Briefing report, page-5

Overview

I would be worried if the drop in the share price suggested that Noxopharm had run into problems, but the presentations yesterday were entirely positive. The slide shows were released prior to the meeting and religiously followed by presenters, but the selling today suggests to me that some people have not been able to join the dots.

Let’s see if I can help.

Noxopharm

• CEP – 1. These patients were VERY sick, had no treatment options and would certainly have quickly died, without treatment. They received NOX66 at 400 mg and at 800 mg plus Carboplatin (that they had already failed). The important aspect of this trial that is shown in the ASCO abstract but which might easily be missed is the absence of peripheral Neuropathy; a common, debilitating side effect of chemotherapy. There is an inference that NOX-66 acts as a neuro-protectant, which would make it a candidate to be used with ANY chemotherapy.
• DARRT.
  • There is a great temptation to ‘peek’ at early data from a clinical trial, which risks data contamination. Noxopharm has taken a deliberate decision to NOT look at any DARRT-1 data until the first three cohorts have all had their 6-week scans and the data has been assessed by three independent experts.
    • Incidentally, Noxopharm has access to progressive PSA measurements but has decided to NOT look at these either. Apart from the data contamination issue, it is probable that early PSA data will be unreliable anyway because of a thing called ‘PSA spike’, in which PSA in some patients can shoot up before dropping.
  • I expect the first DARRT results to be announced in early August.
  • As soon as the preferred dose of NOX66 is established, the Company will commence an all-comers DARRT trial.
• LuPIN
  • LuPSMA was licenced to Endocyte Inc in late 2017. Since then, the market cap of Endocyte has risen from about $80 m to $860 m.
  • The Peter MacCallum hospital has been trialling LuPSMA in prostate patients, with good results. An ASCO abstract from Peter Mac noted that median PSA PFS was 7 months and OS of 13.5 months.
  • Significantly, another ASCO abstract noted that patients who did not qualify for the LuPSMA trial had median survival of about 10 weeks. Clearly, the treatment works.
  • St Vincent’s has also been testing LuPSMA, apparently with similar results those achieved by Peter Mac. It was St Vincent’s who contacted Noxopharm to ask whether they could add NOX66 to the treatment regime.
    • GK made a very interesting point: It appears that PSA PFS initially fell with LuPSMA alone, but started to rebound after 3 or 4 months. This is implied by the ASCO abstract published this week, but would have been known by NOX in 2017.
    • The question to be asked, therefore, is whether the addition of NOX66 can delay the PSA PFS rebound.
  • The ‘NOX’ patients at St Vincent’s were scheduled to receive four one-monthly treatments, but St Vincent’s recently asked whether this could be extended by two sessions.
  • The ‘NOX’ patients are now in their fifth month of treatment, so my guess is that things are going well.

Nyrada

Well! This presentation was eye-opening.

Nyrada has three programs, each potentially worth billions of dollars to Big Pharma, and each doing well. Noxopharm owns two thirds of Nyrada, so if one program was bought for say $1 billion, this would be worth about five dollars per NOX share.

One program could not be described at the meeting because disclosure might have risked the imminent lodgement of patent applications. We received comprehensive updates on the other programs (which implies that patent documents have already been lodged)

Stroke

• Professor Garry Housley of UNSW gave an impressive illustration of the damage caused by calcium ions after injury to the brain of a mouse; and the amazing response after NYX-104 had been rectally administered.
  • This provided proof-of-concept, in an animal, that LIPROSE technology enables certain drugs to cross the blood-brain barrier; and that the particular drug had a significant effect.
  • Professor Housley’s team will now test the motor skills, behaviour etc. of treated mice.
• Stroke costs about $34 billion per year in the US.
• But the function of NOX-104 as a neuroprotectant means that it could be used to treat concussion, stroke and even loss of hearing.
• This is a hidden gem for most shareholders.

Cholesterol

• Statin drugs were the biggest selling drugs in history until they came off-patent. Even now, sales are about $19 billion per year.
• Statins try to lower LDL-cholesterol in the blood, but in the process increase the number of PCSK9 proteins, which put the LDL proteins back into the blood.
• Big Pharm discovered this phenomenon many years ago and tried to design an oral drug that would lower PCSK9. They failed.
• Pharma them developed an intravenous inhibitor of PCSK9. It worked, but
  • Has to be injected every 2-4 weeks, for life
  • Costs $14,000 per year
  • With no reimbursement for most patients.
• When used intravenously, these drugs inhibited PCKS9 and LDL cholesterol dropped, providing proof-of-concept.
• Ian Dixon and a couple of chemists in Melbourne worked out how to design an oral inhibitor of PCSK9, and proved that it worked in an animal model.
• The next step is to convert it into a oral form, which apparently should be an easy step.
• This drug might not even get into the clinic, in my opinion. Big Pharma is desperate for an effective cholesterol inhibitor, particularly an oral version.

Summary

I think investors need to look at the entire picture.

Nyrada is majority-owned by Noxopharm and each of its three programs has billion-dollar potential. Even at this early stage, proof-of-concept has been overwhelming positive, yet the share price of Noxopharm suggests that no value has been included for Nyrada.

Noxopharm has three programs of its own, each assessing NOX66 in different ways, but I doubt that many shareholders consider the cumulative affect of this approach when off-label use is contemplated. NOX is steadily creating a database of NOX66 and the company is already getting approached by oncologists who want to use the drug in different ways.

Professor Housley and the other three members of the scientific advisory board own Nyrada shares. I don’t know about the others, but Garry Housley told me he asked whether he could buy some; and did. He also owns NOX shares.

In terms of risk/reward, I feel that the risk of a disaster on all fronts is negligible; whereas the reward of success on even one front will be enormous.

I continue to hold.