On September 18, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that overcome tumor immune evasion and drug resistance, reported new positive biomarker findings for its lead oncology therapeutic candidate CM24 (Press release, Purple Biotech, SEP 18, 2024, View Source [SID1234646720]). These data were presented yesterday at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Advances in Pancreatic Cancer Research currently ongoing in Boston, in a poster titled, "Exploratory biomarker evaluation of the randomized Phase 2 cohort of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer".
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"We are excited to present additional positive data from our Phase 2 study with CM24. CEACAM1 as a novel target in oncology continues to be supported by these data, underscoring its potential given its high expression on cancer cells, tumor infiltrating leucocytes and on NETs, suggesting the potential multiple roles of CM24 in overcoming immune evasion," stated Purple Biotech CEO Gil Efron. "Moreover, these data enable us to potentially design biomarker- guided studies for CM24 for the treatment of pancreatic ductal adenocarcinoma (PDAC), as well as other cancers."
Purple Biotech’s Phase 2 study is evaluating CM24 in combination with Bristol Myers Squibb’s PD-1 inhibitor nivolumab plus standard of care (SoC) chemotherapy as a second line treatment of patients with PDAC and compared to SoC chemotherapy alone. Sixty-three patients have been enrolled in the randomized study across 18 centers in the U.S., Spain, and Israel.
The following is a summary of findings presented in the poster:
Mechanism of Action
CM24 blocks CEACAM1 interactions, which have key roles in cancer progression, immune escape and metastasis. CEACAM1 is part of the NET complex, involved in tumor immune evasion, metastasis and cancer-associated thrombosis, affecting patient survival. Purple Biotech has previously presented data that demonstrates that CM24 binds to CEACAM1 on NETs, suppresses NET-induced migration of cancer cells and inhibits in-vivo tumor metastasis. In the poster, Purple Biotech presents data that demonstrates that CM24 also inhibits NET-induced platelet aggregation, an in-vitro assay imitating the thrombosis process.
CM24+nivolumab+Nal-IRI/5FU/LV treatment of PDAC patients reduced serum levels of the NET marker, MPO, and showed potential overall survival (OS) benefit to patients with reduced post-dose MPO as compared to the control arm.
NET Marker MPO as a Potential Serum Biomarker for Patient Selection for CM24-Based Therapy
An analysis of patients with serum MPO levels < 350 ng/mL, demonstrated a potential 62% reduction in risk of death (HR=0.38) for CM24+nivolumab+Nal-IRI/5FU/LV therapy in PDAC patients, and prolongation of 3.3 months in median OS. This compared to an analysis of all patients which demonstrated a potential 25% reduction in risk of death (HR=0.75) and prolongation of 2.1 months in median OS.
High Tumor CEACAM1 & Low PDL1 as Potential Biomarkers for CM24-Based Therapy
An analysis of patients with high CEACAM1+tumor cells (H-score > 115) or low PDL1 (CPS ≤ 1) demonstrated a potential 45% and 65% reduction in risk of death (HR=0.55 and 0.35), respectively.
Combining these two potential biomarkers, suggests augmented outcome of 90% reduction in risk of death (HR=0.1) for CM24+nivolumab+Nal-IRI/5FU/LV therapy in PDAC patients, and prolongation of 4.1 months in median OS (p value 0.01).
"A serum biomarker for patient selection is a major advantage for cancer patients in general and PDAC patients in particular. The additional interim data suggesting serum NET levels as a potential biomarker for improving the outcome of CM24-based therapy, together with the ability of this therapy to reduce serum NET levels in PDAC patients and to inhibit NET-related activities in vitro, add supporting evidence for NETs as a new mechanism of action (MoA) and potential biomarker for CM24-based therapy," said Dr. Hadas Reuveni, VP R&D of Purple Biotech. "Additional encouraging results suggesting that the CM24/ nivolumab/chemotherapy effect is most pronounced among patients with high CEACAM1 expression and low PDL1 also relate to the CM24/nivolumab MoA and support the CM24/nivolumab combined treatment. This may open a new opportunity for patients who are not eligible for anti-PD1 therapy in various indications. A larger sample size is required to confirm the results and better define the cutoff values."
Interim data from Purple Biotech’s Phase 2 study presented in June at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting demonstrated improvement in OS, progression free survival (PFS), objective response rate (ORR) and all other efficacy endpoints in the CM24+nivolumab+Nal-IRI/5FU/LV experimental arm as compared with the SoC control arm. Topline data are expected in the fourth quarter of 2024.
The poster is available on the Publications section of Purple Biotech’s website and in the following link: View Source