lonodelestat (POL6014) / Spexis, Cold Spring Harbor Laboratory - LARVOL DELTA

Lonodelestat: Initiation of P2a trial for cystic fibrosis in H2 2022 (Santhera) - Company Presentation

New P2a trial • Cystic Fibrosis

Clinical Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of POL6014 in Patients With CF (clinicaltrials.gov) - P1/2; N=32; Completed; Sponsor: Santhera Pharmaceuticals; Recruiting ➔ Completed; Trial primary completion date: Dec 2019 ➔ Dec 2020

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

Macrocycle Therapeutics to Treat Life-threatening Diseases. (PubMed, Chimia (Aarau)) - "Furthermore, POL6014, an inhibitor of neutrophile elastase and balixafortide, a CXCR4 inhibitor have been discovered and developed from the platform. Currently a combination of balixafortide and eribulin is in Phase III clinical trial for the treatment of patients with advanced metastatic HER2-negative breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Infectious Disease • Oncology • Solid Tumor • CXCR4 • ELANE • HER-2

Santhera Announces Positive Results with Lonodelestat in Early Phase Cystic Fibrosis Trial (GlobeNewswire) - P1b, N=40; NCT03748199; Sponsor: Santhera Pharmaceuticals; "Santhera Pharmaceuticals...announces positive results from its multiple ascending dose Phase 1b study with lonodelestat...in patients with cystic fibrosis (CF)....A total of 32 patients were randomized in four cohorts of eight patients each and received lonodelestat...Results showed a linear dose-exposure relationship over the dose range from 40 mg to 160 mg, with no accumulation in plasma or sputum....The findings from this study will be taken into account in the design of future studies....'After additional analyses of the results, we will be optimizing the further clinical development program to advance lonodelestat for the treatment of CF. In parallel, we are proactively pursuing collaborations with partners to assess and exploit the potential of lonodelestat in other pulmonary diseases'."

Licensing / partnership • P1 data • Cystic Fibrosis • Respiratory Diseases

Santhera Announces Corporate Update and Proposal to Strengthen Capital Structure (GlobeNewswire) - “Santhera continues to advance its clinical-stage candidate lonodelestat…developed in cystic fibrosis. Data readout of the double-blind, placebo-controlled dose escalation Phase 1b study in patients with cystic fibrosis…is expected in the coming weeks…Based on data from this early clinical proof of concept trial, the Company plans to design the further clinical development program….Company is currently also seeking opportunities for outlicensing agreements for lonodelestat in pulmonary indications beyond cystic fibrosis.”

Licensing / partnership • P1 data • Cystic Fibrosis

Lonodelestat: Completion of P1b part of P1b/2a trial (NCT03748199) for cystic fibrosis in Q4 2020 (Santhera) - Corporate Presentation: Data from P1b/2a trial for cystic fibrosis in early 2021

P1/2 data • Trial status • Cystic Fibrosis

Santhera Implements Reorganization and Secures Financing to Advance Vamorolone to Pivotal Read-out in Duchenne Muscular Dystrophy (GlobeNewswire) - "Vamorolone, the only dissociative steroid in development, is currently in a pivotal Phase 2b study in DMD patients with a 6-month readout expected in the second quarter of 2021. If successful, the results could lead to an NDA submission with the FDA in the fourth quarter of 2021 which is subject to a fast track review. Santhera currently anticipates to be first to market with a dissociative steroid in the US in 2022...The European regulatory authorities require 12-month treatment data and a filing with the EMA could occur in the first half of 2022 followed by launch approximately one year later. The Company estimates the peak sales potential for vamorolone for the DMD indication alone to be in excess of USD 500 million in the US and the largest five EU countries combined."

European regulatory • Financing • NDA • P2b data • Duchenne Muscular Dystrophy

Lonodelestat: Completion of P1b part of P1b/2a trial (NCT03748199) for cystic fibrosis in Q4 2020 (Santhera) - Corporate Presentation

Trial status • Cystic Fibrosis

POL6014: Patent expiry in 2036 (Santhera) - Annual Report 2019

Patent

Santhera reports 2019 annual results and highlights pipeline progress in Duchenne muscular dystrophy (GlobeNewswire, Santhera Pharmaceuticals Holding AG) - "With CHF 80.7 million, total operating expenses slightly surpassed the previous year’s level (2018: CHF 78.7 million). The increase in development expenses to CHF 41.2 million (2018: CHF 38.2 million) reflects expenses for ongoing late stage clinical studies such as the Phase 3 SIDEROS trial in DMD, efforts associated with the pending marketing authorization application for Puldysa for DMD in Europe, ongoing post-authorization studies for LHON, as well as clinical work with Santhera’s early stage development compound POL6014 for cystic fibrosis."

Commercial

POL6014: Completion of P1b part of P1b/2a trial (NCT03748199) for cystic fibrosis in Q2 2020 (Santhera) - Annual Report 2019

Trial status

POL6014: Data from of P1b/2a trial (NCT03748199) for cystic fibrosis in H2 2020 (Santhera) - Annual Report 2019

P1/2 data

Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis. (PubMed, J Cyst Fibros) - "Inhalation of POL6014 can safely lead to high concentrations within the lung and simultaneously low plasma concentrations, allowing for a clear inhibition of NE in the sputum of subjects with CF after single dosing."

Clinical • Journal