genistein nanosuspension (BIO 300) / Humanetics - LARVOL DELTA

Phase 1 BIO 300 Oral Suspension (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Humanetics Corporation | Recruiting ➔ Completed

Trial completion

Prophylactic Administration of BIO 300, A Radiation Medical Countermeasure, Improves Erythrocyte-Associated Parameters in the Rhesus Macaque Model. (PubMed, Mil Med) - "The data presented here suggest that BIO 300 IS radioprotective efficacy is mediated by improving red blood cell and platelet counts while also reducing adverse histopathological findings in NHPs undergoing TBI. These results suggest a potential novel mechanism of action for BIO 300 involving the protection of the megakaryocyte-erythropoietic progenitor population."

Journal • Hematological Disorders

Humanetics Corporation Announces Positive Phase 2 Clinical Trial Results in COVID-19 Study Aimed at Improving Pulmonary Function (Businesswire) - P2 | N=50 | NCT04482595 | "Humanetics Corporation (Humanetics) announced today the results of its Phase 2 clinical trial of BIO 300 Oral Suspension (BIO 300) for the mitigation of impaired pulmonary function in COVID-19 patients recently discharged from the hospital....Improvement in Pulmonary Function: Participants who received BIO 300 demonstrated a statistically significant improvement in pulmonary function at 12 weeks, which was maintained at 12 months, as measured by forced expiratory volume in one second (FEV1). Additionally, clear statistical trends for improved pulmonary function were observed in BIO 300-treated participants at 12 weeks, 6 months, and 12 months, as measured by the diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC)."

P2 data • Novel Coronavirus Disease

Phase 1 BIO 300 Oral Suspension (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Humanetics Corporation | Not yet recruiting ➔ Recruiting

Enrollment open

Phase 1 BIO 300 Oral Suspension (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Humanetics Corporation

New P1 trial

BIO 300 Oral Suspension in Previously Hospitalized Long COVID Patients (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Humanetics Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • IL1B • IL6 • TGFB1 • TNFA

BIO 300 Attenuates Whole Blood Transcriptome Changes in Mice Exposed to Total-Body Radiation. (PubMed, Int J Mol Sci) - "In all, four signaling pathways of interest were identified that were differentially enriched in irradiated animals treated with BIO 300: pathogen-induced cytokine storm signaling, S100 family signaling, pulmonary fibrosis idiopathic signaling, and wound-healing signaling. These pathways should be explored to identify potential biomarkers of BIO 300 that can be used for human dose translation."

Biomarker • Journal • Preclinical • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

BIO 300: A Prophylactic Radiation Countermeasure for Acute Radiation Syndrome. (PubMed, Mil Med) - "BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems."

Journal • Febrile Neutropenia • Hematological Disorders • Neutropenia

BIO 300 Oral Suspension in Previously Hospitalized Long COVID Patients (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Humanetics Corporation | Trial completion date: Mar 2024 ➔ Apr 2025 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • IL1B • IL6 • TGFB1 • TNFA

Humanetics Corporation Receives Funding to Study New Drug for Idiopathic Pulmonary Fibrosis (Businesswire) - "Humanetics Corporation (Humanetics) announced today that it has been awarded a Small Business Innovation Research (SBIR) grant from the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. The funding will support a series of studies with its new drug candidate, BIO 300. BIO 300 is believed to prevent and mitigate acute and chronic inflammatory pulmonary diseases, including radiation toxicities. The studies will focus on the ability of BIO 300 to attenuate progressive pulmonary fibrosis as a potential treatment for idiopathic pulmonary fibrosis (IPF). IPF is a progressive and ultimately fatal lung disease that affects approximately 3 million people worldwide. IPF is associated with a particularly poor prognosis, with most patients succumbing to the disease within 3-5 years from diagnosis."

Financing • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease

Multicenter Phase 1b/2a Clinical Trial of Radioprotectant BIO 300 Oral Suspension for Patients with Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy. (PubMed, Int J Radiat Oncol Biol Phys) - "The low toxicity rates, along with the pharmacodynamic results and tumor response rates, support further investigation of BIO 300 as an effective radioprotector."

Journal • P1/2 data • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TGFB1

Humanetics Corporation Publishes Positive Clinical Trial Results of BIO 300 in Patients with Non-Small Cell Lung Cancer (Businesswire) - P1/2 | N=21 | NCT02567799 | Sponsor: Humanetics Corporation | "The study found that BIO 300 was safe and well tolerated, and no dose-limiting toxicities were reported. Patient-reported quality of life and body weight were stable throughout the study period. The tumor response rate was 65%, with a complete response rate of 20%. BIO 300 did not alter the pharmacokinetics of standard chemotherapy. Serum TGFβ1, a pro-inflammatory/pro-fibrotic cytokine implicated in pulmonary fibrosis and radiation pneumonitis, was reduced in a dose-dependent manner across cohorts....The pharmacodynamic results, combined with the tumor response and low toxicity rates, support further investigation of BIO 300 as an effective radioprotective drug in patients with NSCLC."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The radioprotectant nano-genistein enhances radiotherapy efficacy of lung tumors in mice. (PubMed, Transl Lung Cancer Res) - "There were no treatment-related histopathological findings noted in the skin adjacent to the tumor, esophagus, or uterus. These results, including the safety following extended dosing, support the continued evaluation of nano-genistein as an adjunctive treatment for patients with NSCLC undergoing radiotherapy and serve as the basis of a phase 1b/2a multicenter clinical trial."

Journal • Preclinical • Esophageal Cancer • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor

BIO 300 Enhances Radiotherapy Efficacy Against Lung Tumors in a Nonclinical Model (Businesswire) - "A recently published paper in Translational Lung Cancer Research details encouraging results from nonclinical studies conducted with Humanetics Corporation’s (Humanetics) novel radioprotective drug, BIO 300. The studies evaluated the therapeutic utility of BIO 300 when lung cancer undergoes treatment by radiation therapy. The positive results showcased that BIO 300 can protect normal tissues from collateral damage associated with radiotherapy without protecting the lung tumor, while potentially sensitizing the tumors to radiotherapy."

Preclinical • Lung Cancer • Oncology • Solid Tumor

BIO 300 Oral Suspension in Previously Hospitalized Long COVID Patients (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Humanetics Corporation | Trial completion date: Nov 2023 ➔ Mar 2024 | Trial primary completion date: Feb 2023 ➔ Jun 2023

Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CRP

The Radioprotectant, BIO 300, Protects the Lungs from Total-Body Irradiation Injury in C57L/J Mice. (PubMed, Radiat Res) - "Results in the C57L/J mice were compared to those in CD2F1 mice, which are less prone to lung injury following total-body irradiation. Taken together, these studies indicate that BIO 300 is a promising MCM that is able to prophylactically protect against DEARE-lung."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Safety, Pharmacokinetics, and Biomarkers of an Amorphous Solid Dispersion of Genistein, a Radioprotectant, in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "RNA sequencing analysis revealed that the majority of drug-related changes in gene expression occurred 8-12 hours after the sixth dose in the MSD study. Based on these results, the putative effective dose in humans is 3000 mg."

Biomarker • Journal • PK/PD data • Gastrointestinal Disorder

Humanetics Receives FDA Clearance to Begin Studies in Second Oncology Indication (Businesswire) - "Humanetics Corporation...announced today that it has received FDA clearance of its Investigational New Drug (IND) application for BIO 300 to mitigate erectile dysfunction in men undergoing radiation treatment for prostate cancer."

IND • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Pharmacokinetic and metabolomic studies with a BIO 300 Oral Powder formulation in nonhuman primates. (PubMed, Sci Rep) - "These study results are consistent with our previous studies focused on the PK and metabolomic analysis for parenteral and oral aqueous nanosuspension formulations of BIO 300. This study affirms that administration of a single dose of up to 200 mg/kg of BIO 300 Oral Powder is safe in NHPs and conferred no metabolomic-mediated safety features."

Journal • PK/PD data

BIO 300 Oral Suspension in Discharged COVID-19 Patients (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Humanetics Corporation | Trial completion date: Dec 2022 ➔ Nov 2023 | Trial primary completion date: Mar 2022 ➔ Feb 2023

Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CRP

Interspecies Comparison and Radiation Effect on Pharmacokinetics of BIO 300, a Nanosuspension of Genistein, after Different Routes of Administration in Mice and Non-Human Primates. (PubMed, Radiat Res) - "Future studies should use SC and IM routes to maximize drug exposure when administered postirradiation. The allometric coefficient is useful in predicting therapeutic drug dose regimens across species for drug approval under the FDA animal rule."

Journal • PK/PD data • Preclinical

Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure. (PubMed, Anim Microbiome) - "Overall, the data presented show that radiation exposure led to a relative depletion of commensals like Lactobacillus leading to an inflammatory metabolic phenotype while the majority of the drug-treated mice showed alleviation of this condition primarily by restoration of normal gut microbiota. These results indicate that the radioprotective effects of BIO 300, at least in part, may involve correction of the host-microbiome metabolic axis."

Journal • Preclinical

A novel oral formulation of BIO 300 confers prophylactic radioprotection from acute radiation syndrome in mice. (PubMed, Int J Radiat Biol) - "We investigated the efficacy of a BIO 300 Oral Powder (OP) formulation as a prophylactic radiation medical countermeasure against a lethal dose of cobalt-60 gamma-radiation in CD2F1 male mice while comparing to other formulations of BIO 300 and Neulasta (PEGylated filgrastim), a standard of care drug for H-ARS. Its radioprotective efficacy in the murine model was comparable to the efficacy of a single subcutaneous (sc) injection of Neulasta administered after total-body radiation exposure. Our results demonstrate that BIO 300 OP, which can be administered orally, is a promising prophylactic radiation countermeasure for H-ARS."

Journal • Preclinical

Humanetics Corporation’s BIO 300 Receives Fast Track Designation from FDA (Businesswire) - "Humanetics Corporation (Humanetics) announced...that BIO 300, a drug under development to increase survival in persons exposed to high levels of radiation, has been granted Fast Track status by the U.S. Food and Drug Administration...Humanetics recently completed a clinical trial of BIO 300 in lung cancer patients aimed at mitigating pulmonary injury related to their radiation treatments..."

Fast track designation • Lung Cancer • Non Small Cell Lung Cancer • Oncology

BIO 300 Oral Suspension in Discharged COVID-19 Patients (clinicaltrials.gov) - P2; N=66; Recruiting; Sponsor: Humanetics Corporation; Trial completion date: May 2022 ➔ Dec 2022; Trial primary completion date: Aug 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CRP