Algernon Pharmaceuticals Inc (AGNPF)

[Money $hot]

Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel

Published By:
European Respiratory Society

Online ISSN:
2312-0541

History:
Received November 26, 2021
Accepted January 14, 2022
Published online March 14, 2022.

https://openres.ersjournals.com/content/8/1/00667-2021

Introduction

Chronic cough lasting >8 weeks is a common health problem that affects 2–18% of adults worldwide [1]. Although clinicians can often identify and effectively treat known causes of cough—including asthma, COPD, bronchiectasis, gastro-oesophageal reflux disease and upper airway cough syndromes—many patients, despite treatment targeting these underlying conditions, experience refractory chronic cough (RCC) [2, 3]. In others, clinical assessment fails to identify a cause, and patients are classified with unexplained chronic cough (UCC) [2, 3]. Patients with RCC/UCC often exhibit cough hypersensitivity syndrome, defined as a troublesome cough triggered by low levels of thermal, mechanical or chemical irritants [4].

Objective cough frequency using the VitaloJAK monitor represents the most common primary end-point in antitussive clinical trials [10]. Cough monitors provide direct insight into whether treatment improves cough frequency by quantifying spontaneous coughs over a defined period. Existing monitors are limited, however, in that they are typically only used over a 24-h period, they can pose a burden for patients to wear repeatedly and they are expensive to administer [11]. Furthermore, they cannot assess whether other dimensions of cough (i.e. intensity) may be improved with treatment. A measure that directly assesses patients’ experience of cough and sequelae (herein referred to as “symptom severity”) might address the limitations of currently available instruments.

We aim to develop a cough symptom severity instrument—the McMaster Cough Severity Questionnaire—for use in patients with RCC/UCC. To inform item generation for the instrument, we conducted a systematic survey in which we identified 43 items addressing the following domains: urge-to-cough sensations (subdomains: frequency and intensity) and cough symptom (subdomains: frequency, control, bout duration, intensity and associated features/sequelae) [16]. To assess the comprehensiveness and appropriateness of items, domains and subdomains identified in our systematic survey, we conducted patient focus groups and consultation with clinical experts, and report here our findings.

Expert consensus study

We elicited feedback from an international panel of chronic cough experts on the comprehensiveness and appropriateness of items and domains identified from the systematic survey and patient focus groups. Using purposive sampling, we invited 14 key opinion leaders in chronic cough, all of whom agreed to participate. The final group consisted of 18 members (the steering group: E.K., G.H.G., P.M.O.B., I.S., and 14 experts: R.A., H.B., L.P.B., R.C., P.D., L.D., S.K.F., .CL.F., P.G.G., R.S.I., P.M., L.M., J.A.S., W.J.S.). Experts came from the UK, USA, Canada and one each from Australia, Belgium, China, Ireland, Saudi Arabia and South Korea.

Results

The 16 focus group patients had a median age of 61 years. Most identified as female (68.8%), reported no history of smoking (81.3%) and coughed for a median duration of 13.5 years (table 1).

Expert consensus

An open-ended survey to members of the expert panel identified 32 potential items/domains considered relevant to cough symptom severity (table 3). During the consensus meeting, experts agreed that severity should be conceptualised as an overarching term encompassing domains of frequency, intensity, duration, quality and associated features/sequelae. Experts also agreed that urge-to-cough is an important symptom to capture in a cough severity instrument. A small minority viewed the impact of cough symptoms on QoL (i.e. daily activities, ability to speak, social life) as a necessary aspect of symptom severity. Experts raised cough hypersensitivity as a potentially missing concept from the framework. Thus, the steering group added “triggers” as an additional subdomain (figure 1).

Figure 1


Footnotes

Provenance: Submitted article, peer reviewed.

Author contributions: I. Satia is the guarantor of the study. E. Kum, G.H. Guyatt, P.M. O'Byrne and I. Satia formed the steering group and conceived the study. E. Kum, C. Munoz, S. Beaudin and S-A. Li contributed to data collection. R. Abdulqawi, H. Badri, L-P. Boulet, R. Chen, P. Dicpinigaitis, L. Dupont, S.K. Field, C.L. French, P.G. Gibson, R.S. Irwin, P. Marsden, L. McGarvey, J.A. Smith and W-J. Song served as expert panel members. E. Kum, G.H. Guyatt and I. Satia analysed and interpreted the data. E. Kum wrote the first draft of the manuscript. All authors critically reviewed and approved the final manuscript.

Conflicts of interest: E. Kum, G.H. Guyatt, C. Munoz, S. Beaudin, S-A. Li, R. Abdulqawi, H. Badri, L. Dupont and L. McGarvey report no conflicts of interest. L-P. Boulet reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi-Regeneron, and personal fees from AstraZeneca, Covis, Novartis, GlaxoSmithKline, Merck and Sanofi-Regeneron, outside the submitted work. R. Chen reports grants and personal fees from AstraZeneca and GlaxoSmithKline, and personal fees from Novartis and Merck, outside the submitted work. P. Dicpinigaitis reports consulting fees from Merck, Bellus, Bayer, Shionogi and Chiesi, outside the submitted work. S.K. Field has served on advisory boards for GSK and Merck, has given sponsored talks for Boehringer Ingelheim, GlaxoSmithKline and Novartis, and has received research funding from AstraZeneca, CIHR, InsMed and Novartis, outside of the submitted work. C.L. French and R.S. Irwin disclose that they are co-developers and hold the copyright of the CQLQ and have each received less than $700 in fees over the past 3 years for its use in studies. P.G. Gibson reports grants from GlaxoSmithKline, and personal fees from AstraZeneca, Chiesi, GSK, Novartis and Sanofi, outside the submitted work. P. Marsden reports an investigator-initiated grant from Merck Sharpe & Dohme Ltd outside the submitted work. W-J. Song reports grants from MSD and AstraZeneca, consulting fees from MSD and AstraZeneca, and lecture fees from MSD, AstraZeneca, GlaxoSmithKline and Novartis, outside the submitted work. J.A. Smith reports grants from Merck, Ario Pharma, GlaxoSmithKline, NeRRe Pharmaceuticals, Menlo, Bellus and Bayer, and personal fees from Chiesi, Ario Pharma, GlaxoSmithKline, NeRRe Pharmaceuticals, Menlo, Bellus, Bayer, Boehringer Ingleheim, Genentech and Neomed, outside of the submitted work. J.A. Smith is a named inventor on a patent, owned by Manchester University NHS Foundation Trust and licensed to Vitalograph Ltd, describing the detection of cough from sound recordings. The VitaloJAK cough monitoring algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd). MFT receives royalties that may be shared with the clinical division in which J.A. Smith works. P.M. O'Byrne reports grants and personal fees from AstraZeneca and Medimmune, personal fees from GlaxoSmithKline and Chiesi, and grants from Novartis and Biohaven, outside the submitted work. I. Satia reports an ERS Respire 3 Marie Curie Fellowship, grants and personal fees from Merck Canada, and personal fees from GlaxoSmithKline and AstraZeneca, outside the submitted work.

My best guess is the above finding will create a MASH-UP of Moreau's Chronic Cough 2.0 study at Phase 2. Maybe HealthMngr has a better understanding of the recent study. Also, Jacky Smith (Medical and Scientific Advisory Board @ Algernon) is a member of the assembled "international expert panel". IMO, Jacky Smith should be appointed to the Board Of Directors. In a previous post I stated Dr. Mark Williams and Jacky Smith (mistakenly named Marilyn Huestis) should be the two persons/Doctors running Algernon Pharmaceuticals versus the current board members with a 10 Year failure rate at Miraculins Inc and/or longstanding ties to Kulwant Malhi. Lastly, see the extensive Footnotes above. Notice the myriad of companies in the mix of All Things Chronic Cough. Algernon Pharmaceuticals remains a non entity at any level of recognition in the Chronic Cough space. I firmly believes 2H 2025 is the likely timeline before the 1st Phase 2 data readout (“Everybody wants in at Phase 2” - Christopher Moreau) that's powered for statistical significance to be reported to the masses. That’s 3 years from now. Even longer if current management still cannot get a handle on pipeline timelines that change like your weekly weather report.

M$

PostScript

Andre Uddin @ Research Capital

“Ifenprodil is in a Phase 2a trial in IPF/chronic cough where results are expected in H2 2021, and AGN’s DMT (a repurposed psychedelic compound) is expected to enter into a Phase 1 trial in stroke in H2 2021,” Uddin wrote. “Investors should re-focus their attention towards the IPF/cough data expected in H2 ’21.”

“Investors should note our AGN valuation is based on the IPF and chronic cough indications of ifenprodil – we are currently keeping our financial assumptions for the two indications intact in our model. We never assumed any revenues from ifenprodil’s COVID-19 indication,” he said.

Along with the new “Hold” rating, Uddin has cut his price target from CAD $0.80 to $0.25, saying the drop is due to a decrease in assumed success rate for Ifenprodil. At the time of publication, the new target represented a projected one-year return of negative 15 per cent.

To date, 0 of 2 ratings by Andre Uddin were profitable. I surmise Uddin's ratings will remain unsuccessful as Algernon's timelines and massive dilution remain a severe hindrance to the long term stock price. Simply look at the timeline Uddin previously expected data results. It's an analysis from someone who has way more information at his disposal than the average investor. Algernon Pharmaceuticals has the ability to make everyone look bad and they never disappoint. It's another page from the Kulwant Malhi playbook where everything he touches dies a slow death.

Andre Uddin's stock analyst ranking among his peers:

www.tipranks.com/experts/analysts/andre-uddin

Of Note: Andre Uddin's price target of CAD $0.25 converts to 20 Cent USD. Which means the target price is $20 per share post consolidated shares of 100 to 1.

Bottom line: I do not believe Uddin's latest CAD $0.25 target price will be realized upon the readout of the long awaited IPF/Chronic Cough data in Australia/New Zealand. Uddin is on a path to a 3rd strikeout in his analysis of Algernon Pharmaceuticals.

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