Welichem Biotech Inc.


Welichem Biotech Inc.
316-4475 Wayburne Drive Burnaby BC Canada V5G 3L1
Telephone 604 432 1703 Fax 604 432 1704

Liren Tang, CEO, lirentang@welichem.com
Michael Lyle, VP, mikelyle@welichem.com


Welichem Biotech Inc. is engaged in the discovery and development of novel small molecule therapeutics. Using its Symbiochem® technology platform, the Company has developed a robust pipeline of patent-protected compounds that target various diseases including inflammatory diseases and cancers.

Welichem's lead drug candidate, WBI-1001, targets autoimmune/inflammatory skin disorders such as psoriasis and eczema. Four clinical studies were completed by the Company using WBI-1001 creams for the treatment of atopic dermatitis and psoriasis. In July 2012, the WBI-1001 technology was acquired by Stiefel, A Glaxo Group Limited (GSK) company, for further development, regulatory approval, and commercialization.

Welichem's other lead drug candidate, WBI-2100, selectively targets certain types of hard-to-treat cancerous tumours. This is achieved in part through inhibition of angiogenesis and metastasis. Animal tests have shown that WBI-2100 is effective as a monotherapy and also synergistically increasing the effectiveness of several commonly used chemotherapeutic products. The uniqueness of this small molecule cancer chemotherapeutic is that in pre-clinical studies it increases the number of neutrophils in the peripheral blood. The boosting of neutrophils in animal studies in the presence of the cancer therapeutic, cyclophosphamide, supports its potential therapeutic application for chemotherapy induced neutropenia.

With its proven Symbiochem® technology platform, Welichem will advance its pipeline of drug candidates at a rate and time commensurate with resources and target need, and is well positioned as a drug discovery and early stage drug development company developing novel small molecule therapies for unmet medical needs.


Management

Dr. Liren Tang joined the Company in 2006 as the Head of Life Sciences directing a team of Biologists and Medicinal Chemists in drug discovery and early stage development in the fields of inflammatory diseases and cancers. From 2007-2009, as the Director of Clinical Development at the Company, Liren led a clinical research team to a total of four clinical trial application approvals and all four clinical trials were successfully completed with convincing clinical safety and efficacy data. Since November 2011, Liren has been the President and CEO of the Company. He has raised multiple millions of dollars through private placements, loans and rights offerings to fund the company's drug discovery and development programs. With the compelling clinical data, Liren successfully led a team of experts of multiple disciplines including drug R&D, business development, legal counsels, clinicians, patent transferring experts, and regulatory affair experts for drug approvals etc, to reach an Asset Purchase Agreement for the company's lead immunology drug program with Glaxco Group Limited (GSK) for a total price of up to $230 million dollars in the year 2012. Prior to joining Welichem, Liren was a principal or co-principal investigator at the Vancouver Coastal Health Research Institute for diverse scientific and clinical research projects addressing various aspects of inflammatory diseases and cancers. He is an author of over 30 peer-reviewed scientific publications. Liren received his PhD in Cell and Developmental Biology at the University of British Columbia.

Dr. Michael Lyle was appointed as the Vice President of Research and Development in December 2009 after being the former Director of Chemistry at the company. In addition to leading the overall CMC program for the Company’s proprietary compounds, Dr. Lyle led two successful clinical trial applications related to the Company’s lead compound, WBI-1001, for the topical treatment of atopic dermatitis and psoriasis. Michael received his PhD in Chemistry at Simon Fraser University.


WBI-2100: A Novel Anti-cancer Compound with Neutropenia-prevention Activity

WBI-2100 is being developed by Welichem as a treatment for solid cancers both as a monotherapy and synergistically in combination with other chemotherapies. In addition, WBI-2100 boosts neutrophil levels and prevents chemotherapy-induced neutropenia (CIN). There are no other anti-cancer drugs possessing such dual activities.

Preclinical Anti-cancer Efficacy:

WBI-2100’s anti-cancer activity has been demonstrated in various mouse tumour models (lung, breast, kidney, liver, pancreas, ovarian cancers and melanoma) both as a monotherapy and as a synergistic combination-therapy with Cisplatin, Taxol, Gemcitabine, or Dacarbazine. In a melanoma model, more than 80% tumour growth inhibition was achieved when combining WBI-2100 with Taxol compared with approximately 40% with Taxol alone. More importantly, no obvious adverse effects, such as neutropenia was observed in the mice treated with WBI-2100.

Unique Modes-of-Action:

Cancer is a heterogeneous disease comprised of cancer cells that are themselves biologically diverse. Compounds possessing multiple modes of action can potentially be very effective anti-cancer drugs. The cytotoxicity of WBI-2100 has been demonstrated to be selective for solid cancer cells over hematological cancer cells. When tested on the National Cancer Institute’s panel of 60 cancer cell lines, its LC50 was significantly lower (approximately 100 fold) for all solid cancer cell lines than that of leukemia and lymphoma cell lines. WBI-2100 has been shown to be anti-angiogenic in vitro and in vivo. Angiogenesis plays a critical role in solid tumour growth and invasion. Various anti-angiogenesis drugs have been developed recently, and they all need to be combined with other chemotherapeutic drugs to be effective in the clinic. It appears that WBI-2100 possesses both anti-angiogenesis and anti-cancer activity. In vitro, WBI-2100 induces apoptosis in human umbilical vein endothelial cells (HUVEC) cells and inhibits vascular network formation (tube formation) of HUVEC cells at sub-toxic doses. Using an in vivo Matrigel plug assay, WBI-1001 was able to block FGF-induced angiogenesis in mice in a dose-dependent manner. WBI-2100 has strong anti-metastasis activity. Metastasis causes more than 90% of human cancer deaths. In vitro, using Boyden chamber assay, WBI-2100 strongly inhibited tumour cell invasion at sub-toxic concentrations. In vivo, dose-dependent inhibitory effects on both lung and breast cancer metastasis have been demonstrated.

Neutrophil Stimulatory Activity:

Chemotherapy induced neutropenia (CIN), which refers to abnormally low levels of neutrophils in the circulating blood and creates a substantial risk of life-threatening infection, is a common side effect of cancer chemotherapy. When patients experience neutropenia during chemotherapy, their scheduled treatment may have to be delayed or the doses reduced, thus exposing the patients to a lower chance of survival or cure of the cancer. In contrast to other chemotherapy drugs on the market, other than its anti-cancer activity, WBI-2100 has a unique property of boosting neutrophils in different animal species. Such stimulatory effects are specific for neutrophils, and other hematopoietic cells are not affected by the WBI-2100 treatment. More interestingly, when WBI-2100 is combined with the chemotherapeutic drug cyclophosphomide, chemotherapy-induced neutropenia is prevented. These combined activities of WBI-2100 as a novel cancer drug candidate that also stimulates neutrophils suggests that it has the potential of being a unique cancer chemotherapy that negates the serious side effects normally experienced by patients undergoing cancer chemotherapy. In theory, by having the unique dual activity, WBI-2100 can be combined with any chemotherapeutic cancer drugs to increase other drug’s anti-cancer efficacy and at the mean time to prevent or treat the CIN. WBI-2100 could potentially be developed as a small molecule treatment for CIN. The only drugs available on the market are the biologics, Neupogen and Neulasta. Both of which are recombinant hematopoietic growth factors. Depending on the receptors expressed by the target cancer cells, Neupogen and Neulasta may stimulate cancer cell growth and thus potentially reduce the anti-cancer efficacy of the chemotherapy drugs when treating CIN. As a small molecule and an anti-cancer drug, WBI-2100 is obviously advantageous to treat CIN.


SYMBIOCHEM®: A UNIQUE DRUG DISCOVERY PLATFORM

SYMBIOCHEM® is proprietary know-how and technology that Welichem developed and employs for the discovery of novel compounds from symbiotic organisms and it is a registered trademark of Welichem Biotech Inc. During the past several years, a large number of compounds have been identified, using SYMBIOCHEM®. Many of these compounds are new to science and have bioactivities that are of great interest to the pharmaceutical industry.

General Protocol of SYMBIOCHEM®:

As a general process SYMBIOCHEM® utilizes several conventional microbiological and natural chemistry methods. These include isolation, characterization, and fermentation of bacteria, purification and characterization of compounds from the secondary metabolites. The initial biological component of the process normally takes one to two weeks; the purification and identification of compounds may take from several days to several months depending on the complexity of a particular chemical. The bacterial isolation and fermentation is based on published microbiological methods, but with important modifications. These modifications include a certain level of expertise and/or know-how that is the core of SYMBIOCHEM®. The successful isolation and fermentation of the primary form bacteria requires experience. Special culture conditions and media composition are required in order to produce the particular metabolites of interest. Chemical purification and characterization demands in depth knowledge and experience of natural products chemistry and reliable bioassays are needed to guide the process. This process is not high throughput but rather a focused screening and the rate of novelty is exceptionally high.

Natural Small Molecular Compounds Generated through SYMBIOCHEM®:

Over 40 secondary metabolites have been identified from cultures of Xenorhabdus and Photorhabdus by Welichem using only antimicrobial activity as an assay. These metabolites belong to diverse chemical classes that include aromatic, heterocyclic compounds, nuc1eosides and macrolides. Some of these compounds were already known and some are produced by other organisms such as streptomycetes. However, more than 50 % of the compounds identified through SYMBIOCHEM® have not been reported previously. Most species of Xenorhabdus and Photorhabdus produce more than one group of bioactive secondary metabolites, and the metabolites from Xenorhabdus are more diverse than those from Photorhabdus. Different bacterial species produce different kinds of secondary metabolites. These metabolites not only have diverse chemical structures, but also a wide range of bioactivities of medicinal and agricultural interest, such as antibiotic, antimycotic, insecticidal, nematicidal, antiulcer, antineoplastic and antiviral.