Glyko Biomedical Ltd.'s 27%-owned Affiliate, BioMarin To Acquire Enzyme Products From IBEX Technologies.

Business Editors/Health & Medical Writers

NOVATO, Calif.--(BW HealthWire)--Oct. 10, 2001

Neutralase(TM) to Enter Phase III Clinical Program for

Coronary Artery Bypass Graft; Phenylase in Preclinical

Development for Phenylketonuria

Conference Call and Webcast to be Held Today

at 4:15 PM EDT (2215 CET)

Glyko Biomedical Ltd.'s (OTCBB:GLYK; TSE:GBL; BVD-Berlin:GLY) 27%-owned affiliate, BioMarin Pharmaceutical Inc. (Nasdaq and SWX New Market:BMRN) today announced that BioMarin has reached a definitive agreement with IBEX Technologies Inc. (Toronto Stock Exchange:IBT) to acquire the rights to all IBEX pharmaceutical assets. IBEX's portfolio of enzyme therapeutics will complement BioMarin's existing pipeline of products for serious, life-threatening diseases and conditions.

New Product Additions to the BioMarin Pipeline

IBEX's lead product, Neutralase(TM), is an injectable heparinase that reverses the anticoagulation of blood by heparin and other new heparin-like anticoagulants. Neutralase is a carbohydrate-modifying enzyme that cleaves heparin, a glycosaminoglycan (GAG), in a manner similar to the activity of BioMarin's two enzyme replacement therapies: Aldurazyme(TM) for the treatment of MPS I and rhASB for the treatment of MPS VI. Based on promising safety and efficacy data from IBEX's clinical trials of Neutralase, BioMarin plans to initiate a Phase III trial of Neutralase in Coronary Artery Bypass Graft (CABG) surgery in 2002.

In addition, IBEX has an early development stage program for Phenylase, an orally active enzyme with the potential to treat Phenylketonuria (PKU), a genetic disease caused by an enzyme deficiency that can lead to progressive, severe, and irreversible mental retardation.

Terms of the Agreement

Under the terms of the agreement, BioMarin will acquire IBEX's pharmaceutical assets for US$10.5 million, with all but US$2 million payable in shares of BioMarin common stock.

BioMarin will also make contingent payments of up to US$9.5 million to IBEX upon U.S. FDA approval of products acquired from IBEX.

The boards of directors of BioMarin and IBEX have approved the transaction, which is subject to customary closing conditions. The transaction is expected to close in the fourth quarter of this year. Leerink Swann & Co. acted as financial advisor to BioMarin with regard to this transaction.

Fredric D. Price, BioMarin's Chairman and Chief Executive Officer said, "Neutralase and Phenylase represent novel approaches to solving medically-important problems that affect hundreds of thousands of patients in North America and Europe. The acquisition of these promising compounds further expands BioMarin's portfolio of treatments developed through our enzyme and carbohydrate chemistry expertise.

"Neutralase is a unique late-stage product with the potential to significantly reduce the serious problems associated with heparin reversal. With the addition of Neutralase, BioMarin will have five drug candidates in clinical trials next year: Aldurazyme, rhASB, Vibriolysin, Neutralase, and a fifth product that will advance from our internal development pipeline."

Robert Heft, Ph.D., Co-founder, President, and Chief Operating Officer of IBEX, added, "BioMarin's expertise in enzyme research, production, quality control and assurance, process development, and clinical trials management will greatly enhance the ability to effectively advance Neutralase and Phenylase through their next stages of development. I am looking forward to assuming my new position as Vice President, Product Development at BioMarin and contributing, with my team here in Montreal, to BioMarin's success."

Background on Neutralase and Phenylase Markets

There are approximately 300,000 CABG procedures and 725,000 angioplasties each year in the United States that could potentially benefit from heparin reversal. Estimates for the European markets are projected to be as large as those in the U.S. In addition, preclinical studies have shown that Neutralase may be effective as a reversal agent for the low molecular weight heparins (LMWHs) that are used in many surgeries such as hip and knee replacements as well as for a new class of drugs, pentasaccharides, that are also being developed for these indications.

Currently, protamine is the only product commercially available for the reversal of heparin anticoagulation. Protamine has continued to be used in the absence of an appropriate alternative, despite being associated with the following adverse effects: sudden decreases in blood pressure, depression of heart function, pulmonary hypertension, acute allergic reactions, complement activation, and strokes. IBEX's clinical trials have indicated that Neutralase reverses heparin anticoagulation without the hemodynamic changes associated with protamine. Additional data suggest that Neutralase may address other serious problems that have been linked to protamine usage as well.

Jeffrey Borer, M.D., Chief, Division of Cardiovascular Pathophysiology, Weill Medical College of Cornell University, noted, "Protamine complications during heart surgery are well known, but currently there are no other heparin antidotes. In clinical testing during open heart surgery, Neutralase has demonstrated the potential of being an effective alternative to protamine without its unwanted hemodynamic complications."

Jean-Francois Tanguay, M.D., Montreal Heart Institute, and principal investigator for IBEX's Phase II trial of Neutralase in angioplasty, commented, "Heparin reversal following angioplasty is uncommon because of the lack of a suitable drug. Initial clinical evaluation in patients undergoing angioplasty demonstrated that Neutralase has the ability to significantly reduce the time to sheath removal and the time required for safe patient ambulation."

PKU affects approximately 50,000 patients in North America and Europe. There are no drugs currently approved for treatment of PKU, and patients are required to adhere to strict, protein avoiding diets. The special formulas and foods are estimated to cost more than $5,000 per patient per year over normal food requirements. Many patients over five to ten years of age have difficulty maintaining this dietary regimen, and their elevated phenylalanine levels lead to a variety of problems with brain function. Phenylase is an oral enzyme therapy that has the potential to reduce phenylalanine levels while allowing a less restricted, more palatable diet.

Charles R. Scriver, M.D., Alva Professor of Human Genetics, McGill University, said, "Up to now, treatment of thousands of PKU patients has been accomplished by changing lifestyle, diet and the intake of protein and phenylalanine. Almost fifty years of dietary treatment reveal how arduous and difficult it is. Oral enzyme substitution therapy with Phenylase has been demonstrated in a PKU animal model. It is time to move Phenylase forward so that it can be studied and used in the human patient."

BioMarin will host a conference call and webcast to discuss this acquisition today at 4:15 PM EDT (2215 CET). This event can be accessed on the BioMarin website at: http://investor.biomarinpharm.com.

Date: Wednesday, October 10, 2001

Time: 4:15 PM EDT (2215 CET)

U.S. & Canada Toll-free Dial in No.: 1-800-997-8642

International Dial in No.: 1-973-694-6836

Replay Toll-free Dial in No.: 1-800-428-6051

Replay International Dial in No.: 1-973-709-2089

Replay Code No.: 212381

Questions and Answers Related to the Transaction

In order to provide comprehensive information to all investors regarding this transaction, BioMarin is taking this opportunity to present questions and answers related to this transaction on the accompanying pages.

Glyko Biomedical Ltd.'s principal asset is a 27% ownership in the capital stock of BioMarin Pharmaceutical Inc.

BioMarin specializes in the development and commercialization of therapeutic enzyme products to treat serious, life-threatening diseases and conditions.

IBEX is a biopharmaceutical company developing enzyme-based therapeutics for a variety of applications, particularly cardiovascular disease and diseases of genetic origin.

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., and the acquisition of the assets to be acquired from IBEX and the products of IBEX. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. Results may differ materially depending on the completion of the acquisition, progress of BioMarin's product programs, including the ability to integrate the programs being acquired from IBEX, the actual results of the current and proposed clinical trials, actions of regulatory authorities, future availability of capital, future actions in the pharmaceutical market and developments by competitors, and those factors detailed in BioMarin's filings with the Securities and Exchange Commission such as 10Q, 10K and 8K reports. Stockholders are urged not to place undo reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation, to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.

The securities to be issued in connection with this acquisition have not been registered under the Securities Act of 1933, as amended, or state securities laws and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements. The Company has agreed to use its best efforts to register all of the common stock relating to this transaction with the SEC following the closing of this acquisition.

BioMarin Pharmaceutical Inc.

QUESTIONS AND ANSWERS RELATING TO THE ACQUISITION OF

NEUTRALASE AND PHENYLASE FROM IBEX TECHNOLOGIES

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QUESTIONS ON NEUTRALASE

1. Question: What kind of an enzyme is Neutralase and how does it work?

Answer: Neutralase (heparinase I) is a carbohydrate-modifying enzyme that cleaves heparin at specific places important for anticoagulation. By cleaving heparin, Neutralase reverses heparin's anticoagulative effects. Importantly, studies have shown that Neutralase can also cleave and neutralize the anticoagulative effects of the new low molecular weight heparins (LMWHs) and the synthetic heparin-like pentasaccharide Arixtra(R) (fondaparinux sodium) from Sanofi-Synthelabo and Organon. We are unaware of any product other than Neutralase with the potential to reverse all of these new products.

2. Question: How does Neutralase fit into BioMarin's pipeline of enzyme products?

Answer: Like all of our existing products that treat genetic diseases, Neutralase is a carbohydrate-modifying enzyme. It cleaves heparin, a type of glycosaminoglycan or `GAG' (carbohydrate). Our two lead products -- Aldurazyme for MPS I and rhASB for MPS VI -- also cleave GAGs.

3. Question: What are the potential indications for Neutralase and what is its competition?

Answer: Neutralase has the potential for use as a reversal agent for heparin anticoagulation in open-heart surgery such as coronary artery bypass graft (CABG) procedures, interventional cardiology procedures such as angioplasty, and whenever heparin or heparin-like anticoagulants need reversal. Protamine sulfate is the only agent currently commercially available to reverse heparin and its use is associated with numerous side effects as detailed in question number four below. In addition, protamine has not been shown to efficiently reverse the activity of low molecular weight heparins, heparinoids or Arixtra. Neutralase, on the other hand, has been shown to reverse these newer anticoagulation products in preliminary studies (Yang et al., 1986; Jeske and Fareed, 1999; Zmuda et al., 2000; Daud et al., 2001; Yu et al., 2000).

Protamine is used more than 2,000,000 times annually (Carr and Silverman, 1999) in the U.S. alone, and Neutralase could potentially be used to reverse heparin in all of these situations as well as in the other situations in which reversal of heparin is currently avoided due to protamine's side effects.

4. Question: What is protamine and what problems associated with its use complicate and limit its utility?

Answer: Protamine is a positively charged polymer derived from salmon sperm that inactivates heparin by binding to it, forming large macromolecular complexes. Protamine has been known to cause significant problems during reversal of heparin anticoagulation, but it has continued to be used in the absence of an appropriate alternative (Carr and Silverman, 1999; Weiler et al., 1985; Weiler et al., 1990; Kimmel et al., 1998). Some of these known problems are detailed below:

-- Sudden decreases in blood pressure. Protamine is known to cause sudden
decreases in blood pressure during administration for reversal of heparin
during bypass surgery. This effect may be due to the large protamine-heparin
complex that causes the release of mediators that dilate blood vessels and
lower blood pressure. In addition, it may have a direct effect on decreasing
cardiac function (Del Re et al., 1993; Carr and Silverman, 1999).
Anesthesiologists must infuse protamine slowly and provide immediate blood
pressure support in patients during heparin reversal after open-heart surgery
in order to try to manage this common problem.

-- Increased pulmonary blood pressure (pulmonary hypertension). The reversal of
heparin with protamine routinely induces sudden increases in pulmonary blood
pressure (pulmonary hypertension) due to the release of mediators, such as
thromboxane, which can put excess strain on the heart immediately following
surgery and lead to catastrophic consequences (Morel et al., 1987; Lowenstein
and Zapol, 1990; Carr and Silverman, 1999).

-- Acute allergic reactions. Most patients having acute allergic reactions to
protamine have not had prior protamine exposure and have no known predisposing
condition. Patients with prior exposure to protamine, such as diabetics using
protamine-formulated insulin (also called NPH), can have acute anaphylaxis
reactions during heparin reversal with protamine (Weiss et al., 1989; Porsche
and Brenner, 1999). A study by Gupta et al 1986 (Gupta et al., 1989) found that
3% of all insulin dependent diabetics and 0.2% of all persons undergoing
vascular surgery at their institution had anaphylactoid reactions to protamine
and an associated overall mortality rate of 36%. Though less common, these
allergic reactions can be severe.

-- Complement activation. The large protamine-heparin complexes formed after
protamine administration can activate the classical complement pathway, a type
of inflammatory immune response (Morel et al., 1987; Carr and Silverman, 1999).
The activation of complement components and subsequent complement cascade has
been associated with post-operative arrhythmias (Bruins et al., 2000).
Indiscriminate activation of complement can cause tissue injury, as the
complement cascade leads to the production of activated complement complexes
that bind and attack tissues and release secondary mediators, such as
thromboxane. These actions are associated with temporary organ dysfunction and
morbidity after surgery.

-- Platelet dysfunction and leukocyte sequestration. Protamine alters the
function of platelets and leukocytes and associated cell surface receptor
expression which leads to decreased or abnormal platelets and decreased
leukocytes (Mochizuki et al., 1998; Ammar and Fisher, 1997).

-- Strokes when used in carotid endarterectomy (CEA). Protamine is often
avoided in vascular surgery because it can promote clot formation at the
surgical site. Mauney et al (Mauney et al., 1995) published a report on a
consecutive series of 348 patients undergoing carotid surgery and found a
postoperative stroke rate of 2.6% when protamine was used versus no strokes
without protamine.

5. Question: What are the most important results from the Neutralase Phase I and II clinical trials?

Answer: The data from Phase I and Phase II clinical trials described below indicate that Neutralase was well tolerated and reversed anticoagulation by heparin in a dose-dependent fashion. The data suggest that Neutralase can reverse heparin anticoagulation without the changes in systolic blood pressure and pulmonary blood pressure associated with protamine usage.

-- Results from use in CABG surgery. A randomized, double blind,

active agent controlled Phase II study using a Neutralase dose

of 10 ug/kg or 15 ug/kg demonstrated successful reversal of

heparin. In the study, patients were randomly assigned to one

of three treatment arms -- Neutralase 10 ug/kg, Neutralase 15

ug/kg, or protamine. This trial was initiated to assess a

higher baseline dose of Neutralase and an improved treatment

regimen for re-administration in line with current clinical

practice. Seventeen hospitals in the U.S. and Germany

participated in the first stage of the trial. An interim

analysis was conducted after the first 94 patients undergoing

CABG surgery were enrolled. The results indicated adequate

reversal with both the 10 ug/kg and 15 ug/kg doses of

Neutralase and suggested improved blood pressure

characteristics of reversal with Neutralase over protamine.

-- Results from use in angioplasty. A Phase II trial in

angioplasty demonstrated that the time to sheath removal was

reduced by one and a half to two hours and patients could

ambulate three to four hours sooner (Tanguay et al., 2001).

6. Question: What happened to the first Phase III Neutralase trials initiated by IBEX

Answer: An inadequate dose and dosing regimen were used in the first Phase III trial and led to inadequate reversal of heparin. An appropriate dose and dosing regimen have been determined based on the Phase II trial noted above and will be used in subsequent trials. Additional detail is provided below.

The initial Phase III trial in CABG patients showed that the dose used (7 ug/kg) and the dosing regimen were not sufficient to completely reverse heparin in comparison to protamine. In the first Phase III, the criterion for clinically successful reversal was an activated clotting time of less than 20 seconds. This criterion was not stringent enough and allowed some patients to receive an inadequate dose of Neutralase. In addition, the protocol did not take into account specific common practices in CABG such as the return of heparinized pump blood to the patient, which would necessarily require more reversal agent. The Phase III trial was stopped after 169 total patients were enrolled due to apparent study design flaws and an inadequate Neutralase dose. In spite of these dosing-related issues, a decreased incidence of blood pressure problems after reversal with Neutralase was observed in comparison to protamine.

7. Question: Which indication will BioMarin pursue first, why, and what other indications might it pursue?

Answer: BioMarin plans to initiate a Phase III trial of Neutralase in the CABG indication first in 2002, because the use of Neutralase in CABG is the most advanced clinical development program. CABG is performed over 600,000 times in the U.S. and Europe each year and reversal of heparin is required in all procedures performed using heart-lung bypass.

Subsequent to initiating the Phase III trial related to CABG, BioMarin intends to study the use of Neutralase in angioplasty. Angioplasty is performed approximately 1.4 million times in the U.S. and Europe annually. Currently, heparin is used in angioplasty procedures to prevent thrombosis during or after the procedure. Protamine is avoided because it can cause thrombosis and blockage of the artery just opened. By avoiding protamine, the patient remains immobilized and is anticoagulated for hours after the procedure, waiting for the heparin to dissipate on its own before the sheath is removed and the patient can ambulate. Neutralase has been shown in a Phase II trial to safely reverse heparin and allow earlier sheath removal and earlier ambulation (Tanguay et al., 2001). Reversal of anticoagulation with Neutralase retains some of the residual anti-thrombosis effect of heparin (known as anti-Xa activity), which may be a further advantage of using Neutralase for this indication.

8. Question: In addition to reversing heparin, does Neutralase have the potential to reverse the new agents such as Low Molecular Weight Heparins (LMWHs) and Arixtra (the new pentasaccharide from Sanofi/Organon)?

Answer: Neutralase is the only agent known to efficiently reverse these new heparin-like anti-clotting agents. Neutralase is able to inactivate these agents because it cleaves the recognition site for anti-thrombin III. The binding of anti-thrombin III to these agents is required for the inhibition of coagulation enzymes such as Factor IIa and Factor Xa. Studies have shown that Neutralase can cleave Arixtra, the new pentasaccharide agent from Sanofi, into an inactive trimer and a dimer (Daud et al., 2001; Yu et al., 2000). These studies show that protamine does not work at all on Arixtra and works poorly on the other low molecular weight compounds. It has a relatively low affinity to bind these small heparin-like molecules

9. Question: How is Neutralase manufactured?

Answer: Neutralase is manufactured in large-scale batch culture of Flavobacterium heparinium. IBEX successfully manufactured clinical product through the use of a contract manufacturer at commercial 2,000 liter scale. BioMarin believes this manufacturing process will be further scaleable to larger commercial production levels.

10. Question: What is the Neutralase intellectual property position?

Answer: Neutralase is protected by a collection of patents regarding the heparinase enzyme, composition of matter, method of use, and methods of production.

QUESTIONS ON PHENYLASE

1. Question: What kind of an enzyme is Phenylase and how does it work?

Answer: Phenylase is a special stabilized microcrystalline form of the enzyme phenylalanine ammonia lyase (PAL). Phenylase is designed to degrade phenylalanine in the gut after oral administration. In doing so, it lowers blood phenylalanine levels, which are elevated in phenylketonuria (PKU) patients.

2. Question: What is the indication for Phenylase?

Answer: Phenylase is being developed as an oral enzyme therapy for patients with PKU. PKU is a genetic disease in which the body cannot properly metabolize phenylalanine. The elevated levels of phenylalanine lead to brain damage and severe mental retardation if left untreated. There are about 50,000 patients in the US and Europe with PKU. Patients with PKU are diagnosed at birth by newborn screening and their phenylalanine levels are controlled by restrictive diet. With adequate control, brain damage can be avoided. Phenylase is currently in the preclinical stage of development.

3. Question: What do patients do today since there are no approved drugs on the market?

Answer: The current standard of care for PKU is dietary control of phenylalanine intake. A phenlyalanine free diet is easy to maintain in babies on formula but is difficult and expensive later in life. Older patients use a special phenylalanine free formula as their main food item and supplement that with expensive special foods that are engineered to be low in phenylalanine. The special dietary foods and formulas are expensive, costing more than $5,000 per patient per year over normal food requirements, and are unpalatable for many patients. Most school age children, teenagers, and adults have difficulty maintaining the degree of control over phenylalanine intake recommended to achieve adequate protection of the brain. Teenagers and adults frequently go off the diet in spite of the fact that the phenylalanine control is now recommended for life (Phenylketonuria NIH consensus statement). Phenylase has the potential to provide a convenient oral medication that would allow patients to eat a normal diet and maintain a better degree of control of phenylalanine intake.

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