■ Enolase-1 Antibody
HuniLife in-licensed ENO1 (enolase-1, also known as alpha-enolase) antibody patented technology from National Health Research Institute (NHRI) and Development Center for Biotechnology (DCB) in Taiwan with worldwide exclusivity in 2015. HuL001, is a first-in-class humanized monoclonal antibody with highly specific binding affinity to ENO1, but not ENO2 and ENO3. Investigational Drug Application (IND) of HuL001 has been approved by US FDA for clinical trials in multiple sclerosis (MS) and Taiwan FDA for idiopathic pulmonary fibrosis (IPF). We completed phase I study in healthy volunteers and the results showed favorable safety and tolerance. All our ENO1 antibody programs is developed from the ENO1-targeting technology (original name: HuL001).
■ Mechanism of Action
HuL001 is designed to block ENO1-mediated per-cellular plasmin activation and unexpectedly also intracellular glycolysis. Both mechanisms contribute to the multi-factorial efficacy of targeting ENO1 in attenuation of cell migration/invasion (thus inflammation, angiogenesis, and cancer metastasis) and reduction of pro-inflammatory and pro-fibrotic factors secretion (thus again inflammation and notably fibrosis).
■ Clinical Program
We currently have two clinical programs available, HL247 for treating multiple sclerosis (MS) and HL217 for idiopathic pulmonary fibrosis (IPF). Due to limited resources, we currently focus our efforts in HL217 program.
➣ HL247 for Multiple Sclerosis (MS)
MS is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage could disrupt the ability of the nervous system related to communication and mobility, resulting in a wide range of symptoms, including physical, mental, and psychiatric problems. Current therapy can only control of slow the disease progression of MS, which is designed to target at T lymphocyte, B lymphocyte, or modulation of the immune system. Infiltration of monocyte into the central nervous system (CNS) is a hallmark of MS patients and is commonly used to facilitate the diagnosis of MS. The presence and critical role of monocyte in CNS was demonstrated in EAE (experimental autoimmune encephalomyelitis) mouse models of MS. ENO1 is expressed on activated monocytes or macrophages. With this unique feature, in vivo therapeutic efficacy was established in EAE models. We believe HL247 might offer a safe and novel profile of therapeutic, compared to current therapy, to treat MS.
➣ HL217 for Idiopathic Pulmonary Fibrosis (IPF)
IPF is a devastating lung disease of unknown cause, which is characterized by accumulation of scarring or fibrotic tissues in the lungs. Patients are suffered from progressive difficulty to breath and with a median survival of 3~5 years from diagnosis. Only two drugs were approved in 2014, nintedanib (Ofev®) and pirfenidone (Esbriet®), which can help slow down the decline of lung function of IPF patients. Alternative therapies are still in high demand. Therapeutic efficacy of HL217 is established in in vitro and in vivo preclinical models. Our HL217 program is the most mature asset which is undergoing phase I clinical trial (ClinicalTrials.gov Identifier: NCT04540770). Phase Ia study results in healthy volunteers showed favorable safety and tolerance. IPF patients are recruiting in phase Ib study. We are actively seeking partnering opportunities to facilitate the next phase II study.
■ Preclinical Program
Besides HL217 in clinical development for IPF, we are trying to explore more potential indications for the ENO1 targeting antibody. We have preclinical programs of HL217 for other respiratory diseases, HL227 for oncology use, and HL257 for angiogenesis-driven disorders.
➣ HL217 for Respiratory Diseases
In our journey to develop HL217 for treating pulmonary fibrosis, we established in vivo anti-fibrotic efficacy of HL217 in both bleomycin and radiation models. Since radiation-induced pulmonary fibrosis (RIPF) is a common complication of radiation therapy for tumors of the thorax, we hope to collect more evidence to validate the potential of HL217 for treating RIPF. Moreover, ENO1 has been recently reported to play critical roles of not only pulmonary fibrosis not also skin fibrosis (PMID: 34935642). Two important reports implicated ENO1 in regulation of pulmonary artery smooth muscle cells (PMID: 30242159) and endothelial cells (PMID: 36883457) in pulmonary arterial hypertension (PAH). The program is initiated currently this year (2023) to test HL217 in preclinical models of systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD). For PAH, we are looking for collaboration.
➣ HL227 for Oncology Application
Ample literature had demonstrated overexpression of ENO1 in various types of cancers and correlated to worse clinical outcome. Preclinical efficacy of ENO1 targeting antibody in pancreatic cancer (PMID: 25860938), lung cancer (PMID: 23894455, 33579362, and 34145039), and cervical cancer (PMID: 34094663) were also reported by academic research groups. HuniLife’s proprietary HL227 ENO1 antibody for oncology use was first demonstrated in advanced prostate cancer for its unique mechanism by targeting not only tumor cells themselves but also multiple tumor microenvironment (TME) niches (HuniLife’s publication, PMID: 35700013). Therapeutic efficacy of HL227 was demonstrated in this study by reducing tumor growth, angiogenesis, cell migration and chemotaxis, cytokine secretion, and osteoclastogenesis. HL227 is currently tested in multiple myeloma preclinical models. Furthermore, excellent synergy of HL227 with radiotherapy was found in pre-clinical colon cancer model. Our data suggest HL227 might be a TME modifier as well as radiotherapy enhancer for application in the oncology space.
➣ HL257 for Ophthalmology Application
Owing to the promising anti-angiogenesis activities of ENO1 antibody HL257 in various in vitro and ex vivo assays, we are currently working on in vivo studies to validate therapeutic potential of HL257 in angiogenesis-driven eye diseases, including wet age-related macular degeneration (AMD) or diabetic macular edema (DME). We welcome any partnering opportunity for this early preclinical stage ophthalmology asset to accelerate its development.
