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

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

Effect of carotuximab (ENV105)-mediated CD105 blockade on osimertinib sensitivity in EGFR-mutant non-small cell lung cancer persister cells. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

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

Kairos Pharma Adds City of Hope Cancer Center for Phase 2 ENV105 Clinical Trial (Businesswire) - "Kairos Pharma Ltd...announces the addition of City of Hope Cancer Center in Duarte, California to the Phase 2 clinical trial for ENV105 for castrate-resistant prostate cancer patients...City of Hope Cancer Center is the first of several planned new centers to be added in the coming weeks to support the Company’s randomized trial for patients receiving either apalutamide or apalutamide+ENV105 combination therapy. The additional centers allow Kairos Pharma to test ENV105 in a broader patient population to identify blood markers that could help select patients expected to benefit most from ENV105 treatment. The trial is supported by Kairos Pharma Ltd. and a grant from the National Cancer Institute (NCI)."

Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Kairos Pharma Enters Agreement with PreCheck Health Services to Develop Biomarkers to Identify Patients Responsive to ENV105 to Target Cancer Drug Resistance in Prostate and Lung Cancer Patients (GlobeNewswire) - "Kairos Pharma Ltd...announces a groundbreaking collaboration with PreCheck Health Services Inc...The partnership focuses on the development of companion biomarkers for Kairos Pharma’s cancer therapy, ENV105, which targets prostate and lung cancers. This strategic agreement aims to advance the precision of patient screening and therapy monitoring for Kairos Pharma’s Phase 1 and Phase 2 clinical trials, with the aim of advancing cancer treatment by identifying patients who will benefit most from ENV105....Kairos Pharma and PreCheck Health Services will utilize advanced molecular diagnostics to corroborate and further develop biomarkers previously identified in a Phase 2 clinical trial. These biomarkers are designed to predict patient responses to ENV105 prior to treatment, offering a more personalized approach to cancer care."

Diagnostic • Licensing / partnership • Genito-urinary Cancer • Lung Cancer • Oncology • Prostate Cancer

Kairos Pharma Prices $6.2 Million Initial Public Offering (GlobeNewswire) - "The Company intends to use the net proceeds from the offering to fund its Phase 1 trial in lung cancer and Phase 2 trial in prostate cancer for its lead product candidate ENV 105, designed to reverse resistance to standard of care drugs. The proceeds will also advance preclinical candidates, including KROS 101, a small molecule agonist for the GITR ligand, designed to promote T cell growth and cytotoxic function against cancer."

Commercial • Genito-urinary Cancer • Oncology • Prostate Cancer

Study of Apalutamide With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Edwin Posadas, MD | Trial completion date: Oct 2026 ➔ Jan 2027 | Trial primary completion date: Oct 2026 ➔ Jan 2027

Metastases • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Kairos Pharma Doses First Patient in Phase 2 Trial of Lead Drug Candidate ENV105 with Apalutamide to Improve Therapy Sensitivity for Castrate-Resistant Prostate Cancer (GlobeNewswire) - "Kairos Pharma, Ltd...announces the dosing of its first patient in its Phase 2 trial testing a combination therapy for its lead therapeutic candidate ENV105 in combination with apalutamide for the treatment of castrate resistant prostate cancer (CRPC)....The multi-site trial aims to enroll 100 patients who have already developed resistance to androgen receptor signaling inhibitors."

Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Kairos Pharma Doses First Patients in Phase 1 Trial of Lead Drug Candidate ENV105 with Osimertinib to Improve Therapy Sensitivity for EGFR-Driven Lung Cancer (GlobeNewswire) - "Kairos Pharma, Ltd...announces the dosing of its first two patients in its Phase 1 trial testing a combination therapy for its lead therapeutic candidate ENV105 in combination with osimertinib for the treatment of non-small cell lung cancer."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Endoglin inhibitor TRC105 with or without bevacizumab for bevacizumab-refractory glioblastoma (ENDOT): a multicenter phase II trial. (PubMed, Commun Med (Lond)) - P2 | "Single-agent TRC105 lacks activity in bevacizumab-refractory GBM, possibly secondary to upregulated VEGF-A expression. Meaningful mOS in bevacizumab+TRC105 cohort warrants further trials to investigate efficacy of combination therapy."

Journal • P2 data • Brain Cancer • Cerebral Hemorrhage • CNS Tumor • Glioblastoma • Hematological Disorders • Oncology • Solid Tumor • ENG

Study of Apalutamide With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Edwin Posadas, MD | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2025 ➔ Oct 2026 | Trial primary completion date: Nov 2025 ➔ Oct 2026

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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 | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=15 | Completed | Sponsor: University of Alabama at Birmingham | Active, not recruiting ➔ Completed

Metastases • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Endoglin, a novel biomarker and therapeutical target to prevent malignant peripheral nerve sheath tumor growth and metastasis. (PubMed, Clin Cancer Res) - "Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease."

Biomarker • Journal • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • ENG • TGFB1

Endoglin and squamous cell carcinomas. (PubMed, Front Med (Lausanne)) - "On the functional level, endoglin, both in a ligand dependent and independent manner, did not influence proliferation or migration of the SCC cells. In conclusion, these data show endoglin expression on individual cells in the tumor nests in SCCs and a role for (soluble) endoglin in paracrine signaling, without directly affecting proliferation or migration in an autocrine manner."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Vulvar Cancer • ALK1 • ENG • SMAD1 • TGFB1

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

A phase I/II study of preoperative letrozole, everolimus, and TRC105 in women with newly diagnosed local or locally advanced potentially resectable hormone-Receptor positive and Her2 negative breast cancer (SABCS 2017) - "Premenopausal women at the time of enrollment will receive goserelin 3.6 mg SC q4 weeks to achieve ovarian suppression. Current Status: Cohort 1 of the Phase 1 complete. Cohort 2 of Phase 1 actively enrolling."

Next-generation sequencing • P1/2 data • HER2 Breast Cancer • Hormone Receptor Breast Cancer

A Phase 1b Dose-Escalation Study of TRC105 in Combination with Nivolumab in Patients with Metastatic Non-Small Cell Lung Cancer (WCLC 2017) - "Nivolumab (N) has demonstrated clinical benefit in advanced non-small cell lung cancer (NSCLC) patients (PTS) who have progressed to platinum-based chemotherapy: improved overall survival (OS) versus (Vs) docetaxel in squamous NSCLC (median OS of 9.2 months [mo} Vs 6 mo) and in non-squamous NSCLC (median OS of 12.2 mo Vs 9.4 mo). Section not applicable"

Combination therapy • P1 data

A Phase 1b Dose-Escalation Study of Carotuximab in Combination with Nivolumab in Patients with Metastatic NSCLC (IASLC-WCLC 2019) - "Carotuximab at its RP2D of 10 mg/kg weekly x 4 and then 15 mg/kg every 2 weeks was tolerable with nivolumab in patients with NSCLC, and demonstrated preliminary signs of efficacy"

Clinical • Combination therapy • IO Biomarker • P1 data • PD(L)-1 Biomarker

An open-label phase Ib/2 trial of TRC105 plus sorafenib in patients with advanced/metastatic hepatocellular carcinoma (HCC) (NCT01806064). (ASCO-GI 2019) - P1b; "TRC105 dosed at 10 mg/kg wkly was required to achieve target conc. due to higher clearance in HCC pts, which may have been influenced by a higher rate of ADA compared to studies of TRC105 in other tumor types. The combination of TRC105 + S demonstrated encouraging signs of activity, including durable PR in 2/9 evaluable pts in Phase 1b and 1/5 pts thus far in Phase 2."

Clinical