DAN-222 / Dantari - LARVOL DELTA

PRECLINICAL EFFICACY OF DAN-222, A NOVEL POLYMERIC NANOPARTICLE, IN PEDIATRIC SOLID TUMOR MODELS (CTOS 2024) - P1 | "Six treatment arms were tested: (1) Vehicle, (2) Irinotecan + temozolomide (TMZ), (3) DAN-222, (4) DAN-222 + TMZ (or DAN-222 + vincristine in the WT model), (5) DAN-222 + olaparib, and (6) olaparib. DAN-222 demonstrates significant preclinical antitumor activity across multiple pediatric solid tumor models, both alone and in combination with chemotherapy or PARP inhibition, providing preclinical rationale for clinical investigation in pediatric solid tumors."

Preclinical • Breast Cancer • Ewing Sarcoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Wilms Tumor

A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects With Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Dantari, Inc. | Active, not recruiting ➔ Completed

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

Results from a first-in-human study of DAN-222, a novel high-capacity drug conjugate in metastatic breast cancer as monotherapy and in combination with a PARPi [NCT05261269] (SABCS 2023) - P1 | " A phase 1 study of DAN-222 as monotherapy and in combination with niraparib is being conducted in heavily pretreated patients with metastatic breast cancer. No DLTs were observed in monotherapy or combination therapy in the dose escalation phase of this study. This study demonstrates the feasibility for DAN-222 to be combined with a PARPi at clinically relevant doses. The reduced myelotoxicity of DAN-222 will also enable combination with other therapies to treat patients with other types of cancer."

Combination therapy • Metastases • Monotherapy • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • BRCA • HER-2 • HRD

Dantari's Novel High-Capacity Drug Conjugate DAN-222 Shows Promising Antitumor Activity in Patients with Metastatic HER2-Negative Breast Cancer (PRNewswire) - P1 | N=30 | NCT05261269 | Sponsor: Dantari, Inc. | "Dantari, Inc...announced that data from the completed dose-escalation Phase 1 clinical trial showed that DAN-222 was safe, well tolerated, and demonstrated promising antitumor activity in patients with metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Results showed stable disease (SD) in 38% of participants receiving DAN-222 as monotherapy and SD in 67% of participants receiving DAN-222 in combination with a PARP inhibitor (niraparib) across all dose levels. These data will be presented today in a poster session at the 2023 San Antonio Breast Cancer Symposium (SABCS)....Pharmacokinetics showed the designed control of DAN-222 payload was linear and dose-proportional. The mean half-life ranged from 25.2 to 33.5 hours across all cohorts."

P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects With Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Dantari, Inc. | Recruiting ➔ Active, not recruiting | N=72 ➔ 30 | Trial completion date: Dec 2025 ➔ Oct 2023 | Trial primary completion date: Aug 2025 ➔ Sep 2023

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

A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects With Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Dantari, Inc. | N=30 ➔ 72 | Trial completion date: Apr 2024 ➔ Dec 2025

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

A dose-escalation study of the safety and pharmacology of DAN-222 in subjects with metastatic breast cancer NCT05261269 (SABCS 2022) - P1 | "The efficacy of DAN-222 was evaluated alone and in combination with a PARP inhibitor (niraparib) in HRD+ breast cancer (MDA-MB-436) and HRD- ovarian cancer (OVCAR-3) xenograft models. The clinical pharmacology will be presented and demonstrates the designed behavior of the nanoparticle. A design feature of the nanoparticle is that the payload and linker are sequestered in the core, protecting them from circulatory components. Moreover, the covalent attachment of the payload allows for tunable release kinetics via a hydrolytic linker, preventing burst release and associated toxicities common to physical encapsulation-based nanoparticle systems (e.g., liposomes, micelles)."

Clinical • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD

Dantari Debuts with $47 Million Series A to Advance Best-in-Class Targeted Medicines for Solid Tumors (PRNewswire) - P1/2 | N=30 | NCT05261269 | Sponsor: Dantari, Inc. | "This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics (PK) of intravenously (IV) administered DAN-222 and includes a dose-escalation of DAN-222 in combination with niraparib in patients with HER2-negative metastatic breast cancer....Results from the first three cohorts showed that the PK profiles of DAN-222 are linear and dose proportional, and that DAN-222 is stable and releasing the payload with consistent kinetics with very low variability between patients (CV% = 7.1 - 20.5). The PK profile of DAN-222 is consistent with and without niraparib."

P1 data • PK/PD data • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects With Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Dantari, Inc. | N=96 ➔ 30 | Trial completion date: Jun 2023 ➔ Apr 2024

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

A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects With Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Dantari, Inc.

New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

A novel investigational nanoparticle therapeutic (DAN-222) for breast cancer and other solid tumors (SABCS 2021) - "Results in the mouse xenograft models showed that DAN-222 had a superior and sustained efficacy compared to CPT and irinotecan (an approved topoisomerase-1 inhibitor) as demonstrated by tumor growth inhibition. We demonstrate the ability to modulate the payload release kinetics from the nanoparticle therapeutic by the choice of linker, with species-independent release rates. With an optimal linker selected, DAN-222 shows enhanced and sustained efficacy over native CPT. Since DAN-222 has previously been shown to have reduced bone marrow exposure of chemotherapy, it may provide a significant therapeutic advancement with a wider therapeutic index based on both enhanced efficacy and improved safety."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

[VIRTUAL] Efficacy of DAN-222, a novel investigational polymeric nanoparticle with topoisomerase I inhibitor, as monotherapy in breast cancer models and when combined with PARP inhibitor. (ASCO 2021) - "DAN-222 is a novel investigational polymeric nanoparticle conjugated with camptothecin, a topoisomerase I inhibitor, that provides significant accumulation of drug in tumor tissues via the enhanced permeability and retention (EPR) effect and significantly reduced bone marrow exposure compared to native chemotherapy...The groups evaluated include multiple dose levels of DAN-222 as monotherapy and those also combined with niraparib... Combining a PARP inhibitor with a topoisomerase I inhibitor delivered via this polymeric nanoparticle delivery system (DAN-222) has synergistic efficacy in both HRD+ and HRD- xenograft tumor models . These data support continued development of DAN-222 to treat solid tumors and its combination use with PARP inhibitors."

Clinical • Monotherapy • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA • HER-2 • HRD