Health Check: Just the news we ‘kneed’ as Paradigm aims to kick-start US osteo trial

With the blessing of US regulator FDA, Paradigm Biopharma hopes to launch its pivotal trial of its knee osteoarthritis drug candidate.

Pic via Getty Images

• Paradigm Biopharmaceuticals says it is ready to apply to the US regulator to start its delayed phase III trial for knee osteoarthritis

• AFT Pharmaceuticals has entered a deal with two European partners to develop a secret novel drug

• PYC Therapeutics wins US ‘orphan’ status for its drug candidate for a children’s blindness disorder

Paradigm Biopharmaceuticals (ASX:PAR) says it will submit its revised protocol for its long-awaited phase III trial for dodgy knees to the US Food & Drug Administration (FDA) by the end of the month – with first patient enrolment targeted for the March 2025 quarter.

Crucially, the company isn’t going rogue and ignoring the agency’s counsel – as a disturbing number of biotechs are wont to do.

The submission will “incorporate amendments that were suggested and agreed upon during a comprehensive review process with the FDA” over five months and multiple review rounds.

 “Given the extensive engagement with the FDA, the company is confident that the final protocol aligns with the FDA's expectations,” Paradigm says.

The company says four global contract research organisations have been selected and one more is pending, with the trial initially covering 10 Australian sites.

Paradigm is repurposing a drug called pentosan polysulfate sodium, trademarked as Zilosul, for inflammatory diseases – notably knee osteoarthritis (knee OA).

Knee OA is the most common musculoskeletal disorder that affects more than half a billion people aged over 45 globally, with no effective treatment outside of opioid pain relief.

In mid September, Paradigm said it had received a detail response from the FDA, following a so-called Type D meeting in April.

The agency confirmed that the company’s preferred dosing – two milligrams per kilogram of the substance injected twice-weekly over six weeks – was the right way to go.

To date, Paradigm has gathered evidence of Zilosul’s efficacy from 600 patients – including Australian Rules footballers and Australian basketballers – under the local Therapeutic Goods Administration’s early access scheme.

‘Life changing’ is a common patient response, but the company needs a full-blown, placebo-controlled trial to convince the regulators.

The company says the revised submission includes tweaks to improve patient convenience and reduce trial costs. The company had expected to enrol about 500 patients, but a lower number may suffice.

Meanwhile, the company has addressed corporate governance concerns about the board’s structure, with Dr. Donna Skerrett relinquishing her executive director role at the upcoming November 19 AGM to focus on her chief medical officer responsibilities

The board will consist of founder and executive chairman Paul Rennie and two non-executive directors, Amos Meltzer and Matthew Fry.

“This structure ensures strong governance and oversight as the company continues to advance its strategic priorities,” Paradigm says.

The company also has cancelled the long-term incentive(LTI) rights approved for Rennie and Skerrett at last year’s AGM, due to the “inability to achieve the targeted milestone of completing the within the original timeframe.”

However investors this time around will vote on fresh LTIs for Rennie and Skerrett, nominally valued at $62,736 and $44,284 respectively.

Paradigm adds the board and staff have purchased shares on-market, “reinforcing confidence in the company’s progress".

As a loyalty measure, the company has also pledged an alternative reward to holders of well out-of-the-money Paradigm options when they expire on November 30.

With the delays and trial funding uncertainties, Paradigm shares have lost more than 60% of their value over the last year.

Selling remains persistent, with the stock falling 9% this morning to 24 cents despite the positive tidings.

Shh! AFT Pharmaceuticals' big drug secret

Come on guys! It’s too early in the day for Guess Who? (or Guess What, strictly speaking).

Trans-tasman drug house AFT Pharmaceuticals (ASX:AFP) says it’s entered a deal with two European partners to complete late-stage R&D on a novel injectable medicine “containing a patented new chemical entity".

The medicine – and the targeted condition – are confidential, but addresses a US$3 billion market forecast to grow to US$7 billion by 2023.

“The medicine is delivered as a single dose for the majority of patients, offering potential advantages over existing treatments, which generally require two injections.”

Mmm … could it be? … nah, no idea.

AFT produces an array of branded and non-branded medicine, both over the counter and prescription. Its lead product is Maxigesic, which combines paracetamol and ibuprofen for pain relief.

Given the novel mystery product is to be subject to a 1000-patient phase III trial, we suspect it may move the dial a bit more. AFT reported revenue for the year to March 2024 of NZ$195.4 million, up 25% and a net profit of NZ$15.6 million (up 47%).

“This is an exciting project that offers us rapid entry into a highly attractive and significant global market,” CEO Hartley Atkinson teases.

One of AFT’s products is Maxiclear, a sinus and anti-inflammatory treatment that “breaks the bad” of pseudoephedrine because the bikies’ favourite ingredient is hard to isolate for nefarious purposes.

We’ll pay that one.

AFT shares were unchanged at $2.98.

FDA grants favoured status to PYC Therapeutics' rare drug candidate

The US FDA has granted ‘orphan’ drug status to PYC Therapeutics' (ASX:PYC) drug candidate for retinitis pigmentosa type 11 (RP11), a genetic blinding disease that affects about one in 100,000 children.

Known as VP-001, PYC’s candidate is the first RP11 treatment to get to human trial stage.

Earlier, PYC released “encouraging” efficacy data from a single-dose study, with additional data from two multiple dose studies due out in the current quarter.

Orphan designation confers benefits including seven years’ marketing exclusivity in the US, tax breaks on clinical programs and fee exemptions.

An RNA (gene) therapies specialist, PYC targets monogenic diseases – those controlled by a single gene with the highest likelihood of success in clinical development.

RP11 is caused by a mutation in one copy of the PRPF31 gene, leading to a protein insufficiency. VP-001 seeks to return PRPF31 levels to normal.

PYC has also started human trials in a second drug program targeting another blinding eye disease, autosomal dominant optic atrophy.

Human trials for a third program, targeting polycystic kidney disease, are expected to start in early 2025.

PYC estimates a $1 billion-plus addressable market for RP11 – and we all know by now that because of generous reimbursement rare diseases can be extremely lucrative.

PYC has taken years to get to where it’s at – the company is no ‘orphan’ in that regard – but investors are listening with its shares climbing 230% over the last year for a hefty market cap of $911 million.

The shares this morning were unchanged at $0.20.

At Stockhead we tell it like it is. While Paradigm Biopharmaceuticals is a Stockhead advertiser, it did not sponsor this article.

Originally published as Health Check: Just the news we ‘kneed’ as Paradigm aims to kick-start US osteo trial