carbon monoxide (HBI-002) / Hillhurst Biopharma - LARVOL DELTA

Clinical safety of oral administration of hbi-002 carbon monoxide drug product in healthy subjects and individuals with sickle cell disease (ASH 2025) - P1, P1/2 | "4 of the 6 subjects were receiving hydroxyurea. A second subject's PICC line became occluded withan axillary vein thrombosis (grade 2). Overall, all 6 subjects tolerated the HBI-002 dosing with only minorHBI-002-related adverse events, but with PICC line-associated AEs in 2 of the 6 subjects."

Clinical • Back Pain • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Sickle Cell Disease • Thrombosis

A Safety, Efficacy, and Pharmacokinetic (PK) Study of HBI-002, an Oral Carbon Monoxide (CO) Therapeutic, in Subjects With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1/2 | N=9 | Recruiting | Sponsor: Hillhurst Biopharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HMOX1

LoCaMoTE-PD: Low-dose Carbon Monoxide (HBI-002) Trial to Evaluate Safety, Tolerability, PK, and Biomarkers in Parkinson's Disease (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Hillhurst Biopharmaceuticals, Inc.

Biomarker • New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Hillhurst gets $6.3M funding for HBI-002 clinical study (Parkinson's News Today) - "Hillhurst Biopharmaceuticals said it’s been awarded $6.3 million to fund a Phase 2a clinical study to test the efficacy of HBI-002, its low-dose liquid formulation of carbon monoxide, in preserving dopaminergic neurons, those that are lost to Parkinson’s disease, with the goal of slowing or stopping disease progression....The study is scheduled to launch in early 2025, and will involve 36 people diagnosed with Parkinson’s, according to Hillhurst. Over the course of 14 days, researchers will look at HBI-002’s safety, its pharmacokinetics — how it moves into, through, and out of the body — and its effects on certain biomarkers."

Financing • New P2a trial • Parkinson's Disease

A Safety, Efficacy, and Pharmacokinetic (PK) Study of HBI-002, an Oral Carbon Monoxide (CO) Therapeutic, in Subjects With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1/2 | N=8 | Not yet recruiting | Sponsor: Hillhurst Biopharmaceuticals, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity. (PubMed, J Am Heart Assoc) - "These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage."

Journal • Breast Cancer • Cardiovascular • Gastrointestinal Disorder • Oncology • Solid Tumor • HMOX1

A Safety, Efficacy, and Pharmacokinetic (PK) Study of HBI-002, an Oral Carbon Monoxide (CO) Therapeutic, in Subjects With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1/2 | N=8 | Not yet recruiting | Sponsor: Hillhurst Biopharmaceuticals, Inc. | Initiation date: Jan 2024 ➔ May 2024 | Trial primary completion date: Jun 2024 ➔ Oct 2024

Trial initiation date • Trial primary completion date • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Safety, Efficacy, and Pharmacokinetic (PK) Study of HBI-002, an Oral Carbon Monoxide (CO) Therapeutic, in Subjects With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1/2 | N=8 | Not yet recruiting | Sponsor: Hillhurst Biopharmaceuticals, Inc.

New P1/2 trial • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Neuroprotection with low dose carbon monoxide in three models of Parkinson’s Disease (PSG 2023) - "Treatment with low dose CO reduced cell death and aSyn pathology in animal models of PD. Low dose CO may have therapeutic activity in PD."

A Study to Assess the Safety and Pharmacokinetics of HBI-002, an Oral Carbon Monoxide Therapeutic, in Healthy Volunteers (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Hillhurst Biopharmaceuticals, Inc. | Recruiting ➔ Completed | Trial primary completion date: Jan 2023 ➔ Apr 2023

Trial completion • Trial primary completion date • Anemia • Hematological Disorders • Sickle Cell Disease

Low Dose Carbon Monoxide Is Neuroprotective in Models of Parkinson's Disease (AAN 2023) - "HBI-002 upregulated heme oxygenase-1, HIF-1a, and cathepsin D. In the rotenone model, treatment with low dose CO reduced cell death. Conclusions These results demonstrating reduced cell death and aSyn pathology in animal and cell models support the therapeutic potential of low dose CO for PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • CTSD • HIF1A • HMOX1

A Study to Assess the Safety and Pharmacokinetics of HBI-002, an Oral Carbon Monoxide Therapeutic, in Healthy Volunteers (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Hillhurst Biopharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Oct 2022 ➔ Feb 2023 | Trial primary completion date: Sep 2022 ➔ Jan 2023

Enrollment open • Trial completion date • Trial primary completion date • Anemia • Hematological Disorders • Sickle Cell Disease

Ameliorative role of low-dose carbon monoxide exposure in an animal model of parkinsons disease. (CAN-ACN 2022) - "- Our findings suggest that a low-dose carbon monoxide could be a neuroprotective therapy for Parkinson's disease."

Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease • HIF1A • HMOX1

CARBON MONOXIDE AT LOW DOSES REDUCES DOPAMINE CELL LOSS AND ALPHA-SYNUCLEIN PATHOLOGY IN MODELS OF PARKINSON’S DISEASE (ADPD 2022) - "These results demonstrating reduced dopamine cell death and aSyn pathology advance low dose CO as a potential neuroprotective strategy for PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • HIF1A • HMOX1

A Study to Assess the Safety and Pharmacokinetics of HBI-002, an Oral Carbon Monoxide Therapeutic, in Healthy Volunteers (clinicaltrials.gov) - P1; N=20; Not yet recruiting; Sponsor: Hillhurst Biopharmaceuticals, Inc.; Trial completion date: Oct 2021 ➔ Oct 2022; Trial primary completion date: Sep 2021 ➔ Sep 2022

Clinical • Trial completion date • Trial primary completion date • Anemia • Hematological Disorders • Sickle Cell Disease

[VIRTUAL] Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity (AHA 2021) - "Introduction : Doxorubicin (DOX) and other anthracyclines comprise important anticancer drugs. Collectively, these findings support HBI-002 as a promising cardioprotective agent against DOX toxicity and warrant further development as a therapeutic."

Oncology

A Study to Assess the Safety and Pharmacokinetics of HBI-002, an Oral Carbon Monoxide Therapeutic, in Healthy Volunteers (clinicaltrials.gov) - P1; N=20; Not yet recruiting; Sponsor: Hillhurst Biopharmaceuticals, Inc.; Trial completion date: May 2020 ➔ Oct 2021; Trial primary completion date: Feb 2020 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • Anemia • Hematological Disorders • Sickle Cell Disease

[VIRTUAL] NEUROPROTECTION OF LOW DOSE CARBON MONOXIDE IN GENETIC AND TOXIN MODELS OF PARKINSON’S DISEASE (ADPD 2021) - "AAV-aSyn rats treated with HBI002 retained 74±12% (SD) of right striatal dopamine versus left, compared to 36±7% in vehicle-treated rats (p=0.03). Low-dose CO protects nigral dopamine neurons, preserves striatal dopamine content, and reduces aSyn pathology in animal models of PD. Low dose CO may have disease-modifying activity in PD."

CNS Disorders • Movement Disorders • Parkinson's Disease

A Study to Assess the Safety and Pharmacokinetics of HBI-002, an Oral Carbon Monoxide Therapeutic, in Healthy Volunteers (clinicaltrials.gov) - P1; N=28; Not yet recruiting; Sponsor: Hillhurst Biopharmaceuticals, Inc.

New P1 trial