Purple Biotech Reports Final Data from Phase 2 Study of CM24 in Pancreatic Cancer Patients at AACR 2025 Annual Meeting: Improved Outcomes and Significant Efficacy in Biomarker-Enriched Subgroups
Purple Biotech announced final data from its Phase 2 study of CM24 in pancreatic cancer patients at AACR 2025. The study showed significant efficacy in biomarker-enriched subgroups, with up to 90% reduction in death risk in specific patient populations.
Key findings include:
- 78% reduction in death risk for patients with specific CEACAM1 ranges
- 61% reduction in death risk for patients with defined CEACAM1 or MPO levels
- 90% reduction in death risk for patients with high tumor CEACAM1 and low PD-L1 CPS
The combination therapy of CM24, nivolumab, and chemotherapy was well-tolerated and showed improvements in all efficacy measures. The study identified CEACAM1 as a potential biomarker, both in serum and tumor tissue. Based on these results, Purple Biotech plans to conduct a biomarker-driven Phase 2b study, potentially expanding into gastric and biliary tract cancer treatments.
Purple Biotech ha annunciato i dati finali del suo studio di Fase 2 su CM24 in pazienti con tumore pancreatico durante l'AACR 2025. Lo studio ha evidenziato un'efficacia significativa in sottogruppi arricchiti con biomarcatori, con una riduzione del rischio di morte fino al 90% in specifiche popolazioni di pazienti.
I risultati principali includono:
- Riduzione del rischio di morte del 78% per pazienti con specifici intervalli di CEACAM1
- Riduzione del rischio di morte del 61% per pazienti con livelli definiti di CEACAM1 o MPO
- Riduzione del rischio di morte del 90% per pazienti con elevati livelli tumorali di CEACAM1 e basso PD-L1 CPS
La terapia combinata di CM24, nivolumab e chemioterapia è stata ben tollerata e ha mostrato miglioramenti in tutte le misure di efficacia. Lo studio ha identificato CEACAM1 come potenziale biomarcatore, sia nel siero che nel tessuto tumorale. Sulla base di questi risultati, Purple Biotech intende condurre uno studio di Fase 2b guidato dai biomarcatori, con possibile estensione ai trattamenti per il cancro gastrico e delle vie biliari.
Purple Biotech anunció los datos finales de su estudio de Fase 2 con CM24 en pacientes con cáncer de páncreas en el AACR 2025. El estudio mostró una eficacia significativa en subgrupos enriquecidos con biomarcadores, con hasta un 90% de reducción del riesgo de muerte en poblaciones específicas de pacientes.
Los hallazgos clave incluyen:
- Reducción del riesgo de muerte del 78% en pacientes con rangos específicos de CEACAM1
- Reducción del riesgo de muerte del 61% en pacientes con niveles definidos de CEACAM1 o MPO
- Reducción del riesgo de muerte del 90% en pacientes con alta expresión tumoral de CEACAM1 y bajo CPS de PD-L1
La terapia combinada de CM24, nivolumab y quimioterapia fue bien tolerada y mostró mejoras en todas las medidas de eficacia. El estudio identificó a CEACAM1 como un posible biomarcador, tanto en suero como en tejido tumoral. Basándose en estos resultados, Purple Biotech planea realizar un estudio de Fase 2b impulsado por biomarcadores, con posible expansión a tratamientos para cáncer gástrico y de vías biliares.
Purple Biotech는 AACR 2025에서 췌장암 환자를 대상으로 한 CM24의 2상 임상시험 최종 데이터를 발표했습니다. 연구 결과, 바이오마커가 풍부한 하위 그룹에서 유의미한 효능을 보였으며, 특정 환자군에서는 사망 위험이 최대 90% 감소하였습니다.
주요 결과는 다음과 같습니다:
- 특정 CEACAM1 범위를 가진 환자에서 사망 위험 78% 감소
- 정의된 CEACAM1 또는 MPO 수치를 가진 환자에서 사망 위험 61% 감소
- 종양 내 CEACAM1이 높고 PD-L1 CPS가 낮은 환자에서 사망 위험 90% 감소
CM24, 니볼루맙, 화학요법의 병용 치료는 내약성이 우수했으며 모든 효능 지표에서 개선을 보였습니다. 연구는 혈청과 종양 조직에서 CEACAM1을 잠재적 바이오마커로 확인했습니다. 이러한 결과를 바탕으로 Purple Biotech는 바이오마커 기반의 2b상 연구를 계획 중이며, 위암 및 담도암 치료로 확대할 가능성이 있습니다.
Purple Biotech a annoncé les données finales de son étude de phase 2 sur le CM24 chez des patients atteints de cancer du pancréas lors de l'AACR 2025. L'étude a démontré une efficacité significative dans des sous-groupes enrichis en biomarqueurs, avec jusqu'à une réduction de 90 % du risque de décès dans certaines populations de patients.
Les résultats clés incluent :
- Réduction de 78 % du risque de décès chez les patients présentant des plages spécifiques de CEACAM1
- Réduction de 61 % du risque de décès chez les patients avec des niveaux définis de CEACAM1 ou MPO
- Réduction de 90 % du risque de décès chez les patients avec un taux élevé de CEACAM1 tumoral et un faible CPS PD-L1
La thérapie combinée de CM24, nivolumab et chimiothérapie a été bien tolérée et a montré des améliorations dans toutes les mesures d'efficacité. L'étude a identifié CEACAM1 comme un biomarqueur potentiel, tant dans le sérum que dans le tissu tumoral. Sur la base de ces résultats, Purple Biotech prévoit de mener une étude de phase 2b axée sur les biomarqueurs, avec une possible extension aux traitements du cancer gastrique et des voies biliaires.
Purple Biotech gab auf der AACR 2025 die endgültigen Daten seiner Phase-2-Studie mit CM24 bei Patienten mit Bauchspeicheldrüsenkrebs bekannt. Die Studie zeigte eine signifikante Wirksamkeit in biomarker-angereicherten Subgruppen mit bis zu 90% Reduktion des Sterberisikos in bestimmten Patientengruppen.
Wesentliche Ergebnisse umfassen:
- 78% Reduktion des Sterberisikos bei Patienten mit spezifischen CEACAM1-Bereichen
- 61% Reduktion des Sterberisikos bei Patienten mit definierten CEACAM1- oder MPO-Werten
- 90% Reduktion des Sterberisikos bei Patienten mit hohem Tumor-CEACAM1 und niedrigem PD-L1 CPS
Die Kombinationstherapie aus CM24, Nivolumab und Chemotherapie war gut verträglich und zeigte Verbesserungen in allen Wirksamkeitsparametern. Die Studie identifizierte CEACAM1 als potenziellen Biomarker sowohl im Serum als auch im Tumorgewebe. Basierend auf diesen Ergebnissen plant Purple Biotech eine biomarkergetriebene Phase-2b-Studie mit möglicher Erweiterung auf Behandlungen bei Magen- und Gallengangskarzinomen.
- 78% reduction in risk of death in CEACAM1 biomarker subgroup, showing strong efficacy
- 90% reduction in risk of death in high tumor CEACAM1/low PD-L1 CPS subgroup
- Higher objective response rate in treatment arm (25%) vs control (6.7%)
- Higher disease control rate in treatment arm (62.5%) vs control (46.7%)
- Well-tolerated treatment combination showing improved outcomes across all efficacy parameters
- Biomarker identification enables targeted patient selection for future trials, potentially increasing success rates
- Results limited to small subgroups (31 patients total, with even smaller biomarker subgroups)
- Without biomarker consideration, overall survival improvement was not statistically significant (p=0.575)
- Additional Phase 2b study required before potential commercialization, extending timeline and costs
- Treatment only effective in specific biomarker-defined patient populations, limiting market potential
Insights
Purple Biotech's CM24 shows significant survival benefit in biomarker-selected pancreatic cancer patients, creating clear path for biomarker-driven Phase 2b study.
Purple Biotech's final Phase 2 data for CM24 reveals a compelling precision medicine strategy in pancreatic cancer. While overall results showed consistent but non-significant improvements, the biomarker analyses demonstrate remarkable efficacy in specific patient subgroups. In patients with defined CEACAM1 levels, the treatment reduced death risk by
What's scientifically significant is the mechanism - CM24 targets CEACAM1's dual role in neutrophil extracellular traps (NETs) affecting systemic immune evasion and local tumor microenvironment modulation. The
The identification of clear predictive biomarkers (serum/tumor CEACAM1 and MPO) transforms what could have been considered modest overall results into a precisely targeted approach. The company's plan to implement biomarker selection in their next Phase 2b study in pancreatic, gastric, and biliary tract cancers represents a derisked development strategy consistent with modern precision oncology practices.
Strong biomarker data significantly derisks CM24's development path, potentially expanding addressable indications beyond hard-to-treat pancreatic cancer.
Purple Biotech's Phase 2 biomarker data represents a significant clinical development milestone. The post-hoc analyses revealed statistically significant survival benefits in defined patient populations, with hazard ratios substantially more impressive than typically seen in pancreatic cancer trials. The
From a development perspective, identifying predictive biomarkers (CEACAM1 and MPO) early in clinical development significantly enhances CM24's prospects. The mechanistic coherence between the biomarkers and CM24's target strengthens the scientific rationale for this approach. Purple Biotech's pivot to biomarker-selected studies aligns with industry best practices in precision medicine.
The company's plan to expand development beyond pancreatic cancer to include gastric and biliary tract cancers suggests broader potential applications. Particularly valuable is the finding that CM24 benefits patients with low PD-L1 expression, potentially addressing significant unmet needs in immunotherapy-resistant populations. Given that pancreatic cancer has historically been resistant to immunotherapies, these results in biomarker-selected patients represent a meaningful advancement in this difficult-to-treat malignancy.
- Statistically significant efficacy in biomarker subgroup analyses was observed:
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78% reduction in risk of death and81% reduction in risk of progression or death in defined pretreatment ranges of serum or tumor CEACAM1 subgroup61% reduction is risk of death and72% reduction in risk of progression or death in defined pretreatment ranges of serum CEACAM1 or myeloperoxidase (MPO) subgroup90% reduction is risk of death and81% reduction in risk of progression or death in high tumor CEACAM1 and low PD-L1 combined positive score (CPS) subgroup
- The biomarkers identified in the Phase 2 study are planned to be used for patient selection in the next Phase 2b study
REHOVOT, Israel, April 30, 2025 (GLOBE NEWSWIRE) -- Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance, announced today that a poster presentation titled “Final analysis of the randomized Phase 2 cohort of CM24 with nivolumab and chemotherapy in pancreatic cancer & potential serum biomarkers” is being presented during the session “Liquid Biopsy: Circulating Nucleic Acids 4 / Predictive Biomarkers 1” at the Annual Meeting of the American Association of Cancer Research (AACR 2025) on Wednesday, April 30, 2025.
“These statistically significant biomarker results, with up to a
At AACR 2025, Purple Biotech presented final data from its randomized, controlled, open-label, multicenter Phase 2 study (NCT04731467), which established proof of concept in a biomarker-enriched subgroup of 31 patients with advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) who were post-first line therapy, and compared treatment with CM24 + nivolumab + Nal-IRI/5FU/LV against treatment with Nal-IRI/5FU/LV alone.
The following is a summary of the findings.
The combination of CM24, nivolumab and Nal-IRI/5FU/LV chemotherapy was well tolerated and demonstrated quantitative improvement in all efficacy parameters, including OS, PFS, objective response rate (ORR), disease control rate (DCR) and CA19-9, in previously treated PDAC patients.
Without consideration of biomarkers, a consistent improvement in the treatment arm compared to the control arm was observed, as follows:
- Prolongation of 2.4 months in OS HR=0.81 (p-0.575) and prolongation of 1.9 months in PFS HR=0.75 (p=0.463) vs. control arm
- Higher ORR in experimental arm vs control arm (
25% vs6.7% ) - Higher DCR in experimental arm vs control arm (
62.5% vs46.7% ) - Consistent and continuous decrease in CA19-9 was observed in experimental arm vs control arm increase
Biomarker results included the following:
A statistically significant benefit to patients with defined pre-treatment ranges of serum CEACAM1 or tumor CEACAM1 expression (H score) compared to the control arm (representing a subgroup of
-
- Subgroup analyses of 16/31 patients meeting the criteria of CEACAM1+Tumor cell H score 115-275 or serum CEACAM1 levels 6K-15K pg/mL
78% reduction in risk of death (HR 0.22,95% CI 0.07-0.7, p=0.006) and95% reduction in the risk of progression or death (HR 0.05,95% CI 0.01-0.44, p=0.0003)- Prolongation of 3.7 months in OS and 2.9 months in PFS
Statistically significant results in patients with defined pre-treatment serum CEACAM1 or myeloperoxidase (MPO) levels (representing a subgroup of
-
- Subgroup analyses for 24/30 patients meeting the criteria of MPO levels 200-600 ng/mL or serum CEACAM1 levels 6K-15K pg/mL
61% reduction in risk of death (HR = 0.39,95% CI 0.16-0.98, p=0.039) and72% reduction in the risk of progression or death (HR=0.28,95% CI 0.11-0.73, p=0.006)- Prolongation of 2.4 months in OS and 2.2 months in median PFS
A statistically significant benefit for CM24-nivolumab treatment in patients with high CEACAM1+Tumor cell H score and low PD-L1 CPS (representing a subgroup of
-
- Subgroup analyses of 10/26 patients meeting the criteria of high CEACAM1+Tumor cell H score ≥ 115 and Low CPS ≤ 1 (
90% reduction in risk of death (HR = 0.1,95% CI 0.01-0.89, p=0.013) and81% reduction in the risk of progression or death (HR = 0.19,95% CI 0.04-1.02, p=0.033)- Prolongation of 4 months in OS and 2 months in PFS
“The identification of CEACAM1 as a potential biomarker, both in serum and at the tumor, corresponds with the multi-faceted function of CEACAM1, as part of the neutrophil extracellular trap (NET) structure affecting NET-related tumor immune evasion, metastasis and other cancer-associated complications, such as thrombosis, at the level of the whole body, as well as modulation of the tumor microenvironment (TME)," stated Purple Biotech VP of Research and Development, Dr. Hadas Reuveni. "Targeting CEACAM1 by CM24 suggests a potential new approach that may address tumor-associated mechanisms affecting the patient at the levels of the tumor, the TME and the whole body. The biomarker data accumulated in this clinical study may help us to direct the treatment of patients who might have a higher chance to benefit from the treatment and could expand our understanding of CEACAM1 and NETs in cancer biology.”
Final conclusions from the study:
- The combination of CM24, nivolumab, and Nal-IRI/5FU/LV chemotherapy was well tolerated and
demonstrated quantitative improvement in all efficacy parameters, including OS, PFS, ORR and CA19-9, in previously treated PDAC patients.
- Based on post-hoc analyses - serum CEACAM1 and MPO, a NET marker, are demonstrated as potential predictive biomarkers for CM24-based therapy, consistent with its mechanism of action (MoA) in targeting CEACAM1 to modulate immune evasion and NET activities.
- Results imply that both serum and tumor CEACAM1 levels are potential predictive biomarkers for CM24 based therapy, suggesting multifaceted MoA and the crosstalk of the tumor with the TME and the whole body.
- Improved outcome in patients with high tumor CEACAM1 expression and low PD-L1 CPS further support the mechanistic rationale of the CM24/nivolumab combination and highlight its potential in disease settings where immuno-oncology is less effective.
“The design of the randomized trial enabled us to evaluate the benefit of CM24 and nivolumab in combination with standard of care chemotherapy and to analyze potential biomarker data to better prepare for the next study.” stated Purple Biotech Head of Clinical and Regulatory Affairs, Dr. Michael Schickler. "We currently expect the design of the next Phase 2b study to include an additional group testing CM24 alone in combination with standard of care with patients selected based on the identified biomarkers, potentially in indications such as gastric and/or biliary tract cancer, in addition to PDAC.”
The poster will be available at the Publication section on Purple Biotech’s website following its presentation at the conference.
About Purple Biotech
Purple Biotech Ltd. (NASDAQ/TASE: PPBT) is a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance. The Company's oncology pipeline includes CM24, NT219, and CAPTN-3. CM24 is a humanized monoclonal antibody that blocks CEACAM1, which supports tumor immune evasion and survival through multiple pathways. CEACAM1 on tumor cells, immune cells and neutrophil extracellular traps is a novel target for the treatment of multiple cancer indications. As proof of concept of these novel pathways, the Company completed a Phase 2 study for the treatment of pancreatic ductal adenocarcinoma (PDAC) with CM24 as a combination therapy with the anti-PD-1 checkpoint inhibitor nivolumab and chemotherapy, demonstrating clear and consistent improvement across all efficacy endpoints and the identification of two potential serum biomarkers. NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3. A Phase 1 dose escalation study was concluded as a monotherapy and in combination with cetuximab, in which NT219 demonstrated anti-tumor activity in combination with cetuximab in second-line patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The Company is advancing NT219 into a Phase 2 study in collaboration with the University of Colorado, to treat R/M SCCHN patients in combination with cetuximab or pembrolizumab. The Company is advancing CAPTN-3, a preclinical platform of conditionally activated tri-specific antibodies, which engage both T cells and NK cells to induce a strong, localized immune response within the tumor microenvironment. The cleavable capping technology confines the compound's therapeutic activity to the local tumor microenvironment, thereby potentially increasing the anticipated therapeutic window in patients. The third arm specifically targets the Tumor Associated Antigen (TAA). The technology presents a novel mechanism of action by unleashing both innate and adaptive immune systems to mount an optimal anti-tumoral immune response. IM1240 is the first tri-specific antibody in development that targets the 5T4 antigen, which is expressed in a variety of solid tumors and is associated with advanced disease, increased invasiveness, and poor clinical outcomes. The Company's corporate headquarters are located in Rehovot, Israel. For more information, please visit https://purple-biotech.com/.
Forward-Looking Statements and Safe Harbor Statement
Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements that are not statements of historical fact, and may be identified by words such as "believe", "expect", "intend", "plan", "may", "should", "could", "might", "seek", "target", "will", "project", "forecast", "continue" or "anticipate" or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. You should not place undue reliance on these forward-looking statements, which are not guarantees of future performance. Forward-looking statements reflect our current views, expectations, beliefs or intentions with respect to future events, and are subject to a number of assumptions, involve known and unknown risks, many of which are beyond our control, as well as uncertainties and other factors that may cause our actual results, performance or achievements to be significantly different from any future results, performance or achievements expressed or implied by the forward-looking statements. Important factors that could cause or contribute to such differences include, among others, risks relating to: the plans, strategies and objectives of management for future operations; product development for NT219, CM24 and IM1240; the process by which such early stage therapeutic candidates could potentially lead to an approved drug product is long and subject to highly significant risks, particularly with respect to a joint development collaboration; the fact that drug development and commercialization involves a lengthy and expensive process with uncertain outcomes; our ability to successfully develop and commercialize our pharmaceutical products; the expense, length, progress and results of any clinical trials; the impact of any changes in regulation and legislation that could affect the pharmaceutical industry; the difficulty in receiving the regulatory approvals necessary in order to commercialize our products; the difficulty of predicting actions of the U.S. Food and Drug Administration or any other applicable regulator of pharmaceutical products; the regulatory environment and changes in the health policies and regimes in the countries in which we operate; the uncertainty surrounding the actual market reception to our pharmaceutical products once cleared for marketing in a particular market; the introduction of competing products; patents obtained by competitors; dependence on the effectiveness of our patents and other protections for innovative products; our ability to obtain, maintain and defend issued patents; the commencement of any patent interference or infringement action against our patents, and our ability to prevail, obtain a favorable decision or recover damages in any such action; and the exposure to litigation, including patent litigation, and/or regulatory actions, and other factors that are discussed in our Annual Report on Form 20-F for the year ended December 31,2024 and in our other filings with the U.S. Securities and Exchange Commission ("SEC"), including our cautionary discussion of risks and uncertainties under "Risk Factors" in our Registration Statements and Annual Reports. These are factors that we believe could cause our actual results to differ materially from expected results. Other factors besides those we have listed could also adversely affect us. Any forward-looking statement in this press release speaks only as of the date which it is made. We disclaim any intention or obligation to publicly update or revise any forward-looking statement or other information contained herein, whether as a result of new information, future events or otherwise, except as required by applicable law. You are advised, however, to consult any additional disclosures we make in our reports to the SEC, which are available on the SEC's website, https://www.sec.gov.
CONTACTS:
Company Contact:
IR@purple-biotech.com
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