Snake venom is probably not the first thing that springs to mind when thinking about treatments or therapies, but the potential biotechnological and biomedical applications of animal venom components are actually widely recognized in scientific research. Now, Dublin-based startup Celtic Biotech is harnessing the potential of snake venom in an attempt to come up with a novel treatment option for people with cancer.
There are more than 100,000 venomous animal species that have been identified worldwide, with each one capable of producing venoms that often contain up to 100 different molecules.
These venoms are composed of different complex chemical mixtures containing pharmacologically active components, including proteins, peptides, and enzymes that have specific biological activities. Additionally, despite their name, most toxins are not actually toxic, meaning they can be used for therapeutic applications.
Celtic Biotech is making use of these beneficial therapeutic applications, developing therapies sourced from specialized receptor-binding proteins found in snake venoms, with the aim of making a viable and potentially curative treatment option for cancer patients with late-stage aggressive tumors.
Co-founded by brothers Paul Reid, who is also chief executive officer (CEO) of the company, and John Reid, who is chief operating officer (COO), the company has a lead candidate, CB-24, which has been isolated from the venom of a South American rattlesnake called Crotalus durissus terrificus, and could be a promising therapy for the treatment of solid tumors and cancers.
Celtic Biotech’s CB-24: a promising snake venom-based cancer therapy
Observed to be highly toxic to various tumor cell lines in pre-clinical and early clinical studies, CB-24 is created from crotoxin, a heterodimeric cytotoxic phospholipase complex protein that has an inbuilt targeting mechanism and selectivity for tumor cells.
The therapy contains two subunits: A and B. “Once injected into the body via infusion pump, the A subunit actively and selectively locates malignant cells while bypassing healthy cells. Once cancerous cells are located, it locks on and releases its destructive B subunit,” explained Paul.
The B subunit then attacks the cancer cell surfaces. By disrupting the surfaces, it allows for the influx of calcium ions, which activates the intracellular phospholipases that release arachidonic acid and protein kinase C enzymes to destroy the cancer cells at an accelerated rate.
Paul explained that CB-24-induced cytotoxic effects appear to be highly active in cell lines that express a high density of epidermal growth factor receptor (EGFR) – a protein on cells that helps them grown – which suggests that EGFR could be a surrogate marker for efficacy.
Furthermore, anti-tumor efficacy in vivo, with daily administration of CB-24, has been demonstrated in Lewis lung carcinoma, with an 83% growth inhibition, and in MX-1 human mammary carcinoma, with a 69% growth inhibition. However, a lower activity (44% growth inhibition) was observed with HL-60 leukemia cells, which Paul said suggests that CB-24 may have a certain specificity towards solid tumors.
Since these pre-clinical studies, Celtic Biotech has now advanced the snake venom-based cancer therapy into phase 1 human trials. The results were presented at the American Association for Cancer Research (AACR) annual exposition in Chicago in 2018 for innovative new cancer therapies.
“Our trials so far have exceeded expectations. The clinicians are very pleased with the safety profile of CB-24 using our innovative protocol and the side effect profile has been exemplary. In addition, whereas phase 1 studies are usually designed to establish safety only, we have already seen some clinical responses in patients. Further, the remarkable analgesic properties of the drug were also reported during trials,” said Paul.
Snake venom: a novel approach to cancer treatment?
Using venom for therapeutics is not necessarily a new idea; in fact, snake venoms have been used as medical tools for thousands of years, particularly in traditional Chinese medicine.
John explained that venoms were introduced into western medicine in the mid 1800s: “…in the late 1800s, Stypven, made from Russell’s viper venom, was a product made in the U.K. to stop bleeding following dental extractions. There was a revival in the use of snake venoms to treat illness in the early 1900s and, by the 1940s, several venom products were FDA-approved injectable drugs.”
But, John said, despite seemingly falling out of favor after the 1960s – probably because it was believed that synthetic pharmaceutical drugs would be more effective – there is now a broad body of research in the area of venom peptides for therapeutic use in humans. “Even research into the research!” said John.
Plus, other biotech companies are also developing venom-based therapies for various indications, especially as companies look to grow innovative pipelines and patients seek more natural therapies, commented John.
But, as far as he knows, Celtic Biotech is one of the only – if not, the only – company with a snake venom-based product currently in clinical trials specifically for the treatment of cancer, meaning the company has a unique proposition in its development of CB-24.
Celtic Biotech: “Not so much a startup, as a restart”
Celtic Biotech was actually officially founded in October 2003, but things didn’t quite go to plan back then for the company.
“Paul was already involved for several years in the U.S. developing therapeutics derived from snake venoms for applications in pain and diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS),” explained John.
“Whilst trying to find something that might help some friends we knew that were stricken with late-stage cancer, he came across a snake venom peptide that had shown some real potential both in-vitro, in-vivo, and had some success in early human trials in South America. To cut a long story short, the development had stalled for various reasons.”
It’s for this reason that John referred to the company as more of a ‘restart’ than a ‘startup’.
Future plans for Celtic Biotech
And, it is fair to say that Celtic Biotech has very much been resurrected, after a pretty successful year. “In terms of validation and support for our development programme and business plan, we received Enterprise Ireland Client HPSU designation September 2022,” said John.
“In June this year we were awarded the EU European Innovation Council (EIC) Accelerator €2.5 million ($2.7 million) grant, with EU equity blended finance of €7.5 million ($8 million) being an option in 24 months time. In July we were successful in the European Institute of Innovation & Technology (EIT) Health Catapult competition, emerging out of the Ireland/UK regional finals, to qualify for the European semi-finals in 2024.”
So, what are the next steps now for Celtic Biotech after this recent success?
Well, Paul said the immediate focus is growing the company’s team – which currently includes a world class scientific advisory board, with top oncologists from France and Ireland, as well as one of the foremost academics in the field of neurotoxins – and completing phase 1 clinical trials.
Thereafter, the company wants to progress CB-24 through the required efficacy studies towards regulatory and marketing approvals, as well as continue its pre-clinical research into the rest of its pipeline candidates, which Paul said also have “extraordinary potential” for anti-cancer and anti-inflammatory therapeutic applications.
Ultimately, Paul believes that snake venom really does have the potential to benefit patients suffering from cancer and other illnesses all around the world.
“As a result of developing a strong expertise in this area, I now have a conviction that we can revive the use of these natural therapeutic peptides for the benefit of thousands, if not millions, of patients suffering from illnesses as diverse as acute and chronic pain to lethal cancers and pandemic viral infections,” he said.
This content was originally published here.
