This article was originally published in Life Sciences Magazine. Read the full digital edition here.
B.C.’s life sciences sector is growing faster than other such clusters in the rest of Canada, and it is rapidly becoming a hub for what some are calling the fourth-generation of therapeutics.
That is not an empty buzz phrase. There really are distinct generations of scientific development.
Industry insiders tend to agree that the initial generation of medicines were small-molecule drugs – chemical-based compounds that could block signals, such as pain. Aspirin, created in the late 1800s, is one example of this kind of drug.
The next wave of drugs, they say, are “biologics,” or ones made from human organisms. Insulin, discovered in 1921, is one of those drugs.
Then there is some divergence among those in B.C.’s life sciences sector about whether antibody-based drugs should be in that second generation of medications, or a new third wave of therapeutics.
A consensus does emerge that a new generation of drugs is being developed that is in a different tier from all that has come before.
Executives, such as Aspect Biosystems CEO Tamer Mohamed, say this new evolution in drug-making is a significant evolution and is one where B.C. is excelling.
“At the highest level, there are three pillars [in the history of making therapeutics,]” he says. “Chemistry, then biology and then living systems.”
Mohamed’s company takes material from stem cells to create human tissue that can be implanted into patients to help their livers or pancreases function properly.
The concept is for surgeons to eventually operate on patients to insert credit-card-sized pieces of liver tissue under skin, or pancreas tissue in abdomens.
“The goal would be not necessarily to rebuild that organ, but to provide a remote functional tissue in another place in the body that’s essentially supplementing, or replacing, the missing function of the organ,” he tells BIV.
His said his goal is to start clinical trials within two years and have an approved drug therapy within the decade.
Mohamed’s 80-employee company is on a hiring spree thanks to a capital infusion earlier this year. He says he believes his company will have significantly more than 100 employees by the end of 2023.
Aspect’s capital comes from a pact with Denmark’s Novo Nordisk, announced in April. The partnership provides Aspect with US$75 million up front, and then milestone payments up to US$650 million for each of four products. That means that the company could generate US$2.6 billion from those milestone payments.
Another B.C. life sciences company involved in the cellular-therapy niche is Notch Therapeutics.
Its technology also starts by using stem cells but in the end aims to create off-the-shelf cell therapies that are accessible, less expensive and able to be produced at a large scale, its CEO, David Main, tells BIV.
Cell therapies use immune cells as drugs. Those who have cancer have cells that are not effectively fighting off cancer. Healthy people, in contrast, have immune cells able to fight cancer, Main says.
Notch’s science aims to create a therapy that can be matched to specific patients, and then provided to the patients via intravenous (IV) bags, much like how blood transfusions are conducted.
“We’re administering cells that act like little factories,” Main says. “The cells that we administer can release antibodies. They can release other kinds of chemicals, called cytokines. The cell itself becomes the drug, but it’s like a little drug factory, and it can do multiple things.”
Main says the exciting thing about new cellular therapies is how they are more complex than those in past generations of drugs.
Cures long ago were created to treat diseases that are simple to address, he says. The diseases that remain without cures are more complex and have multiple elements that need to be contemplated, he says.
Being able to administer immune cells that can provide a wide variety of benefits are therefore likely to be successful with the complex diseases, he adds.
His company landed US$85 million in Series A financing in February 2021 that was led by a private equity firm that was not named in press releases.
Given Notch’s board of directors, that company is likely Baker Brothers Investments. The funding round also included participation from pre-existing investors such as Allogene Therapeutics, Lumira Ventures and CCRM Enterprises Holdings Ltd. Other investors included Casdin Capital, Samsara BioCapital and Amplitude Ventures.
“That money was designed to last three to four years so we’re just now starting to think about the next financing,” Main says.
When Main joined Notch in mid-2020, he was its fourth employee. There are now 85 employees but the company is not aiming to recruit any more staff for the time being, he says.
Lipid nanoparticles are ‘revolutionizing medicine’
The B.C. life sciences sector’s biggest contribution to global science since the start of the pandemic is arguably in the lipid nanoparticle niche.
“Vancouver has led the world in the lipid-nanoparticles space for decades,” Farris LLP partner and life sciences lawyer James Hatton tells BIV.
“Pieter Cullis’ work at the University of British Columbia (UBC) has spun out the companies that have built the global lipid-nanoparticle business, delivered COVID-19 vaccines, and are now designing lipid nanoparticles for the targeted delivery of therapeutics for cancer and other diseases.”
Indeed, established researcher and UBC emeritus professor Cullis was honoured with prestigious awards to celebrate his contribution to helping Pfizer and BioNTech create a COVID-19 vaccine that was injected into more than a billion people, perhaps saving millions of lives.
He worked with Germany-based Katalin Kariko and U.S.-based Drew Weissman, and the trio won Canada’s Gairdner International Award, Vietnam’s VinFuture Grand Prize and Taiwan’s Tang Prize.
Combined those awards netted the three nearly US$5 million.
Kariko and Weissman’s expertise was in engineering messenger RNA to be the active ingredient in the vaccine, while Cullis’ role was to create the system for getting the vaccine’s active ingredient into human cells.
Lipid nanoparticles are essentially little bubbles that encase genetic material, cancer drugs, vaccine components or other items, and transport them to specific cells without degrading in the process.
The method is somewhat like a security team transporting an important dignitary through a crowd of rowdy protesters to a key destination.
“What we are doing is essentially delivering nucleic-acid based drugs, RNA and DNA, into the body and getting them into cells where they can actually have a therapeutic effect,” Cullis tells BIV.
Without being able to transport the essential material into cells, the vaccines would not work, he adds.
Cullis is widely revered in the Canadian life sciences industry, and the 77-year-old has a long history of working in his field.
He co-founded his first company, Lipex Biomembranes, in 1985. Through the years he also co-founded Canadian Liposome Co., Inex Pharmaceuticals and Acuitas Therapeutics.
Acuitas remains active and continues to innovate. Its president and CEO, Thomas Madden, was one of EY’s 10 Canadian national winners in its 2023 Entrepreneur of the Year program.
“Lipid nanoparticles are revolutionizing medicine,” Cullis says. “The potential is unbelievable.”
He predicts that the future of lipid nanoparticles will dwarf the global impact of the COVID-19 vaccines that the technology enabled.
“In addition to a myriad of vaccine applications, the diseases being treated range from cancer to heart disease to many rare diseases,” he says.
He then sent BIV a table with 20 lipid-nanoparticle therapeutics that are in clinical trials around the world.
Radiopharmaceuticals are another next-generation therapy
The next generation of therapies includes more than just tissue printing, cellular therapies and lipid nanoparticles. It also includes radiopharmaceuticals.
Amplitude venture partner Nancy Harrison knows lipid nanoparticles and radiotherapeutics technologies well.
She invested in technology that used larger lipids in the first decade of this century, back when she ran Ventures West’s life sciences practice and her firm helped capitalize Celator Technologies.
She says she thinks of lipids as being somewhat like what happens when someone puts oil in water and shakes up the container. The result is little oil vessels that protect what is inside, she says.
Lipid nanoparticles, such as the ones that Cullis engineered to be able to enter specific cells, are like this, but much smaller than full lipids.
“Radiopharmaceuticals is not like that,” says Harrison, who is on the board of directors at the radiopharmaceutical company Abdera Therapeutics.
Radiopharmaceuticals do not encapsulate material the way lipid nanoparticles do, she says.
“You have to have a targeting vector. In our case, at Abdera, that is a portion of an antibody. Then you have to have a linker, and a chelator, to be able to attach it to the radioisotope,” says Harrison.
That means that radiopharmaceuticals have a four-piece mechanism that scientists have engineered to deliver radiation in a targeted way.
“It is like it has like a tag on it, which recognizes the tag on a cancer cell,” Harrison says. “It docks onto a cancer cell and it deposits its radio pharm.”
Amplitude in the spring of 2021 co-led a financing round worth an undisclosed amount that was in the tens of millions of dollars, she says.
In April 2023, Abdera announced that it had raised a total of US$142 million.
Alpha-9 Theranostics is another B.C.-based radiopharmaceutical company that is on the cusp of innovation.
Its chair, Simon Pimstone, explains that while Abdera uses an antibody in its treatments, Alpha-9 uses a peptide, or a protein molecule.
“The similarity is in the targeting of tumour cells more selectively,” Pimstone said. “The difference is in how the technology delivers to the tumour.”
Alpha-9’s technology similarly has what the company calls “scaffolds,” which are comprised of four components: A binder, a linker a chelator and a radioisotope.
Pimstone estimates that Alpha-9 has about 20 employees and he says that the company is hiring and is likely to have more than 30 staff by the end of the year.
At the end of 2022, Alpha-9 raised US$75 million in a Series B round led by Nextech Invest, with participation from Frazier Life Sciences, Samsara BioCapital and Quark Venture in addition to existing investors Longitude Capital and BVF Partners.
B.C.’s life sciences sector growth outpaces other hubs
The companies pushing the innovation envelope in the fourth generation of drug-making are part of B.C.’s larger life-sciences ecosystem and helping it become stronger.
“We are competing for talent,” Life Sciences BC CEO Wendy Hurlburt tells BIV.
“We are competing for capital.”
Recent corporate success is important because the province needs anchor companies and growing life sciences niches to entice people to move to B.C. to work in the industry, she says.
The larger the ecosystem is, the more those people will realize that they have multiple options if they decide to embark on a career in the field in the province, she adds.
A profile of the life sciences sector in the province, which Life Sciences BC released in May, says that between 2018 and 2021, the industry grew faster than the overall B.C. economy.
Many life sciences companies have no employees because they are headed by academic researchers with other day jobs.
Excluding those companies, B.C. had 1,338 life sciences companies in 2021, up 26.5 per cent from 2018 – the fastest growth rate in Canada.
That compares with Ontario’s 19.3-per-cent growth rate for life sciences ventures to 3,192 companies in 2021.
Canada’s second largest life-sciences hub is Quebec, where there were 1,361 companies in that sector in 2021, up a comparatively small 10.5 per cent from 2018.
“The gap with Quebec is very much diminishing,” Hurlburt says.
This article was originally published in Life Sciences Magazine. Read the full digital edition here.