"Im sure with the formalities now in play for the new ticker...

"Im sure with the formalities now in play for the new ticker code, it would be good to have solid, educational and informative threads ready to bring a comprehensive overview of the company for new investors having a little look to see what we are all about."

That’s the plan — a point source of updated info for new investors.

There’s a lot of history behind the transition from PAA >> NUZ.

There’s a lot of complex science.

There’s a lot of moving parts and integrated action currently happening simultaneously in parallel.

For starters, many potential investors in a company look first to the management quality of a company, and in particular the experience of the heads of the leadership group in the company — and do they have skin in the game — as a start point for investment research.

You can check the company web site for those details:

https://www.neurizon.com/#team

But you’re here to find out what current investors think, and gather the collective thoughts on — is this company worth investing in.

There are numerous great contributors within the PAA/NUZ threads that I’m sure will contribute their insight and viewpoints, their summary of NUZ and what NUZ means to them, and provide feedback on any questions you may have. So it’s a safe space to ask those basic or complex questions.

In particular, the thoughts, insights and actions of the MD & CEO of a company are highly relevant to many potential investors.

The following is from a recent interview with the NUZ MD & CEO Dr. Michael Thurn.

You can find the interview here:

https://www.couriermail.com.au/business/*/health-kick-podcast-pharmaust-in-the-fight-against-mnd-and-als-with-lead-drug-monepantel/news-story/5f052a4e60d502592cc4c95f64f4cd0d

There’s something solid about seeing details in print form — like it’s set in concrete — being able to read through it, revisit it again, take notes, copy/paste etc. [It is a long read, but way more efficient than trawling through the vast thread history of PAA.]

Those company perspectives below — from that same interview above — are from that most recent in-depth interview on record, and from the most-informed shareholder in our company, fleshed out into written text.

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NUZ Timelines & Catalysts — 24 Sept. 2024 — Health Kick interview

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“Welcome to Health Kick talking about taking old molecules and using them for something completely different, and it’s not just recycling for the sake of it, a big advantage is that someone else, has done a lot of the work to prove safety and efficacy of the old proposed drug, so the whole process is cheaper and quicker.

Now in the case of the ASX-listed Pharmaust, the old substance is called Monepantel. Now this one was approved as a sheep dip believe it or not.

But as Pharmaust chief Dr Michael Thurn will explain; it shows great promise in treating motor neurone disease, also known as ALS, and possibly other neurological disorders as well, so welcome Michael.”

Thanks Tim! Yes spot on there with Monepantel — certainly captures the excitement of a repurposed drug in terms of being able to offer benefit — we hope in a short period of time to patients with motor neurone disease.

“Fair to say Pharmaust has an interesting history.

What’s the sort of potted background and how did you get to this point? “

I’ve only, in fact, I’ve just ticked over my 12 months at being in the hot seat at Pharmaust. The history, in terms of Monepantel, came back, with a reverse merger, if you like, with Pitney pharmaceuticals. So that dated back to 2012, and the result of that is obviously been the genesis of Monepantel being potentially, very useful for a range of different neurodegenerative diseases.

Back in 2012, the discovery if you like was Monepantel had activity in a range of anti-cancer cells that was shown by professor David Morris back in 2012 from the University of New South Wales.

He looked at a range of anti-cancer cell lines, and the activity of Monepantel against those various anti-cancer cells and was able to show that it was effective, and promising as a potential anti-cancer agent.

He then went on, and as most academics do, they bring on a PhD student - that PhD student then looked at the mechanism of action that Monepantel was using to kill those anti-cancer cells, and lo and behold, it came out that it was an mTor inhibitor.

Now where we’re using mTOR inhibition, is using that as a way of stimulating, enhancing autophagy in normal cells, and autophagy is that natural process, that your cell uses to remove junk — remove that metabolic waste — that builds up during normal activity — to enhance that autophagy process — and it’s almost used as the Holy Grail, if you like, for anti-ageing these days, but we’re using that autophagy, stimulating autophagy, for the betterment of motor neurone disease.

So in motor neurone disease, you have a toxic buildup of metabolic waste —typically unfolded proteins — that cause the neurodegeneration and we’re using autophagy, to clean up those, that toxic buildup of protein and in, motor neurone disease it’s well characterised - it’s TDP 43. That’s the misguided protein, in other neurodegenerative diseases.

There’s also that pathology , that common pathology of the buildup of toxic protein and in Alzheimer’s it’s well characterised- it’s beta Tau - in other neurodegenerative diseases, it’s just a different protein.

So we hope, that by, uncovering the benefit of Monepantel in motor neurone disease that, it will act as a way, a gateway if you like, to the more widespread use of Monepantel in those more prevalent types of diseases like Alzheimer’s, Parkinson’s and Huntington’s.

So, we’re on we’re on a path.

A path that we’re on is, first of all showing benefit of using Monepantel in motor neurone disease, and then, potentially down the track those other neurodegenerative diseases — so really exciting time.

“You’ve described the company as it was, as a bit of a hotch-potch. From the looks of it, the company has disposed of the animal - vet side of things, which was a legacy of Pitney, it’s now very much focused on the human side and specific neurological indications rather than cancer.”

We are, and there’s lots of good reasons for that, and you know, the most obvious one is that, rare diseases and the advantages that you have in developing a drug for rare diseases.

So not only do we take the advantage of it being a repurposed drug, and as you eloquently pointed out in the introduction, that there’s already a safety package — you know you can manufacture the drug.

We’re in a position now, to take advantage of what’s on offer for a rare disease. And there’s multiple aspects of that, and for neurone disease in particular, if you look at the history of drugs that are being developed for motor neurone disease, the most recent drug that was approved — it was approved under Accelerated Approval through the FDA — in as few patients as 89 patients, which is you know from a typical normal biotech offering — a considerable truncation of the development pathway.

So where that leaves us is, that we have an opportunity now based on the promising phase 1 data that we released earlier in the year, to do just one more study — one more study that is a relatively few number of patients — in our case it’s likely to be somewhere between 160 and 200 — and we’ll talk about that in a minute through the acceptance in the Healey platform trial, but it’s a different offering to your normal biotech, so we have a very real proposition should this drug show efficacy, in the next study that we do, of being in a position to get the drug approved by the FDA, through that Accelerated Approval process and potentially be available to patients as early as 2026.

So we’re quite a different offering, if you like, to your normal biotech that that’s ASX listed.

“Ok, just to recap, you’ve done your Phase 1 trial, and you’re heading to a Phase 2/3 FDA study. You mentioned the Healey platform — can you elaborate on that?”

Since day one when I joined the company just over 12 months ago — I’d recognised that there was an opportunity for the Pharmaust to be a part of the Healey platform.

So the Healey platform trial was put together by two leading neurologists in motor neurone disease or ALS. They wanted to, develop a platform, where it was an opportunity to, with the FDA’s blessing, to bring on promising new drugs and develop them as fast as possible to that approval point in order to make it available to people that have ALS.

And the reason why they wanted to do that was because the lack of effective treatments for ALS. So we looked at the history of drugs that have been developed for ALS.

It’s a pretty pretty sad tale.

“And how many drugs are out there?”

So there’s really only three drugs.

So those three drugs, and I almost feel the pain of the patients that unfortunately have ALS, that they don’t really have, a lot of prospects, because the drugs that are available really do very little in order to enhance one, the quality of life, but two, prolong their life expectancy.

So as I mentioned before, the first drug that was approved, Riluzole, was back in 1995, and you know that’s a generic now.

It prolongs life, in clinical studies that have been done, by just 2 to 3 months.

The next drug it took them 22 years. 22 years to provide patients with an additional four months. So going from 2 to 3 months, to 6 months.

“Yes, it’s fairly insubstantial isn’t it, the benefit, I suppose 3 months is three months, hmm, but anyway!”

It is. Those patients have to go in … and receive an intravenous infusion … so the quality of life is is not great.

There has been, somewhat considered a breakthrough for patients with ALS, but only patients that have the SOD1 mutation.

So quite recently last year there was a drug Tofersen, that addresses as a gene therapy, that addresses about 3% of the patient population with ALS mutation in the SOD1, which again received accelerated approval — so it should through the FDA and the EMA — and that, that has shown 3% of patients with the ALS something to, some hope, a much needed, extension of their life, but it’s still the other 97% that are unfortunately, faced with the best drug out there — six months.

So, we’re working feverishly to bring potentially Breakthrough Therapy to these patients and certainly the phase 1 data that we have generated offers considerable hope.

And I’m not, yeah, it’s not just me saying that.

This drug was accepted into the Healey platform trial.

That’s, that’s a competitive process.

The leading minds in ALS reviewed our data from our phase 1 study and thought, you know, this is looking promising — we’ve got to find a way of accelerating this to multiple sufferers of ALS.

That’s where the platform trial comes in — we’re about a month away.

It’s been a two-three month process, where we’re working with the Healey team to design our regimen-specific arm of the Hailey platform trial,

and we closing in on that,

and hope to be in a position to finalise that about midway through October,

and that means that we can hopefully start the study,

towards the end of this year or, early, very early next year.

“And I take it that, by doing the trial via the Healey Platform, there are economies of scale, the cost will be substantially lower, than the many millions you would have to spend doing it yourself.”

That’s correct. Yeah it is. The advantages of being in the Hayley platform trial are considerable.

So the common things that investors would look to mark us against, like reducing the cost of our clinical development program through to approval.

Does it guarantee that the trial is gonna be run faster?

Well yes it does. 50% faster in fact, but the real catch at the Healey platform trial, and how it stands alone, is the ability to share the placebo group.

So as you can imagine your patients with ALS — they don’t want to go onto a trial where there’s a chance that they’re in the Placebo group, they want to be on the Active group. So if we were to do the trial as a stand alone, we would have to do your normal type of scenario, where you might have a 1-1 ratio — active to placebo, or 2 to 1.

The placebo ratio in the Healey platform is 3 to 1.

So it really ratchets up, the prospect of being on the active arm, as opposed to the placebo arm.

Because of that, and that alone, that then,

• contributes to the trial being faster
• contributes to lowering the cost
• and it contributes to patients wanting to be involved in the Healey platform trial.

So all kudos to Professor Merit Cudkowitz and Professor Sabrina Paganoni, who’s been behind this — this is their brainchild. They’d set it up properly. They went to the FDA. They got their input. They’ve lined up 73 sites in the US, that all feed into the Healey platform trial.

“So how many patients are you enrolling? You mentioned it earlier …”

It’s gonna be … once the regimen is — and there’s a lot of simulation that goes into it — discussion with the FDA — but where we looking at, because of that 3 to 1 ratio, active to placebo, we can really dial down the numbers of (-?-) patients that need to be enrolled in that study.

We’re probably looking at, somewhere between 160 - 180 patients in total, that will be involved in that study, and that will give us the necessary power to have with confidence that the drug’s working, that will see that statistically significant result, that will lead potentially to accelerated approval.

So it’s a major coup for the company, particularly when you think about it, — we’re based in Australia — to be placed on that platform, the Healey platform trial — it’s been an incredible milestone, and just opens up so many other possibilities in terms of partnering, because the platform trial is so well recognised.

The PR, that’s associated with it — so the Healey platform trial have their own talks at symposiums — ‘what’s new in the Healey platform trial?’

The PR engine in the US is just immense.

So this small Australian biotech that’s trying to make a difference to the patients with ALS, we’re suddenly, you know, from the shadows, being catapulted into the limelight of being the next regimen for the Healey ALS platform trial.

“Yeah, great. Just broadly, can I ask you why motor neurone disease has proven so difficult? It’s kind of uh, a celebrity disease I guess for want of a better term. It’s got a very high profile. In Australia of course there is Neale Daniher with his efforts with the Big Freeze, which I think has raised many millions — progress has been slow. I guess you could say the same with MS as well.”

Exactly and a lot of those neurodegenerative diseases — Alzheimer’s, Parkinson’s disease…

“Well yes of course…”

It just seems to be inherent. I don’t know how much money has been spent — tens of billions of dollars on Alzheimer’s disease — so they’re hard nuts to crack — and specifically getting back to Fight MND and the ice bucket challenge and Neale — Fight MND funded our phase 1 study — so we’re very grateful to Fight MND and Neale.

I think the main reason for ALS, is that, while there’s a genetic component — that genetic component is being around about 10%. So 10% of patients with ALS — you can track it back to a mutation in a gene.

Whereas 90%? It’s all sporadic. They really have no idea why you’re seeing your motor neurones degenerate.

There’s some theories out there — blue green algae — Professor Dominic Rowe…

“I hadn’t heard that one…”

Yeah. There’s actually a concentrated group, down in the Riverina area of New South Wales and they think there’s a potential link to blue green algae. And then if you talk to some of the some of the partners of patients that have sadly passed away. They all seem to recall their partners swimming in blue green algae.

Whether there’s any, whether that’s just an association because they’ve heard of that, but there seems to be a strong link.

And then, there’s also the really high concentration/ high prevalence of ALS in Michigan, of all places Michigan in the States and they’ve tracked that to pollution. So Michigan, there’s a number of sites that you have, back in, I think it was World War II where they dumped and buried a lot of waste. So there is a concentration.

So they think, motor neurone disease is going to increase markedly by 70% out to 2040, and that kind of fits with that hypothesis of greater pollution — it’s linked somehow to pollution whether that’s blue green algae, man-made waste, or coming into contact with microbes that affect the brain.

So I guess what I’m saying is, that, yeah, that’s one of the reasons why it’s hard.

It’s not like making a gene therapy that targets the majority of the mutation that’s associated with the development of that disease. They’ve done that successfully for ALS in the 3% that have the SOD1 mutation.

Where we fit into this though,

is that we have an opportunity to use a mechanism that’s kind of downstream from any genetic aberration.

By stimulating that autophagy process, we’ve got an opportunity here to be well downstream, and mop up any toxic buildup of protein, metabolic waste, that’s associated with that neuronal degeneration.

So there’s great prospect that we have an opportunity to treat the majority of cases with ALS.

“Ok. And just to wrap up. Can you just summarise, your timeline in terms of what investors should look out for? I presume the trial recruitment via Healey will be a big focal point?

It will be. Yeah. We’re fortunate that we going to be news flow rich.

So you know, one of the things that you look for, when you make an investment in a biotech, is,

‘what’s their news flow going to be?’

‘what’s the catalysts?’

What’s really gonna drive in the company! and really fortunate to say that we’ve got multiple catalysts coming up.

And they’re things that you wouldn’t normally expect, and stuff that that we certainly haven’t / we’ve taken somewhat for granted, so you’ve talked about the recruitment in the Healey ALS platform trial, but it’s the other stuff that comes around that.

So things like:

• Opening your IND.

• It’s doing the manufacturing associated with — look, we’re in a position to potentially get this drug approved within 12 to 18 months.

• So we need to make sure that our registration batches, to support that approval, but also the batches that we’re going to use to potentially launch the product, are being done. And being done by quality organisations.

• So there’s a lot of stuff going on in the background, that adds to the news flow.

• Even ODD, yesterday we announced, that we filed for OMPD which is the European equivalent of the FDA’s ODD.

• And then, there’s all the other designations that come into play as you develop the drug, moving more and more closely to Accelerated Approval.

• Will we apply for Fast Track? Yes we will!

• Well, is there an opportunity at Breakthrough Therapy designation? Yeah! There is a possibility based on our ongoing clinical study - our open label extension study that we have currently ongoing here in Australia.

• Is there an opportunity to do something with the TGA ODD?

• Is there an opportunity to do something with the Japanese regulators ? - they have an orphan drug designation program.

• So there’s multiple activities that are going on simultaneously somewhat in parallel — that are building value in the proposition — in order for us, to make us an attractive partnering program,

• but also an attractive target for a large multi-national pharmaceutical company to completely take us out.

So that’s just on ALS.

What we’re building in the background to support that, is, going back to the fundamentals.

If we’re turning on a natural cleaning mechanism, in cells, that have a toxic buildup of protein:

— there might be application in Alzheimer’s disease.

— there might be an application in Parkinson’s and Huntington’s disease.

So we’re actively looking at, those disease types, in, in vitro and in vivo models.

So that, again, over the next 6 to 12 months, fills in the gap in news flow, as we wait for the results to read out from the Healey platform trial.

Incredibly exciting time for Pharmaust.

I feel somewhat fortunate to be involved.

You mentioned it earlier, that it’s a fairly high profile rare disease, but I think it also, you know that the path that we’ve taken — it illustrates that there’s a real opportunity to, add value very quickly, for rare diseases, and the various advantages that are associated with developing drugs for rare diseases.

So we hope to capitalise on that.

We hope to be in a position this time next year, to be closing in on completing enrolment in our Healey platform trial, and delivering the interim 24 week data that everyone will be, you know, looking towards as being that inflection point, that point where we can say we’ve got something that’s breakthrough.

It’s a major advancement in the way that we we treat ALS and then obviously the rewards associated with that with delivering on that will flow from that

— whether it’s an increase in the share price

— the value of the company

— or be in a position to do a really high value acquisition,

— or partnership with a major pharmaceutical company.

That’s what’s driving us over the next 12 to 18 months, and all things going well, it’s all down to the drug now — we’ve certainly set it all up.

We’ve put the wheels in motion,

— we’re collaborating with the right groups,

— we’re talking to the regulators,

— we’ve got a product that’s showing promise from our phase one study,

so we’re well set up, to deliver that. It all comes down to the drug performing.

“That’s great! Excellent, that’s all very exciting. And this is probably the last time I’ll be talking to you as Pharmaust because you’re changing your name!

We are. We are re-branding, and we want to show that we are committed to developing promising new treatments for neurodegenerative diseases and the company is going to be re-branded to Neurizon Therapeutics.

We’re very excited about that, and I think it really, the name really captures where we’re heading and hopefully those new treatments for ALS are just on the horizon.

“That’s great Michael great. Great to chat and I look forward to talking to you under the Neurizon banner.”

Thanks! Really appreciate it.

“Cheers!”

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For me, it’s a compelling, informative recap of where we’re up to, as of 24 Sept. 2024.

The recent AGM thread contains the last 3 weeks of updates.

What I like about Michael, and this interview from last month, is that he gives such a straightforward honest explanation of how-it-is. Lots of takeaways embedded into the dialogue; lots of detail in the timelines; lots of captivating insights.

What I absolutely love about MT’s understated style is that he naturally speaks from a personal shareholder perspective, and gives a realistic assessment of the history, pathway, journey, and trajectories, all from that group SH perspective. Some of the few times that it’s not; then he’s emphasising what this means from the patients’ viewpoint. Sometimes it’s from the monepantel perspective. No self-importance on being CEO/MD.

It’s a company that I’m proud to be associated with.

Best wishes for your investment decisions.

Cheers,

Ice