The Celtic Biotech logo is based a combination of three symbols. The staff with the snake has long been a symbol of medicine and the medical profession. It originates from the story of Asclepius, who was revered by the ancient Greeks as a god of healing and whose cult involved the use of snakes. The Celts also revered the snake, traditionally associated with healing, regeneration and rebirth. Many Celtic healers appear with snakes, often associated with water, rivers and curative spirits. The serpent represents the cyclic nature of life due to the annual shedding of its skin. It is a symbol of rebirth, shedding its old skin and re-emerging in the spring from the winter's hibernation, seemingly immortal. The Celtic knot also symbolises the cyclic nature of life with its symbolic pattern of a looped knot that has no start or finish. The looped pattern goes on infinitely, symbolising the eternity of life.
Can you spot the 3rd symbol?
Celtic Biotech is researching therapeutic components of venoms from the South American rattlesnake Crotalus Durissus and it’s sub-species. The Company is also examining the combination of these protein components with proteins from cobra venom, in particular cardiotoxin. These therapies are elaborated on further in the Pipeline Section of the website.
CB-24 is a nicotinic antagonist that can attach to several subtypes of nicotinic receptors. It is reported that alpha nicotinic receptors are highly expressed on a variety of malignant cell types (Pucci et al., Frontiers in Cellular Science. 2022), being enhanced due to remodelling of cellular membranes in malignant cells to include more negatively charged phospholipids such as phosphatidylserine (Szlasa et al., Bioenerg Biomembr. 2020). It has been well established that nicotine and nicotine-derived nitrosamines have been identified as the major and potent carcinogens. Upon binding of CB-24 to its receptor the PLA2 B subunit is released and attracted by the more negative membrane surface on the malignant cells, initiates its enzymatic action to digest the membrane releasing palmitate and arachidonic acid (Kattah et al., Toxicon 2002). The membrane is compromised and there is an influx of Ca2+ further activating L-type Ca2+ channels. Malignant cells have a significantly poorer membrane repair capacity compared to normal cells increasing their sensitivity to this form of attack (Frandsen et al., J Membrane Biol, 2016). Elevation of Ca2+ activates intracellular PLAs that further generate arachidonic acid triggering an intracellular cascade resulting in the synthesis of anti-apoptotic prostaglandins and lipoxygenase metabolism (Snider et al., PNAS, 1984) to produce LXA4 and its analogue 15-epi-LXA4 (Brigatte et al., Mediators Inflamm, 2016). Arachidonic acid causes apoptosis exclusively through the mitochondrial pathway which is preceded by permeability transitioning pore opening, cytochrome c release, and cleavage of caspase 9 and 3 LXA4 and its analogue 15-epi-LXA4 are potent immunomodulators that can also suppress tumour proliferation and modulate immune cells through formyl peptide receptors: a secondary and useful effect of CB-24.
The drugs, Crotoxin and CTC-310, possess several desirable properties as therapeutics:
For clinical trial summaries, please see our webpage on Clinical Trials.
CB24 (Crotoxin) is the lead drug candidate for Celtic Biotech. It has been employed alone and in combination with Cardiotoxin. Both products have been employed in human cancer treatments.
Of 72 patients clinically treated to date 31 (43%) achieved a therapeutic benefit with 10 having stabilised disease (SD), 13 a partial response (PR) and 8 achieved remission (R), i.e. no disease detected. Diseases with recorded responses (SD, PR or R) include; breast, pancreatic, adenocarcinoma, liposarcoma, mesothelioma, fusocellular sarcoma, glioma, NSCLC, cervical, ovarian, rectal, squamous cell, chordoma, larynx, thyroid, fibrosarcoma, malignant histiocytoma, and prostate (this is not to say that all patients with these diseases had responses and further clinical trials are required to confirm early indications and identify optimum treatment protocols).
However, these results are remarkable for patients who have serious advanced disease and having failed pre-treatment with approved therapies. It is further remarkable that the dosage regime for Crotoxin has yet to be optimised (with patients in the Celtic Biotech trials so far receiving a low therapeutic dosage over a very short time span. This conservative approach was designed to confirm i.v. therapeutic levels in an escalating protocol with patient safety utmost in mind). The Company's planned Phase I part 3 will provide increased dosage over a longer treatment period with a larger cohort of patients recruited.
The maximum tolerated dose (MTD) is not yet established. The purpose of the planned Phase I part 3 is to identify exactly this before moving on to Phase II efficacy trials. So far patients in Celtic Biotech trials have had few drug related adverse events (only one serious adverse event (SAE) was reported during Phase I Part 2. This may also have been due to prior treatments the patient had. The patient responded to treatment.
The Company’s lead compound has indicated therapeutic action against a variety of solid tumours, lung cancer among them. Due to the large unmet need in the lung cancer therapeutic field the Company deems it prudent to initially target this patient group.
Facts about lung cancer:
In 2020, lung cancer occurred in 2.2 million people and resulted in 1.8 million deaths globally. It is the most common cause of cancer-related death. According to data provided by the US National Cancer Institute, the median age at diagnosis of lung cancer in the US is 70 years, and the median age at death is 72 years.
Lung cancer recently surpassed heart disease as the leading cause of smoking-related mortality. Most lung carcinomas are diagnosed at an advanced stage, conferring a poor prognosis. Despite 25 years of intense R&D, patient five-year survival rates have failed to improve within the most common form of lung cancer, Non-Small Cell Lung Cancer (NSCLC).
For these reasons lung cancer will be a prime target of the Company's research. However any disease type in which the company products indicate beneficial activity will be supported, with the Company particularly interested to target Orphan diseases.
Apart from any earlier possibilities under regulatory Compassionate Release programmes, the Company believes that approval to market this drug could be obtained as early as 2025. This will largely hinge on the success of the clinical programme and regulatory approval applications
There are many factors that determine if patients can participate in clinical trials. Only centres that are involved in the conduct of clinical trials can enroll patients. The Company will promote future proprietary trials on its website, with details of location and recruitment policies.
Several Phase I Human Clinical trials had already been completed with Crotoxin and VRCTC310. The Company has since completed 2 parts of its own proprietary Phase I study with a new method of administration which has reconfirmed the tolerability and safety indications of the product with i.v. method of administration. The ultra-cautious treatment protocols also confirmed the potential for efficacy, and in Part 2, whilst administered in the untypical setting of the patient’s home.
Employing venoms as therapeutics is not new and is fast-growing as pharma-biotech companies push to grow innovative pipelines and patients seek more natural therapies. A large number of well-known pharmaceutical companies are developing novel therapies derived from snake venoms and other reptiles. Most of those using snake venoms employ the anticoagulant enzymes usually from viperids (adders and rattlesnakes) though elapids (cobra family) are unusual.
In China, a pain-killing drug, Ke Tong Ning, that has been on sale since 1978 contains cobratoxin (from cobra venom) as its primary ingredient. Several companies are working with scorpion toxins mainly in the anticancer field.
Botox (botulinum toxin) a bacterial neurotoxin, is a most toxic biological product, and is being developed for a number of applications by Allergan (now AbbVie) and Elan (now Perrigo) but has been increasingly popular for cosmetics applications.
A number of Companies are using venom components;
Abbot Laboratories – acquired Knoll Pharmaceuticals from 3M who are developing a drug, ANCROD, which is formulated from the venom of the Malayan pit viper to be administered following stroke. Epibatide, from poisonous frogs, was recently dropped by Abbot for an application to the treatment of pain.
Amylin Pharmaceuticals developed a peptide, extending-4, from the saliva of the Gila monster (poisonous lizard) that promotes the release of insulin. It was subsequently licensed to Eli Lilly.
Bristol Myers Squibb developed Captopril from the venom of the adder Bothrops as an inhibitor of angiotensin converting enzyme (ACE) for antihypertensive applications.
British Biotech PLC, (now merged with Vernalis) began the development of Marimastat, a metalloprotease inhibitor from snakes for cancer applications.
Cognetix, Utah, developing Conussnail venom anticholinergic peptides for stroke therapy.
COR Therapeutics and Schering-Plough Corpco-market Integrilin, known generically as eptifibatide, is based on a protein called disintegrin taken from the pygmy rattlesnake.
Elan Pharmaceuticals, purchased Neurex to acquire rights to SNX111 (Ziconitide), a pain killing peptide from Conus snails.
Merck makes a heart drug called Aggrastat, which is also based on disintegrin - this non-peptide agent is taken from the African saw-scaled viper snake.
Pentapharm (Switzerland) market two venom-derived products, Defibrase and Haemocoagulase, similar to Ancrod (Abbott Labs).
ReceptoPharm USA developed cobra venom for the treatment of HIV and multiple sclerosis.