fenretinide oral (LAU-7b) / Laurent Pharma - LARVOL DELTA

RESOLUTION: Study of LAU-7b for the Treatment of Coronavirus Disease 2019 (COVID-19) Disease in Adults (clinicaltrials.gov) - P2/3 | N=351 | Terminated | Sponsor: Laurent Pharmaceuticals Inc. | N=125 ➔ 351 | Completed ➔ Terminated; Phase 2 completed normally, Phase 3 terminated for futility due to lack of aggravation events.

Enrollment change • Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ESSOR: Study of LAU-7b for the Treatment of Long COVID in Adults (clinicaltrials.gov) - P2/3 | N=272 | Completed | Sponsor: Laurent Pharmaceuticals Inc. | Active, not recruiting ➔ Completed

Trial completion • Novel Coronavirus Disease

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2/3 | N=125 | Completed | Sponsor: Laurent Pharmaceuticals Inc. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Efficacy and safety of LAU-7b in a Phase 2 trial in adults with cystic fibrosis. (PubMed, J Cyst Fibros) - "Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development."

Journal • P2 data • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Clinical Stage Drug Candidate LAU-7b Shows Potent Antifibrotic Properties in Several Preclinical Models of Pulmonary Fibrosis (ATS 2024) - "We studied the effects of LAU-7b in bleomycin-induced lung fibrosis models (BLM), in cell-culture assays using normal human lung fibroblasts (HLF), and in human lung-on-a-chip microtissue model. LAU-7b showed positive, dose-dependent antifibrotic effect in all models tested, comparable or better than pirfenidone. These results warrant transition to clinical development of LAU-7b in pulmonary fibrosis."

Late-breaking abstract • Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CASP3 • CASP7 • TGFB1

ESSOR: Study of LAU-7b for the Treatment of Long COVID in Adults (clinicaltrials.gov) - P2/3 | N=272 | Active, not recruiting | Sponsor: Laurent Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Novel Coronavirus Disease

ESSOR: Study of LAU-7b for the Treatment of Long COVID in Adults (clinicaltrials.gov) - P2/3 | N=270 | Recruiting | Sponsor: Laurent Pharmaceuticals Inc. | N=204 ➔ 270

Enrollment change • Novel Coronavirus Disease

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2/3 | N=125 | Active, not recruiting | Sponsor: Laurent Pharmaceuticals Inc. | Trial completion date: Dec 2023 ➔ May 2024

Trial completion date • Infectious Disease • Novel Coronavirus Disease

ESSOR: Study of LAU-7b for the Treatment of Long COVID in Adults (clinicaltrials.gov) - P2/3 | N=204 | Recruiting | Sponsor: Laurent Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Novel Coronavirus Disease

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2/3 | N=125 | Active, not recruiting | Sponsor: Laurent Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting | N=508 ➔ 125

Enrollment change • Enrollment closed • Infectious Disease • Novel Coronavirus Disease

LAU-7b restores total and membrane CFTR protein expression inhibited by Aspergillus fumigatus infection (NACFC 2023) - "Treatment options for CF have advanced with the discovery of new CFTR modulators, including a combination of elexacaftor-tezacaftor-ivacaftor (ETI). These results demonstrate that fenretinide treatment enhances F508del CFTR rescue by ETI during infection and may provide additional clinical benefit for PwCF. Combining LAU-7b with ETI could be an effective treatment option for PwCF."

Genetic Disorders • Infectious Disease • Pulmonary Disease • Respiratory Diseases • CFTR

ESSOR: Study of LAU-7b for the Treatment of Long COVID in Adults (clinicaltrials.gov) - P2/3 | N=204 | Not yet recruiting | Sponsor: Laurent Pharmaceuticals Inc.

New P2/3 trial • Novel Coronavirus Disease

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2/3 | N=508 | Recruiting | Sponsor: Laurent Pharmaceuticals Inc. | Trial completion date: Jun 2023 ➔ Dec 2023 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2/3 | N=508 | Recruiting | Sponsor: Laurent Pharmaceuticals Inc. | Trial primary completion date: Mar 2023 ➔ Jun 2023

Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2/3 | N=508 | Recruiting | Sponsor: Laurent Pharmaceuticals Inc. | Trial completion date: Oct 2022 ➔ Apr 2023 | Trial primary completion date: Oct 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Results from APPLAUD Phase 2 Study with Pro-Resolution Drug Candidate LAU-7b in Adults with Cystic Fibrosis (NACFC 2022) - "Although the number of subjects was small, similar positivetrends were noted in subjects already treated with CFTR modulators,including elexacaftor/tezacaftor/ivacaftor. Compared to placebo, LAU-7b treatment reduced loss of lungfunction by 50% at 24 weeks in the overall subject population and by 77% inthe subgroup of subjects with mild lung disease (FEV 1pp≥70%), suggesting a potential beneficial effect on the loss of lung function over 24 weeks. LAU-7b was well tolerated and had a favorable safety profile, similar topreviously obtained data. The final efficacy data, including inflammationbiomarker analyses, will be presented at the North American Cystic FibrosisConference."

Clinical • P2 data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Combinatory treatment of LAU-7b with triple therapy results in improved lung physiology and restored fatty acid and lipid levels (NACFC 2022) - "Treatment with the triple combination drugtherapy, elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), has become thestandard of care, so we wanted to assess if LAU-7b can complement theefficacy of ELX/TEZ/IVA.To examine the effect of combining LAU-7b oral treatment andtriple therapy on lung function, a F508deltm1EUR mouse model displayinglung abnormalities relevant to human CF was used. Combination of triple therapy with LAU-7b oral treatmentsignificantly improved multiple markers of CF lung disease, including lungfunction and airway histopathology, in the F508del tm1EURmouse model. The results in mice suggest a potential clinical benefit of the combinatorytreatment of LAU-7b and ELX/TEZ/IVA for people with CF."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Laurent Pharmaceuticals Presents Results from Phase 2 Clinical Study of LAU-7b in Cystic Fibrosis at the NACFC 2022 (Businesswire) - P2 | N=122 | APPLAUD (NCT03265288) | Sponsor: Laurent Pharmaceuticals Inc. | "Laurent Pharmaceuticals...announces the presentation of results from its placebo-controlled Phase 2 APPLAUD 24-week clinical study in adults with CF...Study results achieved a statistically significant treatment difference in favour of LAU-7b in the absolute change in the percent predicted forced expiratory volume in one second (ppFEV1), the primary variable, through 24 weeks (1.23 percentage points; p=0.0486) in people that completed at least five months of treatment (Per Protocol population, N=122), and a clinically meaningful reduction of 49% in the loss of lung function at 24 weeks, relative to placebo. Statistically significant clinical benefit was also observed in the relative change in ppFEV1 through 24 weeks (2.34 percentage points; p=0.0351)."

P2 data • Cystic Fibrosis • Genetic Disorders

Treatment With LAU-7b Complements CFTR Modulator Therapy by Improving Lung Physiology and Normalizing Lipid Imbalance Associated With CF Lung Disease. (PubMed, Front Pharmacol) - "Treatment with the Triple combination drug therapy, TRIKAFTA, is composed of three drugs: Elexacaftor (VX-445), Tezacaftor (VX-661) and Ivacaftor (VX-770). We examined the effect of combining LAU-7b oral treatment and Triple therapy combination on lung function in a F508del mouse model that displays lung abnormalities relevant to human CF. We assessed lung function, lung histopathology, protein oxidation, lipid oxidation, and fatty acid and lipid profiles in F508del mice."

Journal • Cystic Fibrosis • Fatigue • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Laurent Pharmaceuticals receives Health Canada’s approval to initiate Covid-19 clinical trial (Businesswire) - "Laurent Pharmaceuticals Inc....today announced that it has obtained the approval from Health Canada to initiate RESOLUTION, a Phase 2 randomized placebo-controlled trial testing once-a-day oral LAU-7b as a potential drug candidate to help combat the COVID-19 disease. The trial, which is planned to start imminently in multiple hospitals in Canada, will enroll approximatively 200 hospitalized COVID-19 patients....The RESOLUTION trial...will measure the patient health status on a 7-point ordinal scale as primary outcome."

Canadian regulatory • Infectious Disease • Novel Coronavirus Disease

Oral Covid-19 Antiviral Candidate LAU-7b Demonstrates 100% Reduction of the Risk of Progression to Mechanical Ventilation and Death in Hospitalized Moderate-to-Severe Covid-19 Patients (ATS 2022) - "LAU-7b showed positive results in the trial’s Phase 2 portion on both survival and avoidance of mechanical ventilation in moderate-to-severe COVID-19. The confirmatory Phase 3 portion was triggered and received approval from the FDA and Health Canada, focusing on moderate-to-severe COVID-19 and using the “Proportion of patients requiring mechanical ventilation and/or death by Day 60” as primary efficacy endpoint."

Clinical • Late-breaking abstract • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2/3 | N=508 | Recruiting | Sponsor: Laurent Pharmaceuticals Inc. | Phase classification: P2 ➔ P2/3

Phase classification • Infectious Disease • Novel Coronavirus Disease

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2; N=508; Recruiting; Sponsor: Laurent Pharmaceuticals Inc.; Active, not recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease

RESOLUTION: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults (clinicaltrials.gov) - P2; N=508; Active, not recruiting; Sponsor: Laurent Pharmaceuticals Inc.; Completed ➔ Active, not recruiting; N=240 ➔ 508; Trial completion date: Jul 2021 ➔ Aug 2022; Trial primary completion date: Jul 2021 ➔ Aug 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Study of LAU-7b in the Treatment of Cystic Fibrosis in Adults (clinicaltrials.gov) - P2; N=166; Completed; Sponsor: Laurent Pharmaceuticals Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases