L-DOS47
Product Description
- Back to TopHelix’s L-DOS47 is a new drug in development that offers an innovative approach to the debilitation and destruction of non-small cell lung cancer cells. Based upon Helix’ DOS47 Technology, it is designed to function by using a plant-derived substance called urease to act upon a natural substance in the body called urea, in order to produce a potent cancer cell killing effect. L-DOS47 further employs a non-small cell lung cancer-specific targeting antibody in order to localize its actions primarily to the cancerous tissues. Helix believes that L-DOS47 is unlike any cancer therapeutic on the market today. Its pharmacological effect is based on a biochemical reaction, whereby urease is able to act enzymatically to convert urea to ammonia and hydroxyl ions in a continuous manner.
Pharmacological Mechanism
L-DOS47 is derived from a natural plant enzyme generally known as urease. The enzyme rapidly hydrolyzes a substance that is naturally occurring in the body called urea, through which ammonia and other metabolites are generated. In mammals, the body actively converts ammonia, a toxic metabolic waste product, to urea for safe elimination through the urine. L-DOS47 is intended to essentially reverse this cycle locally at the site of cancerous tumors in the body, which in turn is postulated to negatively suppress the active metabolic machinery of tumor cells through a combination of effects. Among these effects, the local production of ammonia at the site of cancerous tumors is believed to disrupt cancer cells via chemical destruction.
As well, the local production of ammonia is thought to lead to a cascade reaction which raises the pH of the local microenvironment surrounding cancerous cells, effectively reversing the acidic extra-cellular conditions in which most cancer cells are believed to exist and multiply (see the DOS47 animation to see how this mechanism works).
L-DOS47 is designed to act in a precisely targeted manner, thereby being able to recognize lung cancer cells of the non-small cell lung cancer type preferentially over any other cells in the body. In order to do this, L-DOS47 applies a variation on a technology that has been used safely in medicines for many years. Specifically, the L-DOS47 drug molecule includes, in addition to the urease compound, a highly specialized single-domain antibody designed to identify non-small cell lung cancer cells in particular. Helix believes this combination will allow L-DOS47 to specifically target cancer tissues, in order to minimize unwanted actions on healthy, non-target tissues in the body.
Medical Need
Lung cancer is now the leading form of cancer as well as the leading cause of death due to cancer for both men and women around the world. More people die each year of lung cancer than of colon, breast, and prostate cancers combined. Treatment strategies today for patients with lung cancer are unfortunately of limited effectiveness and, given the mortality rates, they are generally considered to be more palliative than curative. If detected early, surgical removal of the cancerous tissue is a patient’s best option today. However, in the vast majority of cases (70-80%), the cancer is not typically identified until it has advanced to a level at which surgical intervention is no longer an option. In the cases of inoperable lung cancer, treatment strategies consist of one or more of today's leading chemotherapeutic drugs for lung cancer used in combination with thoracic radiation therapy. Typically, these regimens relieve symptoms and, at best, delay progression of the disease. Unfortunately, however, today's drug and radiation regimens generally lack the power to destroy the cancerous tissues sufficiently in order to halt their ultimate fatal impact.
Market and Competition
Helix believes that there is a substantial market opportunity for L-DOS47 given that (i) its target therapeutic indication, inoperable, locally-advanced, recurrent or metastatic non-small cell lung cancer (NSCLC), represents a significant and unmet medical need worldwide and (ii) therapeutics for such oncology applications have commonly been high revenue generators for the pharmaceutical sector.
Based on information published in “Cancer Facts and Figures 2010” by the American Cancer Society, Helix estimates the incidence of inoperable, locally advanced, recurrent or metastatic NSCLC to currently be an estimated 160,000 people annually in the U.S. alone.
Treatment strategies today for patients with inoperable, locally advanced, recurrent or metastatic NSCLC are of limited effectiveness and they are generally considered to be more palliative than curative. If detected early, surgical removal of the cancerous tissue is currently a patient’s best option. However, in the vast majority of cases, the cancer is not typically identified until it has advanced to a level at which surgical intervention is no longer an option.
In the cases of inoperable, locally advanced, recurrent or metastatic NSCLC, treatment strategies consist of one or more of today’s leading chemotherapeutic drugs for lung cancer (e.g. platinum therapy together with Avastin™, Erbitux® or Alimta®) used in combination with thoracic radiation therapy. Typically, these regimens relieve symptoms and, at best, delay progression of the disease.
Technological competition from pharmaceutical companies, biotechnology companies and universities is intense and is expected to increase. Many competitors and potential competitors have substantially greater product development capabilities and financial, scientific, marketing and human resources than the Company. However, despite the wide range of available therapies today, and the intense competition, cancer mortality rates have not improved substantially in recent history.
Work To Date
Initially, Helix began working with the urease compound at the heart of the L-DOS47 molecule alone, without the addition of the lung cancer-specific antibody entity. Using the urease compound, Helix has gathered compelling evidence in support of its safety and effectiveness in experimental laboratory and animal studies.
Following this work, Helix began to develop its lung cancer-specific drug compound L-DOS47. To develop the L-DOS47 molecule, Helix combined DOS47 with a highly specialized single-domain antibody invented by Canada’s highly respected National Research Council (NRC). Helix subsequently conducted a comprehensive series of laboratory investigations that demonstrated the potent anti-cancer capabilities of the L-DOS47 drug compound using well-established lung cancer laboratory models, and accordingly licensed the antibody component from the NRC.
Pharmacology studies have been conducted in animals demonstrating that L-DOS47 inhibits the growth of tumors derived from a human lung adenocarcinoma cell line. In addition, pilot repeat-dose animal toxicology studies have been conducted, through which L-DOS47 was well-tolerated at doses within and above the dose range shown to be efficacious in the tumor growth inhibition studies. Furthermore, definitive GLP, rodent and primate, repeat-dose toxicology studies have been completed and demonstrated a good safety profile in an expanded number of rodent and primate test animals, building upon Helix’s positive findings from its pilot repeat-dose toxicology studies. As well, Helix has completed initial quality testing for its first GMP clinical batch of L-DOS47 and it is continuing to undergo required stability testing.For more information describing Helix’ DOS47/L-DOS47:
- DOS47 Video Animation
- Helix's Research Findings Published in the Journal of Experimental Therapeutics and Oncology
- Helix Presents L-DOS47 Lung Cancer Research Findings - View the Poster
L-DOS47 is an early-stage drug candidate under investigation by Helix BioPharma Corp. Descriptions of the mechanism by which L-DOS47 functions are purely speculative and are based on scientific theories advanced by the Corporation. The Corporation is actively engaged in ongoing investigative research with L-DOS47, through which it will attempt to test its theories. The Corporation offers no guarantee that its theories will be proven, nor that L-DOS47 will ultimately yield a medicinal therapeutic.