Biotech Company

Pharma Company

Type/Product

Amount

Terms Details

Affymetrix Inc.

Hewlett-Packard Co. (NYSE:HWP)

Redefined 11/94 agree- ment to develop the GeneArray scanner to read DNA probe arrays (incorporated Affy- metrix¿s GeneChip technology)

ND

Affymetrix reacquired all marketing rights to its GeneChip products, including the co-developed p450 drug metabolism assay; Affymetrix also expanded its rights to sell the GeneArray scanner as part of the GeneChip system worldwide; companies will continue to cooperate in marketing and distribution worldwide (2/97)

Alexion Pharma- ceuticals Inc.

United States Surgical Corp. (NYSE:USS)

Modification of 8/95 agreement on trans- genic pig organs for human transplants

$6.5M (equity; % ND)

U.S. Surgical made additional $3M equity investment; U.S. Surgical gets exclusive license to an additional patent application on method for creating transgenic livestock; Alexion also trans- ferred certain xenograft manufacturing assets to U.S. Surgical for $3.5M (10/97)

Algene Biotech- nologies Corp. (TSE:AGN.B; Canada)

Janssen Pharma- ceutica NV (Belgium; subsid- iary of Johnson & Johnson; NYSE:JNJ)

Extension of 9/95 strategic alliance to identify genes for schizophrenia

ND

Algene will undertake new series of gene mapping experiments to identify chromosomal regions that could harbor causal genes; Janssen will fund all research with embedded profit for Algene (6/97)

Alkermes Inc.

Janssen Pharma- ceutica N.V. (Belgium; subsid- iary of Johnson & Johnson; NYSE:JNJ)

Expansion of 5/96 agree- ment to develop an inject- able, sustained release form- ulation of an undisclosed Janssen drug (based on Medi- sorb delivery technology)

ND

Alkermes was already manufacturing clinical supplies of the product; if the product is developed and commer- cialized, Alkermes will manufacture commercial supplies for Janssen (8/97)

Alliance Pharma- ceutical Corp.

Hoechst Marion Roussel Inc. (sub- sidiary of Hoechst AG; Germany)

Modification of 3/96 licensing and develop- ment agreement on LiquiVent (biologically inert oxygen-carrying liquid; a.k.a.perflubron ) for treating acute respira- tory failure (Phase III trial was halted in 4/97 due to decrease in mor- tality rate for control group, but will be re- started by year end 1997)

$10M

Alliance will get $10M under its license and supply agreement ($2.5M milestone, $5M reimbursement for development expenses and $2.5M for Hoechst Marion¿s purchase of perflubron for use in future trials); certain milestone payments will be adjusted and method for reimbursing expenses will be revised temporarily; Alliance will now conduct and fund product development in North America and Hoechst Marion will fund else- where through 12/97; beginning in 1/98, Hoechst Marion will resume funding worldwide (note: this entire collaboration was terminated in 12/97; see below) (6/97)

Amgen Inc.

Hoffmann-La Roche Ltd. (Switzerland)

Extension and expan- sion of 9/88 AMRO agreement on granulo- cyte-colony stimulating factor (G-CSF; Neupogen)

ND

Companies will develop a 2nd- generation product for marketing in European Union; Roche will grant to Amgen rights to certain intellectual property in U.S. and other markets; also, Roche will sell Neupogen in European Union until 2010; original profit-sharing levels have been changed (but ND) (4/97)

Amylin Pharma- ceuticals Inc.

Johnson & Johnson (NYSE:JNJ)

Agreement to broaden scope of 6/95 collabora- tion on pramlintide (analogue of human pancreatic hormone amylin) to include all amylin agonists for treating fuel metabolism disorders, including diabetes

$6M

Johnson & Johnson exercised its 1st option for additional rights to 2nd generation peptide analogues of amylin; Amylin will get $6M for these rights (3/97)

Amylin Pharma- ceuticals Inc.

Johnson & Johnson (NYSE:JNJ)

Agreement to broaden scope of 6/95 collabora- tion on pramlintide (analogue of human pancreatic hormone amylin) to include all amylin agonists for treating all human diseases

$3M

Johnson & Johnson exercised its 2nd option to broaden scope of collaboration; Amylin got $3M licensing fee (6/97)

ArQule Inc.

Abbott Laboratories (NYSE:ABT)

Extension of 6/95 agree- ment to develop drugs via ArQule¿s Mapping Array and Directed Array chemistries and compound libraries

ND

ArQule will provide additional Mapping Array sets to Abbott through 3/99; ArQule gets addi- tional delivery fees for the Arrays and continued R&D funding (1/97)

ArQule Inc.

Pharmacia Biotech AB (Sweden)

Extension of joint research collaboration to develop advanced separations products, especially to develop affinity ligands via ArQule¿s combinatorial chemistry and structure- guided design; agree- ment dates from 3/95

ND

This is the 3rd extension; the collaboration will be extended for 6 months; further details ND (7/97)

Arris Pharma- ceutical Corp. (since merged with Sequana Thera- peutics Inc. to form Axys Pharma- ceuticals Inc.)

Bayer AG (Germany)

Modification of R&D collaboration on tryptase and chymase inhibitors (original agreement dates from 11/94; expanded in 10/96)

ND

Arris will reacquire rights to tryp- tase inhibitors for treating psoriasis and inflammatory bowel disease; Bayer has option to re-enter these programs at end of Phase IIb clin- ical studies; Arris will continue clinical development of APC-366 for asthma through Phase IIb, at which time Bayer will take over if certain endpoints are met; Bayer will continue to develop BAY35-8535 (2nd gener- ation inhaled compound for asthma); beginning in 12/97, Bayer will take over all research on oral tryptase inhibitors and will end research funding to Arris (7/97)

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

Eli Lilly & Co. (NYSE:LLY)

Extension of research collaboration on Alz- heimer¿s disease; partners will now focus exclusively on drugs that reduce beta- peptide (principle protein of amyloid plaques) (collab- oration dates from 11/88)

ND

Companies will extend collabora- tion through 8/13/98; research has now identified prototype com- pounds that may reduce beta-pep- tide (2/97)

Biomira Inc. (Canada)

Tosoh Corp. (Japan)

Tosoh exercised option (from 8/93 agreement) to license Biomira¿s B27.29 antibody against the CA27.29 antigen (for breast cancer diagnosis)

ND

Tosoh will incorporate the breast cancer antibody into its diagnostic kits; Biomira gets initial up-front payment and milestone payment on product launch in Japan or U.S.; Biomira also gets royalties (5/97)

BioTransplant Inc.

Novartis Pharma AG (Switzerland)

Expansion of 1991 collaboration in xeno- transplantation technol- ogy (which focused on gene therapy approaches) to include BioTransplant¿s mixed bone marrow chimerism approach for creating specific transplant tolerance

$36M

Novartis gets worldwide license to mixed bone marrow chimerism technology in exchange for license payments, research funding and milestones totaling $36M; agree- ment covers 3 additional years; BioTransplant gets royalties and retains co-promotion rights in North America (10/97)

Cadus Pharma- ceutical Corp.

Bristol-Myers Squibb Co. (NYSE:BMY)

Extension and expan- sion of 7/94 R&D collaboration on drugs directed at G protein- coupled receptors (which transfer external signals into cells to regulate most functions); other molecular targets inclu- ded (ND)

$10M

Bristol Myers exercised option to extend collaboration for 2 years; Bristol-Myers has confirmed hits with Cadus drug discovery screens; Cadus gets $10M in addi- tional research funding, plus milestones and royalties (1/97)

Cell Therapeutics Inc.

R.W. Johnson Pharmaceutical Research Institute and Ortho Biotech Inc. (subsidiaries of Johnson & Johnson; NYSE:JNJ)

Expansion of 11/96 collaboration on liso- fylline to include devel- opment of compound for treating patients receiv- ing induction chemo- therapy for acute myeloid leukemia (Phase II trial completed) (original agreement covered use in cancer patients undergoing bone marrow transplants)

ND (includes equity)

R.W. Johnson will fund 600f development costs related to additional indication through FDA approval; Cell Therapeutics and Ortho will co-promote product for all indications in U.S. and share equally in profits/ losses; Ortho has commercial rights elsewhere (except Canada); Cell Therapeutics gets royalties; Johnson & Johnson will pay $1M for expansion of this agreement, plus additional milestones and equity purchases (9/97)

Cephalon Inc.

TAP Holdings Inc. (U.S.-based joint venture between Abbott Laboratories and Takeda Chemi- cal Industries Ltd.; Japan)

Renewal of 5/94 collaboration on use of tyrosine kinase inhibitors for treating prostate cancer

ND

The parties expanded this agreement in 7/96; TAP is currently conducting Phase I trials of CEP-2563 and will continue; it will also fund R&D for 1 more year (11/97)

Chiron Corp.

The Green Cross Corp. (Japan)

Agreement to expand clinical trials of HIV-IT (V) gene therapy to include evaluation of product in combination with HIV protease inhibitors (Phase II monotherapy trials initiated 12/94) (product composed of retroviral vector that delivers HIV env and rev genes via intramuscular injection)

$4M

This stems from the 1991 agree- ment between Green Cross and Viagene Inc. (which Chiron acqui- red in 9/95); Green Cross will pay additional $4M during 1997 to support Phase II combination trial; Chiron responsible for R&D and manufacturing; Green Cross retains worldwide marketing rights; Green Cross will initiate trials in Japan in 1997 (2/97)

Clontech Labor- atories Inc.*

Roche Bioscience (division of Roche Holding Ltd.; Switzerland)

Expansion of 3/96 col- laboration on use of receptor and ion- channel pharmacology to identify molecular targets for diseases; new targets include asthma, arthritis and other inflammatory conditions

ND

ND (6/97)

CoCensys Inc.

Warner-Lambert Co. (NYSE:WLA)

Renewal and expansion of 10/95 agreement on subtype-selective NMDA receptor antag- onists for treating stroke and other central nervous system disorders to include AMPA modula- tors (another class of glutamate receptor)

$23.5M (equity; % ND)

Warner-Lambert will make $7M equity investment and pay $16.5M in milestones, as well as royalties; collaboration renewed for 2 years; CoCensys retains option to parti- cipate in U.S. development, com- mercialization and profit-sharing (10/97)

CombiChem Inc. (IPO pending)

Teijin Ltd. (Japan)

Extension of 4/96 collaboration to discover antagonists of a specific G-protein coupled receptor via combina- torial chemistry and molecular design programs

ND

Companies will extend collabora- tion for 1 year; details ND (5/97)

Cortech Inc.

Ono Pharmaceutical Co. Ltd. (Japan)

Amendment of 3/95 collaboration to develop orally bioavailable elastase inhibitors for treating chronic inflam- matory disorders

ND

Ono will take over all responsib- ilities for research activities during last 6 months of this 3-year collab- oration; Ono not required to pay Cortech $1.5M in research sup- port; Cortech¿s rights to any com- pounds discovered remain un- changed outside Ono¿s territory (4/97)

Corvas Inter- national Inc.

Pfizer Inc. (NYSE:PFE)

Pfizer exercised option to license and develop neutrophil inhibitory factor (NIF) as a stroke therapy

$31M

Pfizer¿s option stems from a 10/95 agreement between the 2 firms; Pfizer had extended its option in 9/96 to allow it to complete its pre- clinical evaluation of the product; Corvas to get $29M in develop- ment funds and milestones, plus royalties; Pfizer gets exclusive worldwide rights to product and will fund all further development, including clinical trials; Corvas got $1M on execution of agree- ment and will get $1M on submis- sion of IND (2/97)

Cubist Pharma- ceuticals Inc.

Merck & Co. Inc. (NYSE:MRK)

Expansion of 6/96 collaboration on com- pounds that inhibit function of amino acyl-tRNA synthases for treating drug- resistant bacteria and fungi to include 3 more Cubist drug targets and Merck¿s natural products com- pound library

ND

Cubist will continue to conduct automated screening and lead com- pound characterization; Merck will provide additional research funds (10/97)

Cytel Corp.

Sumitomo Pharma- ceuticals Co. Ltd. (Japan)

Sumitomo exercised option to license Cytel¿s P-selectin humanized monoclonal antibody CY-1748 for preventing deep vein thrombosis and restenosis; agreement to develop drugs based on cell adhesion molecules dates from 10/91

ND

Sumitomo also licensed rights to Cytel¿s drug Cylexin (currently in Phase II trials); over next 12 months, Sumitomo will complete its evaluation of both products to determine whether to move for- ward with clinical development in Japan (2/97)

EntreMed Inc.

Bristol-Myers Squibb Co. (NYSE:BMY)

Reassignment of commercial rights to thalidomide and thal- idomide analogues; original agreement dates from 12/95

ND

EntreMed reacquired rights to dev- elop thalidomide for treating can- cer and blindness; Bristol-Myers retains rights to thalidomide ana- logues under development as oral anti-angiogenic drugs; Bristol- Myers will continue to fund R&D on analogues but EntreMed no longer gets milestones related to thalidomide; EntreMed renewed Bristol-Myers¿ warrant to buy $10M in common stock (0.44M shares at $22.50 each) while it evaluates new analogues (8/97)

EnzyMed Inc.*

Eli Lilly & Co. (NYSE:LLY)

Extension of 9/96 research agreement on use of EnzyMed¿s com- binatorial biocatalysis technology to optimize new leads for drugs to treat infectious diseases

ND

ND (9/97)

Genome Thera- peutics Corp.

Astra Research Center Boston (division of Astra AB; Sweden)

Extension of 9/95 R&D collaboration on anti-infectives and vaccines for Helico- bacter pylori infection (peptic ulcers, gastritis, stomach cancer) based on sequence data from H. pylori genome

ND

Extension based on Genome Therapeutics¿ completion of genome sequencing; collaboration extended through 9/98; further details ND (7/97)

Gensia Sicor Inc.

Sankyo Co. Ltd. (Japan)

Modification of 4/97 collaboration on drugs for treating Type II diabetes to include pay- ment to Gensia Sicor¿s subsidiary Metabasis Therapeutics Inc.

$7.3M (8% equity)

Gensia Sicor has transferred its pharmaceutical R&D business to its new subsidiary Metabasis; as part of the original agreement be- tween Gensia Sicor and Sankyo, Sankyo agreed to equity invest- ment in Gensia Sicor or its subsid- iary; Sankyo bought $7.25M equity in Metabasis Therapeutics for an 8take (12/97)

Genzyme Trans- genics Corp.

SMI Genzyme Ltd. (joint venture of Genzyme Trans- genics and Sumi- tomo Metals Ltd. of Japan; formed in 1990)

Renewal of funding under 5/94 agreement to produce recombinant antithrombin III (regu- lates blood clotting) in the milk of transgenic goats

$4.4M

SMI will provide $4.4M in addi- tional funds for continued product development; SMI gets access to additional information on the pro- duct (3/97)

Geron Corp.

Pharmacia & Up- john Inc. (NYSE: PNU)

Definitive agreement to collaborate on anticancer drugs that inhibit telo- merase enzyme (essential for maintaining cancer cell immortality)

$58M (equity; % ND)

Geron will get $58M, including $10M equity, research funds and milestones; Geron also gets limited co-promotion rights in U.S. and royalties on product sales; agreement signed in 12/96, at which time Pharmacia & Upjohn made $2M equity investment (3/97)

Gliatech Inc.

Janssen Pharma- ceutica NV (Belgium; subsid- iary of Johnson & Johnson; NYSE: JNJ)

Extension of 10/94 collaboration on com- pounds for Alzheimer¿s and other neurodegen- erative diseases, espec- ially drugs that act as anti-inflammatories

ND

Collaboration was already expan- ded in 1/96, when Janssen increa- sed research funding and mile- stones by 50%; currently, Janssen will extend collaboration for 1 more year and has retained rights to extend for an additional year; Janssen will continue to fund research and pay milestones at current levels (10/97)

Human Genome Sciences Inc.

Hoffmann-La Roche Ltd. (unit of Roche Holding Ltd.; Switzerland)

Extension of 3/96 collaboration to se- quence genome of Streptococcus pneumoniae and license to use sequence infor- mation to identify molecular targets for anti-infectives and antibiotics

ND

Human Genome achieved 1st and only milestone when it completed sequencing of S. pneumoniae; collaboration extended to include genome of Enterococcus faecalis; Roche gets non-exclusive license to use sequence information to identify molecular targets for anti- infectives and antibiotics; Human Genome gets up-front payment and royalties on certain products (7/97)

Icos Corp.

Abbott Laboratories (NYSE:ABT)

Expansion of 4/95 collaboration on small molecule drugs that modulate intracellular signal transduction of cell adhesion molecules; broadened scope will apply Abbott¿s drug discovery tool SAR By NMR (structure-activity relationship by nuclear magnetic resonance) to targets of interest

ND

Each company will have exclusive rights to drugs against specific molecular targets with milestones and royalties to be paid to other party; each company is responsible for development, registration and commercialization of its own pro- ducts (9/97)

ImClone Systems Inc.

Abbott Laboratories (NYSE:ABT)

Amendment of 12/92 strategic alliance on AmpliProbe (technology for signal amplification in DNA probe assays) and other diagnostic products

ND

As a result of the settlement of a patent infringement suit between Abbott and Chiron Corp., Abbott now has right to sublicense parti- cular ImClone patents to Chiron; royalties paid by Chiron to Abbott will be passed to ImClone (1/97)

ImClone Systems Inc.

Merck KGaA (Germany)

Expansion and amend- ment of 12/90 collab- oration on therapeutic cancer vaccines, espec- ially BEC2 anti-idiotypic vaccine for use in small cell lung cancer and malignant melanoma; now includes co-mar- keting agreement

$65.5M (equity; % ND)

Partners will continue to develop BEC2 for U.S. and international markets and will co-market in North America; Merck will continue to have exclusive rights elsewhere; Merck will fund clinical development worldwide for one indication (partners had been sharing expenses); ImClone will manufacture product; Merck will pay $15M more in milestones and will immediately buy $40M in ImClone convertible preferred stock (ImClone will transfer stock in 4 tranches, up to 25 0n 1st 2 years at conversion rate of $12.50 per share; the rest converts over 5 years); Merck will pay $10M for clinical trial costs and ImClone gets $0.5M signing fee (12/97)

Incyte Pharma- ceuticals Inc.

Hoechst Marion Roussel Inc. (sub- sidiary of Hoechst AG; Germany)

Amendment to 10/95 agreement on Incyte¿s LifeSeq DNA sequence and gene expression database

ND

As part of the 3/97 agreement between Hoechst Marion Roussel and Ariad Pharmaceuticals to form a joint venture in genomics, the Hoechst-Ariad Genomics Center will be an installation site for the LifeSeq database; Incyte will get access fees, milestones and royalties on future products (3/97)

Incyte Pharma- ceuticals Inc.

Monsanto Co. (NYSE:MTC)

Extension of 9/96 agreement in plant genomics to provide Monsanto with a com- prehensive set of Incyte¿s genomic technologies

ND

Multi-year partnership; Monsanto gets non-exclusive access to Incyte¿s full range of genomic and bioinformatic know-how and services for use by all sectors of its life sciences business; Incyte could get future royalties; details ND (10/97)

Incyte Pharma- ceuticals Inc.

Pfizer Inc. (NYSE:PFE)

Extension of 6/94 genomic database partnership

ND

Pfizer will continue to have access to Incyte¿s databases, including its LifeSeq gene sequence and expression database; details ND (12/97)

Incyte Pharma- ceuticals Inc.

Pharmacia & Up- john Inc. (NYSE: PNU)

Extension and expansion of genomic database agreement (signed in 12/94 with The Upjohn Co.) to include access to LifeSeq FL database of full-length genes, LifeSeq Atlas gene mapping database, LifeSeq Gene Album reagents and the new ZooSeq animal model reference database (genomic information on rats and mice)

ND

Partners extended agreement for 4 years, through 12/01; Pharmacia & Upjohn will pay yearly access fees and satellite database fees; Incyte could get milestones and royalties if any products come out of agreement; details ND (5/97)

Inhale Therapeutic Systems

Baxter Inter- national Inc. (NYSE:BAX)

Renegotiation of certain terms of 3/96 collabora- tion on use of Inhale¿s dry powder pulmonary delivery system as tech- nology platform for 4 Baxter compounds

ND

Companies are renegotiating terms due to increase in overall program scope and cost (10/97)

LeukoSite Inc.

Warner-Lambert Co. (NYSE:WLA) and Kyowa Hakko Kogyo Ltd.(Japan)

Expansion of Leuko- Site¿s existing agree- ments with each partner (Warner-Lambert 11/94; Kyowa Hakko 4/97) to discover small molecule antagonists that block 4 different chemokine receptors in leukocytes as treatments for inflam- mation and autoimmune diseases

ND

Partners formed multinational drug discovery alliance and will combine resources; research col- laboration complemented by mar- keting agreements (Kyowa Hakko is primary marketer in Asia, War- ner-Lambert in rest of world); LeukoSite gets license fees, research funding, milestones and royalties (11/97)

Microcide Pharmaceuticals Inc.

Daiichi Pharma- ceutical Co. Ltd. (Japan)

Extension of 11/95 collaboration on small molecule drugs to pre- vent antibiotic resistance in Gram-negative bac- teria (by inhibiting efflux pump mechan- isms)

$3.5M

Daiichi will extend collaboration for 1 more year and will provide an extra $3.5M in research support (12/97)

Millennium Pharmaceuticals Inc.

Eli Lilly & Co. (NYSE:LLY)

Extension of 10/95 collaboration on use of genetics and genomics to develop drugs for atherosclerosis and expansion of scope to include research on genetic basis of con- gestive heart failure

$12M

Collaboration extended to 5 years; Lilly will fund the last 2 years at level of more than $12M; further details ND (9/97)

Millennium Pharmaceuticals Inc.

Pfizer Inc. (NYSE:PFE)

Expansion of 3/95 collaboration on anti- fungal drug targets and leads (which Pfizer init- iated with ChemGenics Pharmaceuticals Inc., since acquired by Millen- nium) to include use of transcript profiling and ultra-high-throughput screening technologies

ND

Pfizer will add additional research personnel to project; further details ND (12/97)

Myriad Genetics Inc.

Schering-Plough Corp. (NYSE:SGP)

Licensing of rights to Myriad¿s MMAC1 gene-based therapeutics (MMAC1 = mutated in multiple advanced cancers); part of 4/97 agreement to discover genes and therapies for various cancers

$2M

Myriad characterized the MMAC1 gene and delineated its biochemi- cal pathway; Schering-Plough licensed therapeutic rights to the gene (and paid $2M fee); Myriad retains worldwide rights to diag- nostics and gets additional mile- stones and royalties (10/97)

Neurogen Corp.

Schering-Plough Corp. (NYSE:SGP)

Extension of 6/95 collaboration on drugs for treating neuropsy- chiatric disorders, inclu- ding drugs that bind selectively to specific types (e.g., NGD 94-4, a dopamine D4 antagonist)

$3.6M

Schering Plough will extend col- laboration through 6/98; Neurogen gets $3.6M extra in research funds during that period (4/97)

NeXstar Pharma- ceuticals Inc.

Schering AG (Germany)

Extension of 6/93 R&D agreement to develop aptamers (short oligonucleo- tides, created via NeXstar¿s SELEX combinatorial chemistry) as in vivo imaging agents for cardiac and oncology indications (Schering targets)

ND

Schering increased research pay- ments from $1M to $2.4M per year; NeXstar also gets milestones and royalties for each agent devel- oped (2/97)

NPS Pharma- ceuticals Inc.

SmithKline Beech- am plc (NYSE: SBH; U.K.)

Extension of 12/93 research and license agreement on orally active small molecule drugs to treat osteoporo- sis via calcium receptors

$8M (equity; % ND)

SmithKline extended agreement for up to 3 years, with additional research funding of $2M/year; SmithKline also bought $2M in stock at premium to market (0.16M shares at $12.21/ each) and will buy additional equity annually as long as extension remains in place; SmithKline will conduct clinical trials and market products world- wide; NPS gets royalties; NPS retains option to co-promote in U.S. (12/97)

OSI Pharma- ceuticals Inc. (formerly Onco- gene Science Inc.)

Hoechst Marion Roussel Inc. (subsid- iary of Hoechst AG; Germany)

Extension of R&D collab- oration on small molecule drugs based on regulation of gene transcription (for treating cardiovascular and inflammatory diseases); also, consolidation of separate research agreements with Marion Merrell Dow, Hoechst A.G. and Hoechst Roussel (prior to the 7/95 formation of Hoechst Marion Roussel)

12.5

Companies will extend R&D collaboration to 3/31/02; they will continue to focus on orally active small molecule drugs; OSI will get up to $12.5M in research funding plus royalties on future sales (agreement in principle 6/96; finalized 7/97)

OSI Pharma- ceuticals Inc. (formerly Onco- gene Science Inc.)

Pfizer Inc. (NYSE:PFE)

Continued funding of cosmeceuticals joint venture Anaderm Research Corp. (established in 1996) and addition of more targets in skin pigmentation, skin wrinkling and hair growth

$14.3M

Partners will provide Anaderm with $6.65M in committed fund- ing through 1998 and $7.6M through 1999 (depending on per- formance); OSI will continue to own 14% and Pfizer 820f joint venture (12/97)

Pharmacopeia Inc.

Berlex Laboratories Inc. (subsidiary of Schering AG; Germany)

Extension of 2/95 R&D collaboration on use of combinatorial chemistry and high-throughput screening to find drugs for treating multiple sclerosis

ND

Berlex decided to pursue in vivo evaluation of candidate compound identified by Pharmacopeia, for which Pharmacopeia got cash pay- ment; Berlex extended the term of the agreement for an undisclosed period of time (1/97)

Pharmacopeia Inc.

Schering-Plough Corp. (NYSE:SGP)

Extension of 12/94 collaboration on small molecule drugs for treat- ing cancer and asthma to include a specific tar- get in hepatitis

ND

This is the 2nd extension of this collaboration (the 1st was in 10/96); Schering-Plough will pro- vide additional research funding; financial details ND (9/97)

Protein Design Labs Inc.

Boehringer Mannheim GmbH (Germany)

Reassignment of pro- duct rights under 10/93 agreement (with Corange Ltd.) on various human and SMART antibodies; Boehringer is returning rights to 2 products (OST 577, a human anti- hepatitis B antibody; and Protovir, a human anti- cytomegalovirus anti- body) as well as stopping clinical development of OST 577; Boehringer is retaining rights and con- tinuing development of 2 other products (SMART anti-L-selectin antibody; and 1 other humanized antibody for cardiovas- cular indications)

ND

Boehringer Mannheim returned all rights to OST 577 and Protovir and is terminating Phase II trial of OST 577 (product gave rise to side effects in some patients); Pro- tein Design is evaluating data and considering a study combining OST 577 and a nucleoside ana- logue; Boehringer is retaining rights to and continuing develop- ment of other 2 products; Roche Holding is in process of acquiring Corange, Boehringer Mannheim¿s parent (pending regulatory appro- val) (12/97)

Regeneron Pharmaceuticals Inc.

The Procter & Gamble Co. (NYSE:PG)

Expansion of 5/97 research collaboration to include Regeneron¿s Axokine (2nd genera- tion ciliary neurotrophic factor) and related mole- cules, as drugs for treat- ing obesity associated with Type II diabetes

$15M

Procter & Gamble will pay all costsof developing Axokine through prelimi- nary clinical trials, after which com- panies will share further development costs; companies will jointly market products and share equally in profits; Procter & Gamble will pay additional $15M in funding, bringing total for this agreement (including $135M in 5/97) to $150M (9/97)

Ribi Immuno- Chem Research Inc.

SmithKline Beech- am Biologicals (subsidiary of SmithKline Beech- am plc; NYSE: SBH; U.K.)

Expansion of 10/92 agreement on use of Ribi¿s vaccine adjuvants to include use in vaccines for human papilloma- virus (HPV), tubercu- losis and other infect- ious diseases

ND

This is 5th agreement between the 2 parties; SmithKline Beecham Biologicals gets exclusive license to use adjuvants in HPV vaccine, co-exclusive license for tuberculo- sis vaccine and non exclusive licenses for other vaccines; Ribi gets license fees, transfer payments for clinical and commercial quan- tities of adjuvant, royalties and equity investment over 3 years (1/97)

Sequana Thera- peutics Inc. (since merged with Arris Pharma- ceutical Corp. to form Axys Pharma- ceuticals Inc.)

Boehringer Ingel- heim GmbH (Germany)

Expansion of 6/95 R&D collaboration on genetic basis of asthma

ND

Boehringer Ingelheim doubled its funding for research (retroactive to 1/1/97) throughout the term of the agreement (subject to Sequana¿s achievement of certain milestones) (5/97)

Sequana Thera- peutics Inc. (since merged with Arris Pharma- ceutical Corp. to form Axys Pharma- ceuticals Inc.)

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

Intention to renegotiate terms of 7/94 alliance to identify genes involved in Type II diabetes (ex- panded in 2/96 to include obesity)

ND

Sequana made this announcement the same day it announced that it was merging with Arris Pharma- ceutical Corp.; Sequana and Glaxo will renegotiate the terms of their alliance to enable each to retain rights to gene discoveries made independently and to align collab- oration with each party¿s strategic needs (11/97)

Seragen Inc.

Ajinomoto Co. Ltd. (Japan)

Restructuring of 12/94 licensing agreement on Ajinomoto¿s interleukin-2 (IL-2) gene patents for use in Seragen¿s IL-2 fusion protein product

ND

The agreement was restructured in order to reduce and defer Seragen¿s financial obligations to Ajinomoto (including royalties on product sales); as part of restructuring, Seragen¿s partner Eli Lilly & Co. has signed a separate licensing deal with Ajinomoto; Lilly also assumed most of Seragen¿s remaining obligations to Ajinomoto (6/97)

Seragen Inc.

Eli Lilly & Co. (NYSE:LLY)

Amendment to 7/94 alliance on IL-2 fusion protein for treating can- cer (product currently in Phase III trials for cutaneous T-cell lymph- oma)

ND (includes equity)

The terms of the agreement are being altered so that Seragen can seek other partners for non-cancer uses of the product and to support Seragen¿s restructuring; Lilly will assist Seragen in meeting certain 3rd party payments (see above entry); Seragen will issue 1M shares common stock to Lilly in a private placement (4/97)

Sibia Neuro- sciences Inc.

Eli Lilly & Co. (NYSE:LLY)

Second extension of 5/92 R&D collabora- tion on molecules that act on neuronal voltage- gated calcium channels (VGCC); Sibia now has library of genes cloned from human brain tissue coding for many of the VGCC subtypes

ND

Lilly will fund research to identify and characterize a new VGCC sub- type for use in discovery of drugs for central nervous system dis- orders; Sibia retains right to use this target in its internal R&D, subject to Lilly¿s right of 1st negotiation; Sibia gets milestones and royalties on products based on this VGCC subtype (1/97)

Sibia Neuro- sciences Inc.

Eli Lilly & Co. (NYSE:LLY)

Lilly exercised option (granted in 6/95 exten- sion of agreement, which originally dates from 5/92) to license Sibia ¿s patent on instrumentation and assay methods (fluor- escense, chemilumines- cence) for high-through- put functional screening for new drug leads

ND

Lilly exercised option for non- exclusive worldwide fully paid up license; Lilly gets right to practice under patent for internal research purposes only and does not have right to sublicense (11/97)

Somatogen Inc.

Eli Lilly & Co. (NYSE:LLY)

Restructuring of 6/94 manufacturing agree- ment on Optro (recom- binant human hemo- globin)

ND

Companies are exploring options to allow for acceleration of manu- facturing schedule (to make enough supply for clinical trials); including Somatogen taking over the late-stage manufacturing; Lilly has contractual obligation to pay for manufacturing product for Phase III trials (NOTE: this entire collaboration was terminated in 3/97; see below) (2/97)

Synaptic Pharma- ceutical Corp.

Merck & Co. Inc. (NYSE:MRK)

2nd extension of 11/93 joint research program on drugs for treating benign hyperplasia (by blocking activation of alpha-1a adrenergic receptors)

ND

Merck extended collaboration for 1 more year (1st extension was in 10/96); specific financial terms ND (12/97)

Transcend Thera- peutics Inc.

Boehringer Ingel- heim GmbH (Germany)

Exercise of option under 2/97 agreement to devel- op Procysteine IV (neutralizes reactive oxy- gen species when drug delivers cysteine to cells) for treating acute respi- ratory distress syndrome (currently in U.S. Phase III clinical trials)

ND

Boehringer Ingelheim exercised its option to develop product in Japan, where it will be responsible for all development and regulatory expenses as well as marketing, sales and distribution; Transcend gets royalties (12/97)

Triangle Pharmaceuticals Inc.

Mitsubishi Chemi- cal Corp. (Japan)

Triangle exercised option (from 1/96) to develop Mitsubishi¿s non-nucleo- side reverse transcriptase inhibitor MKC-442 for treating HIV infection and AIDS

ND

Triangle acquired worldwide rights to product except in certain East Asian countries (including Japan, China and Taiwan); Mitsubishi will get license fees, milestones and royalties (4/97)

Tularik Inc.*

Merck & Co. Inc. (NYSE:MRK)

Extension of 1/94 R&D collaboration on small molecule therapeutics that inhibit viral replica- tion, specifically HIV and hepatitis C

ND

Merck has worldwide rights to any products from the collaboration; Tularik gets research funding and royalties; collaboration will be extended for 3 years, then renew- able on annual basis (1/97)

Vical Inc.

Merck & Co. Inc. (NYSE:MRK)

Expansion of 6/91 licensing agreement on Vical¿s naked DNA technology to make therapeutic vaccines for HIV and hepatitis B (HBV) (1991 agreement covers use in preventive vaccines for same viruses)

$23M (equity; % ND)

Merck made $5M equity invest- ment at premium to market; Vical will get $18M in milestones, plus royalties; Vical has certain options to co-promote products in U.S.; Merck gets exclusive worldwide rights to use technology in thera- peutic vaccines for HIV and HBV (11/97)

Xenova Group plc (U.K.)

Suntory Ltd. (Japan)

Extension of 4/93 collaboration on fungal compounds with immuno- regulatory activity

ND

Agreement extended until mid- 1998 while Xenova conducts further biological studies on can- didate compound; Xenova gets a milestone payment and continued research funding (11/97)

Terminated Agreements

Biotech Company

Pharma Company

Type/Product

Amount

Terms Details

Alliance Pharmaceutical Corp.

Hoechst Marion Roussel Inc. (sub- sidiary of Hoechst AG; Germany)

Termination of 3/96 licensing and development agreement on LiquiVent (biologically inert oxygen- carrying liquid; a.k.a. perflubron ) for treating acute respiratory failure (Phase III trial was halted in 4/97 due to decrease in mor- tality rate for control group)

-

Hoechst Marion terminated the agreement, citing delays in drug development and thus higher over- all expenses (12/97)

Atrix

Pharmacia & Up- PNU)

Termination of 12/94 for use of Atrigel (drug delivery system) in animal vaccines

-

Pharmacia & Upjohn recently divested the majority of its animal Laboratories Inc.john Inc. (NYSE:licensing agreement vaccine business and thus termi- nated the agreement (4/97)

Cel-Sci Corp.

Sittona Co. BV (the Netherlands)

Termination of licensing agreement on Sittona¿s technology for Multikine (natural mixture of human cytokines)

$4M

Cel-Sci had licensed the technol- ogy from Sittona; it has now pur- chased all rights, including all patents and trade secrets (on which it previously had to pay a 10% royalty on sales and a 15% royalty on sublicenses); Cel-Sci paid Sittona $0.5M in cash and $3.5M worth of Cel-Sci shares (0.75M shares) (3/97)

Cephalon Inc.

Schering-Plough Corp. (NYSE:SGP)

Termination of 5/90 R&D collaboration on drugs for Alzheimer¿s disease, especially pro- tease inhibitors that pre- vent secretion of beta- amyloid peptide

-

Schering-Plough had renewed this collaboration in 11/95 for an addi- tional 5 years (and $32M to Ceph- alon), but now it has decided to discontinue funding this program; both Cephalon and Schering- Plough retain rights to products de- veloped under collaboration; Ceph- alon will either co-market or get royalties from any product that is developed (1/97)

Cephalon Inc.

SmithKline Beech- am plc (NYSE: SBH; U.K.)

Termination of 6/93 collaboration on calpain inhibitors (protease thought to mediate cell death) as treatments for stroke

-

Collaboration concluded 12/1/97; all rights related to calpain inhib- itors granted under Cephalon pat- ents will revert to Cephalon; SmithKline is redirecting its re- sources to other priorities (11/97)

Cima Labs Inc.

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

Termination of collab- oration to use Cima¿s OraSolv drug delivery technology (microen- capsulated drug formu- lated into quick-dissolv- oral dosage tablet) with a Glaxo drug product

-

Companies agreed by mutual con- sent to terminate collaboration (12/97)

CoCensys Inc.

Novartis AG (Switzerland)

Termination of 5/94 R&D collaboration (originally with Ciba- Geigy Ltd.) on co- development of ACEA 1021 for treating stroke and traumatic brain injury (product is antag- onist of glycine site on NMDA receptor)

-

Novartis decided not to participate in further product development after Phase I trial data showed some toxicity and dose-limiting effects; CoCensys regains all rights to drug and will reimburse Novar- tis for development funds only from future product sales (if any); CoCensys will seek new partner after it does further preclinical studies (4/97)

Cortech Inc.

SmithKline Beecham plc (NYSE:SBH; U.K.)

Termination of 11/95 agreement on Bradycor (bradykinin antagonist) for treating traumatic brain injury

-

Agreement terminated after Phase II trials showed that drug had no effect on intercranial pressure (3/97)

Cubist Pharma- ceuticals Inc.

Pfizer Inc. (NYSE:PFE)

Conclusion of 12/95 agreement for Cubist to screen Pfizer¿s compound library against certain amino acyl tRNA synthetase targets and to conduct secondary screens on certain lead compounds

-

The 18-month screening agree- ment expired; Cubist licensed from Pfizer the rights to a selected lead compound; Cubist has no further obligations to Pfizer (6/97)

Cytel Corp.

Pharmacia & Up- john Inc. (NYSE: PNU)

Cytel regained rights to its P-selectin human- ized monoclonal anti- body CY-1748 for treating deep vein thrombosis and restenosis

-

In 4/95, the Upjohn Co. had exer- cised its option to assume all responsibility for product develop- ment; now, based on a review of Pharmacia & Upjohn¿s consoli- dated pipeline, the company decided not to go forward with product development; Cytel will get the preclinical package from Pharmacia & Upjohn (1/97)

Cytel Corp.

Schwarz Pharma AG (Germany)

Termination of 12/95 collaboration to develop carbohydrate selectin blockers, including Cylexin (currently in Phase II trial for pre- venting reperfusion injury in infants undergoing heart bypass surgery for congenital defects)

-

Both companies agreed that the market for the product in its cur- rent indication is not large enough to share (in 6/96, Cylexin failed in Phase II trials for reducing reper- fusion injury in heart attack patients receiving angioplasty); Cytel retained rights to Cylexin (5/97)

Flamel Technol- ogies SA (France)

SmithKline Beech- am plc (NYSE: SBH; U.K.)

Termination of 12/94 collaboration on vaccine delivery (via Flamel¿s Medusa system for proteins and peptides)



Flamel regained full rights to its technology; Flamel¿s 1st formula- tion is for parenterally administer- ed vaccines, but SmithKline¿s principal interests are in oral and nasal formulations (2/97)

Genetics Institute Inc. and Wyeth- Ayerst Internat- ional (subsidiaries of American Home Products Corp.; NYSE:AHP)

Schering-Plough Corp. (NYSE:SGP)

American Home¿s sub- sidiaries reacquired the rights to develop and market recombinant human interleukin-11 (IL-11; which Genetics Institute licensed to Schering-Plough in 1991) (Genetics Institute sub- mited BLA 12/96)

-

Wyeth-Ayerst acquired marketing rights in Europe, Africa and Latin America (it already had rights in Asia, except Japan); Genetics Institute has rights in North Amer- ica; Wyeth Ayerst and Genetics Institute will collaborate to devel- op and market product globally; Schering-Plough sold all rights, interests and obligations to IL-11 for undisclosed cash amount (3/97)

Hybridon Inc. (OTC Bulletin Board: HYBN)

Hoffmann-La Roche Ltd. (unit of Roche Holding Ltd.; Switzerland)

Termination of 2/93 R&D collaboration on antisense compounds for treating human papillomavirus (HPV) and hepatitis B and C infections

-

Under the collaboration, Hybridon had identified lead compounds for both HPV and hepatitis C; Roche decided not to pursue the collabor- ation further (apparently it had not been able to develop animal model for hepatitis C compound); Roche stopped research payments as of 3/97 and will terminate collaborat- ion in 2/98; Roche will assign all agreement-related patent rights and licenses to Hybridon (9/97)

Hyseq Inc.

SmithKline Beech- am Clinical Labor- atories (unit of SmithKline Beech- am plc; NYSE: SBH; U.K.)

Conclusion of 10/95 licensing agreement on Hyseq¿s DNA sequencing-by-hybrid- ization technology for use in diagnostic tests for certain genetic diseases

-

Companies have agreed to explore ways to commercialize Hyseq¿s technology; this agreement came to term and was not renewed (10/97)

Icos Corp.

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

Termination of 10/91 collaboration on phos- phodiesterase inhibitors (PDE) for treating inflammatory and cardio- vascular diseases as well as male impotency

-

Both companies decided that their interests in product development lay in different indications; Icos will continue R&D on PDE-inhi- biting compounds including any arising from collaboration; Icos will pay royalties to Glaxo Well- come on product sales; Glaxo Wellcome is free to pursue re- search independently (2/97)

Inex Pharmaceuticals Corp. (TSE:IEX; Canada)

Schering-Plough Corp. (NYSE:SGP)

Termination of 7/95 R&D collaboration on use of Inex¿s non- viral gene delivery system with Schering- Plough¿s p53 tumor suppressor gene

-

Schering-Plough said it was not prepared to sign a worldwide licensing agreement at the present time; Schering-Plough proposed a new research program, which Inex is considering (2/97)

The Liposome Co. Inc.

Pfizer Inc. (NYSE:PFE)

Termination of 11/90 licensing and joint development agreement on TLC D-99 (liposomal doxorubicin) for treat- ing metastatic breast cancer (currently in international Phase III trials)

$10M

Liposome Co. reacquired all devel- opment, manufacturing and mar- keting rights to product; Liposome Co. will also assume control of all clinical studies; Pfizer gets royal- ties on product sales worldwide (except Japan); Pfizer will provide Liposome Co. with $10M credit line to continue product develop- ment (7/97)

Megabios Corp.

Pfizer Inc. (NYSE:PFE)

Termination of 6/96 collaboration on gene therapy products for inhibiting angiogenesis in solid tumors



Pfizer decided to discontinue pro- gram with 6 months¿ notice; there- fore it will continue funding through 5/98 (12/97)

Protein Polymer Technologies Inc.

Ethicon Inc. (subsidiary of John- son & Johnson; NYSE:JNJ)

Termination of 1994 R&D collaboration on use of genetically engi- neered protein polymers as surgical tissue adhesives and sealants for wound closure

-

Ethicon declined to proceed with acceptance of specific product formulation for commercial devel- opment; Ethicon relinquishes all rights to technology and has no further financial obligations to Protein Polymer (12/97)

Sibia Neuro- sciences Inc.

Eli Lilly & Co. (NYSE:LLY)

Completion of R&D collaboration on neuronal voltage-gated calcium channel sub- types as targets for drugs for nervous system disorders (stroke, Alzheimer¿s disease, depression); agreement dates from 5/92

-

Lilly extended this collaboration twice, but it concludes in 10/97; companies will independently pursue drug leads that act on tar- gets identified during collabora- tion; Sibia gets milestones and royalties on products Lilly com- mercializes; Sibia can develop compounds it discovers by itself or with partners (8/97)

Somatogen Inc.

Eli Lilly & Co. (NYSE:LLY)

Termination of 6/94 collaboration on use of Optro (recombinant human hemoglobin) as blood substitute in elective surgery

$14M

Lilly decided to discontinue its support for this product under the current agreement (citing assess- ment of marketing opportunities) but expressed interest in restructur- ing agreement with respect to other indications for Optro; Lilly will pay Somatogen $6M in cash and loan it $8M under terms of the termination clause; if the agree- ment is restructured, these terms could change; Somatogen will continue product development in hematopoiesis and cardiopulmo- nary bypass surgery (3/97)

Techniclone Corp.

Alpha Therapeutic Corp. (subsidiary of Green Cross Corp.; Japan)

Techniclone reacquired rights to LYM-1 (Onco- lym) it licensed to Alpha Therapeutic in 10/92 (product is monoclonal antibody linked to radio- active isotope in clinical trials for non-Hodgkin¿s B cell lymphoma)

-

Techniclone will manage further clinical development of product; it will make payments to Alpha based on milestones; Alpha will transfer all clinical data and other information to Techniclone (11/97)

Vertex Pharmaceuticals Inc.

Alpha Therapeutic Corp. (division of Green Cross Corp.; Japan)

Termination of 10/95 licensing agreement on oral butyrate compound VX-366 for treating inherited hemoglobin disorders (including sickle cell anemia and beta-thalassemia)

-

Vertex had performed preclinical and Phase I clinical tests before it signed agreement with Alpha, but after Alpha conducted additional preclinical testing it decided that too much development work still needed to be done prior to clinical trials; Alpha Therapeutic suspend- ed further development; Vertex will not develop drug indepen- dently (9/97)

Xoma Corp.

Pfizer Inc. (NYSE:PFE)

Termination of 6/87 development and mar- keting agreement on monoclonal antibody E5 for treating Gram-neg- ative sepsis

-

The termination follows Pfizer¿s decision in 4/97 to discontinue U.S. Phase III clinical trials due to lack of clear efficacy; all product rights revert to Xoma (6/97)


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