ZymoGenetics Highlights Development Programs at Analyst & Investor Briefing
SEATTLE, Dec. 3 /PRNewswire-FirstCall/ -- ZymoGenetics, Inc. (Nasdaq: ZGEN - News) today told analysts and investors at a meeting in New York that they intend to initiate clinical development for three product candidates within the coming 12 months. These product candidates are recombinant human Factor XIII (rFXIII), for which an Investigational New Drug (IND) application has been filed and patient enrollment is expected to begin in the next several weeks, recombinant human Thrombin (rhThrombin) and TACI-Ig. These three molecules, plus Interleukin 21 (IL-21), which was announced as a development candidate in October of this year, lead the Company's broad based research and development pipeline of therapeutic protein product candidates. (A web cast of today's ZymoGenetics Analyst and Investor Briefing may be accessed at www.zymogenetics.com.)
"This briefing was our first opportunity since becoming a public company to provide the investment community with a detailed overview of our research and development activities for each of our lead programs," commented Bruce L.A. Carter, Ph.D., President and Chief Executive Officer of ZymoGenetics. "We now have four exciting proteins in development, demonstrating the strength of our pipeline. Factor XIII, for which we anticipate initiating clinical studies in the next several weeks, is the first in a long line of proteins coming from our discovery efforts that we expect to advance into the clinic. To strengthen our development capabilities, the Company has added key staff in a number of areas including pharmacology and toxicology, manufacturing, program management and regulatory and medical affairs. We believe that these additions position us for success as we focus our efforts in developing our lead product candidates."
Briefing Highlights
-- ZymoGenetics has designated four therapeutic protein product candidates
for development: These are: 1) TACI-Ig for the treatment of antibody
mediated autoimmune diseases; 2) IL-21 for the treatment of cancer; 3)
rFXIII for the treatment of both congenital and acquired Factor XIII
(FXIII) deficiencies; and 4) rhThrombin for use as a general hemostat
to control bleeding during surgery.
-- ZymoGenetics has filed an IND for the initiation of clinical studies
with rFXIII in patients who are congenitally deficient for FXIII. The
Company anticipates that it will commence human studies within the next
several weeks. The Company further intends to extend its clinical
development activities with rFXIII in 2003 into additional indications,
such as the treatment of bleeding complications associated with
cardiopulmonary bypass procedures, and the treatment of graft versus
host disease (GVHD) induced lesions of the gut.
-- ZymoGenetics reaffirmed that it anticipates initiating clinical studies
with TACI-Ig in H2 2003. In partnership with Serono SA, the companies
intend to focus on Systemic Lupus Erythematosis (SLE) as an initial
clinical indication.
-- ZymoGenetics anticipates initiating clinical studies with rhThrombin in
H2 2003. The Company is developing recombinant human thrombin as a
replacement for currently marketed bovine-derived thrombin.
-- ZymoGenetics indicated that it anticipates initiating clinical studies
with IL-21 in H1 2004 for the treatment of cancer. IL-21 is a novel
protein that regulates a variety of cell types involved in the immune
system, including cytotoxic T-cells and Natural Killer cells, cell
types involved in the body's ability to fight diseases, including
certain cancers.
-- Using a bioinformatics-driven discovery strategy, combined with
ZymoGenetics strength in determining the biology of novel proteins, the
Company has established a deep pipeline of therapeutic protein-based
product candidates, with over 70 proteins in various stages of research
and development that target a broad range of diseases and conditions.
-- Zymogenetics is actively pursuing the establishment of a non-North
American development partnership for rFXIII and intends to complete
such a transaction in 2003.
Development Program Summaries
TACI-Ig
One of the Company's lead product opportunities is TACI-Ig, a soluble fusion protein that links part of a novel cytokine receptor (TACI) to the Fc portion of immunoglobulin (Ig). This product candidate is being developed as a therapy for autoimmune diseases that result from inappropriate activity of B-lymphocytes, and the production of autoantibodies, antibodies that attack an individual's own healthy tissues. Such diseases include SLE, rheumatoid arthritis and idiopathic thrombocytopenia purpura, among others.
TACI-Ig has been demonstrated to bind to and neutralize the activity of BLyS, a cytokine that stimulates B-cell proliferation, and the induction of antibody production. The determination that over-expression of BLyS correlates with the onset and severity of autoimmune disease in animal models, and the observation that elevated levels of BLyS are present in the serum of patients with SLE and various other autoimmune diseases, suggests that an antagonist to BLyS may have therapeutic utility. ZymoGenetics researchers have produced TACI-Ig, an antagonist protein that can "mop up" increased BLyS present in the blood.
In an animal model of SLE, treatment with TACI-Ig was effective in limiting the onset and progression of the disease. Similar positive results were observed with TACI-Ig in a mouse model of arthritis. These data suggest that TACI-Ig may provide a novel approach to treat autoimmune disease.
ZymoGenetics has entered into an exclusive co-development and commercialization agreement with Serono for the development of TACI-Ig, for the treatment of various autoimmune diseases. ZymoGenetics and Serono intend to initiate clinical studies with TACI-Ig in the second half of 2003 with SLE as the first indication.
Interleukin 21 (IL-21)
ZymoGenetics' scientists discovered IL-21, a novel cytokine that the Company is developing as an immunotherapeutic agent. IL-21 has been shown to activate key classes of immune cells, including cytotoxic T cells and Natural Killer cells, cell types that can destroy malignant or infected cells.
In preclinical studies, IL-21 has been found to be an effective therapy in a number of animal models of cancer. In an animal model of metastatic melanoma, a disease for which Interleukin 2 (IL-2) and Interferon-alpha are approved therapies, IL-21 exhibited a high rate of tumor suppression. In clinical practice, IL-2 is an effective therapy in only approximately 5-8% of patients with malignant melanoma. Accompanying this low level of efficacy is a significant side effect profile that profoundly limits the utility of IL-2 in treating disease.
Analysis of IL-21 in animal models further demonstrated a favorable toxicity profile when analyzed for the stimulation of vascular leakage and the induction of inflammatory cytokines, both complications associated with IL-2 treatment.
Based on the mechanism of action of IL-21 to activate cytotoxic T cells and Natural Killer cells, its effectiveness to inhibit tumor growth in a number of animal models, and its favorable toxicity profile, ZymoGenetics is developing IL-21 for the treatment of cancer. The Company anticipates initiating clinical studies with IL-21 in the first half of 2004, with metastatic melanoma and renal cell carcinoma as the first two indications that the Company intends to target.
Recombinant human Factor XIII (rFXIII)
ZymoGenetics is developing rFXIII for the prophylaxis and treatment of bleeding complications and alterations in tissue repair associated with FXIII deficiencies. Today, only human plasma-derived FXIII is available, and only in a limited number of countries. Plasma-derived FXIII is not approved in the United States. The Company has established a robust yeast expression system for the production of rFXIII for use in clinical studies.
FXIII is the terminal enzyme in the clotting cascade and is responsible for making strong clots. Its primary function is to crosslink individual fibrin molecules into a strong fibrin mesh. FXIII further stabilizes the clot and prevents enzymatic degradation by crosslinking alpha 2-plasmin inhibitor into the clot.
The body of clinical experience related to use of FXIII concentrate shows significant potential for FXIII therapy in a variety of indications. Patients with congenital FXIII deficiency are usually diagnosed within hours of birth, when they exhibit bleeding from the umbilical stump. These patients have a high risk of bleeding into the brain and in soft tissues. Prophylactic treatment with plasma-derived FXIII helps these patients manage their disease and reduces their risk of bleeding significantly.
Acquired FXIII deficiency has been associated with various surgical procedures, GVHD of the gut, and ulcerative colitis (UC). In these clinical settings, the level of FXIII activity in the blood is typically 40-60% of normal and associated with abnormal bleeding and delayed wound healing.
ZymoGenetics intends to test rFXIII initially in patients with congenital FXIII deficiency (of which there are approximately 200 individuals worldwide). Following the completion of the initial safety trials of rFXIII in patients with congenital deficiency, the Company intends to expand the clinical development plan to include post-surgical bleeding following cardiopulmonary bypass procedures and GVHD bowel disease. ZymoGenetics intends to initiate human studies with one or both of these indications in 2003.
Recombinant human Thrombin (rhThrombin)
ZymoGenetics is developing rhThrombin as a stand-alone product for use as a topical hemostat to control surgical bleeding. Thrombin has been used as a hemostatic agent for more than 30 years and is applied topically to surgical incisions, sutures and burns to help stop bleeding at these sites. Currently, only thrombin derived from bovine blood is available in the US as a stand- alone thrombin product.
There are important and growing safety concerns related to the use of bovine thrombin. These include a high incidence of immune responses directed against bovine thrombin and to other contaminating proteins in the thrombin product. In addition, a growing concern exists about the potential for transmitting infectious agents from cows to humans, such as BSE (bovine spongiform encephalopathy, the agent that causes "mad-cow" disease), through the use of bovine-derived products. ZymoGenetics believes that rhThrombin may have significant safety advantages over the bovine product and that rhThrombin may be readily accepted by physicians as their product of choice to control bleeding.
ZymoGenetics expects to initiate human studies with rhThrombin in the second half of 2003 for use as a topical hemostat to control bleeding in surgical settings. The Company is evaluating the use of rhThrombin for other potential indications, including its use as a component in surgical sealant.
About ZymoGenetics
ZymoGenetics is a biopharmaceutical company focused on the discovery, development and commercialization of therapeutic proteins for the prevention or treatment of human diseases. Using a product discovery engine, comprising genomics, bioinformatics, protein chemistry and preclinical biology, ZymoGenetics has generated a broad pipeline of proprietary product candidates. ZymoGenetics intends to commercialize these product candidates through internal development, collaborations with biopharmaceutical partners, and out- licensing of its extensive patent portfolio. For further information, visit www.zymogenetics.com.
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on the current intent and expectations of the management of ZymoGenetics. These statements are not guarantees of future performance and involve risks and uncertainties that are difficult to predict. ZymoGenetics' actual results and the timing and outcome of events may differ materially from those expressed in or implied by the forward-looking statements because of risks associated with our unproven discovery strategy, preclinical and clinical development, regulatory oversight, intellectual property claims and litigation and other risks detailed in the company's public filings with the Securities and Exchange Commission, including the company's Annual Report on Form 10-K for the year ended December 31, 2001... |
