All posts by Ian Lyall

A Mission to Make Cancer Treatment More Effective With Fewer Side Effects

Cancer is an oftentimes fatal condition that has touched most people’s lives directly or indirectly. And while there are treatments available, depending on the type of cancer in question and how advanced it is, much of the time they do not work.

Traditional treatments such as radiotherapy and chemotherapy are well understood. When administered in a timely manner for an amenable form of the disease, they perform credibly. But they can be tough on the body and leave lingering side effects.

Beyond this, efficacy can be patchy. Take immunotherapy, now seen as the gold standard for cancer treatment – response rates range between 15% and 35%, depending on the drug and tumour type. Toxicity is also a problem in around 20% of patients.

The broader research into drug efficacy paints a similar picture across different classes of treatment. The problem is not with medication per se. It lies with the nature of cancer itself and the patient’s immune system.

Cancer is not a single defined disease, but a cluster of them that have learned how to fool the human immune system. Even within cancers of a similar type, presentation can vary in ways almost as unique as the DNA that defines us.

As researchers have deepened their understanding of cancer, the idea of a silver bullet treatment has faded. Instead, physicians now favour a more nuanced approach, although we have yet to see truly personalized cancer medicine to date.

Halifax-based Sona Nanotech (CSE:SONA) believes it may have uncovered a nanotech-based approach that could have broader application than many current frontline treatments, working across a range of solid tumours to kill them by leveraging the immune system’s natural defences.

It is also highly targeted in its administration, avoiding the collateral damage that traditional chemotherapies and radiotherapies inflict on healthy tissue.

Sona Nanotech’s advance emerged from an idea conceived by Dr. Kulbir Singh and Dr. Gerrard Marangoni of St. Francis Xavier University in Nova Scotia. It centres on gold nanorods, a technology ripe with potential but historically fraught with drawbacks.

A key impediment has been overcome through extensive R&D work at Sona, led by Singh, which now forms the core intellectual property of the business: the nanorods have been rendered biocompatible, which makes them a very promising candidate for in-human use.

“Lots of people make nanoparticles, and lots of people make nanorods. We’re the only ones who make nanorods at scale that are biocompatible, so they’re ideally suited to what we want to do with them,” says Sona Nanotech Chief Executive Officer David Regan.

As part of a process called targeted hyperthermia therapy (THT), a solution containing hundreds of billions of these tiny particles, undetectable under a regular lab microscope, is injected directly into a solid tumour.

A near-infrared light (NIR) source then activates the particles, heating the tumour from within. Due to its non-ionizing nature, NIR light is harmless to human tissue and can penetrate the skin. For example, an oximeter that is pressed to the finger for oxygen testing uses NIR light.

The precision and temperature control are such that only the malignant area is affected, sparing surrounding healthy tissue.

“Our current ways of killing cancer are brutish in terms you, and even I, can’t comprehend,” says Regan. “Chemo is, of course, but even radiation does a lot of damage, and surgery has huge risks.”

“The idea behind this is we heat the tumour gently from the inside out, and we control the temperature very carefully at around 45°C, in which case you’re only harming cancer cells, not healthy cells, because cancer cells have a lower tolerance for the heat they can withstand.”

In animal models, this approach not only shrinks tumours and kills cancer cells but also stimulates the immune system by presenting tumour antigens (distress-signalling biomolecules) to the patient’s immune system, which otherwise would be kept hidden by the cancer tumour.

This opens the door to treating so-called “cold” tumours that are not recognized by the body’s disease-fighting T cells.

These cold tumours are also where all current immunotherapies, such as Merck’s blockbuster Keytruda, struggle.

Another potential strength of Sona’s technology is its ability to carry immunotherapy drug molecules on the tiny nanoparticles. This raises the prospect of further enhancement of the technology.

This approach fits with one of the current trends in cancer research: antibody-drug conjugates that bring together therapies to create more effective treatments.

Regan also points to its potential use as a neoadjuvant therapy, a treatment given before a primary treatment that enhances the efficacy of drugs.

All of this is promising in theory. But how far along the research and development curve has Sona progressed?

The company is on the cusp of a first-in-human feasibility study, which may bring it to the attention of the industry’s key opinion leaders.

Before reaching this point, significant research was conducted, testing the therapy on melanoma, breast, and colorectal cancers. Mice were given a single injection of gold nanorods, which were then heated using a near-infrared laser. This gentle heat destroyed cancer cells and exposed hidden markers that triggered an immune response.

In colorectal and breast cancer models, combining THT with leading immunotherapy drugs led to near-complete tumour elimination, whereas the drugs alone had little effect. In the melanoma model, THT produced a rare abscopal effect: even tumours not directly treated began to shrink.

Gene activity tests confirmed that THT strongly activated the immune system, but without the toxicity often associated with other treatments.

The next step is a first-in-human deployment of the technology in around 10 people with advanced melanoma that has resisted traditional treatment. The aim is to demonstrate safety and immune-activating potential. Skin tumours are to be chosen partly for practical reasons, as they are accessible for injection and imaging.

While melanoma is typically immunogenically “hot” and responsive to immunotherapy, some late-stage melanomas can become “cold” due to immune evasion mechanisms, leading to poor responses to current drugs.

The study’s primary endpoint is safety. Researchers will monitor how well patients tolerate two applications of THT delivered a week apart. Secondary and exploratory endpoints will assess tumour size and immune system activity, including changes in immune cell populations and cytokine levels.

Top-line results could emerge as early as mid to late summer, according to Regan. In the meantime, Sona will present a poster at the American Society of Clinical Oncology’s annual meeting in Chicago. Additional peer-reviewed papers will follow its debut publication in the journal “Frontiers in Immunology,” which has already drawn interest from researchers and clinicians.

Regan and his team are also looking to expand the pipeline of uses for the biocompatible gold nanorod platform. This will not only boost Sona’s research reputation but also enhance its appeal to potential collaboration partners.

There is also the issue of regulatory pathway. Traditional drugs undergo a three-stage approval process that is both onerous and expensive, often requiring funding from a large pharmaceutical partner.

Given that Sona’s technology is a medical device, it remains to be seen whether it will be eligible for the U.S. Food and Drug Administration’s 510(k) route, a potentially expedited and cost-effective path to market. That decision point will not come until feasibility study results are available and there is clarity on whether the approach qualifies as a device.

In a field where new cancer treatments can cost hundreds of millions of development dollars only to fail at an intermediate hurdle, Sona has so far progressed on a relative shoestring. It is expected that the $3.1 million friends-and-family funding round completed in the fall of 2024 will carry the company through its feasibility study.

If successful, that could provide a platform to attract further investment. The next step would be a pilot study. “We’re already well down the road on setting that up, and we think that would be very well received,” says Regan.

“People think of clinical trials as being tens of millions of dollars. We have a path that is a fraction of that, which we think could be very exciting. And most importantly, we’re looking to accelerate this process.”

This story was featured in Canadian Securities Exchange Magazine.

Learn more about Sona Nanotech at https://www.sonanano.com/.

Adaptability the watchword for Pasinex Resources

This story was originally published at www.proactiveinvestors.com on February 23, 2016 and featured in The CSE Quarterly.

“It is not the strongest of the species that survives, nor the most intelligent that survives. It is the one that is most adaptable to change.”

The quote above is often wrongly attributed to Charles Darwin. But it does, I am told, summarise eloquently his seminal work ‘On The Origin of Species’.

It might equally be applied, in stock market terms at least, to the junior miners that have survived the recession that has decimated the industry.

Adaptability has been the watchword for Pasinex Resources (CSE:PSE), joint owner of the Pinargozu Mine in Turkey’s Adana Province.

It and local partner Akmetal set out in 2012 to compile a significant zinc resource – in the order 10 million tonnes – from claims staked around the historic Horzum Mine.

Pretty soon the cold harsh realities of life caught up with the companies, which luckily enough had a plan B to fall back on.

This was to mine high grade direct shipping quality zinc, crush it and send it off for export.

In a time where the capital markets have been shut to juniors such as Pasinex, the Pinargozu operation has provided manna from heaven – or at least a welcome source of working capital.

To date 16,000 tonnes of zinc material grading around 35% have been unearthed from this carbonate replacement-style deposit.

The extraction costs are currently around US$140-150 per tonne, while Pasinex and its partner receive “well in excess of US$200” a tonne for what they ship from Pinargozu.

With 120 people on-site, production is ramping up from 25-30 tonnes a day to around 60 tonnes.

This equates to output of around 20,000 tonnes a year. As capacity grows, so costs ought to fall.

Exploration work – the company carried out 12,000 metres of drilling last year – is aimed at finding and chasing high grade veins and delineating enough ore to keep the hoppers full.

“There was an old small-scale miner who went in and dug some high-grade zinc at very small tonnage,” says Pasinex chief executive Steve Williams, explaining how Pinargozu came into being.

“But that was clearly an indication that there was more high-grade zinc and that proved to be the case.

“We went in and started exploration and drilling. We found some very high-grade material and quickly realised there was the opportunity to get in and start mining.

“The horrible situation we have in the market and the terrible situation the exploration industry finds itself in was very much a driver for this.”

Located in the Taurus Mountains, Pinargozu is thought to be the sweet spot for a much larger zinc deposit.

In fact the area, which hasn’t been extensively explored using modern techniques, is itself a small part of a belt that extends into Iran and Afghanistan.

In a different world, one where the capital markets were open, share prices were buoyant and there was ready demand for new zinc projects, the Pasinex-Akmetal ground would have been comprehensively explored and its potential tested.

In the current environment compiling an independent resource estimate is a waste of time and money. When the wind changes Pasinex will adapt its plan of attack, says Williams.

In the meantime, it will look at methods to expand output a little further.

The commodity markets haven’t been especially kind to Pasinex. The price of zinc has come down to 77 cents per pound from around US$1.10 at its height last year.

Pasinex’s budgeting is done at 67 cents, which is more conservative than other operators out there.

But like its rivals it is operationally geared to an uptick in the price of the metal.

This could happen if the older, less economic mines continue to be shuttered. Glencore recently turn the spigots down – but then as Williams points out it could very easily push output up when the market conditions become a little more benign.

Demand for zinc might start nudging up in the latter part of 2016, but don’t bet on a recovery in the mining sector this year, says the Pasinex boss.

“Zinc I think will be one of the first metals to move; capacity is being removed.

“The [equity] markets? Well, I’m really not so confident. The big miners still have some big news to shake out. That will keep pressure on share prices.”

In Turkey foreign companies almost always take a partner. Pasinex’s Williams said he’s has had some minor differences of opinion, but the experience with Akmetal has been an “overwhelmingly positive” one.

The Turkish miner has been able to interact more astutely with the politicians than a foreign company might, while it has also been active and effective on the ground with the local population.

This expertise was used to good effect to fully permit and bring Pinargozu into production in about two years.

Practically, Akmetal had the plant and equipment needed to mine the deposit.

The country itself is caught on the fringes geographically but in the middle politically of one of the most volatile regions in the world.

Millions of Syrian refugees have flooded over the border since the hostilities began, and Turkey’s major cities are on red alert after a series of bombings.

But while Adana is near to the border, the mountain mine of Pinargozu remains isolated from what’s going on around it.

“We are in the northern part of the province so it is business as usual and we don’t see anything,” says Williams.

“But the country as a whole has been influenced by the conflict and in particular the refugee crisis.

“Turkey is a strong country, but in a difficult area of the world.”

Pasinex is an oddity on any exchange – a revenue generating mining junior that is able to survive under its own steam.

Is this recognised by the market? Definitely not at the moment. Neither is the long term potential of its zinc assets, or the copper property we haven’t even touched on.

But this is the harsh reality of life for the likes of Pasinex.

“This last three years have been very tough for us as it has for everybody,” says Williams.

“I think doing what we have been doing is the right thing for this moment in time.

“At some point we’ll get recognition for what we have done and the assets we have.”

Learn more about Pasinex at http://pasinex.com/ and on the CSE website at http://thecse.com/en/listings/mining/pasinex-resources-limited