prophetoffacts wrote: Gilles said in the Noble presentation yesterday that in research to be published McMaster researchers have discovered that lung fibrosis and COVID patients overexpress Dectin-1a and Dectin-1b. This research is yet to be published. It is therefore still a '
secret'.
And who can target those Dectin-1 receptors? In the Noble presentation Gilles calls CZO's highly enhanced ability to to bind to the Dectin-1 receptor a "major finding" and a "great hint" concerning the ongoing research with McMaster. CZO may be able to deliver the lowest dose to achieve the same objective by being able to target the receptor of interest. A lower dose can reduce side effects.
McMaster was originally asked by a major pharmaceutical company with an existing oral medication if it could deliver it in an inhaled format. My guess is that it is Roche and the blockbuster Pirfenidone. McMaster contacted CZO. The researchers ultimately discovered PGX-YBG, a hell of a fantastic discovery. McMaster researchers have expressed excitement for PGX-YBG and the Canadian Government has provided significant funding. McMaster has had a long-standing interest in Dectin-1.
Exciting: "Dr. Kjetil Ask added, “If this size optimized PGX-YBG passes the tolerability, safety and therapeutic animal tests that we have already initiated, this material could quite quickly contribute as an immune modulator and anti-fibrotic treatment option for the most severe COVID-19 patients. Additionally, and equally exciting, the possibility of using PGX-YBG as an inhalable carrier of other drugs, would potentially allow the direct delivery of additional treatment options and increase their bioavailability in the lung, while reducing potential side effects.” August News Release McMaster has worked with the following company, Avalyn. It has recently shown in a human clinical trial a high dose of Pirfenidone can cause a trend to
disease stablization. The low dose failed. Patients typically die from this disease in in short order. Stablizing the disease would be a major achievement. Being able to further and safely increase the dose could prove important to stabilizing this disease. Pirfenidone is also being investigated for COVID. In oral format Pirfenidone only slows Idiopathic Pulmonary Disease and has significant side effects.
Avalyn Pharma Reports Update in Ongoing Idiopathic Pulmonary Fibrosis Trial
October 16, 2020 06:00 AM Eastern Daylight Time
SEATTLE--(BUSINESS WIRE)--Avalyn Pharma Inc., a biopharmaceutical company focused on development of improved therapies for life threatening pulmonary diseases, today announced completion of last patient in the initial 24 week evaluation of a Phase I/II clinical study of two dose regimens of AP01 (a formulation of pirfenidone optimized for delivery via inhalation) in patients with idiopathic pulmonary fibrosis (IPF). Ninety-one patients with IPF were randomized to 50 mg once daily (n=46) or 100 mg twice daily (n=45), administered by a PARI investigational eFlow® nebulizer. During the first 24 weeks, the high dose group had a trend toward stabilization of lung function as measured by forced vital capacity (FVC). The low dose group had a progressive loss of lung function. Based on these results the data safety monitoring board recommended conversion of all low dose patients to the high dose during the optional 12 month extension which is ongoing. AP01 was safe and well tolerated at both doses. Flu-like symptoms and GI adverse events most commonly attributed to oral pirfenidone were seen in less than 10% of patients treated with AP01. Adverse events with a frequency of greater than 10% were rash 18%, upper respiratory tract infection 18%, cough 24%.
Most subjects have opted to continue in the 12 month extension. Twenty-four week efficacy and safety data will be presented at an upcoming scientific meeting.
“We are pleased by the efficacy and safety profile we have seen to date with aerosolized pirfenidone in 91 patients over 24 weeks. The six month FVC data of the high dose is very promising as well as the overall safety profile to date,” said Dr. A. Bruce Montgomery, CEO of Avalyn Pharma. "Despite the 2014 approval of two oral antifibrotic therapies, IPF and other fibrotic lung diseases remain fatal diseases with substantial unmet need. We hope to establish improved tolerability and long term efficacy with aerosolized pirfenidone in Phase 3 trials to be initiated in 2021.”
Clinical Need
IPF and other fibrotic lung diseases are characterized by progressive scarring, reduced exercise capacity and ultimate death from respiratory failure and/or co-morbidities. IPF treatments are relatively new, with the first and only approvals coming in 2014: oral pirfenidone (Esbriet®) and oral nintedanib (Ofev®). Both medicines, while effective in slowing disease progression are associated with significant adverse effects that limit dosing and their full potential for efficacy. While these medicines are an important first step to treat IPF, a substantial unmet need remains for therapies with improved safety profiles and better efficacy as either stand-alone or add-on combination therapies in both IPF and other fibrotic lung diseases.
The Inhaled Advantage
Although oral pirfenidone has shown to slow IPF disease progression, it is a low potency drug requiring a very large oral dose to achieve efficacious lung levels. Unfortunately, oral delivery results in blood levels which cause substantial adverse effects and limit the delivered lung dose. In a Phase I single dose study of AP01, we have demonstrated the potential of aerosolized pirfenidone to improve both efficacy and safety. Inhalation of a dose of AP01 equivalent to 1/16 of the licensed oral dose delivered 35-fold higher peak lung levels of pirfenidone.