• Immunotherapy is becoming the new gold standard in treating certain cancers
  • Stockhead talks to Immutep CEO Mark Voigt about Immutep’s LAG-3 programs
  •  Listed: Cancer immunotherapy stocks on the ASX.

Immunotherapy has changed cancer treatment

For many decades, chemotherapy and surgery have been the gold standard in treating certain types of cancers.

But over the last few years, immunotherapy has emerged as a standard pillar, changing the way cancer patients are being treated.

Instead of using toxic drugs, cancer immunotherapy (sometimes called immune-oncology) stimulates the patient’s own immune system to kill the cancer cells by using the immune system’s natural ability to fight the disease.

These therapies have now been integrated into standard of care regimens for many types of cancers, including melanoma, non-small cell lung cancer, and triple-negative breast cancer among others.

Immutep (ASX:IMM) is one of the leading ASX-listed biotechs that focus in this space.

The company’s CEO, Marc Voigt, explained to Stockhead that immune-oncology has only really been around in the last decade.

“Immune-oncology came into play clinically in 2011, based on the approval of a drug of a certain immune checkpoint called CTLA-4,” said Voigt.

“They were then introduced to the market into day-to-day clinical care only in 2013-2014.”

According to GrandView Research, the market for immune-oncology has grown exponentially since then. In 2020, the market size was estimated at US$107 billion, but this could increase to US$127 billion by 2026.

How cancer immunotherapy works

There are several classes of immunotherapies available, but most of the clinical trials performed have focused on two –  CAR-T and immune checkpoint inhibitors.

Chimeric antigen receptor, or CAR-T therapy, is a form of cellular therapy that mostly treats certain blood cancers.

This is where the immune system cells called T-cells are taken from a patient, supercharged in the laboratory, and injected back to the patient to target and kill the patient’s cancer cells.

Then there’s the immune checkpoint inhibitors, which is another type of immunotherapy.

Immune checkpoints are proteins that live on cell surfaces that help to regulate our immune system response.

They effectively keep T-cells inactive, in an “off” state, until they are needed, which keeps the T-cells from harming normal cells.

Natural killer cells attacking a cancer cell. Picture: Getty

Cancer cells often take advantage of these checkpoints to switch the T-cells off, keeping the cancer cells from being killed.

Immune checkpoint inhibitors are drugs that are being developed by companies like Immutep to block these checkpoints – freeing the T-cells to attack the cancer.

“There has been a massive paradigm shift in cancer treatment, and immunotherapy is now well established. In many indications, it’s even become the gold standard,” said Voigt.

“Your own little T-cells in your body can kill one kilo of lung tumour, for instance.”

“In a variety of different indications, combination treatments (with chemo or other drugs) often achieve the best outcome for the patients, and that’s probably the established way forward,” he added.

The most well-known inhibitor drug in the market is Keytruda, a brand name for pembrolizumab developed by Merck & Co which targets the PD-1 checkpoint.

While PD-1 and CTLA-4 have been widely studied, experimental therapeutic agents targeting the LAG-3 immune checkpoint are now being tested in clinical trials for various human cancers.

Breakout year for LAG-3?

“There has always been a big question since 2013-2014, as to what will be the next immune checkpoint,” said Voigt.

Voigt says that LAG-3 has now filled that void, and that Immutep’s focus on LAG-3 has made the company one of the global leaders in the field.

“We are the global leader in terms of LAG-3, and are the only LAG-3 pure play. We have more programs around LAG-3 than anyone else,” he said.

Studies have shown that repeated exposure to tumour antigens causes an increase in the expression of LAG-3, which in turn leads to T-cell exhaustion and suppression of its anti-tumour activities.

Immutep’s lead asset, Efti, is an antigen-presenting cell (APC) activator used to inhibit LAG-3 activities, increasing the T-cells’ response to tumors.

In the clinic, Efti has been proven to induce sustained immune responses in cancer patients when used at low doses.

“Immutep is the only company globally doing this so-called APC activator,” said Voigt.

“What this means is that Efti is activating the generals of the immune system, which direct other cells and provide them with the information on which cells to attack.

“It also creates more of this T-cells, so Efti effectively provides the immune system with a broader push compared to some of the other standard treatments.”

Voigt believes that 2022 could be the breakout year for LAG-3 research, following the first ever FDA approval of a LAG-3-blocking antibody combination drug.

In March, the FDA approved Opdualag, a drug developed by Bristol-Myers Squibb (BMS) that combines nivolumab with relatlimab, the immune checkpoint inhibitor for LAG-3.

“This will open up a lot of doors for Immutep, as we are working now on the validated basis,” explained Voigt.

“This FDA approval will also significantly increase the market’s awareness of our story, and for our drug.”

Immutep is set to deliver a presentation to the ASCO 2022’s Trial-in-Progress Poster event on June 3.

The company will outline the results of its Phase IIb TACTI-003 trial, which is a study of Efti in combination with pembrolizumab (Keytruda).

Tips on picking biotech stocks

There is a handful of immune-oncology stocks on the ASX, which are at various stages of clinical trials.

Voigt has given Stockhead readers some words of advice when investing in biotech companies.

“I believe it’s important to look very closely at each company, because often it’s more difficult to understand the science,” he said.

“How far away is the biotech’s product from the market? Will it take years and years to commercialise?”

“Does the company have big pharma collaborations like Immutep, which means it has been exposed to multiple due diligence?” he added.

Immune-oncology stocks on the ASX

These are the companies that focus on cancer immunotherapy on the ASX.

Imugene (ASX:IMU)

Imugene is building three novel platforms – onCARlytics , CF22 oncolytic virus, and B-cell immunotherapy.

In the B-cell immunotherapy pipeline, Imugene is developing two drugs, HERVaxx and PD1-Vaxx.

HER-Vaxx is designed to treat tumours that over-express the HER-2/neu receptor, such as gastric, breast, ovarian, lung, and pancreatic cancers.

The company has just received an ethics approval to start Phase 2 clinical trial of HERVaxx, called nextHERIZON.

It also has an agreement with Merck to study HER-Vaxx in combination with Merck’s anti-PD-1 therapy, pembrolizumab (Keytruda).

PD1-Vaxx meanwhile is a B-cell immuno-therapy which aims to induce the body to produce polyclonal antibodies that block PD-1 signalling.

It has an anticancer effect similar to Keytruda, Opdivo and the other immune checkpoint inhibitors that are already in the market.


Imugene share price today:


Ad Alta (ASX:AD1)

Ad Alta is using its proprietary i-body technology platform to treat fibrotic diseases.

An i-body is a unique human protein that combines the advantages of small molecules and antibodies in one powerful treatment.

Its lead asset, AD-214, is being currently being studied in a Phase 1 clinical trial.

In August last year, AdAlta flagged its intention to enter the CAR-T space, signing a collaboration agreement with Carina Biotech.

The two companies agreed to develop next-generation i-body enabled CAR-T cells, with the potential to bring CAR-T cell therapy to treat a far greater range of cancers outside of blood cancers.


Ad Alta share price today:


Chimeric Therapeutics (ASX:CHM)

Chimeric has built a portfolio of CAR-T cancer therapies with a focus on glioblastoma.

The company says that while traditional drug development focuses on delaying disease progression in cancer, Chimeric is focusing on finding a cure.

Its CORE-NK platform cells are made by activating and expanding natural killer cells to make them more active and robust.

The company says CORE-NK is a transformative platform technology enabling the development of multiple other next generation, off the shelf NK and CAR-NK products.

It’s currently being studied in a Phase 1 clinical trial in both blood cancers and solid tumours.


Chimeric share price today:


Patrys (ASX:PAB)

Patrys’ deoxymab platform is based on unique, proprietary antibodies for the treatments of a wide range of cancer types.

This includes gliomas (brain cancer), breast, colon, pancreatic, ovarian and prostate cancer.

Studies have shown that deoxymab is capable of penetrating live cell nuclei, binding to DNA directly, and inhibiting the DNA repair process.


Patrys share price today:


Amplia Therapeutics (ASX:ATX)

Amplia is a clinical-stage company developing small molecule inhibitors of Focal Adhesion Kinase (FAK) for the treatment of cancer and fibrotic diseases.

The company has just received the final ethics clearance to conduct a Phase II clinical trial of its FAK inhibitor, AMP945.

Earlier results have shown that the addition of AMP945 to standard care gemcitabine/Abraxane chemotherapy regimen increased survival rates in an animal model by 33%.


Amplia share price today: