treprostinil liposomal (L606) / Pharmosa Biopharm, Liquidia Technologies - LARVOL DELTA

First Quarter 2025 Financial Results (GlobeNewswire) - "Research and development expenses were $7.0 million for the three months ended March 31, 2025, compared to $10.1 million for the three months ended March 31, 2024. The decrease of $3.1 million or 31% was primarily due to a $3.6 million decrease in personnel expenses (including stock-based compensation) due to a shift from activities related to research and development to preparation for the potential commercialization of YUTREPIA. These decreases were offset by a $1.7 million increase in clinical expenses related to our L606 program, and a $0.4 million decrease in expenses related to our YUTREPIA research and development activities."

Commercial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension

Role of Adult Neurogenesis in Memory Loss in a Mouse Model of NMDA Receptor-mediated Epilepsy (AES 2024) - "Funding: NIH P20GM130447 DHHS LB606 Rationale: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) results in chronic epilepsy and permanent cognitive impairment... These findings suggest that memory and learning impairments induced by patient anti-NMDAR antibodies are sustained upon removal of antibodies and are accompanied by aberrant adult hippocampal neurogenesis. Interventions directed at the manipulation of neuronal plasticity in patients with encephalitis and cognitive loss may be protective and therapeutically relevant."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Mood Disorders • Psychiatry

A Phase 3 Study to Evaluate the Safety and Tolerability of L606 in Subjects With PAH or PH-ILD (clinicaltrials.gov) - P3 | N=28 | Active, not recruiting | Sponsor: Liquidia Technologies, Inc. | Recruiting ➔ Active, not recruiting | N=60 ➔ 28

Enrollment change • Enrollment closed • Cardiovascular • Hypertension • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Targeting TROP-2 In Diffuse Pleural Mesothelioma (IASLC-WCLC 2024) - "The efficacy of the TROP-2 antibody drug conjugate (ADC) Sacituzumab Govitecan (SG) was assessed in PDXs with high (MSK_LX307) and intermediate/low (MSK_LX707, MSK-LX606, MSK_LX13) TROP-2 expression (n=10/cohort): vehicle, chemotherapy (gemcitabine; 40 mg/kg/week), and SG (0.5 mg/mouse/twice a week). These data confirm TROP-2 as a therapeutic target in mesothelioma. Based on these findings, we are opening an investigator initiated single arm phase 2 trial to assess the overall response rate of SG in patients with previously treated recurrent/metastatic DPM."

Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor • TACSTD2

A Phase 3, 2-part, Open-label, Multicenter Study to Evaluate the Safety, and Efficacy of Liposomal Treprostinil Inhalation Suspension (l606) in Subjects With Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD) (ATS 2024) - " The study (NCT: 04691154) is enrolling patients ≥18 years who transitioned from nebulized Tyvaso or Tyvaso DPI to L606 ('Transition') with PAH or PH-ILD or added L606 to prostacyclin 'naïve' patients on ≤2 non-prostacyclin oral therapies in PAH subjects. Patients receiving stable doses of nebulized treprostinil successfully transitioned to L606 with no significant safety concerns and the addition of L606 to background oral therapy was also well tolerated. One patient experienced TEAEs consistent with known side effects of inhaled treprostinil, none were severe. The overall AE profile was mild to moderate and generally did not hinder patients' ability to titrate to higher doses as needed."

Clinical • P3 data • Acute Kidney Injury • Cardiovascular • Cough • Dysphonia • Hypertension • Interstitial Lung Disease • Nephrology • Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases

In Vivo T1-weighted Contrast MRI and 1H-MR Spectroscopy in Autoimmune Encephalitis with Cognitive Failure (AES 2023) - "Funding: DHHS LB606 Nebraska Stem Cell Grant... These findings support the feasibility of noninvasive monitoring of rCBV and regional metabolite levels in the hippocampus and cortex of patients with encephalitis and cognitive impairment; these measurements can be applied longitudinally. In the expanded cohort, this approach can be used to assess the correlation of imaging parameters with degree of cognitive loss or seizure burden."

Preclinical • Alzheimer's Disease • Brain Cancer • CNS Disorders • CNS Tumor • Cognitive Disorders • Epilepsy • Glioma • Immunology • Oncology • Solid Tumor

Predicting Pulmonary Pharmacokinetics of Inhaled Liposomal Treprostinil (L606) and Treprostinil Solution in Healthy Adult (ERS 2023) - "With the previous PK data via iv infusion of treprostinil, the multi-compartment modeling was developed to predict the pulmonary pharmacokinetics of L606 and treprostinil solution. Simulation of L606 indicated a sustained pulmonary level as compared with the immediate-release formulation of treprostinil solution. The model shows the potential of predicting the pharmacological effects of inhaled L606 and Tyvaso®.; Public health; Respiratory intensive care; Cell and molecular biology; Transplantation; Epidemiology; General respiratory patient care; Imaging"

Clinical • PK/PD data • Critical care • Transplantation

Liquidia Corporation Reports Second Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Liquidia Corporation...today reported financial results for the second quarter ended June 30, 2023...Submitted amendment to add PH-ILD indication to tentatively approved new drug application (NDA) for YUTREPIA...Liquidia also submitted a paragraph IV certification indicating that the patents listed for Tyvaso® in the FDA’s publication commonly known as the Orange Book are invalid and/or not infringed by YUTREPIA...Expanded pipeline through partnership with Pharmosa Biopharm to develop L606 in North America...Pending input from the FDA from a planned Type B meeting later this year, Liquidia intends to initiate a Phase 3 randomized, placebo-controlled study in 2024 to evaluate treatment of PH-LD patients with L606."

FDA event • Licensing / partnership • NDA • New P3 trial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases

A Phase 3 Study to Evaluate the Safety and Tolerability of L606 in Subjects With PAH or PH-ILD (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Pharmosa Biopharm Inc. | Trial completion date: Aug 2023 ➔ Jul 2025 | Trial primary completion date: Oct 2022 ➔ Aug 2024

Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Extended Pulmonary Retention of Inhaled Liposomal Treprostinil (l606) Correlated With Pharmacodynamics and Plasma Pharmacokinetics (ATS 2023) - "Extended retention of treprostinil in pulmonary tissue is correlated with pulmonary vasodilation and plasma pharmacokinetics of inhalation formulations. L606 is able to extend PAP reduction by prolonging drug retention in pulmonary tissue."

PK/PD data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Multicompartment Modeling for Pulmonary Pharmacokinetics of Liposomal Treprostinil (L606) in Adults (ATS 2022) - "AIM: A multicompartment physiologically-based model was therefore developed to predict the pulmonary drug concentrations of L606 and Tyvaso. The multicompartment model provides a quantitative PK profile in pulmonary tissue to describe the potential extended pharmacological effect of L606. The efficacy still needs to be validated on PAH patients."

Clinical • PK/PD data

A Phase 3 Study to Evaluate the Safety and Tolerability of L606 in Subjects With PAH (clinicaltrials.gov) - P3; N=60; Recruiting; Sponsor: Pharmosa Biopharm Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] A multicompartmemt lung model predicts pulmonary pharmacokinetics of inhaled liposomal treprostinil (L606) in healthy volunteer (ERS 2021) - "AIM: A multicompartment physiologically based model was developed to predict the pulmonary pharmacokinetics of L606 and Tyvaso®. The multicompartment physiologically based model provides a quantitative explanation for the 12-hr extemded effect. However, it needs to be confirmed on the patients with pulmonary arterial hypertension."

Clinical • PK/PD data • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Evaluation of Single Ascending-Dose Pharmacokinetics of Liposomal Treprostinil Inhalation Suspension (L606) in Healthy Volunteers (ATS 2021) - P1 | "The exposure-response (efficacy) relationships of the two formulations (Remodulin® and Orenitram®) are approved by FDA for treatment of patients with PAH (WHO Group 1). Single dose PK of L606 reduces the dosing frequency to twice a day (every 10-12 hours), as well as mitigates the potential impact of off-medication during sleep time. Peak-trough fluctuation of L606 is relatively low in a comparison with Tyvaso® and currently developed dry powder formulations. The phase 3 study is initiated to evaluate the safety profile upon transition from Tyvaso® QID to L660 BID in PAH patients."

Clinical • PK/PD data

Genome sequencing of SARS-CoV-2 in a cohort of Egyptian patients revealed mutation hotspots that are related to clinical outcomes. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "The most common mutations, D614G/spike-glycoprotein and P4715L/RNA-dependent-RNA-polymerase, were linked to transmissibility regardless of symptom variability. E3909G-nsp7 could explain why children recover so quickly. Nsp6-L3606fs, spike-glycoprotein-V6fs, and nsp13-S5398L variants may be linked to clinical symptom worsening. These variations related to host-virus interactions might open new therapeutic avenues for symptom relief and disease containment."

Clinical • Clinical data • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Phase 3 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of L606 in Subjects With PAH (clinicaltrials.gov) - P3; N=60; Not yet recruiting; Sponsor: Pharmosa Biopharm Inc.

Clinical • New P3 trial • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases

Single Ascending Dose Study for Evaluation of Safety, Tolerability and Pharmacokinetics of L606 (clinicaltrials.gov) - P1; N=52; Completed; Sponsor: Pharmosa Biopharm Inc.; Recruiting ➔ Completed; Trial completion date: Feb 2020 ➔ May 2020

Clinical • Trial completion • Trial completion date • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases

[VIRTUAL] Inhaled liposomal treprostinil (L606) shows extended release in healthy volunteer, as well as prolongs pharmacological effect in hypoxia-induced rat. (ERS 2020) - " Liposomal treprostinil solution (L606) extended a detectable plasma level up to 12 hours in human volunteer, as compared to treprostinil solution (Tyvaso®) which disappeared in 4 hours. Liposomal treprostinil solution (L606) demonstrates an extended plasma level and sustained pharmacological effects."

Hypertension • Pulmonary Arterial Hypertension

[VIRTUAL] Comparative Pharmacokinetics Between Tyvaso® and L606, Extended-Release Formulation of Treprostinil for Inhalation Therapy (ATS-I 2020) - "The pharmacokinetics of L606 showed an extend release for 10-12 hour. It is able to reduce the dosing frequency to twice a day (every 10-12 hours) covering sleeping time. The phase 3 study is planned to evaluate the safety profile upon transition from Tyvaso® QID to L660 BID in PAH patients."

PK/PD data • Hypertension • Pulmonary Arterial Hypertension

Comparative Pharmacokinetics Between Tyvaso® and L606, Extended-Release Formulation of Treprostinil for Inhalation Therapy (ATS 2020) - "The pharmacokinetics of L606 showed an extend release for 10-12 hour. It is able to reduce the dosing frequency to twice a day (every 10-12 hours) covering sleeping time. The phase 3 study is planned to evaluate the safety profile upon transition from Tyvaso® QID to L660 BID in PAH patients."

PK/PD data