Pharma Comp


Terms Details

3-Dimensional Pharmaceuticals Inc.*

ViroPharma Inc.

Drug discovery collaboration; use of 3-Dimensional¿s DirectedDiversity technology to discover and refine antiviral drugs for treating diseases caused by RNA viruses

3-Dimensional will search Viro- Pharma¿s compound libraries; ViroPharma will synthesize any candidate compounds and test them in its RNA replication assays; 3-Dimensional gets technology access fee, milestones and royalties; ViroPharma retains commer- cialization rights (1/97)


Genzyme Corp.

Equity investment in ABIOMED as a prelude to collaboration in biosurgery (combines biotechnology and biomedical engineering), with possible target of minimally invasive cardiac surgery

Genzyme bought 1.15M shares of ABIOMED common stock at $13/ each for total of $15M (giving it a 14take); agreement contains standstill provision preventing Genzyme from acquiring more voting stock (6/97)

Acacia Biosciences Inc.*

ArQule Inc.

Collaboration on drug candidates for biological targets involved in cholesterol biosynthesis and metabolism; use of ArQule¿s Mapping Array program to screen Acacia¿s Genome Reporter Matrix (GRM; generates profile of com- pound¿s effect on gene expression within cells) for biological targets; use of ArQule¿s Directed Array program to optimize any lead compounds

Details ND (10/97)

Acadia Pharma- ceuticals Inc.*

Genzyme Corp.

Collaboration to identify drug can- didates for various diseases via Acadia¿s cell-based screening tech- nology (Receptor Selection and Amplification Technology); assay will determine which of Genzyme¿s compounds affect relevant pathways in specifically engineered mammalian cells

Acadia will screen more than 1M compounds in Genzyme¿s compound library; if any hits result, companies will negotiate research agreement covering development and commercializa- tion of active compounds (10/97)

Acorda Therapeutics Inc.*

Elan Corp. plc (Ireland)

Agreement to develop Elan¿s oral sustained release formulation of fampridine (4-amino-pyridine; acts on potassium channels) for treat- ing spinal cord injuries

Elan bought undisclosed equity stake in Acorda; Acorda will de- velop product for spinal cord injur- ies; Elan will continue to develop product for multiple sclerosis and other (unrelated) markets (2/97)

Activated Cell Therapy Inc.*

The Immune Response Corp.

Licensing agreement on Immune Response¿s dendritic cell therapy for cancer and other diseases

Immune Response licensed the issued and pending patents from University of Brussels (Belgium) and sublicensed them to Activated Cell Therapy, which acquired worldwide rights (6/97)

Activated Cell Therapy Inc.*

Osiris Therapeutics Inc.*

Agreement to develop a cell separation device to recover mesenchymal stem cells via Activated Cell Therapy¿s cell isolation and enrichment tech- nology; Osiris will develop cell therapy products based on mesen- chymal stem cells for regenerative tissue therapy

Osiris gets exclusive worldwide rights to use Activated Cell Thera- py¿s cell isolation and enrichment technology specifically for recov- ery of mesenchymal stem cells (5/97)

Advanced Cell Technology Inc.*

Genzyme Trans- genics Corp.

Agreement to produce human therapeutic proteins in milk of cloned transgenic cattle; use of Advanced Cell Technology¿s techniques for producing cloned bovine embryos combined with Genzyme Transgenics¿ genetic engineering expertise; 1st product will be human serum albumin

Genzyme Transgenics will pay $10M to Advanced Cell Technol- ogy over 5 years, subject to achievement of milestones; further details ND (10/97)

Agouron Pharma- ceuticals Inc.

Igen International Inc.

High-throughput screening agree- ment to accelerate identification of drug targets using Igen¿s Origen technology (uses ruthenium labeled probes)

This is a contract service offered by Igen; details ND (10/97)

Alanex Corp. (wholly owned subsidiary of Agouron Pharmaceuticals Inc.)

Icos Corp.

Collaboration to discover small molecule drugs for an Icos molecular target (undisclosed) by screening with Alanex¿s technology

Icos will provide its molecular target, develop initial and second- ary assay systems and preclinical models; Alanex will design and synthesize compound libraries, perform high-throughput screening and combinatorial chemistry optimization; companies will share commercial rights to any products; both companies will contribute equal funds to R&D (5/97)

Alexion Pharmaceuticals Inc.

Genetic Therapy Inc. (wholly owned subisdiary of Novartis AG; Switzerland)

Alexion granted Genetic Therapy rights to its technology (enzymatic remodeling of viral surface carbo- hydrates) to develop immunopro- tected viral gene therapy products for direct in vivo gene therapy

Genetic Therapy gets exclusive worldwide rights; Alexion will get up-front license fees, research pay- ments and milestones totaling $10M; Alexion also gets royalties (1/97)

Alkermes Inc.

Alza Corp,

Stock purchase agreement and pro- duct development collaboration focused on use of Alkermes¿ Pro- Lease or Medisorb drug delivery technology

Alza will buy 2M shares of Alker- mes¿ stock at $25 each for total of $50M (giving it a 9.7take); Alza will also fund development of research program and has worldwide commercial rights; Alk- ermes will manufacture product and gets royalties on sales (ann- nounced 2/97; closed 3/97)

Alkermes Inc.

Alza Corp.

Agreement to develop and com- mercialize Alkermes¿ RMP-7 (receptor-mediated permeabilizer) for delivery of drugs to brain; especially in combination with carboplatin for treating malignant brain tumors

Alza has option to acquire exclusive worldwide rights to RMP-7; Alza will pay $10M up- front to fund 2 new Phase I/II clinical trials; depending on their outcome, Alza will decide whether to exercise option; if it does, it will make additional payments ($30M) for costs associated with advanced clinical development; Alkermes gets milestones ($10-$20M) on commercial- ization; Alkermes will manufacture product; partners will share equally in profits (10/97)

Alkermes Inc.

Genentech Inc.

Collabortion to advance ProLease human growth hormone to Phase III trials in growth hormone-deficient children. ProLease is a sustained release formulation of Genentech¿s human growth hormone based on Alkermes¿ ProLease delivery system

Terms ND (11/97)

Alteon Inc.

Genentech Inc.

Development and marketing agree- ments related to Alteon¿s drug, pimagedine, a treatment for diabetic kidney disease

Genentech will make an initial equity investment of $15M in Alteon, through common and preferred stock. Genentech will fund pimagedine devel- opment with an investment of up to $48M in Alteon convertible preferred stock, payable as an initial $16M cash investment in early 1998, with more to follow. Alteon will get mile- stones up to $50M for regulatory filings in the U.S. and Europe, plus royalties on any sales. Second- generation drugs, which may be selected from Alteon¿s portfolio of other ad- vanced glycostatin end product inhib- itors are exclusively licensed to Genen- tech, with Alteon to receive up to $50M in milestones related to approvals (12/97)

Apoptosis Technology Inc. (subsidiary of ImmunoGen Inc.)

BioChem Pharma Inc. (Canada)

Collaboration on anti cancer therapeutics; use of Apoptosis Technology¿s screens (based on 2 families of proteins involved in apoptosis, Bcl-2 and the insulin- like growth factor receptor) to generate lead compounds

BioChem gets exclusive worldwide license to Apoptosis Technology¿s screens; agreement also covers identification of novel targets and development of new screens; BioChem will develop all products and will finance research for at least 3 years; Apoptosis Technology gets milestones for each product and royalties on sales (8/97)

Aprogenex Inc.

Centocor Inc.

Product development and license agreement on Aprogenex¿s DNA probe in situ hybridization technol- ogy for detecting and quantitating HIV RNA intracellularly (ViraFlow assay)

Centocor gets rights to develop and sell products to detect HIV using instrumentation platforms other than flow cytometry; Apro- genex gets up-front license fee, milestones and royalties; Centocor responsible for product develop- ment, regulatory approvals and marketing (3/97)

AquaBio Products Sciences LLC*

NPS Pharmaceuti- cals Inc.

Technology cross-licensing agreement; AquaBio will use NPS¿ technology to alter calcium physiology in fish and other marine species; NPS gets rights to compounds or biological structures discovered by AquaBio that may have human therapeutic applications

NPS acquired 60f AquaBio¿s stock with options to acquire additional shares in future; further details ND (9/97)

Aquasearch Inc. (NASDAQ:AQSE)

Inflazyme Pharmaceuticals Inc. (NASDAQ: IZYPF; Canada)

Letter of intent for 10-year drug development and manufacturing agreement; Inflazyme will investigate potential therapeutic activity of Aquasearch¿s collection of micro- algae; disease targets include inflammation, cancer, blood dis- orders and cardiovascular diseases

Aquasearch will provide Inflazyme with access to its collection of several thousand different micro- algae; Inflazyme will search each species for therapeutic activity; Inflazyme gets exclusive rights to any compounds discovered; Aqua- search gets cost-plus reimburse- ment of research costs, milestones and royalties (9/97)

Arena Pharmaceuticals Inc.*

Tripos Inc.

Collaboration to discover new drug candidates via Arena¿s receptor identification technology, screening and biology and Tripos¿ molecular informatics technology and Optiverse chemical compound library

Tripos will make undisclosed equity investment in Arena; companies will focus on discover- ing therapeutic targets and lead compounds to partner with pharmaceutical companies (7/97)

Argonex Inc.*

Dyax Corp.*

Collaboration on affinity ligands and separation tools to improve purification processes for urokinase (naturally occurring enzyme with thrombolytic activity) via Dyax¿s phage display-based affinity separa- tions technologies

Details ND (5/97)

Ariad Pharmaceuticals Inc.

Incyte Pharma- ceuticals Inc.

Database subscription agreement on Incyte¿s LifeSeq gene sequence and expression database

Ariad purchased a license concur- rent with its establishment of a joint venture with Hoechst Marion Roussel Inc. (the Hoechst-Ariad Genomics Center LLC); Incyte gets access fees and potential mile- stones and royalties (3/97)

Aronex Pharmaceuticals Inc.

Genzyme Corp.

Amendment of 9/93 agreement on Atragen (liposomal form of all- trans retinoic acid; currently in Phase II trial for acute promyelo- cytic leukemia and Phase II/III trial for Kaposi¿s sarcoma in AIDS)

Genzyme¿s product rights will be converted to option to commercial- ize Atragen; if Genzyme exercises option, Aronex gets $3M in cash, equal co-promotion rights in U.S. and royalties; if Genzyme does not exercise option, Aronex will re- acquire worldwide rights by pay- ing Genzyme $2M in cash plus royalties (3/97)

ArQule Inc.

Genzyme Corp.

Partnership to identify, optimize and develop drug candidates for treating cancer, infectious diseases and autoimmune/inflammatory diseases

Genzyme will use its assays to identify drug leads from ArQule¿s Mapping Array compound sets; companies will optimize leads with ArQule¿s Directed Array program; once efficacy demonstrated in whole animal model, Genzyme will decide whether to continue preclinical development with ArQule or to license out the active leads in exchange for paying ArQule milestones and royalties (4/97)

ArQule Inc.

Signal Pharma- ceuticals Inc.*

Expansion of alliance on use of ArQule¿s Mapping Array and Directed Array technologies to generate drug leads for modulating gene expression

New agreement provides for in- creased number of compounds for Signal to evaluate in its screening assays; depending on (other) exist- ing alliances, the companies will either share ownership rights to any compounds or will get mile- stones and royalties on developed products (1/97)

Artemis Pharmaceuticals (Germany)*

Exelixis Pharma- ceuticals Inc.

Artemis to seek to identify and validate drug screening targets in model vertebrates, using Exelixis¿ expertise in fruit flies and nematodes with Artemis¿ knowledge in zebrafish and mouse genentic technology

Exelixis to make significant minority investment in Artemis, and the com- panies to have overlapping boards of directors and scientific advisors. Fur- ther details ND (12/97)

Atrix . Laboratories Inc

Gensia Sicor Inc.

Temination of 5/95 licensing agree- ment on sustained release version of leuprolide acetate for treating prostate cancer (based on Atrigel drug delivery system)

Based on a relationship brought to Gensia through its 2/97 acquisi- tion of Sicor (relating to develop- ment of leuprolide depot formu- lations), Gensia Sicor terminated its agreement with Atrix (11/97)

Aurora Biosciences Corp.

Allelix Biopharmaceuticals Inc. (TSE: AXB; Canada)

Drug screening collaboration; use of Aurora¿s high-throughput screening and mammalian cell-based fluorescent bioassay on certain of Allelix¿s mole- cular targets in neuropharmaceuticals

3-year agreement; Aurora gets up to $47M in license fees, R&D funds and milestones; it also gets royalties (1/97)

Aurora Biosciences Corp.

Sibia Neuro- sciences Inc.

Cross-licensing of rights to technol- ogies for drug screening and discovery: Sibia¿s transcription-based assay (TBA) and Aurora¿s reporter molecules and fluorescence-based bioassay

Aurora and Sibia each get non- exclusive rights to each other¿s specific technologies; further de- tails ND (1/97)

Axiom Biotechnol- ogies Inc.*

Cadus Pharma- ceutical Corp.

Licensing agreement on Axiom¿s high-throughput pharmacological screening system (HT-PS; measures rapid changes in intracellular signals by natural or genetically engineered human cells in response to test compounds)

Cadus has already bought $2M of Axiom¿s preferred shares for a 26take; if Cadus receives the HT-PS system within specified time, it will buy another $2M in preferred stock (increasing its stake to 38%) (5/97)

BioChem Therapeutic Inc. (wholly owned subsidiary of BioChem Pharma Inc.; Canada)

Oncogene Science Inc. (now known as OSI Pharma- ceuticals Inc.)

Expansion of 5/96 R&D collabo- ration on antiviral drugs for hepatitis C infection and AIDS

Companies will pursue additional viral targets; further details ND (2/97)

Biogen Inc.

The Medicines Co.*

Licensing agreement on Biogen¿s anticoagulant Hirulog (derived from natural anticoagulant hirudin secreted by leeches); Biogen had been developing product as a sub- stitute for heparin in treating acute myocardial infraction and other indications but halted all further development in 10/94

Biogen licensed all rights to Hiru- log to The Medicines Co., which will be responsible for further de- velopment and commercialization of the drug; Biogen will get $30M in up-front fees, milestones and development commitments, as well as royalties (3/97)

Biogen Inc.

Protein Design Labs Inc.

License on Protein Design Lab¿s antibody humanization patents; in particular, for a humanized antibody to a specific target antigen

Biogen gets worldwide non-exclusive license, for which it paid $1M licensing fee to Protein Design Labs; Protein Design Labs also gets royalties (3/97)

Bioject Medical Technologies Inc.

Elan Corp. plc (Ireland)

Joint venture to develop continuous glucose level monitoring system for diabetics; Elan will also participate in development of pre-fill format for needle-free drug delivery tech- nology

Joint venture subject to definitive agreement; Elan will make $3M equity investment in Bioject and will invest $0.5M in development of pre-fill needle-free technology; joint venture will be 80.10wned by Bioject and 19.90wned by Elan; joint ven- ture will pay $15M for exclusive license to certain rights associated with Elan¿s glucose monitoring technology; joint venture will fund clinical development; Elan will make loan to Bioject or acquire significant equity stake (10/97)

Biomira Inc. (Canada)

Chiron Thera- peutics Inc. (unit of Chiron Corp.)

Partnership to co-develop Biomira¿s Theratope immunotherapeutic vaccine (synthetic cancer vaccine designed to stimulate patient¿s own immune system) initially for treating metastatic breast cancer

Chiron Therapeutics will develop, register and market product; Bio- mira responsible for manufacturing vaccine; Chiron has exclusive mar- keting rights in U.S. and Europe; Biomira has rights in Canada; companies will share equally the costs for clinical trials and regis- tration in U.S. and Europe; com- panies will share equally revenues from sales; Biomira gets up-front payment and milestones (5/97)

BioSepra S.A. (France; subsidiary of BioSepra Inc.)

British Biotech plc (U.K.), Oxford Asymmetry Ltd.* (U.K.) and Upfront Chromatography (Denmark)

Formation of consortium to develop next-generation purification tech- nology for biopharmaceuticals, including new composite mineral- organic material expressed with very selective small molecule combinatorial ligands

Consortium received official support from the Eureka organiza- tion of the European Community and the ministries of research of France, U.K. and Denmark; they will fund 50% (about US$4M) of the research budget over next 42 months; BioSepra initiated and will coordinate the consortium; BioSepra retains commercializa- tion rights to new consumable purification media (7/97)

BioSite Diagnostics Inc. (NASDAQ:BSTE)

Scios Inc.

Licensing agreement on Scios¿ B-type natriuretic peptide (BNP) for use in point-of-care diagnostic for congestive heart failure

Scios gets licensing fees and royal- ties; further details ND (3/97)

BioSite Diagnostics Inc. ) (NASDAQ:BSTE

Xoma Corp.

Licensing agreement on Xoma¿s technology and patents for use in point-of-care diagnostic for sepsis (endotoxemia)

Details ND (3/97)

Biovector Therapeutics S.A.* (France)

IAF BioVac Inc. (subsidiary of BioChem Pharma Inc.; Canada)

Agreement to develop nasally delivered vaccine via Biovector¿s supra molecular biovector technology (polysaccharide core surrounded by phospholipid layer); vaccines will be developed for influenza, meningo- coccal meningitis and pneumococcal infections, with 1st target to modify BioVac¿s inactivated split influenza vaccine

BioVac gets rights to vaccine tech- nology and to commercialize prod- ucts; BioVac bought minority equity stake in Biovector and will fund product development and registration costs; Biovector gets royalties on sales; Biovector will supply its vectors and BioVac will manufacture vaccines (5/97)

BreasTek Inc.*

Novopharm Bio- tech Inc. (TSE: NVO; Canada)

Initiation of court proceedings by Novopharm to dissolve agreement to co-develop monitoring test for breast cancer (dates from 5/96)

Novopharm is seeking release from its obligations under a memorandum of understanding, including the return of amounts advanced by Novopharm and other related relief (10/97)

Calypte Biomedical Corp.

Trinity Biotech plc (Ireland)

Collaborative R&D agreement to develop rapid, 1-step HIV test (on urine samples)

Details ND (1/97)

Cambridge Drug Discovery Ltd.

Oxford Molecu- lar Group plc (U.K.)

Cambridge to provide advanced high-throughput screening for discovery research

Oxford pays up to a total $5M in cash

Cantab Pharmaceuticals plc (U.K.)

Xoma Corp.

Licensing agreement on Xoma¿s technology for high-yield production of biopharmaceuticals (via bacter- ial expression system and ferment- ation processes)

Xoma granted non-exclusive license and will get up-front fees, milestones and royalties (3/97)

CardioGenesis Corp. (NASDAQ:CGCP)

Chiron Corp.

Research collaboration to develop methods of enhancing trans-myocard- ial revascularization (TMR) for treating myocardial ischemia; Chiron will provide its cardiovascular compounds

Preclinical research will occur at a university medical center; further details ND (4/97)

Centocor Inc.

ID Biomedical Corp. (Canada)

Contract manufacturing agreement for ID Biomedical¿s rapid culture confirmation test kit for methicillin- resistant Staphylococcus aureus (detects antibiotic resistance gene MecA)

Centocor will manufacture test kits, which ID Biomedical will use in clinical trials (8/97)


Cell Therapeutics Inc.

Manufacture and supply agreement on lisofylline (for preventing or reducing radiation and/or chemo- therapy-related toxicities in cancer patients)

ChiRex will manufacture and supply bulk product for clinical development and commercial sale; it will initially use process technol- ogy developed by Cell Thera- peutics but will also apply its chiral manufacturing processes to improve yield and purity (2/97)

Chiron Corp.

DepoTech Corp.

DepoTech repurchased marketing rights to DepoCyt in Europe and Canada; DepoCyt is injectable sustained release formulation of chemotherapeutic drug cytarabine for use in patients with neoplastic meningitis arising from solid tumors (NDA completed 4/97)

Chiron retains exclusive marketing rights in U.S.; Chiron will continue to share funding of ongoing U.S. clinical trials; DepoTech will make up-front payment to Chiron in 1997 with remainder payable by end of 1998 (contingent on regulatory approval in U.S. or a European country) (6/97)

Chiroscience Group plc (U.K.)

Trega Biosciences Inc.

Research collaboration to develop combinatorial libraries targeted at inhibiting cell adhesion molecules (selectin and other members of lectin family) involved in cancer, inflammation and other diseases

Companies will combine resources to generate targeted small mole cule libraries, which will be basis of licensing deals with big pharma; companies will share proceeds from these transactions (5/97)

Chrysalis International Corp.

Taconic Corp.*

Collaboration to produce transgenic rodent models (via DNA micro- injection technology) for use in biomedical research and drug dis- covery

Taconic will produce, market and distribute the Chrysalis animal models; Taconic also gets expand- ed transgenic breeding and com- mercialization rights under Chrys- alis¿ patent on use of DNA micro- injection to create transgenic animals (2/97)

Cognetix Inc.*

CytoTherapeutics Inc.

Collaboration on cell- and gene- based therapies for central nervous system (CNS) diseases; use of Cognetix¿s conopeptides (derived from venom of Conus marine snails) that are specific to CNS receptor targets (ion channel blockers) and CytoTherapeutics¿ encapsulated cell-based system for delivering drugs to CNS

CytoTherapeutics will make 20 0.000000e+00quity investment in Cognetix over 1 year; companies will share devel- opment costs and profits unless otherwise agreed; companies will jointly decide which drug candi- dates to develop (2/97)

CombiChem Inc. (IPO pending)

Athena Neuro- sciences Inc. (wholly owned subsidiary of Elan Corp. plc; Ireland)

Collaboration on small molecule compounds for treating central nervous system disorders; Combi- Chem will generate lead candidates via its Discovery Engine and Univer- sal Informer Library (i.e., computa- tional drug discovery) for Athena

CombiChem gets up-front and research support payments as well as milestones and royalties; Athena gets worldwide rights to any prod- ucts; Elan made equity invest- ment in CombiChem, which issued 1.25M common shares in aggregate to Athena/Elan and ImClone (see entry below) (10/97)

CombiChem Inc. (IPO pending)

ImClone Systems Inc.

Collaboration on small molecule compounds against selected targets for treating various cancers; Combi- Chem will generate lead candidates via its Discovery Engine and Univer- sal Informer Library (i.e., computa- tional drug discovery) which ImClone will test in its biological assays to determine activity against key receptors and signaling molecules associated with cancer

ImClone will fund research for 2 years; CombiChem also gets mile- stones and royalties; ImClone gets exclusive worldwide rights to any products; ImClone bought equity in CombiChem, which issued 1.25M common shares in aggre- gate to ImClone and Athena/Elan (see entry above) (10/97)

Copernicus Gene Systems Inc.*

Inex Pharmaceutical Corp. (TSE:IEX; Canada)

Research collaboration on improved methods of delivering DNA for gene therapy; combines Copernicus¿ DNA compaction method with Inex¿s Transmembrane Carrier System (for intracellular drug delivery)

Details ND (6/97)

Cubist Pharmaceuticals Inc.

Genzyme Corp.

Collaborative agreement to identify compounds that act against patho- genic bacteria and fungi via small molecule drug discovery and screen- ing of Genzyme¿s compound library (targets include bacterial and fungal amino acyl transfer RNA synthetases)

Cubist will use its genetic targets to screen Genzyme¿s compound library; Cubist has right of 1st negotiation to obtain license for further development of any active compounds discovered (3/97)

CuraGen Corp. (IPO pending)

Biogen Inc.

Collaboration to discover therapeutics in wide range of diseases; companies will also conduct pharmacogenomic analyses of selected products and product candidates of Biogen

Biogen gets access to CuraGen¿s genomics platform and non-exclu- sive access to its subscription data- bases; Biogen will fund research over 5 years; Biogen will invest $5M in CuraGen common stock at the IPO price and will loan Cura- Gen $10M (which is convertible into CuraGen common stock at its option); research support payments and database access fees could total $18.5M; CuraGen also gets milestones up to $18.5M for each therapeutic product developed under exclusive license; Biogen made $1M equity investment in CuraGen in 6/97 during feasibility study period (11/97)

CuraGen Corp. (IPO pending)

Genentech Inc.

Genentech gets access to CuraGen¿s genomics platform in the five-year subscription agreement

Genentech will buy up to $5 million worth of CuraGen stock and provide a $26 million line of credit. After the end of the first year, the drawn-down portion of the credit line is convertible at CuraGen¿s option into CuraGen stock at the fair market price. Genentech will provide up to $24 million in funding over the five-year period (12/97)

CV Therapeutics Inc.

Biogen Inc.

Collaboration on CVT-124 (highly selective adenosine A1-receptor antagonist) for treating edema associated with congestive heart failure (Phase II trial is imminent)

Biogen and its European subsidi- ary Biotech Manufacturing Ltd. get exclusive worldwide rights to develop and sell CVT-124; Biogen and CV Therapeutics will co-de- velop drug but Biogen will pay all costs of commercializing; CV Therapeutics gets up-front pay- ments of $16M, including $5M in cash and $7M in equity (at $10.45 per share), advance funding of a development milestone and partial access to line of credit; CV Thera- peutics also gets milestones and royalties (3/97)

CyberChemics Inc.*

Structural Bio- informatics Inc.*

Collaborative agreement to develop protease inhibitors for hepatitis C via advanced computational technologies

Structural Bioinformatics will design non-peptide drug leads based on computational structural analysis of sequences of highly active viral protease inhibitors generated by application of Cyber- Chemics¿ algorithms (1/97)

CytImmune Sciences Inc.*

EntreMed Inc.

Collaboration to develop specific immunoassays to measure 2 anti- angiogenic proteins (angiostatin and endostatin) for use as cancer prognostic or diagnostic tests

Collaboration involves minority equity investment in CytImmune by EntreMed; further details ND (4/97)

Cytogen Corp.

Elan Corp. plc (Ireland)

Definitive license agreement on use of Cytogen¿s genetic diversity library technology to develop orally delivered drugs

Elan gets worldwide rights to any products; ongoing research collaboration between the companies identified a group of peptides that can bind to gastrointestinal receptors and that can direct transport of drugs from intestine into bloodstream; details ND (1/97)

Cytokine Networks Inc.*

Idec Pharma- ceuticals Corp.

Licensing agreement on Cytokine¿s anti-MIF (macrophage inhibi- tory factor) antibody technology

Idec gets exclusive license to anti-MIF antibody technology for therapeutic and diagnostic applications; Idec will make $3M preferred equity investment in Cytokine Networks and will also pay milestones and royalties (9/97)

Darwin Molecular Corp. (subsidiary of Chiroscience Group plc; U.K.)

Geron Corp.

Joint research collaboration on diseases associated with aging; research will focus on biochemical pathways in cells affected by Werner¿s syndrome (rare genetic disorder, for which Darwin identified the gene); goal is to develop diagnostics and therapies for age-related diseases

Geron gets access to Darwin¿s intellectual property and research in this area; Darwin will provide sequencing and bioinformatics support; Geron gets exclusive license in exchange for payments to Darwin in Geron common stock at milestones; Chiroscience will share profits with Geron (9/97)

CN Biosciences Inc.

StressGen Bio- technologies Corp. (Victoria, B.C.)

Co-distibution agreement; CN Biosciences¿ principal operating subsidiary, Calbiochem, will market more than 150 StressGen signal transduction products under its brand

Terms ND (12/97)

Digital Gene Technologies Inc.

Immunex Corp.

Immunex gets access to Digital Gene¿s total gene expression an- alysis (TOGA) system to search for drugs against inflammatory diseases of the gastrointestinal tract

Immunex will pay $3.5M up front to Digital Gene and $3M more over the next five years. Up to $6.5M per year may be paid, as determined by sample volume and the number of molecules identified as research candidates. For each molecule successfully developed in the U.S. and Europe, Immunex will pay up to $18M in milestones, with a goal of developing 3 molecules. Immunex also will pay royalties on worldwide sales of any products. Digital Gene retains rights to any targets generated outside the field of gastrointestinal inflammation. Immunex has an option to provide license fees, milestone pay- ments and royalties for those molecules as well (12/97)

Dura Pharmaceuticals Inc.

Genentech Inc.

License, development and supply agreement on application of Dura¿s Spiros pulmonary drug delivery technology to macromolecules (an unidentified Genentech protein)

Dura is responsible for formula- tion, development and manufact- uring of finished dosage form; Dura will supply Spiros inhalers to Genentech for clinical testing, commercialization and marketing; Dura gets signing fee, R&D fund- ing, milestones, manufacturing supply profit and royalties; Genen- tech and its sublicensees have worldwide marketing rights (5/97)

Dyax Corp.*

Chiron Corp.

Licensing agreement on Dyax¿s phage display technology for constructing and screening protein and peptide libraries

Chiron gets non-exclusive license for use in therapeutics; Dyax gets signing fee, milestones and royal- ties (5/97)

Dyax Corp.*

IGEN Internat- ional Inc.

Licensing agreement on Dyax¿s phage display technology for constructing and screening protein and peptide libraries

IGEN gets non-exclusive license for use in diagnostics; Dyax gets signing fee, milestones and royal- ties (5/97)

Dyax Corp.*

Tularik Inc.*

Drug discovery collaboration; use of Dyax¿s phage display technology to identify small structured peptides (from Dyax¿s library) that bind to Tularik¿s intracellular targets

Tularik will design and develop orally active small molecule drugs based on information provided by Dyax¿s peptides; Tularik will fund screening and gets exclusive rights to small molecule drugs it designs based on Dyax¿s peptides; Dyax gets milestones and royalties (10/97)

Dyax Corp.*

Utrecht Biotechnology Systems N.V.

Licensing agreement on Dyax¿s phage display technology for constructing and screening protein and peptide libraries

Utrecht gets non-exclusive license for use in research; Dyax gets signing fee, milestones and royal- ties (5/97)

Enzon Inc.

Xoma Corp.

Licensing agreement on Xoma¿s technology for high-yield production of biopharmaceuticals (via bacter- ial expression system and ferment- ation processes)

Xoma granted non-exclusive license and will get up-front fees, milestones and royalties (3/97)

EnzyMed Inc.*

Amylin Pharma- ceuticals Inc.

Agreement on discovery of new drugs for treating obesity and diabetes; EnzyMed will use its combinatorial biocatalysis tech- nology to synthesize small mole- cule chemical libraries for Amylin

EnzyMed gets milestones and royalties on a per-active com- pound basis; both companies may participate in compound optimization; thereafter, Amylin will be responsible for further product development (preclinical and clinical) (9/97)

FibroGen Inc.*

ArQule Inc.

Collaboration to identify and develop drugs for treating fibrotic disorders and post-surgical scarring; will use ArQule¿s Mapping Arrays (small organic compounds) to screen against FibroGen¿s biological targets

If companies identify lead compounds, FibroGen will use ArQule¿s Directed Arrays to optimize leads; companies will share ownership rights to active leads as well as revenues on commer- cialization (6/97)

GelTex Pharmaceuticals Inc.

Genzyme Corp.

Formed 50/50 joint venture (RenaGel LLC) for final develop- ment and commercialization of RenaGel non-absorbed phosphate binder (for controlling elevated serum phosphorus levels in chronic kidney failure patients; 2 U.S.-based Phase III trials completed)

Genzyme will pay GelTex $27.5M ($2.5M in equity [0.1M unregistered shares at $25 each], $15M on receipt of marketing approval by FDA and $10M 1 year afterwards); GelTex will contribute product and underlying patents and technology to the joint venture; Genzyme will handle sales, marketing and inter- national regulatory activities; joint venture has commercial rights worldwide except Japan and certain Pacific Rim countries; companies will share equally all expenses and profits (6/97)

Gene Logic Inc.

Molecular Geri- atrics Corp.*

Collaboration to discover genes related to Alzheimer¿s disease via Gene Logic¿s Accelerated Target Discovery program (based on genomics and bioinformatics) to identify new drug targets and lead compounds

Gene Logic will license drug targets and drug lead compounds to pharma- ceutical partners for development and commercialization; Molecular Geriatrics will license or commercialize discoveries for diagnostic uses; both companies will share revenues (3/97)

Genentech Inc.

Incyte Pharmaceuticals Inc.

Database subscription agreement on Incyte¿s LifeSeq DNA sequence and gene expression database

Genentech will pay yearly access fees; Incyte could get milestones and royalties in future (1/97)

Genovo Inc.*

Ariad Gene Thera- peutics Inc. (subsidiary of Ariad Pharmaceuticals Inc.)

Formation of joint venture to develop gene therapies for controlled, long- term production of therapeutic pro- teins; will combine Genovo¿s gene transfer technologies with Ariad¿s system for regulating gene expression

Genovo and Ariad will share equally in all costs and profits; fur- ther details ND (2/97)

GenPharm International Inc.*

Abgenix Inc. (sub- sidiary of Cell Genesys Inc.) and Japan Tobacco Inc. (Japan)

Patent cross-licensing and settlement agreement for human monoclonal antibody technology (involves gene- tically modified strains of mice that make fully human monoclonal anti- bodies)

As part of cross-license agreement, Cell Genesys was granted worldwide non- exclusive license in field of gene therapy to certain GenPharm technology; agreement resolves all related litigation and claims between the parties; includes worldwide royalty-free cross-licenses to all issued and pending related patents pertaining to generation of fully human monoclonal antibodies in mice; Cell Genesys will issue $15M, 7 0nterest- bearing note due 9/30/98, which is convertible at GenPharm option to 1.67M shares of Cell Genesys stock at $9.00/share; also Japan Tobacco will make cash payment to GenPharm; GenPharm could also get 2 milestones of $7.5M each based on future issuance of certain related patents (3/97)

GenPharm International Inc.*

Centocor Inc.

Collaboration to jointly develop GenPharm¿s HuMAB mouse strain, which contains functional human anti- body genes; focus will be to develop completely human antibodies to several (unnamed) antigens

GenPharm will get up to $57M in research and benchmark payments as well as 2 equity investments (which together will equal a 10take); Centocor gets worldwide manufacturing and marketing rights and will pay royalties to GenPharm (3/97)

GenQuest Inc.*

ArQule Inc.

Collaboration on drug candidates for treating melanoma and breast and prostate cancer; ArQule¿s Mapping Array program will be used to screen GenQuest¿s cancer assays (functional analysis of oncogenes, tumor suppressor genes and tumor-specific antibodies); any lead compounds will be optimized via ArQule¿s Directed Array program

Companies will share ownership rights to any active lead com- pounds and will also share product revenues (8/97)

Genset S.A. (France)

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE: AHP)

Strategic alliance under which Genset will provide (on exclusive basis) its full-length genes encoding human secreted proteins (from its SignalTag library) for inclusion in Genetics Institute¿s DiscoverEase protein development platform

The combined protein library will be offered to all existing and future participants in the DiscoverEase program; agreement subject to antitrust review; Genset gets pay- ments based on number of cDNAs included in DiscoverEase platform and ordered by program partici- pants, up to $20M if 2,000 Genset clones are included; Genset also gets option fees, license fees, mile- stones and royalties on any drugs developed (8/97)

Gensia Sicor Inc.

SangStat Medical Corp.

Definitive supply agreement for commercial-scale production of cyclosporine bulk material (for preventing graft rejection in organ transplantation)

SangStat retains exclusive world- wide rights to product, which Gensia Sicor will manufacture (4/97)

Genzyme Transgenics Corp.

Genzyme Corp.

Establishment of joint venture to market and distribute transgenic antithrombin III (ATIII; plasma protein that helps regulate blood clotting) (Phase II trial in coronary artery bypass graft surgery is complete)

Genzyme will provide 700f development costs, up to $33M; Genzyme Transgenics will fund 30%; companies will share equally any costs in excess of that; both companies will contribute manu- facturing, marketing and other resources and will split profits equally; agreement covers all territories except Asia (7/97)

Guilford Pharmaceuticals Inc.

Amgen Inc.

Amgen acquired rights to Guilford¿s FKBP-neuroimmunophilin ligands (small organic molecules, orally active, that can cross the blood-brain barrier) for use as neurotrophic agents for treating neurodegenerative diseases (by promoting nerve regen- eration and repair)

Amgen gets worldwide rights to compounds for all human thera- peutic and diagnostic applications; Amgen will conduct and fund all clinical development and manufactur- ing plus marketing; Guilford gets $35M on closing ($15M cash signing payment, $15M in equity [0.64M shares at $23.43 each, a 3take] and $5M in share pur- chase warrants [0.7M warrants exercisable at 1500f purchase price, which when exercised will give Amgen 6 0.000000e+00quity stake and will yield $25M more to Guil- ford]); $13.5M in R&D funding over 3 years and milestones for up to 10 specified indications (if all 10 get approved by FDA, Guilford would get $392M); Guilford also gets royalties on product sales and the option to develop and co-pro- mote in the U.S. one product in one indication (8/97)

Hyseq Inc.

Chiron Corp.

Collaboration to identify genetic targets for developing cancer drugs; Hyseq will use its HyX platform gene discovery module and SBH (sequencing by hybrid- ization) technology to analyze Chiron¿s tissue samples (contain normal tissue and adjacent tumor samples of various primary and metastatic cancers)

The companies initiated their agreement in 5/97, but did not disclose the disease area until 10/97; Chiron paid a $1M signing fee and will pay $19.5M over 3 years to fund research; Chiron bought $2.5M in Hyseq stock in a private placement concurrent with its 8/97 IPO, and with its other holdings owns 4.70f Hyseq; Chiron has exclusive rights to any products; Hyseq gets milestones and royalties (10/97)

Icos Corp.

Cambridge Antibody Technology (U.K.)

Collaboration to develop antibody-based therapeutics for inflammation, cancer and allergy

Icos contributes intellectual property and biological informa- tion related to six targets; Cambridge contributes antibody engineering expertise. Further details ND (12/97)

Icos Corp.

Xoma Corp.

Licensing agreement on Xoma¿s technology for high-yield production of biopharmaceuticals (via bacter- ial expression system and ferment- ation processes)

Xoma granted non-exclusive license and will get up-front fees, milestones and royalties (3/97)

Idec Pharmaceuticals Corp.

Genentech Inc.

Termination of marketing agree- ment on IDEC-Y2B8, radioimmuno- therapy for relapsed or refractory non-Hodgkin¿s lymphoma (anti- CD20 antibody coupled to yttrium 90) (agreement dates from 2/96)

Genentech returned its marketing rights on IDEC-Y2B8 to Idec, which now has exclusive U.S. rights; Genentech cited need to focus its own resources as well as perceived smaller market oppor- tunity for this drug (as compared to nonradioconjugate IDEC-C2B8, Rituxan); Idec will fund future development expenses (10/97)

Idec Pharmaceuticals Corp.

Protein Design Labs Inc.

Licensing agreement under Protein Design Labs¿ antibody humanization patents

Idec gets worldwide non-exclusive license for a humanized monoclo- nal antibody; Protein Design Labs gets $1M license fee and royalties (3/97)

Ilex Oncology Inc.

MPI Development Inc.*

Formation of limited partnership to develop Piritrexim (DNA syn- thesis inhibitor) for treating bladder cancer, Kaposi¿s sarcoma and other cancers

Companies will jointly own and manage venture; they will also share equally in profits; Ilex licensed rights to Piritrexim to the venture in exchange for license fee, milestones and royalties; MPI bought $5M in Ilex equity (1/97)

Immunex Corp.

SuperGen Inc.

License agreement on Immunex¿s generic version of anticancer drug etoposide (FDA approved 3/96 for treating small cell lung cancer and refractory testicular cancer)

SuperGen acquired rights to drug, both the finished form and product in inventory; Immunex gets up- front cash payment (1/97)

Inflazyme Pharmaceuticals Ltd. (VSE:IZP; Canada)

SuperGen Inc.

Licensing agreement on Inflazyme¿s small molecule anticancer drugs

SuperGen gets exclusive world- wide license to all anticancer and other applications except inflam- mation; SuperGen will buy 0.1M shares Inflazyme common stock at US$2.41 each; Inflazyme also gets milestones and royalties (4/97)

IntelliGene Ltd.* (Israel)

Ribozyme Pharmaceuticals Inc.

License on use of ribozymes in amplified nucleic acid formats (diagnostic assays for 6 infectious diseases)

IntelliGene gets exclusive world- wide license to develop and sell diagnostics based on ribozymes; Ribozyme Pharmaceuticals gets license fee and royalties, and may assist in R&D (3/97)

International Murex Tech- nologies Corp. (Canada)

Digene Corp.

Extension of 4/93 alliance on DNA probe product development and distribution to include Digene¿s Hybrid Capture II HIV RNA (viral load), cytomegalovirus and hepatitis B diagnostic tests

Murex will distribute tests in U.K., Western and Eastern Eur- ope, Africa, the Middle East and Singapore (9/97)

LeukoSite Inc.

Genentech Inc.

Agreement to develop LeukoSite¿s drug for inflammatory bowel dis- ease, LDP-02

Genentech will make a $4M equity investment, pay up to $8M in milestone payments and provide 2 lines of credit (12/97)

LeukoSite Inc.

Genzyme Corp.

Collaboration to identify drugs for treating autoimmune and inflam- matory diseases; LeukoSite will screen Genzyme¿s compound library against its biological targets related to cell adhesion and inflammatory bowel disease

LeukoSite gets access to Gen- zyme¿s 800,000-compound library; after screening complete, compan- ies will negotiate research collab- oration to develop and commer- cialize active compounds (6/97)

LeukoSite Inc.

Ilex Oncology Inc.

Joint venture (L & I Partners L.P.) to develop the humanized monoclo- nal antibody Campath-1H for treating chronic lymphocytic leukemia; Campath specifically targets and binds to CD52 cell surface antigen on lymphocytes

Companies will jointly own and manage the joint venture, contri- bute equally to funding and share equally in any profits (5/97)

Lidak Pharmaceuticals

Aurora Biosciences Corp.

Licensing and drug discovery agree- ment on Lidak¿s ADIFAB technology (fluorescent 1-step free fatty acid determination method) for use in screening for drug candidates that modulate lipid pathways

Aurora gets exclusive worldwide license to technology with rights to sublicense; Lidak retains rights for human diagnostic and other applications; Aurora will pay Lidak maintenance, milestone and royalties (8/97)

LifeCell Corp.

Lifecore Biomed- ical Inc.

Distribution agreement for dental applications of LifeCell¿s AlloDerm acellular dermal graft (especially for periodontal procedures)

Lifecore has exclusive right to distribute product in U.S. (6/97)

Medarex Inc.

Xenotech LP

Cross-license agreement related to Medarex¿s transgenic mouse technology; Xenotech is joint ven- ture between Cell Genesys Inc., Ab- genix Inc. and Japan Tobacco Inc.

Agreement calls for payments up to $22.5M after $7.5M milestone payment triggered by issuance of European patent for HuMAb-Mouse (11/97)

MedImmune Inc. and BioTransplant Inc.

Protein Design Labs Inc.

License on Protein Design Lab¿s antibody humanization patents; in particular, for MedImmune¿s humanized MEDI-493 (Phase III clinical trials in preventing serious respiratory syncytial virus disease in high-risk infants are completed) and MEDI-507 (in Phase I trials for T cell mediated disorders; this is humanized form of BioTrans- plant¿s monoclonal antibody BTI-322)

MedImmune licensed the patents and BioTransplant sublicensed them through its partner Med- Immune; Protein Design gets license fee, milestones and royal- ties (7/97; 8/97)

Metabolex Inc.*

Affymetrix Inc.

Subscription to Affymetrix¿s GeneChip arrays to monitor gene expression

Terms ND (12/97)

Miravant Inc.

Chiron Corp.

Collaboration on studies directed toward early detection of lung cancer; Chiron Diagnostics, a business unit of Chiron Corp., is developing an assay to be used in clinical trials to diagnose patients at risk for cancer, eligible for trials with Miravant¿s PhotoPoint, which employs light- activated drugs to selectively destroy malignant cells

Terms ND (11/97)

Molecular Dynamics Inc.

Affymetrix Inc.

Formed the Genetic Analysis Tech- nology Consortium to standardize DNA arrays, reagent kits, instrumen- tation, software and database archi- tectures; also, non-exclusive license agreement that gives Molecular Dy- namics the rights to some Affymetrix technology for commercializing low and medium-density DNA arrays

Affymetrix gets royalties on any products sold (12/97)

Mitotix Inc.*

Ariad Pharma- ceuticals Inc.

Licensing of Mitotix¿s intracellular signaling protein FRAP (a.k.a. RAPT1, which is the biological target for orally administered immuno- suppressive drug rapamycin) for use in a system that controls dose of therapeutic proteins delivered by gene therapy

Ariad licensed a portfolio of pend- ing patent applications and related intellectual property rights to FRAP, for which it paid Mitotix an undisclosed fee; Mitotix was granted back a license for diag- nostic applications (7/97)

Molecular Dynamics Inc. and Amersham International plc (U.K.)

Chiron Corp.

DNA microarray technology access agreement; Chiron will use system to discover therapeutics and develop diagnostics in undisclosed disease areas (system compares levels of gene expression in normal and diseased cells)

Molecular Dynamics and Amer- sham will supply their integrated hardware, software and chemistry system; Chiron will provide funds and will evaluate technology in exchange for early access to latest microarray technologies (8/97)

Molecular Dynamics Inc. and Amersham International plc (U.K.)

Incyte Pharma- ceuticals Inc.

Incyte will evaluate Molecular Dynamics¿ technology for use in high-throughput DNA sequencing

Molecular Dynamics and Amer- sham will supply their integrated hardware, software and chemistry system (MegaBACE 1000); Incyte will evaluate technology in exchange for preferential rights to 1st production-level systems (2/97)

Molecular Dynamics Inc. and Amersham International plc (U.K.)

Sequana Thera-. peutics Inc., Mem- orial Sloan-Ketter- ing Cancer Center and their joint venture Genos Biosciences Inc.

DNA microarray technology access agreement; parties will further develop the high throughput microarray system (which compares levels of gene expression in normal and diseased cells)

Molecular Dynamics and Amer- sham will supply their integrated hardware, software and chemistry system; Sequana, Sloan-Kettering and Genos will provide funds and expertise in exchange for early access to latest microarray tech- nologies (7/97)

Molecular Informatics Inc.*

Chiron Corp.

Licensing agreement on Molecular Informatics¿ BioMerge bioinform- atics software (integrates genomic data from multiple sources)

Agreement allows Chiron early access to Molecular Informatics¿ technology, consulting and product services; terms ND (3/97)

Molecular Simulations Inc.*

Incyte Pharma- ceuticals Inc.

Joint development program to integrate Incyte¿s LifeSeq gene sequence and expression database with Molecular Simulation¿s WebLab Gene Explorer software for molecular analysis, design and simulation

Details ND (2/97)

MycoTox Inc.*

Alpha-Beta Tech- nology Inc.

Research agreement on antifungal drugs; MycoTox will screen Alpha- Beta¿s small-molecule carbohydrates against its library of antifungal targets (which inhibit fungal cell- wall assembly)

Alpha-Beta will retain all commer- cialization rights to drug candi- dates; details ND (2/97)


Cangene Corp. (TSE:CNJ; Canada)

Manufacturing agreement for NABI¿s new formulation of H-BIG (hepatitis B immunoglobulin, a highly con- centrated polyclonal antibody pro- duct) for preventing hepatitis B infection (currently in Phase III clinical trials)

This is an expansion of an ongoing relationship (dates from 11/92; Cangene manufactures WinRho for NABI); Cangene will manu- facture H-BIG for at least 3 years after the FDA approves the new formulation ; Cangene will also make clinical trial quantities of product; Cangene gets exclusive distribution rights in Canada for 3 years; NABI will provide plasma for manufacture of H-BIG; com- panies will share in profits on Canadian sales (10/97)

Nastech Pharmaceutical Co. Inc. (NASDAQ: NSTK)

Agouron Pharma- ceuticals Inc.

Agreement to use Nastech¿s nasal drug delivery technology to develop nasally delivered formulation of an Agouron rhinovirus 3C protease (RVP) inhibitor drug (for preventing or treating the common cold)

Nastech will use its technology to identify nasal formulation of 1 or more of Agouron¿s anti-rhino- virus compounds; Nastech gets royalties on product sales; no other details (4/97)

OncorMed Inc.

Affymetrix Inc.

Expansion of 9/96 collaboration on GeneChip-based cancer diagnostics to include the co- development of a GeneChip system for BRCA1 and BRCA2 genotyping (breast cancer)

Affymetrix will license rights to BRCA1 and BRCA2 genes for use in GeneChip arrays; both compan- ies will contribute technology and funds to develop product and soft- ware; OncorMed gets license fees, milestones and royalties; in separ- ate agreement, Affymetrix will supply OncorMed with GeneChip probe arrays that simultaneously monitor expression of up to 250 genes associated with cancer in patient samples (10/97)

OncorMed Inc.

Incyte Pharma- ceuticals Inc.

Broad-based collaboration in clinical genomics with focus on 3 areas: functional studies of selected disease- associated genes from Incyte¿s LifeSeq database; pathology data- base supported by clinical center network; and transfer of high-through- put sequencing technology for clinical diagnostics

Incyte will buy $3M of OncorMed stock (0.37M shares at $8.05 each for 10take); Incyte will buy clinical genomic services from OncorMed for undisclosed amount and will provide license to its high- throughput sequencing technology for use in OncorMed¿s clinical diagnostic services; in exchange for license, Incyte will get addi- tional shares of OncorMed stock and a stock purchase warrant (for an additional 10take) (2/97)

Ontogeny Inc.*

ArQule Inc.

ArQule¿s Mapping Array tech- nology will develop small organic compounds for testing against genetic targets with Ontogeny¿s OntoScreen system of biological assays

Details ND (12/97)

Ontogeny Inc.*

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE: AHP)

Broad alliance to allow all collabo- rators access to Genetics Institute¿s DiscoverEase protein development platform (based on signal sequence trap technology that identifies and isolates fragments of genes coding for secreted proteins)

Ontogeny gets access to library of 5,000 unidentified secreted pro- teins; all partners have access to all proteins; low up-front fees; partner can select individual pro- tein(s) for exclusive licensing on first-come basis; Genetics Institute retains option to co- develop and co-commercialize products; if it chooses not to exercise this option, benchmarks and royalties will apply (1/97)

Ontogeny Inc.*

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE: AHP)

Ontogeny secured rights to a protein from Genetics Institute¿s DiscoverEase protein development platform (based on signal sequence trap technology that identifies and isolates fragments of genes coding for secreted proteins)

Ontogeny exercised 9-month exclusive option to license an un- disclosed protein, its correspond- ing cDNA and related technology, which it picked via its OntoScreen assay system; if the protein proves out, Ontogeny will exercise the option and Genetics Institute will get license fees; Genetics Institute retains right to get milestones and royalties or to co-develop and co- commercialize any therapeutics (6/97)

Orgenics Ltd.* (Israel)

AltaRex Corp. (TSE:AXO; Canada)

Joint R&D project on in vitro point-of-care immunoassays to monitor progress of cancer therapy (via AltaRex¿s tumor-binding agents)

The Canada-Israel Industrial Re- search and Development Founda- tion provided $0.44M, which com- panies will share equally (3/97)

OsteoArthritis Sciences Inc.*

VIMRx Pharma- ceuticals Inc.

Licensing of OsteoArthritis¿s topical wound healing agent for treating partial and full- thickness burns

VIMRx acquired exclusive world- wide rights to issued and pending patents, an FDA-approved IND and sufficent product supplies for Phase I and II clinical trials; Osteo- Arthritis Sciences got $0.3M cash (5/97)

Oxford Asymmetry Ltd.* (U.K.)

LXR Biotechnology Inc.

Collaboration to discover small molecule drugs that target specific apoptosis pathways; will use LXR¿s screening systems for specific gene targets and general mechanisms of apoptosis and Oxford¿s libraries of diverse compounds

Details ND (5/97)

Oxford Molecular Group plc (U.K.)

ImmunoGen Inc.

Collaboration to use antibody re- surfacing and computerized drug design to humanize the C242 mono- clonal antibody (for treating colo- rectal cancer)

This agreement builds on the 3/95 technology cross-licensing agree- ment between the companies; Oxford Molecular has exclusive rights to use ImmunoGen's anti- body resurfacing technology on a 3rd-party basis in fields outside oncology, and case-by-case rights in oncology areas that are not under development by Immuno- Gen; ImmunoGen has all rights to C242 and will be responsible for product development and commer- cialization (4/97)

Oxford Molecular Group plc (U.K.)

PolyMASC Pharmaceuticals plc (AIM:PCP; U.K.)

Strategic collaboration to identify and design key agents that stimulate red blood cell production (for treating cancer, anemia and AIDS)

PolyMASC will fund research and pay Oxford milestones and royal- ties; further details ND (3/97)

Oxis International Inc.

Enzon Inc.

Licensing of Oxis¿ low-molecular- weight form of polyethylene glycol (PEG)

Enzon gets non-exclusive license to product; Oxis gets up-front cash payment, annual maintenance fees, sublicensing fees and royalties (8/97)

Pharm-Eco Laboratories Inc.*

Allelix Biopharma- ceuticals Inc. (TSE:AXB; Canada)

Formation of U.S. based joint ven- ture (Allelix Pharm-Eco LP) to jointly develop 2 families of Pharm- Eco¿s neuropharmaceuticals (in the areas of cognitive enhancement and cocaine addiction treatment)

Allelix will invest $4.6M in a com- bination of cash and shares over 1 year to buy a 60.5 0nterest in the joint venture and to fund preclin- ical development; proportionate ownership of joint venture will be adjusted over time to reflect cash contributions by partners (agree- ment in principle 1/97; final agree- ment 4/97)

Pharm-Eco Laboratories Inc.*

Inflazyme Pharma- ceuticals Ltd. (VSE:IZP; Canada)

Manufacturing contract for large- scale production of apanol (anti- asthma drug)

Inflazyme will use product for completion of its preclinical stud- ies and throughout clinical trials (3/97)

Pharmos Corp.

Chiron Corp.

Agreement to jointly out-license a protein delivery technology that stabilizes polypeptides against denaturation and aggregation (uses cyclodextrin derivatives)

Details ND (7/97)

Prizm Pharmaceuticals Inc.*

Chiron Technol- ogies Center for Gene Therapy (unit of Chiron Corp.)

Collaboration on new approach to gene therapy that combines Chiron¿s DNA-based alphavirus gene delivery vector with Prizm¿s Directin target- ing technology (consists of growth factor ligands that target specific tissues and enhance gene expression)

Details ND (6/97)

Progenitor Inc.

Amgen Inc.

License agreement on Progenitor¿s leptin receptor technology

Amgen gets exclusive worldwide rights to leptin receptor technology for use in human therapeutic, diag- nostic and prophylactic uses; Pro- genitor retains exclusive rights for ex vivo ligand screening, small molecule screening and cell sort- ing as well as rights for all human uses of leptin receptor DNA anti- sense molecules and in vivo uses of leptin receptor-specific mono- clonal antibodies; Progenitor will get $42M total ($0.5M license fee; $5.5M stock purchase by Amgen concurrently with Progenitor¿s IPO; $22M in milestones for 1st product; $14M in milestones for 2nd product, if Amgen takes up its option); Progenitor also gets royalties (1/97)

Prostagen Inc.*

Cytogen Corp.

License agreement on Cytogen¿s prostate specific membrane antigen (PSMA) technology

Prostagen gets exclusive license for use of PSMA in prostate cancer vaccines for certain immunother- apies; Cytogen gets up-front fee, milestones and royalties (1/97)

Protein Design Labs Inc.

Genetics Institute Inc. (wholly owned subsidiary of American Home Products Corp.; NYSE:AHP)

Collaboration to develop modulators of the immune co-stimulatory path- way (involved in immune responses to foreign and self antigens); use of Protein Design¿s antibody humani- zation technology on Genetics Insti- tute¿s antibodies directed at the B7/ CD28/CTLA-4 receptors on antigen- presenting cells and T cells

Protein Design will initially develop 3 humanized monoclonal antibodies from Genetics Institute¿s murine monoclonals; Genetics Institute gets a non-exclusive license to Protein Design¿s technology (in this area); Protein Design will get $2.5M license fee, milestones and royalties; Protein Design has option to co-promote products in North America (1/97)

Protein Design Labs Inc.

Idec Pharmaceuti- cals Corp.

License on Protein Design Labs¿ antibody humanization patents; in particular, for Idec¿s humanized antibody in development for treating steroid-resistant inflam- matory diseases

This is the 2nd license between the parties (1st in 3/97); Idec gets worldwide non-exclusive license; Protein Design Labs gets signing and license fees of $1.3M as well as royalties (9/97)

Protein Design Labs Inc.

NeoRx Corp.

License on Protein Design Labs¿ antibody humanization patents; in particular, for NeoRx¿s humanized monoclonal antibody Avicidin to be used for repeat dosing in cancer therapy

NeoRx gets worldwide non-exclu- sive license; Protein Design Labs gets signing fee and milestones of $2.9M; it also gets annual mainte- nance fees and royalties (9/97)

Protein Sciences Corp.* (formerly MicroGene-Sys Inc.)

Sequus Pharma- ceuticals Inc.

Agreement to develop commercial- scale manufacturing process (via Protein Sciences¿ baculovirus expression system) for CD4 protein (which Sequus will combine with liposomes for treating HIV and AIDS)

Sequus made undisclosed equity investment in Protein Sciences and will fund R&D and purchase pro- duct for use in clinical trials; Pro- tein Sciences will manufacture all of Sequus¿ requirements for commercial-grade CD4 and will get royalties on sales (1/97)

Protogene Laboratories Inc.*

Isis Pharmaceuti- cals Inc.

Renewal and expansion of 1994 agreement to automate Isis¿ small molecule drug discovery program; Isis expanded its use of Protogene¿s combinatorial chemistry synthesis service (custom libraries)

This agreement was already re- newed once in 7/96; details ND (9/97)

Repligen Corp.

Immunomedics Inc.

Licensing of Repligen¿s technology for enhanced production of recombi- nant proteins in mammalian cells; Immunomedics will use it to produce its LymphoCide humanized LL2 antibody product (in Phase I/II clinical trials for non-Hodgkin¿s B cell lymphoma)

Repligen will get up-front licensing fee and royalties on sales (7/97)

Repligen Inc.

T Cell Sciences Inc.

Research collaboration; use of T Cell¿s cell-based functional screen- ing and signal transduction assays to identify small molecule immuno- regulatory therapeutics from Repli- gen¿s combinatorial chemistry library

Both companies will contribute resources to the collaboration and will share any commercial oppor- tunities; further details ND (10/97)

Reprogen Inc.*

Genzyme Molecular Oncology (division of Genzyme Corp.)

Agreement to use Genzyme Mo- lecular¿s SAGE technology (serial analysis of gene expression) to identify genes expressed in different stages of reproductive tissue development; focus will be on diagnostics and gene targets for drugs for reproductive diseases

Details ND (10/97)

RiboGene Inc. (IPO pending)

ArQule Inc.

Collaboration on drug candidates for treating bacterial and viral infections; combination of RiboGene¿s genomics technology (focused on translational control of gene expression) and ArQule¿s Mapping Array program to identify active compounds, followed by use of ArQule¿s Directed Array program to optimize drug leads

Companies will share ownership rights to active lead compounds and revenues on commercializa- tion; further details ND (10/97)

RiboGene Inc. (IPO pending)

Pharmacopeia Inc.

Collaboration on drug candidates for treating infections caused by 2 clin- ically important pathogens (not dis- closed); RiboGene will screen Pharmacopeia¿s small molecule combinatorial chemistry libraries for active compounds

Companies will share ownership rights to active lead compounds and revenues on commercializa- tion; further details ND (10/97)

RiboGene Inc. (IPO pending)

Trega Biosciences Inc.

Extension of 5/95 drug discovery col- laboration; Trega will contribute its small molecule combinatorial chemis- try libraries which RiboGene will screen with its biochemical and cell- based high-throughput assays designed around pathogen-specific translation mechanisms

Scope of original agreement has been refined to focus joint efforts in areas of antiviral and anticancer drugs; companies will jointly own drug candidates (7/97)

RTP Pharma Inc. (Canada; IPO pending)

Elan Corp. plc (Ireland)

Joint venture, The Cyclosporine Co. Ltd. (TCC), to develop improved versions of immunosuppressant cyclosporine (including using RTP¿s insoluble drug delivery [IDD] technology)

Elan will invest US$12.5M in RTP (in form of equity and debt), part of which can be converted into ownership of TCC (up to 50take); Elan also gets RTP Pharma warrants; TCC will develop and run clinical trials of new cyclo- sporine formulations; TCC gets worldwide rights for cyclosporine- related products, patents and know- how from each partner; Elan will also participate in RTP¿s IPO (10/97)

SangStat Inc.

Amgen Inc.

Marketing agreement for Sang- Stat¿s cyclosporine product in the Asia/Pacific rim

Terms N/D (12/97)

Sarco Inc.

ICAgen Inc.

Sarco to use combinatorial chem- istry technology to assist ICAgen in finding drugs to interact with ion channels; compound libraries gener- ated by Sarco will be screened by ICAgen¿s proprietary assays

Sarco gets access fee and ICAgen gets commercialization rights to any drugs discovered (12/97)

Scotia Pharmaceuticals Ltd. (U.K.)

SuperGen Inc.

Collaboration to co-develop next gen- eration SuperGen drugs via Scotia¿s combinatorial lipid technology (i.e., reformulation method that involves chemically attaching bioactive lipids to drug of interest)

SuperGen gets U.S. rights to any products developed; Scotia gets European rights; companies will jointly hold rights elsewhere; companies will pay each other royalties on sales (9/97)

Scriptgen Pharma- ceuticals Inc.*

BioChem Phar- ma Inc. (Quebec)

License agreement and equity in- vestment by BioChem in Scriptgen for drug candidates in hepatitis B, dimerescent receptor research

BioChem invests $20M in Scriptgen, gets exclusive rights to drug candidates in hepatitis B; Scriptgen to provide BioChem with small-molecule candidates for novel targets in hepatitis B research; after the investment, BioChem obtains 200f Scriptgen¿s equity, and five-year warrants for 5% more equity (12/97)

Sepracor Inc.

Labopharm Inc. (TSE:DDS; Canada)

Memorandum of understanding for licensing and co-development agree- ment on solid oral dosage forms of Sepracor¿s levalbuterol (R-albuterol; a beta-agonist bronchodilator for treating asthma); will use Labo- pharm¿s Contramid controlled drug release technology

Labopharm will handle formula- tion of drug and contribute $2M to Phase I clinical trials; Sepracor will complete product development and registration worldwide; Labo- pharm gets milestones and royal- ties (1/97)

Sepracor Inc.

Oncogene Science Inc. (now known as OSI Pharma- ceuticals Inc.)

Collaborative venture on small molecule drugs for selected indi- cation; combines Oncogene Science¿s drug discovery plat- form with Sepracor¿s combina- torial chemistry libraries

Companies will provide equal funding for R&D and will also share profits equally; further details ND (3/97)

Sequus Pharmaceuticals Inc.

Gensia Labora- tories Ltd. (wholly owned subsidiary of Gensia Sicor Inc.)

Product development and supply agreement for manufacturing of Sequus¿ Stealth liposomal products (especially for oncology)

5-year agreement; details ND (10/97)

SeqWright LLC*

Vyrex Corp.

Research collaboration to use Vyrex¿s CD-Tagging technology (simultaneously tags gene, transcript and protein) to construct mouse and human functional genomic libraries

Details ND (2/97)

Sheffield Pharma- ceuticals Inc.

Ion Pharma- ceuticals Inc.*

License agreement for series of com- pounds for cancer, Kaposi's sarcoma and actinic keratosis

Up-front and milestone payments to Sheffield potentially total $4M; added to development cost savings, deal worth up t0 $10M. Sheffield retains 20 0nterest in commercial results; initial milestone payment $500,000 cash and $350,000 of Ion Pharma stock (11/97)

Sibia Neurosciences Inc

Neurocrine Biosciences Inc

Licensing agreement on Sibia's transcription based assay patents (cell-based assays for funtional activity of test compound on cell surface proteins in living cells) for use with specific ( undisclosed) molecular target

Neurocrine Biosciences gets nonexclusive license to sibia's patents. Sibia gets access to Neurocrine's combinatorial chemistry compound library for use in drug discovery and high throughput screening programs at Sibia( receptor, ion channel and enzyme targets associated with nervous system disorders) further details ND(10/97)

Stem Cell Sciences Pty. Ltd.* (Australia)

Genentech Inc.

Evaluation and option agreement on Stem Cell¿s embryonic stem cell renewal factor (ESRF); the focus will be to culture, propagate and use human somatic and multipotential stem cells for human gene therapy

Genentech has option to obtain exclusive license to ESRF for use as human therapeutics, prophylac- tics and diagnostics, including gene therapy using the DNA en- coding ESRF; if it exercises option and a product gets to market, Stem Cell could get $20M in equity investment and milestones; Stem Cell retains rights for xenotrans- plantation, ex vivo human gene therapy and all non-human appli- cations; each party gets royalties on sales in respective fields (5/97)

StressGen Biotechnologies Corp. (TSE:SSB; Canada)

Genzyme Mole- cular Oncology (division of Genzyme Corp.)

Definitive agreement to form joint venture (Stress/Genzyme L.L.C.) in stress gene therapy for treating cancer; 1st target will probably be lung cancer (stress protein genes, which trigger an immune response, will be delivered via Genzyme¿s viral or non-viral vectors)

The Canadian Medical Discoveries Fund (CMDF) will provide $7.3M to finance the joint venture, with the provision that the companies secure another $7.3M in funds over the next year; CMDF gets purchase warrants from the companies and certain rights by which it can recoup at least part of its investment; StressGen has option to buy Genzyme¿s 50 0nterest in its gene therapy tech- nology for cash or stock any time over next 5 years; companies will joint- ly develop and market stress gene therapy oncology products (memo- randum of understanding 3/97; definitive agreement 8/97)

Structural Bioinformatics Inc.*

BioChem Thera- peutics Inc. (subsidiary of BioChem Pharma Inc.; Canada)

Collaboration on drug discovery and design via Structural Bioinformatics¿ computational technologies (genomics- driven/protein structure-based drug design algorithms); targets are small molecule drugs for treating hepatitis C infection and some cancers

BioChem will pay up-front fee and fund research and milestones; Structural Bioinformatics gets roy- alties (8/97)

SynPhar Laboratories Inc.* (Canada)

British Biotech plc (U.K.)

Collaboration to design and synthesize cysteine proteinase inhibitors (CPI) for range of disease targets

British Biotech will fund this 3-year collaboration; British Biotech gets rights to develop SynPhar¿s CPIs for all indications; British Biotech gets global marketing rights except SynPhar retains comarketing rights in Japan and copromotion rights in Canada (4/97)

Synteni Inc.*

Geron Corp.

Agreement to use Synteni¿s gene expression micro-array (GEM) technology in Geron¿s drug discovery programs targeting age-related dis- orders; GEMs will be used to measure gene expression patterns in popula- tions of senescent cells, especially skin fibroblasts

Synteni will make custom GEMs using gene tags provided by Geron; further details ND (7/97)

Systems Integration Drug Discovery Co. (SIDDCO)*

Amylin Pharma- ceuticals Inc.

Agreement to generate small molecule lead compounds to support Amylin¿s discovery of new drugs for treating metabolic diseases

2-year agreement; Amylin has access to chemical libraries to be synthesized by SIDDCO, which Amylin will screen via its metabolic assays; Amylin will fund research at SIDDCO and pay milestones and royalties; Amylin has option of joining SIDDCO¿s combinatorial chemistry consortium any time in next 2 years or it may extend this agreement on annual basis (11/97)

Systems Integration Drug. Discovery Co (SIDDCO)*

NPS Pharma- ceuticals Inc.

Creation of consortium to apply combinatorial chemistry and minia- turized screening technologies to rapid discovery of new drugs

SIDDCO is forming consortium, which pools resources of its mem- bers to finance development of new technology by SIDDCO, which then shares technology with consortium partners; compounds identified from SIDDCO libraries are partner¿s property; NPS is 2nd partner (8/97)

Targeted Genetics Corp.

Genetic Therapy Inc.*

Sublicense agreement in which the Fred Hutchinson Cancer Center joins Targeted Genetics to grant Genetic Therapy a limited, non- exclusive worldwide sublicense to the patent covering a retroviral packing cell line, PG13

Terms ND (11/21)

Terrapin Technologies Inc.*

Pharmagene plc. (U.K.)

Collaboration to identify compounds for migraine headaches and gastrointestinal motility disorders, using Pharmagene¿s proprietary databases with Terrapin¿s chemo- informatics technology for classi- fication and screening and its small-molecule compound library

Terms ND (11/97)

Texas Biotechnology Corp.

Pharmacopeia Inc.

Texas Biotechnology will use Pharmacopeia¿s small-molecule combinatorial chemistry libraries to develop drug candidates for diseases of the vascular endothel- ium, such as stroke and asthma

Ownership rights to active lead com- pounds will be shared, along with revenues if they are commercialized

Theratechnologies Inc. (MSE:TH; Canada)

Chiron Corp.

Collaboration to combine and test technologies in AIDS gene therapy; Theratechnologies will combine its modified Vpr protein with Chiron¿s HIV-specific single-chain intracellular antibodies (to penetrate and neutralize HIV)

Companies will jointly own any discovery resulting from this collaboration; further details ND (11/97)

Trinity Biotech plc (Ireland)

Centocor Inc.

Agreement on develoment of cancer diagnostics using Centocor¿s serum tumor markers

Trinity gets rights to develop, manufacture, market and distribute tests; other details ND (7/97)

Tripos Inc. and MDS-Panlabs Inc. (division of MDS Health Group Ltd.; Canada)

Amylin Pharma- ceuticals Inc.

Amylin will use its receptor binding assays to screen Tripos/Panlabs¿ Optiverse chemical library of 100,000 small molecule compounds for drug candidates with activity against genetic targets associated with diabetes, obesity and dyslipidemia

Amylin will pay a 1-time up-front fee for access to Optiverse library; Amylin has rights to any active compounds discovered via screening and will control all future R&D and marketing; Amylin may partner with 3rd parties for development and/or commercialization; Tripos gets milestones and royalties (8/97)

Tularik Inc.*

Microcide Pharmaceuticals Inc.

Microcide will provide Tularik with a subset of its natural product diversity collection, which Tularik will screen in its drug discovery assays (excluding antibacterial or antifungal assays)

Microcide will provide at least 40,000 extracts initially but may increase that number later; further details ND (7/97)

Tularik Inc.*

Neurogen Corp.

Collaboration to enhance drug discovery capabilities of both companies

Neurogen gains access to selected Tularik screen methodology; Tularik gains access to part of Neurogen¿s combinatorial chemis- try library; both companies eligible for milestones and royalties if any products are developed and com- mercialized (6/97)

Versicor Inc. (majority owned subsidiary of Sepracor Inc.)

Genome Thera- peutics Corp.

Agreement to jointly research and develop antibacterial drugs via Genome Therapeutics¿ PathoGenome sequence database and Versicor¿s screening and synthesis of chemical libraries

Companies will share equally in all license fees, milestones and royalties for any products; com- panies will also split R&D invest- ment through preclinical stages; both companies have right to invest equally in additional devel- opment prior to out-licensing; Versicor retained certain market- ing rights; Genome Therapeutics gets warrants to acquire equity in Versicor (3/97)

ViroPharma Inc.

ArQule Inc.

Collaboration on therapeutics for treating diseases caused by RNA viruses; ArQule will use its Mapping Array program to identify drug leads against ViroPharma¿s targets; these leads will be optimized with ArQule¿s Directed Array program

Companies will share development and commercialization rights for compounds; further details ND (11/97)

Vyrex Corp.

The Immune Response Corp.

Letter of intent to develop treatments for injuries to the nervous system via small molecules and proteins that are involved in nerve growth and repair

Companies will use Vyrex¿s CD- Tagging functional genomics tech- nology; any compounds discovered will be jointly owned; further details ND (3/97)

Xenometrix Inc. (NASDAQ:XENO)

Oncogene Science Inc. (now known as OSI Pharma- ceuticals Inc.)

Strategic technology alliance to develop and implement technologies based on gene profiling (automated systems to generate and analyze data on effects of drug candidates on expression of target genes)

Companies will seek a major pharmaceutical partner to fund large portion of system develop- ment; arrangement includes cross- licensing of intellectual property rights covering human cell-based gene transcription approaches to drug discovery and lead optimi- zation (7/97)

ZymoGenetics Inc. (subsidiary of Novo Nordisk A/S; Denmark)

Sequana Thera- peutics Inc. (Merged with Arris Pharma- ceutical Corp. to form Axys Pharmaceuticals Inc.)

Research agreement on genetics of paracrine/endocrine signaling molecules (PESM)

Sequana will conduct high through put sequencing of cDNA libraries provided by ZymoGenetics; Sequana will create a PSEM- specific candidate gene database; ZymoGenetics gets non-exclusive license to use the database and Sequana¿s technology for research on PESMs and will integrate the information into its database; Sequana gets licensing fee (5/9