NUZ have released the following announcement RE their drug NUZ-001:

US Patent granted for NUZ-001 for the treatment of Neurodegenerative Diseases Highlights:

 Patent granted by the USPTO covering the use of Neurizon’s lead drug candidate, NUZ-001, in neurodegenerative diseases and cancer

 Granted patent provides specific protection for NUZ-001 and structurally related compounds used in treatments for mTOR pathway-related diseases in the US market until 2039

 Considerably strengthen Neurizon’s commercial potential and provides a strong framework for any future licensing negotiations

 Patent grant follows FDA Orphan Drug Designation (ODD) for NUZ-001 in May 2024, further enhancing the Company’s IP estate and market position for NUZ-001 as the clinical trial pipeline advances

At this stage the Phase 2 Healey trial is still held up by the FDA but hopefully in the next few weeks NUZ will have an answer back in regards to the actual reason for the hold so they can move ahead with trial.

Neurizon have released the following announcement about the Phase 2/3 trials for NUZ-001:

Neurizon Therapeutics Limited has received notification from the U.S. Food and Drug Administration (FDA) that it has placed our Investigational New Drug (IND) application for NUZ-001 under clinical hold, pending further clarification and additional information. In their communication, the FDA outlined it has certain concerns about the sufficiency of information to assess the application and any risks to human subjects of the trial and with the proposed dosing regime.

The detailed FDA feedback is expected within 30 days and should provide the specific clarifications needed to progress the IND application. We are committed to thoroughly reviewing this feedback upon receipt, taking all necessary actions, and engaging in constructive dialogue with the FDA to address their feedback and provide the required information so that the FDA provides clearance to the IND. 

The FDA have not informed NUZ of why this has been placed on hold, but it could be something simple such as the FDA asking for a protocol amendment to include some additional patient safety monitoring, if so there will be a hold up of a few months. If it is something more serious then the wait could be longer.

NUZ have been busy over the last few months (unfortunately so have I which is why I am a bit late with this) and have released their interim data from their OLE study as follows:

 Positive 8-month Interim Data from Open-Label Extension Study in Patients with ALS

Highlights:

 Treatment with NUZ-001 remains well-tolerated, demonstrating encouraging results in slowing disease progression and increasing the life expectancy of patients with ALS

 Key findings compared to untreated matched controls from the PRO-ACT Historical Database were:

o NUZ-001 significantly increased survival (χ2=11.67, p=0.00062)

o NUZ-001 significantly reduced the risk of death by 78.1% (HR=0.219, p=0.0044)

 The mean rate of reduction in disease progression measured by ALSFRS-R from baseline was -0.77 points/month

 Patients are now in their 27th month of continuous treatment with NUZ-001

 There have been no serious adverse events related to treatment with NUZ-001

NUZ have also filed their IND application in relation to the Healey phase 2/3 trial as follows

Neurizon Files IND Application to Support HEALEY ALS Platform Trial Highlights:

 · IND application submission to the U.S. Food and Drug Administration (FDA) is a pivotal step in initiating a Phase 2/3 clinical study for NUZ-001

· The IND is a comprehensive dossier of information, including animal and human studies, pharmacokinetic analyses, toxicology studies, and manufacturing information for NUZ-001

 · The FDA has a period of 30 days to review the IND application · NUZ-001 targets TDP-43 protein aggregation, a hallmark of ALS pathology, supported by its demonstrated safety and preliminary efficacy profile in earlier clinical studies

At this stage NUZ has its Phase 2/3 trial which will be done by Healey almost ready to start with it starting in a month or so and will be finished around the end of the year. If the results from OLE are similar in the Healey trial then there will be significant SP appreciation as it has a market cap of around $84 Million at the moment and should move significantly upwards. I hold this in both my Strawman and actual portfolios and am happy to hold until the end of 2025.

Some interesting stuff happening in the HC thread ‘Corporate Action’ for PAA.

A bunch of the top shareholders have come out of the woodwork and are coordinating to push for a board restructure, and the reinstatement of Dr Michael Thurn as CEO. Guessing that’s what’s behind the trading halt.

I’m down on my holding, but it is a very small part of my portfolio so just grabbing the popcorn and enjoying the show on this one!

On Friday 7th of March Amylex revealed that phase III data for its ALS drug Rylevrio failed to outperform a placebo.

612 patients were involved in the study and there was no significant difference found on the all important ALSFRS -R. Rylevrio had a significant drop out rate due to diarrhea side-effects. Unfortunately this drug has been one of the only available candidates for the treatment of ALS and the lack of efficacy is a major blow for patients suffering from this condition.

A voluntary withdrawal from the market is likely by Amylex in the next few weeks. The share price plummeted by 70% on Friday.

Pharm Aust’s now has a huge opportunity if it’s drug can pass successfully through Phase II/III trials starting in June. Rylevrio was seen as a potential $1 billion drug annually and in 2023 had $400 million revenue after just 4 qrtrs.

Phase II/III will see MPL compared for efficacy against a placebo. All 12 Phase I patients have now converted to the MPL open label trial.

Results were released after market and possible impact to PAA share price is not known. If PAA is successful MPL just became one of the only potential future treatments for ALS and likely a whole lot more valuable as an asset.

BULL CASE for Pharm Aust Ltd

This week is a pivotal week for Pharm Aust Ltd (PAA) with Phase I data readout for their only human drug Monepantel (MPL) for treatment of motor neurone disease (MND). Specifically the subtype of the disease amyotrophic lateral sclerosis (ALS) the same one renowned for affecting Steven Hawking. 

I discovered this recently through another biotech investor and trader and started a quick DD. I admit I have jumped in immediately with a small investment given the timing and the fact that the Phase I data will be released this week. Straw investors already on the case include @Quiltman , @secondtake88, and @mmff . Congrats to these investors with some incredible returns noted on Strawman. 

I took a bite at .32 and last week the stock ended at .38c. On successful approval I expect at least 100% rise further from here. 

ALS is a debilitating and life limiting condition. Mean survival time is between 2-5 years from diagnosis. Although some manage to live longer. The condition affects the motor neurons that pass messages from the brain to our muscles. It affects pathways to our extremities, our speech, swallowing and eventually breathing. 

Early symptoms include:

-Muscle twitches, cramps

-Tight stiff muscles

-Muscle weakness 

-Slurred and nasal speech 

-Difficulty chewing and swallowing

The cause of the disease is still not understood. There appears to be a small genetic inheritance component. 

Prevalence rates in the US for MND are quoted as approximately 300,000. Roughly 30,000 people have ALS. (see rates here)

About Pharm Aust

Shares on issue: 386 million

Market cap $131 M

CEO: Dr Michael Thurn (position held for 6 months) involved in Botanix 

Pharmaceuticals previously.

Monepantel (MPL) Origin

Repurposed vet medication for de-worming sheep. 

Human anti-cancer and neurodegenerative potential recognised.

How MPL works in brief

My Investment Interest

·      Likely upcoming Orphan Drug Designation with FDA. 

·      Very limited treatment options currently available.

·      Quick Approval with FDA due to life-threatening condition

·      High drug price tag on approval

·      Combined phase 2/3 study pending phase I results – meaning 1 more study before potential approval and sales. 

·      Phase 2/3 combined study cost estimated at between $20 and $30 million- n=210 patients. FDA has agreed to global enrolment   for study and drug is already produced and placebo is currently being made and ready to roll out. Commencement planned for June 2024. Study duration 24 week for provisional approval and 48 weeks for full approval

·      All 12 participants in phase I study are still alive following 15 months on MPL – well tolerated, minimal side effects and all rolling over on compassionate grounds to remain on drug. 

·      1 in 1000 or 0.1% chance of all 12 patients surviving for 15 months. The question is how much have their symptoms progressed?

·      Looking for a SOC score of less than -1.24 anything lower and will have a survival rate improvement of more than 9 months which is where there competitor Rylevrio sits with their phase 3 study. 

o   Look for -1.0 or better 

·      Attractive licencing or acquisition target for larger pharmaceutical

·      Mode of action of activating autophagy -applications in Alzheimers, Parkinsons’ and other neurodegenerative conditions

Brief look at competitors

This is a quick straw and by no means a deep dive into the 4 drugs available for MND/ ALS currently. 

The current drugs are reported to extend life by as little as 3 months to as much as 9 months. As you can see current drugs for this disease are not outstanding. 

1.Qalsody (Toferson) 

– gained FDA approval in 2023

2.Rilutek (Riluzole)     

– gained FDA approval in 1995

-prolongs life by 3 months

3. Radicava (edaraone) 

         -gained FDA approval in 2017

         -prolongs life by 6 months

-IV formulation that the company has tried to develop into an oral form and this has failed FDA likely to remove approval as results failed in a large study. 

4.Relyvrio (AMX 0035 combination of sodiumphenyl butyrate and taurursodiol) 

         -gained FDA approval in 2023

         -prolongs life by 9 months

         -Study run on 87 patients 

         -Drug price US$158,000

         -granted accelerated approval 

I had heard about Relyvrio through my Neuren Pharmaceuticals research. It is a drug with severe side-effects with a 50% attrition rate due to severe diarrhea. The drug received accelerated approval and its phase 3 read out is due next qrt. Michael Thurn stated in the latest EGM that the drug is likely to fail phase 3 due to side-effects and discontinuation. It is currently treating 3600 patients in the US. 

So 2 drugs may have FDA approval rescinded. 

Amylex Case Study for Market Cap

CEO Michael Thurn states that Amylex is the best case study for PAA. Off the back of its Phase 2 study, involving 87 patients Amylex had a Market cap of US$2.5 billion. This was the only drug this company had. 

Hence the argument that PAA should have a similar market capitalisation if Phase I are more successful than Relyvrio. Only 1 more 24 week study is needed before potential accelerated FDA approval and revenue. 

Interesting resources 

EGM

https://m.youtube.com/watch?v=8l39adr1tCY&t=9s&pp=2AEJkAIB

MTOR pathways drugs- fascinating origin story

https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub

Proactive interview with CEO - Michael Thurn

https://m.youtube.com/watch?si=OhutnOq_osfqRrdm&v=RBd6euPX7Gc&feature=youtu.be

Company is currently working on oral liquid for patients who can’t swallow. This will extend IP and add further protection. 

Summary

I find the case for PAA and MPL compelling. It meets my interest in rare disease treatments that have a chance of an accelerated pathway through the FDA. It will hopefully slow progression of ALS and improve quality of life. The investment should be attractive to large pharmaceuticals and based on the case of Amylex the $131 million dollar Australian market cap seems woefully undervalued if there is successful Phase I read out this week.

Remember watch for a less than -1.24 points per month decline on the ALSFRS-R score which would imply that MPL slows the disease by more than its nearest competitor Relyvrio.

Leiden University Testing Indicates Monepantel and Monepantel Sulphone SARS-CoV-2 Antiviral Activity

•  Previously PAA reported to shareholders that monepantel (MPL) and monepantel sulfone (MPLS) demonstrate antiviral activity in cultured cell infection models of SARSCoV-2, the virus causing COVID-19
•  Leiden University Medical Center (LUMC) has generated indicative data that MPL and MPLS again demonstrate antiviral activity in non-human primate systems
•  High insolubility of MPL in these systems was challenging and required several analyses
•  LUMC is now moving forward and transitioning to human cultured cells

DISC: I hold

Epichem Licensing Agreement to Develop Waste to Fuels Technology

•  Epichem has entered into a license agreement with Thermaquatica for the Oxidative Hydrothermal Dissolution (OHD) technology
•  Epichem will research, develop and promote the novel, innovative, disruptive technology using Flow Reaction
•  Epichem will continue to seek government and project grant funding to accelerate the initiative

...Epichem OHD will advance the novel, disruptive and innovative OHD technology using biomass/feedstock flow reactor material science. The flow reactor is a world-first with its potential to turn a wide range of waste and biomass feedstock into valuable fuels, fine chemicals, agricultural growth stimulants and ethanol....

The flow reactor has the potential to convert:

•  Plastics into renewable fuels
•  Coal into diesel or agricultural biostimulants (diesel, fine chemicals and biostimulants)
•  Rubber tyres into liquid fuels/valuable chemical products
•  Trees into cellulosic ethanol/fine chemicals
•  Leftover stock or crops into liquid fuel – cellulosic ethanol and agricultural biostimulants.

Disc: I hold...bought as a SC Health Stock...only a month ago they called themselves "a clinical stage oncology company". Also Scherobi added a post "History" a month ago

Still very happy to hold 

Phase IIb Clinical Trial Studying Monepantel in Pet Dogs with Treatment Naïve B Cell Lymphoma

~ Recruitment for the trial has commenced

~ Several dogs have already been successfully recruited and have started treatment with MPL tablets

~ Six pet dogs currently treated on a compassionate basis with MPL tablets

15 February 2021 – Perth, Australia: PharmAust Ltd (ASX:PAA), a clinical-stage oncology company, is pleased to provide an update on its Phase IIb trial testing the effects of monepantel upon pet owners’ dogs with treatment naïve B cell lymphoma.

Recruitment for the trial has commenced and several dogs have been successfully recruited and have started treatment with MPL tablets.

Six dogs not eligible for the trial have commenced compassionate treatment with MPL tablets.

PharmAust will be pleased to update the market when a sufficient number of dogs with meaningful trial endpoints have completed their treatment regimen

Disc: I hold

Update: Monepantel COVID-19 Testing in the Netherlands

~ Leiden University continues to evaluate monepantel in their anti-Covid19 systems

~ Experimental work affected by global supply chain shortages

~ Timing not affecting PharmAust’s overall clinical development plans

 PharmAust Ltd (ASX:PAA), a clinical-stage oncology company, is pleased to provide further information on work being conducted in the Netherlands investigating the effects of monepantel upon coronavirus infections.

The coronavirus pandemic has been severely affecting global supply chains and consequently performing experiments in many parts of the world, including the Netherlands, has proven problematic. Tests using monepantel and monepantel sulfone as Covid-19 antivirals, however, continue at Leiden University and PharmAust will be pleased to update the market when results come to hand.

DISC: I hold