Biotech Company**
(Country)

Pharma Company (Symbol/Country)

Type/Product Area

Amount

Terms/Details (Month)

I. MODIFIED AGREEMENTS

Affymetrix Inc.

Hoechst Marion Roussel Inc. (unit of Hoechst AG; Germany)

EasyAccess Gold GeneChip probe array supply agreement; companies originally signed feasibility agreement 4/97

$15M

Non-exclusive, 3-year agreement, giving HMR right to purchase more than 0.1M GeneChip probe arrays capable of monitoring several 100M gene expression profiles for use in research; HMR also has right to purchase custom GeneChip products based on any gene sequence or database available to HMR; Affymetrix will receive annual subscription fee, custom design fees and per-chip fees; payments are expected to exceed $15M (1/99)

Parke-Davis (unit of Warner-Lambert Co.; NYSE:WLA)

EasyAccess Silver agreement; companies originally signed feasibility agreement 6/97

ND

Parke-Davis gains preferential access to standard and custom GeneChip arrays, instrumentation and software to monitor gene expression for use in R&D; EasyAccess packages offer volume discounts; further details ND (2/99)

Pfizer Inc. (NYSE:PFE)

EasyAccess Silver agreement; upgrade of 7/97 supply agreement

ND

Pfizer gains preferential access to standard and custom GeneChip arrays, instrumentation and software to monitor gene expression for use in R&D; EasyAccess packages offer volume discounts; further details ND (3/99)

Cangene Corp.

Apotex Inc.

Extension of 5-year collaboration signed 11/95, which covers development of certain recombinant biochemicals in Cangene's pipeline

$25M

Apotex extended agreement 3 years and committed an additional $25M; original $30M deal runs until 11/00; terms similar to original deal, but provide more flexibility in marketing and revenue-sharing arrangements (2/99)

Catalytica Pharmaceuticals Inc. (subsidiary of Catalytica Inc.)

Glaxo Wellcome Inc. (subsidiary of Glaxo Wellcome plc; NYSE:GLX)

Amendment of supply agreement to provide for manufacture of certain products (3/16)

$70M

Amended agreement provides for manufacture of certain Glaxo Wellcome products by Catalytica in 1999 and 2000, with options to extend deal for another 2 years; Glaxo may also extend sterile products manufacturing portion of agreement for up to 4 years beyond 2000 (3/16)

Cerep SA (France; Nouveau Marché: CEREP)

Sanofi SA (France)

Expansion of 12/97 collaboration, which calls for Cerep to develop private library of compounds for Sanofi, and grants Sanofi use of Cerep's HighThroughput Lead Development technology

ND

Sanofi to double annual funding commitment to Cerep in exchange for Cerep's screening of 2 additional targets (2/99)

Cortech Inc.

Ono Pharmaceutical Co. Ltd. (Japan)

Expansion of 4/97 oral elastase inhibitor program to include Western rights

$11.5M

Cortech and Ono reached an agreement in principle granting Ono Western rights, in addition to previously covered Far Eastern territories; Ono will pay $2M upon signing of definitive agreement and milestones of up to $9.5M; Cortech may also receive royalties of 4% on Ono products based on Cortech patents sold outside the Far East (3/99)

Corvas International Inc.

Schering-Plough Corp. (NYSE:SGP)

Schering returned rights to development and commercialization rights for injectable formulation of recombinant nematode anticoagulant protein 5 (rNAP5) granted under 6/97 agreement

-

Corvas reacquired rights to develop injectable rNAP5 alone or in collaboration with 3rd party; the focus of the companies' collaborative focus is now on oral anticoagulants (3/99)

Cytel Corp.

Nextran (unit of Baxter International Inc.; NYSE:BAX)

License agreement that supercedes 9/96 supply agreement

$4M

Cytel licensed carbohydrate synthesis and manufacturing technology to Nextran for exclusive use in xenotransplantation (3/99)

Entremed Inc.

Bristol-Myers Squibb Co. (NYSE:BMY)

Modification of 8/97 research agreement coverangiostatin (anti-angiogenic protein)

ND

Bristol-Myers returned angiostatin to EntreMed for further preclinical work, but retains an option to reassume development and marketing rights once clinical proof of principle is demonstrated (2/99)

Genelabs Technologies Inc.

DuPont Pharmaceuticals Co. (NYSE:DD)

Renewal for 1 year of collaborative research and license agreement originally signed 12/96

ND

DuPont renewed for an additional year collaboration to discover and develop drugs that control expression of certain disease-associated genes; Genelabs receives research funding, plus milestones up to $20M per gene target; total value could exceed $200M (1/99)

IGEN International Inc.

Novo Nordisk A/S (Denmark; NYSE: NVO)

Purchase of IGEN's M-Series High-Throughput Drug Discovery System; Novo's Zymogenetics Inc. subsidiary signed a screening agreement 8/98 utilizing the Origen M-Series System

ND

Novo agreed to acquire an M-Series System, now in final stages of development, for ultra-sensitive testing in drug development; further details ND (1/99)

Inctye Pharmaceuticals Inc.

Johnson & Johnson (NYSE:JNJ)

Expansion and extension of database subscription launched 1/96

ND

J&J will receive access to Incyte's LifeSeq Gold assembled database, the LifeSeq Atlas mapping database, and the ZooSeq animal gene sequence and expression database; agreement is 2nd expansion of relationship; J&J will pay annual access fees, plus milestones and royalties on products developed using Incyte technology and databases (2/99)

Inctye Pharmaceuticals Inc.

Pharmacia & Upjohn (NYSE:PNU)

Multi-year expansion of database subscription launched 5/97

ND

P&U gains access to Incyte's PathoSeq microbial database of genomic information on bacterial and fungal microorganisms; P&U will pay annual access fees, plus royalties on products developed with Incyte technology and database information (1/99)

Ligand Pharmaceuticals Inc.

Eli Lilly and Co. (NYSE:LLY)

Lilly returned rights to oral Targretin and two other RXR modulators to Ligand; original agreement signed 4/97

ND

Lilly opted not to proceed with development of three 1st-generation compounds in the Retinoid X Receptor diabetes program; all rights to oral Targretin (in preclinical testing for diabetes and advanced clinical trials for cancer) and two other RXR modulators revert to Ligand; the companies are focusing on 2nd-generation compounds from the same program (2/99)

Lynx Therapeutics Inc.

BASF AG (Germany)

Expansion of gene sequencing agreement and widening of the scope of BASF-LYNX Bioscience AG; original agreement signed in 1996

ND

BASF's non-exclusive access to Lynx's Massively Parallel Signature Sequencing amended to include non-exclusive access to other Lynx bead-based technologies and to specify that BASF will pay Lynx's costs plus commercially reasonable profits for any experiments performed for BASF under the agreement; companies also expanded scope of BASF-LYNX joint venture to include additional central nervous system diseases and other fields of interest; BASF will commit additional $10M in funding to JV, of which $4.25M was paid to Lynx for acquisition of CNS program; additional $1M paid directly to Lynx by BASF (1/99)

Millennium Pharmaceuticals Inc.

Pfizer Inc. (NYSE:PFE)

Extension and expansion of 12/94 agreement for additional 2 years; collaboration uses Millennium's platform to discover anti-fungal drug leads

ND

Pfizer elected to extend alliance 2 additional years, to 12/00, and added unspecified resources to the program (1/99)

Eli Lilly and Co. (NYSE:LLY)

Extension of 4/96 oncology alliance for 2 additional years, through 3/01

ND

Original agreement calls for Lilly to fund research program in target discovery and validation; Lilly pays milestones, plus royalties on any products in exchange for worldwide rights to develop and commercialize products (1/99)

Millennium Pharmaceuticals Inc.

AstraZeneca plc (U.K.; NYSE:AZN) Note: Deal was originally with Astra AB (Sweden), which merged 4/99 with Zeneca plc (U.K.)

Extension of 12/95 inflammatory respiratory disease alliance for additional 4 years

ND

Extension to full term is based, in part, on Millennium's successful delivery of inflammation drug targets and on development of Astra's target pipeline during alliance's 1st phase; Extension phase will focus on application of targets for drug discovery and continued quest for new targets; under terms of original agreement, Astra funds research and pays licensing fees; Millennium is also entitled to milestones and royalties on therapeutic products (1/99)

Miravant Medical Technologies

Pharmacia & Upjohn (NYSE:PNU)

Amendment of 7/95 ophthalmology co-development agreement, plus P&U entered right of first negotiation for field of cardiovascular medicine

$41.5M (equity; 7%)

P&U purchased 1.1M shares for $19M ($16.71 per share), and extended a secured line of credit of up to $22.5M; companies amended ophtalmology agreement; P&U assumes control of the clinical and regulatory aspects of joint ophthalmology programs, including SnET2 (tin ethyl etiopurpurin) for age-related macular degeneration; agreement terminates milestone provisions for ARMD and will require Miravant to account for the costs to be borne by P&U for additional responsibilities; companies also agreed that if Miravant develops SnET2 in cardiovascular field, P&U has right to 1st negotiation to acquire marketing rights (2/99)

Nanogen Inc.

Aventis Research and Technologies (affiliate of Hoechst AG; Germany; NYSE:HOE)

Executed definitive research agreement extending program from 2 to 3 years; companies first signed exclusive R&D collaboration to develop microarray platforms and related devices and applications using Nanogen's semiconductor microchip technology in combination with Aventis' Exponential Library by Association of Sublibraries technology

ND

Companies executed definitive collaborative R&D agreement detailing rights and responsibilities of the parties under the collaboration, and extended term of research program from 2 to 3 years, ensuring Nanogen substantial additional funding for the 3rd year (1/99)

Neose Technologies Inc.

McNeil Specialty Products Co. (subsidiary of Johnson & Johnson; NYSE: JNJ)

Expansion and extension of 11/97 joint development project to commercialize manufacturing technologies for certain complex carbohydrates

$4M (equity; 3%)

Neose and McNeil contemplate building a factory capable of producing at least 1 commercially promising complex carbohydrate product within a year; the compound is undisclosed but is currently widely used in food and healthcare industries; McNeil will provide substantially all of the development and capital costs of the project; concurrent with the deal's expansion, Johnson & Johnson Development Corp. agreed to invest $4M at per-share price equal to average closing price of 20 days prior to closing (1/99)

PowderJect Vaccines Inc. (subsidiary of PowderJect Pharmaceuticals plc.)

Glaxo Wellcome plc (U.K.; NYSE: GLX)

Expansion of 3/98 DNA vaccines collaboration

$1.5M

Glaxo exercised option on a DNA vaccine product, in addition to prophylactic DNA vaccine for hepatitis B covered in original agreement; Glaxo also licensed 1 of the 7 vaccines over which it already held an option; PowderJect received $1.5M; PowderJect also received $1M payment for positive clinical trial results for prophylactic hepatitis B vaccine, to which Glaxo has exclusive rights (1/99)

Scios Inc.

Eli Lilly and Co. (NYSE:LLY)

Extension of 4/97 Alzheimer's disease collaboration; development of screening assays has been a major area of focus

ND

Agreement provides additional research funding to Scios and extends deal at least throught 4/01; commercializing partner will pay milestones and royalties (1/99)

Sonus Pharmaceuticals Inc.

Abbott Laboratories Inc. (NYSE: ABT)

Amendments to 10/96 marketing and distribution agreements for EchoGen (perflenapent injectable emulsion)

ND

Royalty rates reduced for international sales, and U.S. and international milestone events were redefined; U.S. royalty rates and aggregate amount of milestone payments were not changed; provisions were added allowing Sonus to request that Abbott make milestone payments in advance of the achievement of certain milestones, in exchange for Sonus common stock (2/99)

Synaptic Pharmaceutical Corp.

Eli Lilly and Co. (NYSE:LLY)

Lilly discontinued commercial development of LY334370 migraine compound covered under 1/91 agreement-

­

Lilly discontinued development following review of data from ongoing confirmatory animal toxicology study; Lilly had earlier delayed start of Phase III trial; Lilly and Synaptic will continue to collaborate on development of alternative selective serotonin 1F receptor agonists with an improved safety profile (3/99)

II. TERMINATED AGREEMENTS

Aronex Pharmaceuticals Inc.

Genzyme Corp.

Aronex regained worldwide rights to Atragen (liposomal formulation of all-trans retinoic acid) granted in 3/93

­

Aronex regained rights to Atragen, for which it filed NDA 12/98; Aronex described the action as consistent with goal of developing sales and marketing capabilities in oncology in the U.S.; the company will pursue partners to market elsewhere in the world (3/99)

Bioject Medical Technologies Inc.

Merck & Co. Inc. (NYSE:MRK)

Merck withdrew from further negotiations under 7/98 agreement giving Merck limited-term, preferential rights to use Bioject's B-2000 jet injection system to study with certain Merck vaccines

­

Companies had been actively negotiating a second agreement that would have given Merck preferred, long-term access to B-2000 jet injection system for use with vaccines (2/99)

Cellegy Pharmaceuticals Inc.

Glaxo Wellcome plc (U.K.; NYSE: GLX)

Glaxo to return worldwide rights to Glylorin (monolaurin) to Cellegy; original agreement signed 11/96

­

Companies reached an agreement in principle for the return to Cellegy of worldwide rights to Glylorin (monolaurin), a potential treatment for ichthyosis vugaris; shift in Glaxo's R&D priorities prompted Cellegy to request return of product; Cellegy plans to seek new partner (3/99)

Chiroscience Group plc

Zeneca Group plc (NYSE:AZN) Note: Zeneca merged with Astra AB 4/99 to form AstraZeneca plc

Chiroscience will take back all rights to Chirocaine granted to Zeneca under 3/98 agreement

$32.2M

Companies reached an agreement in principle for return of Chirocaine rights granted to Zeneca for territories except Japan; action results from European Union regulatory officials' concern that when Zeneca merges with Astra AB, the combined entity, AstraZeneca, would potentially have too large a share of the long-acting anesthetic market in Europe Zeneca will make £10M ($16.1M) payment to compensate for impact, provide transitional funding for clinical trials and regulatory submissions, marketing support for upcoming anestheasia conferences, and an estimated £10M ($16.1M) funding of line extensions; the lock-up period of the Zeneca's 3.5M shares (3.1% stake) in Chiroscience will also be extended, and Zeneca will be required to dispose of shares at the end of the period (3/99)

Hyal Pharmaceutical Corp.

Fujisawa Healthcare Inc. (subsidiary of Fujisawa; Japan)

Fujisawa decided not to license Solarase for North America

­

Fujisawa opted against licensing Solarase for North America (3/99)

Medarex Inc.

Novartis AG (Switzerland)

Medarex reacquired worldwide rights to MDX-210 anti-HER2 cancer product granted 5/95 to Ciba-Geigy Ltd. (which since merged with Sandoz to form Novartis)

­

Novartis returned rights to MDX-210, a bi-specific anticancer antibody targeting HER2; Medarex will seek other partners as the product heads into Phase III trials; Medarex and Novartis will continue in $50M HuMAB-Mouse technology deal, which has produced an initial product candidate (2/99)

NeuroSearch A/S (Denmark; Copenhagen Stock Exchange: NEUS.CO)

Pharmacia & Upjohn (NYSE: PNU)

P&U terminated 7/98 agreement on NS2710 for anxiety, which covered territories not covered by NeuroSearch (Nordic and Baltic countries) or Meiji Seika (Japan and Asia)

­

P&U terminated licensing agreement following completion of first Phase II trial for generalized anxiety disorders, which achieved statistical significance of efficacy but produced sedation at high doses and a few cases of allergic reactions; NeuroSearch will evaluate allergic reactions further and expects to continue development (3/99)