TEST:

Xerna TME™ Panel

Conclusions HST-1011 was associated with dose-dependent changes in peripheral blood pharmacodynamic measures that were sustained with repeated dosing and pre-treatment tumor WTS provided preliminary suggestion of a potential enrichment approach for a study population most likely to benefit from HST-1011. Monotherapy dose-optimization and combination with anti-PD-1 are ongoing.

P1; Conclusion Xernaâ„¢ TME Panel analysis in patients with refractory metastatic pMMR CRC who were treated with regorafenib plus nivolumab might be of value for predictive clinical benefit. Further studies are needed to evaluate the predictive role of Xernaâ„¢ TME Panel analysis in patients with refractory metastatic pMMR CRC.

The Xerna TME Panel classified 49.3% of TNBC patient tumors to IA or IS, suggesting they may respond to ICI therapy. Many (56.2%) patient tumors harbored alterations associated with FDA-approved therapies, providing the potential for novel combination therapies. These findings warrant further study and clinical validation in TNBC patients treated with ICI therapy.

5%) patients harbored alterations associated with FDA-approved therapies, providing the potential for novel combination therapies. 3 These findings warrant further study and clinical validation in CRC patients treated with ICI therapy.

The combination of Bavi and P was well tolerated; observed AEs were consistent with known profiles for each agent. Higher ORRs were observed in CPI-naïve patients with B+ status and baseline NLR<4, and of note, in patients with PD-L1 CPS <1. Future studies may be planned to confirm the activity of Bavi in combination with P with patient selection based on a particular genetic signature.

The Xerna TME Panel shows potential activity as a predictive and pharmacodynamic biomarker for the combination of vidutolimod and pembrolizumab in anti-PD-1 refractory melanoma patients.

P2 | N=28 | NCT03519997 | "OncXerna Therapeutics, Inc....announced final results from a Phase 2 trial of bavituximab plus pembrolizumab in patients with previously untreated advanced hepatocellular carcinoma and new biomarker data demonstrating that the Xerna TME Panel clearly identified trial participants more likely to benefit from treatment. The data were featured in a poster that was presented on January 20, 2023 at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI)....In the study featured in the ASCO GI poster, pre-treatment tumor biopsies were analyzed using the Xerna TME Panel and findings were correlated with objective tumor response to test the hypothesis that tumors with high immune scores (immune active or immune-suppressed TME subtypes [biomarker-positive]) are more likely to respond to bavituximab plus pembrolizumab than those with low immune scores (angiogenic or immune-desert TME subtypes [biomarker-negative])."

"Our study demonstrated that low Treg in tumor microenvironment is correlated with better prognosis in patients with refractory metastatic pMMR CRC who were treated with regorafenib plus nivolumab. Xerna TME panel analysis of these patients also showed trends for predictive clinical benefit. Prospective and larger cohort studies are needed to better define predictive biomarkers for this combination in the future."

Up to 30 patients will be enrolled to each CRC cohort from approximately 8 sites in the US and will receive 3 mg/kg navicixizumab alone (Cohort A1) or in combination with irinotecan (180 mg/m2 on Days 1 and 15 of a 28-day cycle, Cohort A2). Secondary efficacy endpoints include overall survival, time to response, disease control rate, duration of response, and the relationship between antitumor activity of navicixizumab and Xerna TME Panel biomarker subtypes. Clinical trial information: NCT05453825.

"Genialis...is presenting new data and results this week from its biomarker discovery platform, ResponderIDTM. At the Society for Immunotherapy of Cancer (SITC) annual meeting, Genialis Chief Discovery Officer Luka Ausec, Ph.D. is co-presenting a poster with Exact Sciences and OncXerna Therapeutics titled, 'Xerna tumor microenvironment subtypes as a biomarker in lung cancer patients'....The poster explores the relationship between Xerna TME subtypes and DNA-based (e.g. gene variants) biomarkers in NSCLC."

Eligible TNBC patients will have locally advanced or metastatic disease and have received at least 2 and no more than 4 prior lines of standard therapy for metastatic disease, including immunotherapy (for PD-L1 positive TNBC patients), and sacituzumab govitecan...Up to 30 patients will be enrolled to each TNBC cohort from approximately 8 sites in the US and will receive 3 mg/kg navicixizumab alone (Cohort C1) or in combination with paclitaxel (80 mg/m2 on Days 1, 8, and 15 of a 28-day cycle) (Cohort C2)...Cohort continuation and future evaluation decisions will be guided by the boundaries identified by a sequential monitoring procedure. Secondary efficacy endpoints include overall survival, time to response, disease control rate, duration of response, and the relationship between antitumor activity of navicixizumab and Xerna TME Panel™ biomarker subtypes.

Within this group, the prevalence of targetable oncogenic drivers within the IS phenotype, such as KRAS G12C, may represent the potential for novel ICI combination therapies. 4 These findings further highlight the importance of adding TME analysis to comprehensive biomarker testing in NSCLC

P2 | N=924 | PLATFORM (NCT02678182) | "The data featured in the ESMO poster are from retrospective analyses of results from PLATFORM, a randomized Phase 2 trial that evaluated maintenance therapies such as the anti-PD-1 antibody durvalumab in esophagogastric adenocarcinoma patients treated with first-line chemotherapy....Results showed that immune score high patients had a poorer prognosis with active surveillance compared to immune score low patients. However, despite this poorer prognosis, immune score high patients had improved 6- and 12-month progression free survival and 24-month overall survival with durvalumab maintenance therapy compared to the immune score high patients that received active surveillance. Analyses in the poster also compared the predictive potential of Xerna TME Panel classifications in esophagogastric adenocarcinoma to that of classifications based on PD-L1 combined positive score (CPS) status."

P1b | N=44 | NCT03030287 | Sponsor: OncoMed Pharmaceuticals, Inc | "Navicixizumab plus paclitaxel showed promising and durable clinical activity in a heavily pretreated patient population regardless of prior treatment (median of four prior therapies) Overall response rate (ORR) across all evaluable patients: 43% (19/44), ORR in patients previously treated with bevacizumab (Avastin®): 33% (10/30), ORR in patients previously treated with a PARP inhibitor: 45% (9/20),11 of 19 patients with partial or complete response had progressive disease as best response to immediate prior therapy. Median duration of response: 6 months. B+ classification showed enrichment of patients with tumor response. ORR in B+ vs. B- patients: 62% (8/13) vs. 25% (5/20), Best response of progressive disease in B+ vs. B- patients: 0% (0/13) vs. 30% (6/20), Median progression-free survival in B+ vs. B- patients: 9.2 months vs. 3.9 months."

"OncXerna Therapeutics, Inc...announced biomarker data demonstrating the Xerna TME Panel’s prognostic value across multiple indications in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting. Data also suggest the potential for Xerna TME Panel to predict patients most likely to benefit from immune- and angiogenic-targeted therapy."

In a ramucirumab+paclitaxel clinical cohort, the Xerna TME Panel high Angiogenesis score tumors (A and IS) demonstrated a 48% response rate compared to a 31% for low Angiogenesis score tumors (IA and ID). Within the microsatellite stable patients (MSS), which historically have low response rates to ICIs, the Xerna TME Panel was able to enrich for responses between Immune high vs. Immune low score patients (25% vs. 3%). Currently in use to prospectively enroll patients into a Phase 3 ovarian cancer clinical trial and in development as a companion diagnostic (CDx) assay, the Xerna TME Panel is a robust, pan-cancer biomarker assay capable of characterizing TME dominant biologies to further advance the matching of patients with targeted therapeutics.