carotuximab IV (ENV-105) / Tracon Pharma, Kairos Pharma - LARVOL DELTA

Efficacy and Safety of TRC105 Plus Pazopanib vs Pazopanib Alone for Treatment of Patients With Advanced Angiosarcoma: A Randomized Clinical Trial. (PubMed, JAMA Oncol) - P3 | "In this phase 3 randomized clinical trial, carotuximab plus pazopanib did not improve PFS compared with pazopanib alone in patients with advanced angiosarcoma. ClinicalTrials.gov Identifier: NCT02979899."

Clinical • Journal • Angiosarcoma • Fatigue • Hematological Disorders • Hypertension • Oncology • Pain • Sarcoma • Solid Tumor

Kairos Pharma, Ltd…announced today a collaboration with Bayer to evaluate ENV-105 in combination with Bayer’s XOFIGO in metastatic castration-resistant prostate cancer involving bone, according to a press release statement. (Investing.com)

Licensing / partnership • Castration-Resistant Prostate Cancer

Kairos Pharma reports zero Grade 3+ toxicities in Phase 1 ENV-105 + osimertinib trial (TradingView) - "Interim Phase 1 safety analysis: no Grade 3+ adverse events observed in 13 patients treated with ENV-105 + osimertinib; Safety profile described as clean and manageable with standard supportive care, supporting progression toward an early efficacy readout; Trial assesses safety, tolerability, and recommended Phase 2 dose for ENV-105 in EGFR‑mutated advanced NSCLC; ENV-105 is a first-in-class CD105 antibody intended to resensitize tumors to osimertinib by blocking resistance signaling."

P1 data • Non Small Cell Lung Cancer

Novel therapeutic application of endoglin-specific CAR T cells in pediatric medulloblastoma (ASGCT 2026) - "Conclusion ENG is a potential therapeutic target for molecular subgroups of pediatric MB with dismal outcomes. ENG-specific CAR T cells demonstrate tumor control in preclinical models and have strong potential to deliver a new treatment option for children with high-risk MB."

CAR T-Cell Therapy • Clinical • IO biomarker • Brain Cancer • Medulloblastoma • Pediatrics • Solid Tumor • ENG • HER-2 • IFNG • IL15 • IL2 • IL7

Anti-endoglin monoclonal antibody TRC105 prevents the increase of liver inflammatory biomarkers in a mouse model of cholestasis. (PubMed, Cell Mol Life Sci) - No abstract available

Journal • Preclinical • Cholestasis • Hepatology • ENG

Study of Osimertinib With Carotuximab in Advanced, EGFR-mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Karen Reckamp, MD, MS | Trial completion date: Jan 2028 ➔ Jan 2029 | Trial primary completion date: Jan 2027 ➔ Jan 2028

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Endoglin-targeted cancer therapies: current status and opportunities. (PubMed, Expert Opin Investig Drugs) - "TRC105 (carotuximab), a monoclonal antibody against endoglin, progressed through multiple clinical trials and was well tolerated, yet outcomes were disappointing, revealing a gap between preclinical findings and patient benefit...Future progress requires a deeper mechanistic resolution of endoglin's roles across tumor type and disease stage, along with the development of biomarkers incorporating spatial expression patterns. Successful translation will depend on matching endoglin-targeted therapy to patients and tumor ecosystems most likely to benefit, shifting from broad anti-angiogenic application to precision stromal targeting."

Journal • Oncology • ENG

Radiation Reprograms Fibroblasts to Drive Prostate Cancer Therapy Resistance. (PubMed, Endocr Relat Cancer) - "Across subcutaneous and orthotopic models, combined treatment with carotuximab and irradiation reproducibly achieved superior tumor volume reduction relative to single-agent therapy. This study identified the BMP/CD105 axis as a key pathway in radiation resistance, highlighting the potential of targeting fibroblastic CD105 with carotuximab to enhance radiation sensitivity."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ENG • HMGCS2

Cost-effective method for semi-quantitative analysis of soluble endoglin in biological samples after anti-endoglin monoclonal antibody treatment. (PubMed, Sci Rep) - "Its versatility makes it applicable to various soluble protein biomarkers across diseases. As therapeutic mAbs become more widely used, this simple, cost-effective method facilitates mechanistic insights and accelerates targeted therapy development in research."

Biomarker • HEOR • Journal • Cardiovascular • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • ENG

Preliminary safety and clinical activity from a phase II study of apalutamide + carotuximab in advanced, castration-resistant prostate cancer (ESMO 2025) - P2 | "Methods Patients were required to have CRPC that was progressing through up to 2 previous ARSI therapies and were excluded for prior docetaxel treatment. The lead-in did not raise any safety concerns that now allows the trial to proceed. The combination is exhibiting preliminary clinical activity with both delayed radiographic progression and PSA response that merit further study and justify proceeding with full accrual."

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ENG • TGFB1

Kairos Pharma Presents on Phase 2 Trial of ENV-105 in Advanced Prostate Cancer at European Society Medical Oncologists (ESMO) Meeting (Businesswire) - "All responders remained progression-free for at least four months and half remained progression-free beyond one year. Notably, seven of nine evaluable patients experienced a reduction in PSA levels from baseline....The 13.7 median PFS (progression free survival) achieved by imaging with the ENV-105 and apalutamide combination reported would suggest an improvement over current alternatives of chemotherapy and radioligand therapy, in terms of disease control as well as tolerability."

P2 data • Castration-Resistant Prostate Cancer

Kairos Pharma to Present Positive Safety and Efficacy Data from Phase 2 Prostate Cancer Trial at ESMO 2025 (Businesswire) - "Kairos’s presentation, titled, 'Preliminary safety and clinical activity from a Phase 2 study of apalutamide and carotuximab in advanced, castration-resistant prostate cancer' will take place in Berlin....The presentation will highlight results from an interim analysis of the randomized Phase 2 trial evaluating ENV105 (carotuximab), a first-in-class CD105 antagonist. The trial is enrolling 100 men..."

P2 data • Castration-Resistant Prostate Cancer

Combination of Osimertinib and Carotuximab for Advanced, EFGR-Mutated Non-Small Cell Lung Cancer Patients (IASLC-WCLC 2025) - P1 | "Inhibition of epidermal growth factor (EGFR) with tyrosine kinase inhibitors (TKIs) like osimertinib and gefitinib were found to further promote CD105 expression. Clinical trial information: NCT05401110. Support for this trial has been provided by the William and Anna Tenenblatt Foundation and the Cancer Clinical Trials Office of Cedars-Sinai Cancer Center."

Clinical • Metastases • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • EGFR • ENG • TGFB1

Kairos Pharma Announces Positive Interim Efficacy Analysis of Phase 2 Trial of ENV105 in Advanced Prostate Cancer with Median Progression Free Survival of Over One Year (Businesswire) - "This predetermined interim analysis covers the same 10 patients from the safety-arm of the trial....Two of the ten patients withdrew from the trial for unrelated events. Of the eight remaining patients, the median progression-free survival was more than 13 months, with five of the eight patients continuing treatment without progression. Seven of nine patients demonstrated a decrease of their prostate-specific antigen (or PSA) from baseline."

P2 data • Castration-Resistant Prostate Cancer

Kairos Pharma to Present Interim Phase 2 Results for Prostate Cancer Drug ENV105 (City Buzz)

P2 data • Castration-Resistant Prostate Cancer

Kairos Pharma Announces Presentation of New Phase 1 Data on ENV105 Combination Therapy in Non-Small Cell Lung Cancer at the World Lung Cancer Conference September 6-9, 2025 (Businesswire)

P1 data • Non Small Cell Lung Cancer

Kairos Pharma Announces Positive Safety Results from Phase 2 Trial of ENV-105 in Advanced Prostate Cancer (Businesswire) - P2 | N=100 | NCT05534646 | "Kairos Pharma...announces positive safety results from its ongoing Phase 2 clinical trial of ENV-105 (carotuximab) in patients with metastatic castration-resistant prostate cancer (mCRPC). The interim safety analysis of the trial demonstrated that ENV-105, a first-in-class CD105 antagonist, was well tolerated when combined with standard of care hormone therapy, apalutamide, from the first ten enrolled patients. Thus far, there have been no dose-limiting toxicities or unexpected adverse events reported to date. In addition, the treatment-related side effects were manageable with standard supportive care. Notably, no Grade 3 or 4 toxicities were observed...Interim efficacy data from the trial are expected to be reported in September 2025....Kairos Pharma plans to engage with regulatory agencies to discuss the design of a potential pivotal Phase 3 study, based on emerging data."

New P3 trial • P2 data • Castration-Resistant Prostate Cancer

Effect of carotuximab (ENV105)-mediated CD105 blockade on osimertinib sensitivity in EGFR-mutant non-small cell lung cancer persister cells. (ASCO 2025) - P1 | "CD105 targeting provides a novel mutation-independent strategy to overcome resistance in EGFR-mutant NSCLC. Based on the efficacy of carotuximab capacity to limit tumor dormancy and restored osimertinib sensitivity, a Phase 1 trial (NCT05401110) investigating the combination therapy is currently accruing subjects."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ENG

Kairos Pharma Ltd. Announces Department of Defense Grant to Support Its Study of Lead Compound ENV105 to Prevent Drug Resistance in Lung Cancer (Businesswire) - "Kairos Pharma, Ltd...is a clinical stage company involved in treating EGFR-driven lung cancer patients with ENV105 in combination with osimertinib after they fail to respond to single-agent osimertinib in a Phase 1 trial. Based on recent breakthroughs in understanding non-small cell lung cancer mechanism of resistance to first line osimertinib treatment, the U.S. Department of Defense ('DoD') is providing $876,000 to advance a strategy to identify patients that are starting to develop resistance at an early stage....The grant was awarded to identify biomarkers for the Company’s clinical study to address the major challenge in achieving a lasting cure for lung cancer patients."

Financing • Non Small Cell Lung Cancer

Kairos Pharma Ltd. Announces Completed Enrollment of the Safety Arm of Its Phase 2 Clinical Trial of ENV105 in Metastatic, Castration-Resistant Prostate Cancer (Businesswire) - "Kairos Pharma, Ltd...announces the completion of the safety lead-in of its Phase 2 clinical trial of ENV105 for the treatment of metastatic, castration-resistant prostate cancer....The second part of the study, which randomizes patients to receive either apalutamide alone or in combination with ENV105 is ongoing. The Company expects to announce the safety and efficacy data readout from the safety arm of the trial beginning in the first half of 2025."

P2 data • Trial status • Castration-Resistant Prostate Cancer

Kairos Pharma Ltd. Announces Peer Reviewed Publication Highlighting Potentially Groundbreaking Discovery in Overcoming Drug Resistance in Non-Small Cell Lung Cancer (Businesswire) - "In preclinical models, targeting CD105 with ENV105 (carotuximab), a CD105-neutralizing antibody successfully restored treatment sensitivity to EGFR-targeted therapies. Notably, combining osimertinib with ENV105 reinstated susceptibility to EGFR inhibition through metabolic reprogramming and enhanced chromatin accessibility. These findings confirm the efficacy of this novel combination therapy strategy in overcoming drug resistance in this model of non-small cell lung cancer."

Preclinical • Non Small Cell Lung Cancer

Study of Osimertinib with Carotuximab in Advanced, EGFR-mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Karen Reckamp, MD, MS | Trial completion date: Jan 2026 ➔ Jan 2028 | Trial primary completion date: Jan 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Kairos Pharma Adds Huntsman Cancer Institute for Phase 2 ENV105 Clinical Trial (Businesswire) - "Kairos Pharma Ltd...today announces the addition of Huntsman Cancer Institute in Salt Lake City, Utah for the Phase 2 clinical trial for ENV105 for castrate-resistant prostate cancer patients....Huntsman Cancer Center is another renowned center to be added to support the Company’s randomized trial for patients receiving either apalutamide or apalutamide+ENV105 combination therapy. The trial is supported by Kairos Pharma Ltd. and a grant from the National Cancer Institute (NCI)."

Trial status • Castration-Resistant Prostate Cancer

Anti-Endoglin monoclonal antibody prevents the progression of liver sinusoidal endothelial inflammation and fibrosis in MASH. (PubMed, Life Sci) - "In conclusion, we demonstrate that anti-ENG antibody treatment can prevent LSECs inflammation and fibrosis progression in a MASH animal model and LSECs inflammation in vitro. Thus, we propose directly targeted ENG may represent a promising pharmacological approach for addressing LSECs inflammation and liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • CDH5 • ENG • ICAM1 • NOS3 • VCAM1

Combination of Letrozole, Everolimus and TRC105 in Postmenopausal Women With Hormone-Receptor Positive and Her2 Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=15 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Completed ➔ Active, not recruiting | Trial completion date: Dec 2022 ➔ Dec 2026 | Trial primary completion date: Dec 2022 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2