Tim Boreham is one of Australia's best-known small-cap share analysts and business journalists.
Health & Biotech
In its pursuit of a cancer drug for pancreatic cancer and possibly ovarian cancer, Amplia has history on its side given the involvement of its leading figures in a US-approved drug for blood cancer.
The therapy in question, Ojjaara (momelotinib) is a so-called janus kinase (JAK) inhibitor drug to treat myelofibrosis, developed by the formerly ASX-listed Cytopia.
The lead inventors were Melbourne-based scientist and current Amplia CEO, Dr Chris Burns and Cytopia founder Prof Andrew Wilks. They were also proud recipients of the Prime Minister’s prize for innovation in October.
In a typical case of ownership pass-the-parcel, Cytopia was acquired by Canada’s YM Biosciences and the drug then was in the hands of Gilead and Sierra Oncology (for a song).
In 2022 Glaxosmithkline bought Sierra for US$1.9 billion ($2.9 billion) – the highest amount ever paid for an Australian-developed therapy.
The US Food and Drug Administration (FDA) approved the treatment last year – only the third locally-invented drug to be approved by the agency.
(the others were Biota’s flu drug Relenza and Hatchtech’s Xeglyze for head lice and – before you ask – the legendary Gardasil is a vaccine).
“It was a very interesting time,” Dr Burns says, with a touch of understatement.
Amplia certainly can’t be accused of targeting the low-hanging fruit, in that pancreatic and ovarian cancers are notoriously hard to detect and to treat.
Amplia’s lead compound, AMP-945, targets fibrosis: the formation of excessive fibrous connective tissues that can impair the function of organs including the lungs, liver, heart and kidneys. The company has orphan indication for both pancreatic cancer and idiopathic pulmonary fibrosis – another hard-to-treat condition.
Amplia has an – er – interesting history.
In early 2018, the company was known as Innate Immunotherapeutics and it famously had just come a cropper with a phase II multiple sclerosis trial.
There’s even a Trumpian tinge to Amplia’s history, in that former Innate director and major shareholder Chris Collins was Donald Trump’s congressional liaison in his first stint at prez.
Collins was sentenced to 26 months’ jail after pleading guilty to tipping-off his son that the MS trial was less than tickety-boo (and guess what? Trump pardoned him).
After considerable soul-searching the company acquired the privately-owned Amplia and its FAK inhibitor program (more on FAKs later).
Amplia was owned by parties including the now legendary Dr Chris Behrenbruch, Burns and Peter MacCallum Cancer Centre researcher Dr Mark Devlin (now an Amplia scientific adviser).
Initially, the program was the work of the Melbourne based, Federal Government-funded Cancer Therapeutics Cooperative Research Centre. While developed here, the rights resided with Cancer Research UK. But the organisation wasn’t actively developing it, so Burns and Behrenbruch re-claimed the tech.
Burns took over from Dr John Lambert as CEO in December 2022. Dr John had replaced Simon Wilkinson in June 2019. Burns has 30 years in drug discovery and development, including CEO positions at public and private companies.
Along the way, Behrenbruch resigned from Amplia’s board in 2020 to focus on Telix Pharmaceuticals – a sage decision given the radiotherapy outfit now has a market value approaching $9 billion.
Innate changed its name to Amplia shortly thereafter and bunkered down to focus on its current programs.
Amplia’s lead compound AMP-945 (narmafotinib) is a focal adhesion kinase (FAK) inhibitor.
Most cancer treatments are designed to attack tumours directly by either poisoning them, or starving them of nutrients. This is fine when it works, but tumours are cunning in that they mount a defensive response which blunts the effect of many cancer drugs.
It is hoped AMP-945 will suppress a bodily agent suspected of aiding and abetting the spread of tumors and fostering fibrosis. AMP-945 removes the protective shields, rendering the tumours more responsive to chemotherapy.
AMP-945 was discovered at the former Cancer Therapeutics Cooperative Research Centre, with the help of scientists from Monash Institute of Pharmaceutical Services and Peter MacCallum Cancer Centre, St Vincent’s Institute of Medical Research, the Walter and Eliza Hall Institute of Medical Research and the CSIRO.
A great team effort all round, guys and gals!
Dubbed Accent, Amplia’s clinical trial efforts centre on a phase 2a, two-phase open-label combination trial for advanced metastatic or non-resectable (inoperable) pancreatic cancer.
On December 12 Amplia disclosed more data from the study, which tests AMP-945 in combination with a standard-of-care generic gemcitabine and nab-paclitaxel (Abraxane).
Nine patients recorded a partial response, which means at least a 30% decrease in the overall size of tumour lesions, sustained for at least two months.
Given the trial has enrolled 26 patients to date, this makes for a 35% response rate, “significantly better than the 23% reported for the historical trial being used as the benchmark for this study.”
The median duration period on trial for the 26 patients was 172 days, a 47% improvement over the historic average of 117 days.
Currently 11 patients from the initial 26 enrolled remain on trial. This may sound like a lot of attrition, but bear in mind that pancreatic cancer is one of the most fatal cancers.
Recognising this, the primary endpoints for the trial (apart from safety) are the response rate and duration on trial, with the secondary endpoints of progression-free survival and overall survival (how long the patients live, no matter their condition or quality of life).
The company says recruitment of the final 24 patients is ahead of schedule, with 12 enrolled after recruitment re-opened in October.
Recruitment is expected to complete by the end of the March quarter.
The trial is being carried out at sites in Australia and South Korea. As for the latter, the company says the current political unrest there has not affected the study.
It should be stressed that with so many other cancer drugs, AMP-945 is not pitched at a pancreatic cancer cure – it’s all about buying more quality time for the patient.
In February 2024 the FDA approved a Folfirinox variant called Nalirifox, a cocktail of four drugs for metastatic pancreatic cancer patients, who have not received previous treatment.
Trials of Nalirifox showed an overall survival of 11.1 months, a statistically significant improvement over the 9.2-month overall survival with gemcitabine/Abraxane. “You don’t need to do much for the community to be enthusiastic about new developments,” Burns says.
Based on its animal studies to date Amplia hopes it can do better – and with less toxicity than the standard-of-care chemo.
“There’s very clear evidence from the literature that inhibiting FAK synergises with the activity of gemcitabine,” he says. “We know if we put those together, we are supercharging gemcitabine activity.”
Burns says pushing out the overall survival out from seven months to 12 months or beyond would be a “profound improvement” on the standard of care.
“If we could add four months or more that would be fantastic – patients could make it to their next Christmas, or their daughter’s wedding.”
Because pap/cervical smears do not pick up the condition, around 70 % of ovarian cancers are picked up in late stage and mortalities are high. “As with pancreatic cancer, ovarian cancer is highly fibrotic, it’s very difficult to treat and turns up quite late in testing,” Burns says.
In October 2023, Amplia presented pre-clinical ovarian cancer data to the American Association for Cancer Research special ovarian cancer pow-wow held in Boston. The mice model pertained to the highest grades of the disease, which account for 90 % of all ovarian cancer patients.
The data “clearly demonstrated” that narmafotinib improved tumour growth inhibition in chemotherapy-resistant ovarian cancer, relative to the standard-of-care, called niraparib.
The company is eying an investigator-initiated study, by which Amplia supplies the drug while another party funds the study and finds the patients. Burns is encouraged that the Boston-based Verastem Oncology received accelerated FDA approval for a combo FAK drug for ovarian cancer (defactinib).
However, Verastem is targeting a low-grade ovarian cancer (which affects about 10% of patients), while Amplia focuses on the remaining high-grade patients. Thus, the Verastem program validates the FAK approach whilst not being a competitor.
In November, Amplia finalised an underwritten rights issue, which alongside an institutional placement raised around $13 million at 11.5 cents apiece.
In May the raised $4.27 million in a rights offer, with most of the proceeds from both whip-‘rounds earmarked for the Accent trial.
The stock is well-supported institutionally with Platinum Investment Management, Pengana Capital and Acorn Capital all gracing the register.
Over the last 12 months, Amplia shares have ranged from a low of 6 cents on July 23, to a zenith of 17 cents exactly two months later.
In the post-Innate era, the stock peaked at 80 cents, in March 2018.
So far, the federal government’s ‘Made in Australia’ push has centred on solar panels and critical minerals, but should it be extended to drugs as well?
“Despite years of government funding and academic work, not many drugs have got to phase III and only two have been approved,” Burns says.
“Others developed by Australian companies were bought in or were natural products.”
If Burns and Amplia have their way, a third drug (for pancreatic cancer) will be proudly bearing the made – or technically, discovered – in Australia logo.
“The difference with this drug [compared with the myelofibrosis drug] is I want to drive it locally for as long as we possibly can and see more of the success come back to Australia.”
Patriotism aside, the unmet need is startling. In the US, 66,000 pancreatic cancer cases were diagnosed last year, with 50,000 deaths. The current cost of treatment in the US alone is US$6 billion and is estimated to grow to US$36 billion by 2036.
Disclosure: Dr Boreham is not a qualified medical practitioner and does not possess a doctorate of any sort. This column was proudly made in Australia.
Health & Biotech
Health & Biotech
Health & Biotech
