Jef: A fabulous backgrounder on the WF 10 product of OXO Chemie-- of which DMX owns 20%. The press just gets better and better for dmx now. The momentum grows. Mark B first came up with this on the weekend. Thxs for the heads up.--it is in the public domain now--this reprinted from Stockhouse today.
Article reproduced from Bidding on Bay Street-- with thxs.
Tom D.
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DIMETHAID RESEARCH [T.DMX]
January 23, 2000 Bidding On Bay Street
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Dimethaid Research [T.DMX] ($4.80)
Featured October 1999 @ $4.18
In a recent press release, Dr. Meuer , of OXO Chemie is quoted saying "With WF10, OXO Chemie has a story on gene regulation of a level never seen before." The release also says "The data provide evidence for WF10's potential to achieve sustained down-regulation of inappropriate immune activation in HIV disease, considered to be the driving force for viral replication."
When I first introduced Dimethaid, I concentrated mainly on their proprietary drug delivery system and first product developments using that system as good reasons to follow the progress of this Canadian Biotech. As we await announcements on further progress in this area - namely completion of UK PENNSAID© approvals received late in '99, finalization of a marketing/distribution agreement with Johnson & Johnson [JNJ], FDA & Canadian regulatory approvals for PENNSAID©, announcement of a major European distributor for PENNSAID©, application to fast-track approvals for PENNSAID© throughout Europe, naming of a co-developer for the anti-fungal - I would like to spend some time looking at the OXOChemie side of the Dimethaid story.
There have been muted and totally unsubstantiated rumors on the Internet that the ongoing Phase III trial of WF10 could be 'fast-tracked'. While this is most likely just wishful thinking, it may be useful to have a better understanding of WF10 and the trial process, in order to be able to evaluate test results as they are released.
DMX has a 20% interest in OXOChemie as well as all Canadian rights to products utilizing OXO's treatment agent, WF10. DMX may also have an option to increase its interest in OXO. For the researchers among you, there is excellent information to be found on the OXOChemie website: www.oxochemie.com. While DMX' prospects seem exciting enough with the products they have or are developing, there are some investors who chose this company as an investment principally on its interest in OXOChemie.
There is always a proliferation of information on companies working on promising AIDS, cancer and other research projects and until the very long process of trials and testing has been concluded, it is always a good idea to proceed with great caution when assessing the information. The scientific and medical communities are the ones to make the final decisions on the usefulness of new treatments and drugs.
The information on WF10 is not always easy for someone outside the medical/research field to fully comprehend but I will try to outline some of the basics from what is available in press releases and on the OXO website. My own interpretation may not be entirely accurate and I have used direct quotes extensively.
UNDERSTANDING THE POSSIBLE ACTION OF WF10
WF10 is a drug that appears to stimulate or augment the effectiveness of MACROPHAGES. "Macrophages are white blood cells in tissue. When they are in a healthy state, they "eat" invading bacteria and viruses and help lymphocytes function. But diseases, such as AIDS, can render macrophages ineffective. The safety and pathogenesis studies, conducted at the University of California, San Francisco, indicate that WF10 appears to cause important changes in the immune system. "In late-stage AIDS, macrophages are the bodys last line of defense in the weakened immune system. Our studies suggest that WF10 can stimulate macrophage function without changing the AIDS virus load."
"Advanced laboratory studies show that WF10 increases the healthy activity of macrophages, thereby reconstituting an important defense mechanism. The most exciting piece of this preliminary clinical research is that WF10 activation of macrophages may encourage the immune system to better fight AIDS and opportunistic infections."
WF10 will also be investigated for treatment of patients with chronic inflammatory diseases, autoimmune diseases and certain cancers. "WF10 is currently undergoing initial clinical testing in a study at Stanford University on the treatment of lymphoma."
** early studies have revealed positive changes in new immunologic factors thought to relate to slowing HIV disease progression
** Macrophage activation is central to a wide variety of immune responses. WF10's activity stems from its ability to directly and/or indirectly activate macrophages by binding to membrane-bound heme complexes
** WF10 treatment appears to have few if any side effects and can be administered intravenously on an out-patient basis.
** The primary study of WF10 appears to be looking at its effects on late stage hiv patients, who often die of immune-deficiency-related complications
** "One of the greatest shortcomings of existing AIDS drugs is that over time, or with poor compliance, the virus becomes resistant to even anti-retroviral "cocktail" therapy in the blood plasma ." "The studies also showed that WF10 decreased the blood levels of CD38, a marker that is a possible predictor of AIDS progression, and increased the blood levels of CD8 cells, an important T-lymphocyte that helps combat the virus."
** I"n addition, the studies showed that WF10 did not increase the amount of HIV in the blood or cause reoccurrence of resistant strains of the virus, one of the major disadvantages of immune stimulation."
** OXO is currently engaged in a Phase 3 trial with WF10. "The study is a randomized, double-blind, placebo-controlled trial of 240 late-stage AIDS patients that investigates the effects of WF10 on survival, progression of AIDS, and prevention of opportunistic infections. The drug is intended as adjunctive therapy to current combination antiretroviral and opportunistic infection prophylaxis regimens.
In the Phase 3 study, the drug is being additionally tested for possible augmentation of the cellular immune response in patients receiving standard HIV treatment, including highly active antiretroviral therapy (HAART). Scientists are particularly interested in determining WF10ûs effects in conjunction with antiretroviral therapy because its proposed mechanism of action targets macrophages, a known reservoir of the HIV virus in AIDS patients. In addition, in these late-stage patients the macrophages remain the last viable component of the immune system.
The ongoing trial is expected to enroll patients from more than 30 key medical centers and universities in North America. Patients participating receive treatment for an 11- week period with follow-up periodically for up to two years. "
** PHASE 2: "The U.S. company launched the Phase 3 study on the heels of encouraging results from Phase 2 clinical results published by the University of California, San Francisco that showed WF10 was well-tolerated and revealed positive changes in new immunologic factors thought to relate to slowing HIV disease progression.
Results from an earlier well-controlled clinical trial at Vanderbilt University in Nashville, TN were published in the journal Infection (August 1998). The study indicated that AIDS patients receiving WF10 experienced a lower frequency of opportunistic infections, fewer hospitalizations, and longer survival."
** "In an early 7 patient study among patients with significant CD4 cell loss WF10 was associated with a specific change in expression of markers of inappropriate immune activation. These data suggest that WF10 may reduce disease progression among persons with <300 CD4 cell/æL"
GENE EXPRESSION DETECTION SYSTEM
QUANTIFYING EFFECTS OF WF10
There was a recent press release (Dec. 6 '99 - www.oxochemie.com) from OXOChemie which spoke of "exciting data of quantitatively detectable changes of gene expression pattern in macrophage and PBMCs of patients treated with WF10."
The release suggests OXO researchers have made progress in developing a "gene expression detection system" which is allowing them to rapidly QUANTIFY macrophase gene expression. This could be a significant development in assessing the quantitative effects of WF10 on gene expression in addition to qualitative effects on desease progression of patients.
"The newly developed system allows rapid *quantitation* of the expression of more than 100 genes encoding inflammatory molecules, chemokines, growth factors, and proteins involved in programmed cell death, or apoptosis. Dr. Meuer stated, "It is the *first time we have been able to measure the effects of immune therapeutics*, particularly macrophage-targeted drugs, in blood by quantitative determination of the change in gene expression patterns. With WF10, OXO Chemie has a story on gene regulation of a level never seen before."
The reported results provide evidence that administration of WF10 to patients with chronic inflammatory / autoimmune diseases may be associated with changes in macrophage gene expression from an inflammatory to an anti-inflammatory phenotype. The expression of genes that normally maintain homeostasis of immune function may be altered in states of inappropriate immune activation. According to Dr. McGrath, "The sustained modification of gene expression in macrophages and peripheral blood monocytes apparently associated with WF10 treatment may help to restore the appropriate balance of immune function."
ADDITIONAL SELECTED INFORMATION
"WF10 may decrease T cell activation and down-regulate inflammatory macrophages. A potential explanation for the results observed in a Phase 2 trial was that WF10 shifted the macrophage function from an antigen-presenting and inflammatory compartment back towards a phagocytic compartment. In vitro data suggest that WF10 induces and/or augments the expression of the alternative activation pathway in macrophages. This pathway is slowly induced in vitro and in vivo, inhibited by gamma interferon, and plays a role as an important negative regulatory element of inflammation and antigen presentation. This alternative activation pathway appears to be a more fundamental component of the immune system in that those cells are predominantly phagocytic and apparently do not cause T cell activation or inflammation, both characteristics of the adaptive (higher organism T and B cell function) immune system. HIV infected patients with end stage disease have no normal T cell function. WF10 may block inappropriate T cell activation and inflammation, while at the same time augmenting phagocytosis. This potentially may be useful changes for survival."
"Helping the immune system mount an effective defense against AIDS and its associated infections is a new research frontier being discussed at the 12th World AIDS Conference here. While current treatments for HIV disease focus on attacking the virus, new research suggests another approach aimed at long-term survival: enhancing certain white blood cells (macrophages) to fight infections and restore immune system function."
"New Frontier in AIDS Research Focuses on Enhancing Immune System Defenses
GENEVA (June 28, 1998) - Helping the immune system mount an effective defense against AIDS and its associated infections is a new research frontier being discussed at the 12th World AIDS Conference here. While current treatments for HIV disease focus on attacking the virus, new research suggests another approach aimed at long-term survival: enhancing certain white blood cells (macrophages) to fight infections and restore immune system function.
Leading AIDS researchers will discuss their findings during a satellite symposium of the World AIDS Conference and offer two poster presentations. The research focuses on the stimulation of macrophages with WF10, a drug that appears to augment their effectiveness.
Macrophages are white blood cells in tissue. When they are in a healthy state, they "eat" invading bacteria and viruses and help lymphocytes function. But diseases, such as AIDS, can render macrophages ineffective. The safety and pathogenesis studies, conducted at the University of California, San Francisco, indicate that WF10 appears to cause important changes in the immune system. "In late-stage AIDS, macrophages are the bodys last line of defense in the weakened immune system. Our studies suggest that WF10 can stimulate macrophage function without changing the AIDS virus load," said Brian Herndier, Ph.D., M.D., associate professor, Department of Pathology, University of California, San Francisco.
"One of the greatest shortcomings of existing AIDS drugs is that over time, or with poor compliance, the virus becomes resistant to even anti-retroviral "cocktail" therapy in the blood plasma,"
The studies also showed that WF10 decreased the blood levels of CD38, a marker that is a possible predictor of AIDS progression, and increased the blood levels of CD8 cells, an important T-lymphocyte that helps combat the virus. In addition, the studies showed that WF10 did not increase the amount of HIV in the blood or cause reoccurrence of resistant strains of the virus, one of the major disadvantages of immune stimulation.
Because macrophages are one of the early and key components of the immune system, research also suggests that WF10 may prove beneficial in the treatment of other chronic inflammatory diseases. To this end, WF10 is currently undergoing initial clinical testing in a study at Stanford University on the treatment of lymphoma.
ABOUT OXO CHEMIE
OXO Chemie, calls itself "The Macrophage Company", "an international pharmaceutical company dedicated to the development of therapeutics by changing macrophage-mediated immune responses to treat diseases."
"While the Company intends to focus its own development efforts on these important diseases, it believes that WF10 and related compounds may prove useful in the treatment of a broad range of viral, inflammatory and proliferative diseases, and certain cancers."
"OXO Chemie has expanded to create a worldwide presence since its founding in 1986 by Dr. Friedrich-Wilhelm Khne, a scientist with more than 35 years of experience in research and development in the pharmaceutical industry and medical field. A Swiss-based firm, OXO Chemie holds worldwide patents for WF10 except for Germany, where separate licensure and all manufacturing facilities are maintained. Key research is conducted at OXO Chemie sites in Wanzleben, Germany, Bangkok, Thailand, and South San Francisco, California."
"The people of OXO Chemie - from innovative healthcare and pharmaceutical companies both large and small, and from around the globe - bring to the firm a depth of experience in Research, Integrated Drug Development, Finance, Marketing, and Management. "
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