tanfanercept (HL036) / Daewoong Pharma, Harbour BioMed - LARVOL DELTA

Quintessence of currently approved and upcoming treatments for dry eye disease. (PubMed, Graefes Arch Clin Exp Ophthalmol) - "Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED...Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include..."

Journal • Review • Conjunctivitis • Dry Eye Disease • Ocular Infections • Ocular Inflammation • Ophthalmology • Sjogren's Syndrome • ICAM1

VELOS-4: A Study to Evaluate the Efficacy and Safety of Tanfanercept (HL036) in Dry Eye Disease (clinicaltrials.gov) - P3 | N=750 | Suspended | Sponsor: HanAll BioPharma Co., Ltd. | Recruiting ➔ Suspended

Trial suspension • Dry Eye Disease • Ophthalmology

VELOS-4: A Phase 3 Study in Dry Eye Disease (clinicaltrials.gov) - P3 | N=750 | Recruiting | Sponsor: HanAll BioPharma Co., Ltd.

New P3 trial • Dry Eye Disease • Ophthalmology

Tanfanercept ophthalmic solution, a topical TNF inhibitor, significantly improved tear volume in subjects with dry eye disease in a Phase 3 study (VELOS-3) (ARVO 2024) - "Tanfanercept ophthalmic solution 0.25% confirmed safety and efficacy in a Phase 3 study, improving tear volume in subjects with DED."

Clinical • P3 data • Dry Eye Disease • Ocular Inflammation • Ophthalmology

TNF is a critical cytokine in age-related dry eye disease. (PubMed, Ocul Surf) - "Treatment of mice at an early stage of aging (12-14-month-old) with TNF inhibitor tanfanercept eye drops for eight consecutive weeks decreased cytokine levels in tears, improved goblet cell density, and decreased the marginal zone B cell frequency in the lacrimal gland compared to vehicle-treated animals. Our studies indicate that modulation of TNF during aging could be a novel strategy for age-related dry eye disease."

Journal • Dry Eye Disease • Ocular Inflammation • Oncology • Ophthalmology • CTSS • CXCL1 • IFNG • IL10 • IL17A • IL18 • IL1B • IL2 • IL2RA

HanAll Biopharma, clinical re-challenge with Shermer test…Looking at FDA standards [Google translation] (Pharm E Daily) - "HanAll Biopharma plans to change the design of the phase 3 clinical trial of HL036, a treatment for dry eye syndrome, and again challenge for product approval. HanAll Biopharma is considering the Sheerer test as a key evaluation variable for the next clinical trial. We are looking forward to it once again as there are products that have obtained product approval from the US Food and Drug Administration (FDA) based on that indicator....HanAll Biopharma plans to conduct the next clinical trial based on the analysis....According to the FDA's 'Guidelines for New Drug Development for dry eye Syndrome', it is mentioned that product approval is possible if statistical significance is demonstrated between the test substance and placebo for at least one objective symptom and subjective prior symptom."

Clinical protocol • FDA event • Dry Eye Disease • Ophthalmology

A Study Evaluating HBM9036 Efficacy and Safety on Moderate to Severe Dry Eye (clinicaltrials.gov) - P3 | N=674 | Recruiting | Sponsor: Harbour BioMed (Guangzhou) Co. Ltd. | Trial completion date: Jan 2023 ➔ Apr 2023

Trial completion date • Dry Eye Disease • Ophthalmology

VELOS-3: A Study to Assess the Efficacy and Safety of Tanfanercept (HL036) Ophthalmic Solution in Participants With Dry Eye (clinicaltrials.gov) - P3 | N=260 | Completed | Sponsor: HanAll BioPharma Co., Ltd. | Recruiting ➔ Completed | Trial completion date: Nov 2022 ➔ Apr 2022 | Trial primary completion date: Nov 2022 ➔ Apr 2022

Trial completion • Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology

VELOS-3: A Study to Assess the Efficacy and Safety of Tanfanercept (HL036) Ophthalmic Solution in Participants With Dry Eye (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: HanAll BioPharma Co., Ltd. | Trial completion date: Jul 2022 ➔ Nov 2022 | Trial primary completion date: Jul 2022 ➔ Nov 2022

Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology

A Study Evaluating HBM9036 Efficacy and Safety on Moderate to Severe Dry Eye (clinicaltrials.gov) - P3 | N=674 | Recruiting | Sponsor: Harbour BioMed (Guangzhou) Co. Ltd. | Trial completion date: Jun 2022 ➔ Jan 2023 | Trial primary completion date: Feb 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology

VELOS-2: A Study to Assess Efficacy and Safety of HL036 in Subjects With Dry Eyes (clinicaltrials.gov) - P3 | N=637 | Completed | Sponsor: HanAll BioPharma Co., Ltd. | Recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

TNF-α inhibitor tanfanercept (HBM9036) improves signs and symptoms of dry eye in a phase 2 trial in the controlled adverse environment in China. (PubMed, Int Ophthalmol) - P2 | "Tanfanercept demonstrated improvements in favor of active as compared to placebo in the signs of DED, being safe and well tolerated. These data support further evaluation of tanfanercept for the treatment of DED in China."

Journal • P2 data • Dry Eye Disease • Ophthalmology

VELOS-3: A Study to Assess the Efficacy and Safety of Tanfanercept (HL036) Ophthalmic Solution in Participants With Dry Eye (clinicaltrials.gov) - P3; N=300; Recruiting; Sponsor: HanAll BioPharma Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Dry Eye Disease • Ophthalmology

VELOS-3: A Study to Assess the Efficacy and Safety of Tanfanercept (HL036) Ophthalmic Solution in Participants With Dry Eye (clinicaltrials.gov) - P3; N=300; Not yet recruiting; Sponsor: HanAll BioPharma Co., Ltd.

Clinical • New P3 trial • Dry Eye Disease • Ophthalmology

A Study Evaluating HBM9036 Efficacy and Safety on Moderate to Severe Dry Eye (clinicaltrials.gov) - P3; N=674; Recruiting; Sponsor: Harbour BioMed (Guangzhou) Co. Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Dry Eye Disease • Ophthalmology

A Phase 3 Study Evaluating the Efficacy and Safety on Moderate to Severe Dry Eye (clinicaltrials.gov) - P3; N=674; Not yet recruiting; Sponsor: Harbour BioMed (Guangzhou) Co. Ltd.

Clinical • New P3 trial • Dry Eye Disease • Ophthalmology

Association Between Plasma Polyunsaturated Fatty Acids and Subclinical Interstitial Lung Disease: The MESA Study (ATS 2018) - "Rationale: Prior cellular and murine studies have suggested that n-3 polyunsaturated fatty acids (PUFAs) attenuate pulmonary fibrosis, perhaps through regulation of eicosanoid production and activation of the peroxisome-proliferator-activated receptor- pathway. Lower levels of plasma n-3 PUFAs were associated with greater HAA, a higher prevalence of ILA, and higher levels of serum MMP-7 in community-dwelling adults. Several n-6 PUFAs were associated with greater risks of subclinical ILD. These data suggest that investigation of the role of PUFAs might identify a modifiable risk factor for ILD."

Atherosclerosis • Biosimilar • Dyslipidemia • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Systemic Sclerosis

The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation. (PubMed) - Korean J Ophthalmol - "HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dry eye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome."

Journal • Biosimilar • Dry Eye Disease • Immunology

HL036 Ophthalmic Solution, a TNF-a Inhibitor, Significantly Improves Signs and Symptoms of Dry Eye in a Phase 2 Trial (VELOS-1) (AAO 2019) - "There were no serious adverse events. Conclusion HL036 is safe and well tolerated, with statistically significant improvement in the signs and symptoms of DED, compared to placebo."

P2 data

HL036 Ophthalmic Solution, a TNF-a Inhibitor, Significantly Improves Signs and Symptoms of Dry Eye in a Phase 2 Trial (VELOS-1) (AAO 2019) - "There were no serious adverse events. Conclusion HL036 is safe and well tolerated, with statistically significant improvement in the signs and symptoms of DED, compared to placebo."

P2 data

Efficacy of HL036 versus cyclosporine A in the treatment of naturally occurring canine keratoconjunctivitis sicca. (PubMed, Curr Eye Res) - "Our findings suggest that topical aqueous HL036 is well-tolerated and more effective than 1% CsA for treating naturally occurring canine KCS."

Clinical • Journal

Changes In Health-related Quality Of Life In A 12-month Behavioral Weight Loss Intervention: The Heart Health Study (ACSM 2019) - "Weight significantly decrease in all groups at 12 months (DIET: -9.2±5.8 kg, DIET+PA150: -10.2±6.4 kg, DIET+PA250: -9.5±5.4 kg; p<0.001) with no significant difference between groups. There were significant improvements in HRQOL components of physical function, energy and fatigue, and change in health (Table); however, these did not differ by group. There were no significant changes in social function, mental health, pain, and general health.CONCLUSION : The addition of moderate or higher levels of physical activity to an energy restricted diet for weight loss did not improve quality of life compared to the diet alone."

Clinical • HEOR

Change in Visceral Adiposity with a 12-Month Behavioral Weight Loss Intervention with Varying Doses of Physical Activity: The Heart Health Study (ACSM 2019) - "The interventions were successful at reducing body weight and improving body composition in adults with obesity. The lack of additional weight loss, reductions in body compositon and VAT with participation in MVPA at two different doses may suggest that there is a compensatory response in factors influencing energy balance that warrant further investigation. Supported by: NIH (R01 HL103646)"

VELOS-2: A Study to Assess Efficacy and Safety of HL036 in Subjects With Dry Eyes (clinicaltrials.gov) - P3; N=630; Recruiting; Sponsor: HanAll BioPharma Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

VELOS-2: A Study to Assess Efficacy and Safety of HL036 in Subjects With Dry Eyes (clinicaltrials.gov) - P3; N=630; Not yet recruiting; Sponsor: HanAll BioPharma Co., Ltd.

Clinical • New P3 trial