alphalex-exatecan (CBX-12) / Cybrexa Therap - LARVOL DELTA

CBX-12-101: Study of CBX-12 in Subjects with Advanced or Metastatic Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Active, not recruiting | Sponsor: Cybrexa Therapeutics | Trial completion date: Mar 2025 ➔ Jun 2025

Trial completion date • Appendix Cancer • Breast Cancer • Colorectal Cancer • Epithelial Ovarian Cancer • Esophageal Cancer • Gastric Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Urothelial Cancer

CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

Metastases • New P2 trial • Colorectal Cancer • Oncology • Solid Tumor • SLFN11 • TOP1

Cybrexa Therapeutics Announces First Patient Dosed with First-in-Class Peptide-Drug Conjugate CBX-12 in Phase 2 Trial in Ovarian Cancer (GlobeNewswire) - "Cybrexa Therapeutics...announced that the first patient has been dosed in a Phase 2 clinical trial evaluating CBX-12 in patients with platinum-resistant or refractory ovarian cancer....Cybrexa plans an additional Phase 2 study of CBX-12 in colorectal cancer in 2025 in collaboration with the National Cancer Institute (NCI), as well as other Phase 2 studies evaluating CBX-12 as a monotherapy and in combination across a range of solid tumors."

New P2 trial • Trial status • Colorectal Cancer • Ovarian Cancer • Solid Tumor

CBX-12-101: Final results of a phase I study of CBX-12, a peptide drug conjugate (PDC) in patients (pts) with metastatic solid tumors (ESMO 2024) - P1/2 | "Tumor targeting facilitated by this pH sensitive peptide made possible an improved safety profile despite the administration of a 5-fold increase in the dose of exatecan compared to unconjugated exatecan. The dose limiting toxicity is myelosuppression. CBX-12 demonstrated broad activity with 5 confirmed responses in three malignancies."

Clinical • Metastases • P1 data • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thymus Cancer

Cybrexa Therapeutics Announces Positive Final Data at ESMO 2024 from Phase 1 Study of Peptide Drug Conjugate CBX-12 in Advanced Solid Tumors (GlobeNewswire) - P1/2 | N=130 | NCT04902872 | Sponsor: Cybrexa Therapeutics | "Specifically, in 10 ovarian cancer patients who were TOP1-naïve, there was one confirmed complete response, one confirmed partial response (PR), and two unconfirmed PRs, with eight out of 12 patients showing clinical benefit. In seven TOP1-naïve breast cancer patients, there were two confirmed PRs and one unconfirmed PR. All evaluable breast participants were HER-2 negative and HR positive....The PK of CBX-12 and exatecan exhibited linear dose-proportional behavior, with a mean half-life ranging from 14 to 22 hours across the dose range studied....An additional Phase 2 study in colorectal cancer is planned for 2025 in collaboration with the National Cancer Institute (NCI), as well as other Phase 2 studies in solid tumors as a monotherapy and in combination."

New P2 trial • P1 data • PK/PD data • Breast Cancer • Colorectal Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Gynecologic Cancers • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thymic Carcinoma

A Study of CBX 12 in Subjects With Platinum Resistant or Refractory Ovarian Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Cybrexa Therapeutics | Trial completion date: Apr 2026 ➔ Jul 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

CBX-12-101: Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Active, not recruiting | Sponsor: Cybrexa Therapeutics | Trial completion date: Sep 2024 ➔ Mar 2025 | Trial primary completion date: May 2024 ➔ Jan 2025

Metastases • Trial completion date • Trial primary completion date • Appendix Cancer • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Urothelial Cancer

Pilot study of CBX-12 pharmacodynamics in patients with advanced solid tumors. (ASCO 2024) - P1, P1/2 | "Mandatory biopsies will be collected at baseline, 24-36 hours post first dose, and on cycle 3 day 1 to assess both short- and long-term effects of CBX-12 on the tumor. Mandatory research blood samples will be collected at specified timepoints for pharmacokinetic, circulating tumor cell, and cell-free DNA analyses."

Clinical • Metastases • PK/PD data • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • CD8 • TOP1

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2025 ➔ Oct 2026 | Trial primary completion date: Mar 2025 ➔ Oct 2026

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • RAD51

A Study of CBX 12 in Subjects With Platinum Resistant or Refractory Ovarian Cancer (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Cybrexa Therapeutics

New P2 trial • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

Cybrexa Regains Rights to CBX-12 (GlobeNewswire) - "Cybrexa Therapeutics...today announced the Company will regain all rights to CBX-12 (alphalex™ exatecan), a clinical-stage, first-in-class peptide drug conjugate that utilizes Cybrexa’s proprietary alphalex technology to enhance delivery of exatecan to tumor cells, as its collaboration partner, Exelixis, Inc., has provided a notice of termination for the right to acquire CBX-12....This collaboration has positioned Cybrexa to move CBX-12 into phase II trials later this year..."

Licensing / partnership • New P2 trial • Oncology • Solid Tumor

CBX-12-101: Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Active, not recruiting | Sponsor: Cybrexa Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2024 ➔ Sep 2024 | Trial primary completion date: Feb 2024 ➔ May 2024

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Appendix Cancer • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Urothelial Cancer

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Oct 2023 ➔ Feb 2024

Metastases • Trial initiation date • Oncology • Solid Tumor • RAD51

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Apr 2023 ➔ Oct 2023

Metastases • Trial initiation date • Oncology • Solid Tumor • RAD51 • TOP1

CBX-12-101: A first-in-human study of CBX-12, an alphalex peptide drug conjugate (PDC) in patients (pts) with advanced or metastatic solid tumors. (ASCO 2023) - P1/2 | "In this FIH study of a pH-targeting alphalex PDC, CBX-12 demonstrated single-agent antitumor activity including 4 responses with the dominant toxicity of myelosuppression. Phase 2 expansion cohorts are planned in pts with platinum-resistant ovarian cancer and hormone-receptor positive, HER2 negative breast cancer. Clinical trial information: NCT04902872."

Clinical • Metastases • P1 data • Anemia • Breast Cancer • Fatigue • Febrile Neutropenia • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Infectious Disease • Neutropenia • Oncology • Ovarian Cancer • Septic Shock • Solid Tumor • Thrombocytopenia • HER-2 • TOP1

Cybrexa Therapeutics To Present Data at ASCO 2023 Highlighting First-In-Human, Dose-Finding Study of Lead Candidate CBX-12 (GlobeNewswire) - P1/2 | N=130 | NCT04902872 | Sponsor: Cybrexa Therapeutics | "Cybrexa Therapeutics...announced that new data for its lead compound, CBX-12, a first-in-class investigational PDC, will be presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago on June 2-6. The maximum tolerated dose (MTD) for CBX-12 was established on two different dosing paradigms, with myelosuppression being the primary dose-limiting toxicity. In addition, treatment with CBX-12 resulted in four objective responses....Among the single-agent antitumor activity demonstrated by CBX-12 in the study, one patient achieved a complete response in ovarian, and three achieved partial responses, two in breast and one in ovarian, per the RECIST 1.1 criteria."

P1/2 data • Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Exelixis Announces First Quarter 2023 Financial Results and Provides Corporate Update (Businesswire) - "...'We are on track to initiate additional pivotal studies for zanzalintinib in 2023'....Cybrexa is planning to present updated phase 1 data for CBX-12 at the ASCO Annual Meeting in June."

New trial • P1 data • Oncology • Solid Tumor

Utilizing a pH sensitive peptide (pHLIP) for tumor targeted delivery of an immunogenic peptide motif (AACR 2023) - "pHLIP-conjugates have undergone extensive development for drug delivery, with one notable candidate CBX12 entering phase I clinical trials in 2021...Cumulatively, these initial results suggest that pHLIP-SIINFEKL can be delivered to tumors to recruit OT1 cells to engage in antigen recognition and lead to efficacy in tumor growth delay in vivo. This technology has the capability to provide a novel approach to decorate solid tumors with engineered antigens for enhanced immune recognition and anti-tumor efficacy."

Melanoma • Oncology • Solid Tumor • CD19

CBX-12-101: A first-in-human study of CBX-12, an alphalex peptide drug conjugate (PDC) in patients with advanced or metastatic solid tumors (AACR-NCI-EORTC 2022) - P1/2 | "Conclusions In this FIH study of a pH-targeting alphalex PDC, CBX-12 demonstrated good tolerability, single-agent anti-tumor activity including 2 confirmed responses, and an AE profile consistent with the TOP1 payload, exatecan. Phase 2 cohort expansions are planned in patients with ovarian and SCLC."

Clinical • Late-breaking abstract • P1 data • Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • TOP1

[VIRTUAL] A phase 1/2 trial of CBX-12, an alphalexTM peptide drug conjugate, in patients with advanced or metastatic refractory solid tumors (AACR-NCI-EORTC 2021) - No abstract available

Clinical • P1/2 data • Oncology • Solid Tumor

Exelixis Announces Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (Businesswire) - "acceleration of the XB002 clinical program into full development by year-end; advancement of the XL102 QUARTZ-101 phase 1 study into the tumor-specific cohort-expansion stage and in planned combination cohorts; in collaboration with partner Cybrexa, progression of phase 1 clinical study for CBX-12, including dose-expansion cohorts; expected IND filing for ADU-1805 in the first quarter of 2023 by partner Sairopa; advancement of DCs XB010, XB014 and XB628 toward IND filings."

Clinical • Clinical protocol • IND • New P1 trial • Oncology • Solid Tumor

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1 trial • Oncology • Solid Tumor • RAD51 • TOP1

Exelixis Announces Preliminary Fourth Quarter and Full Year 2022 Financial Results, Provides 2023 Financial Guidance, and Outlines Key Priorities and Milestones for 2023 (Businesswire) - "In 2023, Exelixis intends to advance the first-in-human QUARTZ-101 phase 1 trial evaluating XL102, its potent, selective, irreversible and orally bioavailable small molecule CDK7 inhibitor into the cohort expansion and potential combination cohorts....Exelixis expects to evaluate the anti-tumor activity and efficacy of XL102 in additional patients in the single-agent dose-escalation cohorts, in the tumor-specific cohort-expansion stage and in planned combination cohorts....Exelixis expects its partner Cybrexa to continue to advance its phase 1 clinical study program for CBX-12 throughout 2023, including dose-expansion cohorts."

P1 data • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor

Antigen-independent tumor targeting by CBX-12 (alphalex-exatecan) induces long-term antitumor immunity. (PubMed, Immunotherapy) - "CBX-12 stimulates expression of MHC 1 and PD-L1 and is an inducer of immunogenic cell death, producing long-term immune recognition of tumor cells and resultant antitumor immunity. The authors' data provide the rationale for exploring immunotherapy combinations with CBX-12 in clinical trials."

IO biomarker • Journal • Immune Modulation • Inflammation • Oncology • PD-L1 • TOP1

Cybrexa Therapeutics Presents Findings from First-in-Human Study of CBX-12 as a Plenary Oral Presentation at 34th EORTC-NCI-AACR Symposium (GlobeNewswire) - P1 | N=112 | NCT04902872 | Sponsor: Cybrexa Therapeutics | "Cybrexa Therapeutics...presented findings as a plenary oral presentation at the annual EORTC-NCI-AACR (ENA) Symposium on molecular targets and cancer therapeutics. This first-in-human study of CBX-12, an alphalex™ PDC in patients with advanced or metastatic solid tumors, demonstrates tolerability, safety and single-agent anti-tumor activity including two confirmed responses for patients receiving CBX-12....Of the 18 response-evaluable patients in this heavily treated patient population with advanced or metastatic cancers, one patient with ovarian cancer achieved complete response (CR), one patient with breast cancer achieved partial response (PR), and 13 patients maintained stable disease (SD)....The study is also evaluating plasma pharmacokinetics (PK), anti-drug antibodies, and intratumoral levels of CBX-12 and exatecan, anti-tumor activity."

P1 data • Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor