Glyko Biomedical Ltd.'s 30.6%-owned affiliate, BioMarin Completes Important Milestone in the Manufacturing of Aldurazyme.

Business/Health Editors

NOVATO, Calif.--(BW HealthWire)--April 24, 2001

BioMarin Senior Management Provides Comprehensive

Manufacturing Update

Glyko Biomedical Ltd.'s (OTCBB: GLYK; TSE: GBL; BVD-Berlin: GLY) 30.6%-owned affiliate, BioMarin Pharmaceutical Inc. (Nasdaq and Swiss SWX New Market: BMRN) announced today that it has completed the last major manufacturing milestone for Aldurazyme(TM) prior to the submission of a Biologics License Application (BLA) in the U.S. and Marketing Authorization Application (MAA) in Europe. This key step involved the manufacture of the five required process qualification lots of Aldurazyme. Three process qualification lots are required for the submission of a BLA to the U.S. FDA, and five lots are required for the submission of an MAA to the European regulatory authorities.

Aldurazyme, recombinant human alpha-L-iduronidase, is being tested in a Phase III pivotal trial with BioMarin's joint venture partner Genzyme General (Nasdaq: GENZ) as enzyme replacement therapy for patients with MPS-I, a debilitating, life-threatening genetic disease.

Raymond W. (Bill) Anderson, BioMarin's Chief Operating and Chief Financial Officer, said, "Progress at our cGMP commercial manufacturing facility has exceeded our expectations with regard to the amount, quality, and reduced cost of formulated bulk enzyme produced for the Aldurazyme development program. With improvements developed by our Process Development group, we increased productivity by a factor greater than four and reduced costs proportionately. At the same time, we have completed validation studies that, combined with a rigorous quality system, help ensure product and process quality. As a result, we are confident that we will be able to meet the commercial demand for Aldurazyme."

John L. Jost, Ph.D., BioMarin's Vice President, Manufacturing, added, "We have developed an efficient manufacturing process in which the enzyme is properly glycosylated and phosphorylated. This enables us to produce Aldurazyme that has therapeutic effects (as reported by the New England Journal of Medicine, January 18, 2001) at a dose of only 0.7 mg per kg of patient weight per week - approximately one and a quarter grams per average patient per year. The reason for this low dose is that the enzyme produced by our Chinese Hamster Ovary (CHO) cell line has the proper structure of mannose-6-phosphate (M-6-P) ligand needed to ensure efficient uptake by the M-6-P receptors that are present on all of each patient's cells. Our CHO cells directly produce recombinant human alpha-L-iduronidase without the complexities inherent in additional manufacturing steps to remodel the enzyme."

Frequently Asked Questions About Manufacturing at BioMarin

"As a relatively young company, members of the investment community frequently ask us about our manufacturing capabilities," Mr. Anderson said. "In order to provide comprehensive information to all investors, we are taking this opportunity to present 13 of the most commonly asked manufacturing questions with answers provided by me, John L. Jost, Ph.D., Vice President, Manufacturing, and Robert A. Baffi, Ph.D., Vice President, Quality Assurance and Quality Control on the following five pages."

Glyko Biomedical Ltd.'s principal asset is a 30.6% ownership in the capital stock of BioMarin Pharmaceutical Inc.

BioMarin specializes in the development and commercialization of therapeutic enzyme products. Since inception in 1997, BioMarin has applied its proprietary enzyme technology to develop products for lysosomal storage diseases and for the treatment of serious burns. Glyko, Inc., a BioMarin subsidiary, provides analytical and diagnostic products and services in the area of carbohydrate biology.

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including the following potential future products: Aldurazyme for MPS-I and rhASB for MPS-VI. Results may differ materially depending on the progress of BioMarin's product programs, actions of regulatory authorities, 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.

Aldurazyme(TM) is a trademark of BioMarin/Genzyme LLC, which was formed in 1998 to develop and commercialize Aldurazyme throughout the world.

BioMarin's releases and other information on the Company and its products and technologies are available on the World Wide Web at: http://www.BioMarinPharm.com.

Biographies of Mr. Anderson, Dr. Jost, and Dr. Baffi can be found on the World Wide Web at: http://www.BioMarinPharm.com/about/management.html.

                     BioMarin Pharmaceutical Inc.

         Frequently Asked Manufacturing Questions and Answers

1)   Q - Where will BioMarin manufacture commercial lots of
     Aldurazyme, the Company's enzyme product being developed for
     patients with MPS-I?

     A - Mr. Anderson -"BioMarin's manufacturing facility for
     commercial production is its `Galli Drive' facility located in
     Novato, California. The facility is designed for the commercial
     production of Aldurazyme (alpha-L-iduronidase) for use in enzyme
     replacement therapy for MPS-I. It produced the bulk enzyme for
     our pivotal Phase III trial that will be concluded later this
     year. The production technology used is recombinant CHO cell
     culture using a perfusion process. The Galli drive facility
     currently has approximately 900 liters of bioreactor cell culture
     capacity. The plant has protein purification capacity utilizing
     column chromatographic methods widely used in the biotechnology
     industry. The plant produces formulated bulk enzyme. The bulk
     enzyme is then shipped to our partner Genzyme or to an
     experienced contract manufacturer where it is filled into vials,
     labeled, and packaged for distribution."

2)   Q - What is the physical size of the Galli Drive facility and
     what is the investment necessary to support Aldurazyme commercial
     production?

     A - Mr. Anderson - "The current configuration of the
     manufacturing operations (including related quality assurance and
     quality control functions) occupies approximately 51,800 square
     feet. Of this total floor space, the developed areas include
     12,500 square feet of cGMP (current Good Manufacturing Practice)
     process manufacturing areas, 2,200 square feet of quality control
     laboratories, 8,000 square feet of materials and warehouse and
     29,100 square feet of utilities support area and
     manufacturing-related administrative areas. When current facility
     modifications are completed in Q4 2001, BioMarin will have
     invested $28 to $30 million in the manufacturing areas of the
     facility."

3)   Q - What is the capacity of the Galli Drive facility in terms of
         Aldurazyme market requirements?

     A - Mr. Anderson - "Based on our current production experience
     (without future process improvements), the facility can produce
     bulk enzyme sufficient for the treatment of approximately 2,400
     patients per year. This capacity represents 70% of the 3,400
     patients estimated to be available in the economically developed
     world, which is the primary market for Aldurazyme. At this level
     of output, the facility would be sufficient to satisfy the
     expected market demand for several years post approval."

4)   Q - What manufacturing regulatory steps are necessary prior to
         launch of Aldurazyme?

     A - Dr. Baffi - "The Galli Drive facility was constructed in
     1999, and full effort on the preparation and start-up of cGMP
     operations began in January 2000. The facility was licensed for
     the production of product for use in clinical trials by the
     California Food and Drug Branch in June 2000. Under cGMP
     procedures and disciplines, we completed production of clinical
     enzyme sufficient for the Phase III clinical trial of Aldurazyme
     in September 2000. In the production `campaign' that began in
     October 2000 and that is scheduled to end in May 2001, we have
     completed five Process Qualification (PQ) runs and will complete
     three additional runs for validation studies. Three PQ runs are
     required for the U.S. BLA submission and five PQ runs are
     required for the European MAA submission. We anticipate that the
     U.S. FDA will inspect the facility in a Pre-Approval Inspection
     (PAI) about two months after the filing of the BLA, and the
     European regulatory authorities will conduct their separate
     inspection approximately six months after the filing of the MAA.
     The preparation for both inspections is a major activity for the
     facility staff in the second half of 2001 and early 2002. The
     current staff, which is sized for cGMP production operations at
     schedules anticipated to be required for the near term, includes
     73 professionals.

     "We are now conducting real time and accelerated stability studies
     in compliance with the International Conference on Harmonization
     (ICH) guidelines. Based on results to date, we are planning on
     dating of 18 to 24 months for final product."

5)   Q - What level of success has BioMarin had with the Aldurazyme
         process to date?

     A - Dr. Jost - "The current process for the production of
     Aldurazyme yields enzyme with purity levels that meet or exceed
     industry standards for injectable proteins. The process to date
     has proven to be both robust and repeatable. For planning
     purposes, the Company's long-term capacity projections assume a
     manufacturing run success rate of 70%. However, the recent
     manufacturing run success rate is greater than 90%. With the
     complexity and variability inherent in biological processes, this
     is a highly positive result.

    "Most important, the production output in terms of vial equivalents
     per run in the current campaign has increased by a factor of at
     least four from earlier start-up runs and from our earlier
     projections. Like all active processes in early stages, we have a
     number of promising process development initiatives which we will
     be investigating to further improve production yields."

6)   Q - What is the current status of quality systems for Aldurazyme?

     A - Dr. Baffi - "Over the last year, we have greatly strengthened
     the systems that are required to certify the product quality of
     Aldurazyme. We have developed and are validating a series of 19
     assays to support product quality. The quality system is
     consistent with the leading industry standards and practices in
     the quality area in that it is considered to be `orthogonal'
     (that is, it measures different independent product
     characteristics in multiple, different product `dimensions'.)
     Upon completion of the last validation runs in May, the required
     validation studies and the quality systems will be in place for
     the Pre-Approval Inspections."

7)   Q - What is the significance of the fact that Aldurazyme is
     properly glycosylated and phosphorylated?

     A - Dr. Jost - "Aldurazyme is administered at a dose of 0.7 mg
     per kg of patient weight per week and, as a result, a standard
     patient requires a total dose of about one and a quarter grams
     per year. Our weekly dose is approximately equal to the total
     body content (the calculated amount of enzyme present) in a
     healthy person of the same size. The reason for this low dose is
     that the enzyme produced by our CHO (Chinese Hamster Ovary) cell
     line has the proper structure and is properly glycosylated and
     phosphorylated. Specifically, the enzyme has sufficient
     quantities of mannose-6-phosphate (M-6-P) ligand to ensure
     efficient uptake by the patient's cells. Our CHO cell lines
     directly produce recombinant human alpha-L-iduronidase without
     the complexities inherent in additional manufacturing steps to
     remodel the enzyme.

     "Our manufacturing process has been validated to deliver
     Aldurazyme that is consistently and properly glycosylated and
     phosphorylated. This simple and direct process promises lower
     costs than the much more complex processes that may add extra
     M-6-P ligands. The well-known relationship between the cell
     surface receptor and the M-6-P ligand suggests that additional
     M-6-P ligands will not improve cellular uptake. In addition,
     extra M-6-P ligands may result in immunogenicity concerns and
     unanticipated side effects. Based on pharmacokinetic studies in
     MPS-I canines and in MPS-I human patients, Aldurazyme levels
     achieved in the bloodstream are saturating the M-6-P receptors on
     cells. Further increases in phosphorylation above the current
     level will not improve tissue uptake of the enzyme.

     "Our primary activity test for Aldurazyme is an assay that
     measures the uptake of Aldurazyme by human fibroblast cells
     isolated from an MPS-I patient. This `biomimetic' assay (direct
     measure of a key biological function) is consistent with the
     proposed mechanism of action of Aldurazyme and is considered to
     be a very predictive test of both enzymatic activity and proper
     glycosylation and phosphorylation. Multiple analytical methods
     are employed to assess product quality and consistency. Five of
     the eight assays that evaluate the structural integrity of
     Aldurazyme are sensitive to the quantity of glycosylation and
     phosphorylation."

8)   Q - Have you had problems developing Aldurazyme and bringing it
     into production?

     A - Dr. Jost - "We have had no extraordinary difficulties in
     developing and producing Aldurazyme, but the multitude and
     breadth of the tasks required to be completed in parallel was
     challenging. In approximately nine months of 2000, we brought
     into operation a cGMP compliant new facility, closed and
     transferred the staff from a pilot facility, implemented an
     improved production process, developed a more stable formulation,
     began cGMP operations, made sufficient clinical product to enable
     and complete the Phase III trial, and improved per run output
     significantly.

     "By May, we will have completed eight successful, Process
     Qualification/validation runs that will supply all of our
     clinical product needs up to the time of the projected commercial
     launch with additional product available for the launch."

9)   Q - What were the circumstances and decisions surrounding the
     closing of the Carson Street clinical facility in Torrance,
     California, from which the original Aldurazyme clinical materials
     were produced?

     A - Dr. Jost - "The location of the Carson Street facility was
     selected to be close to the Harbor-UCLA REI laboratory where
     Aldurazyme was originally produced for both preclinical
     requirements and the Phase I clinical trial. The Carson Street
     plant was prepared to meet the initial production needs for
     Aldurazyme while a second cGMP plant at Galli Drive was
     developed, but, being a smaller plant, the production capacity of
     the Carson Street facility could not reach the levels that were
     desired for an efficient commercial launch. When the Galli Drive
     facility came on line, the Carson Street facility was closed to
     improve operational efficiency.

     "We completed the last runs required from the Carson Street
     facility at the end of April 2000 and closed the facility. We were
     pleased that 16 of the 25 technical staff working at Carson Street
     transferred to our Galli Drive facility, thus contributing their
     experience in the production of the enzyme to the new facility."

10)  Q - What is BioMarin's current manufacturing facility for the
     production of rhASB for MPS-VI?

     A - Dr. Jost - "We currently produce bulk rhASB for clinical
     trials in a clinical manufacturing facility in our Bel Marin Keys
     Boulevard (`BMK') facility in Novato, California. Specialized
     fill/finish operations are done by an experienced contract
     fill/finish manufacturer. The production technology is
     recombinant CHO cell culture. For cell culture using a perfusion
     process, the facility will operate at the 110-liter scale. The
     facility has protein purification capacity that is balanced with
     the cell culture capacity. The primary method of protein
     purification is column chromatography. In June 2000, the BMK
     facility was licensed by the California Food and Drug Branch for
     the production of clinical product."

11)  Q - What is the size of and the investment in the BMK facility?

     A - Mr. Anderson - "The BMK manufacturing operations occupy
     approximately 2,700 square feet, of which, 1,500 square feet is
     for cGMP manufacturing process areas, 700 square feet is for
     materials, and 500 square feet is for utilities support and
     manufacturing-related administration. When current modifications
     are completed in July 2001, BioMarin will have invested
     approximately $1.9 million in the clinical manufacturing areas of
     the BMK facility."

12)  Q - What is the capacity of the BMK facility as it relates to
     producing rhASB clinical materials?

     A - Dr. Jost - "We have already made sufficient amounts of rhASB
     to complete the Phase I clinical trial including enough to
     maintain the patients on the drug after the evaluation part of
     the trial is completed this summer. In addition, after facility
     modifications, the capacity will be sufficient for Phase II and
     potentially even Phase III clinical trials of rhASB for MPS-VI."

13)  Q - What is the current status of the production process for
     rhASB?

     A - Dr. Jost - "The productivity of the process using recombinant
     DNA techniques in a CHO host cell line is sufficient to support
     clinical trials. Our assays indicate that rhASB is properly
     glycosylated and phosphorylated (has the proper structure of
     M-6-P ligands) for efficient uptake. With experience gained from
     the Aldurazyme purification process, we now have an improved
     purification process for rhASB with higher net yields and lower
     volumes of material to be handled. In the BMK operation, we have
     also recorded a very favorable production run success rate of
     greater than 90%. From early results of stability studies in
     progress, we anticipate product dating for rhASB that is similar
     to that projected for Aldurazyme."