potential to address immuno-resistance in cancer patients. KVA12123 binds with high affinity to VISTA through a unique epitope distinct from other anti-VISTA candidates. It has high specificity against VISTA and no cross reactivity against other members of the B7 family. Successful binding of KVA12123 to VISTA reverses T cell suppression and induces T cell and NK-mediated monocyte activation. Results have also demonstrated safety as the candidate is well-tolerated in preclinical toxicology studies without antibody-dependent cellular cytotoxicity or induction of CRS-related cytokines. The article concludes that the results establish KVA12123 as a promising candidate with potential as both monotherapy and in combination with pembrolizumab.
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