Company

Partner

Amount

Triggering Effect

Details

Advanced Polymer Systems Inc.

Ortho Dermatology (unit of Johnson & Johnson; NYSE:JNJ)

3

Milestone for FDA approval of product

"FDA approved for marketing Retin-A Micro microsphere 0.1%, a tretinoin gel for topical treatment of acne (employs Advanced Polymer¿s Microsponge delivery system); Ortho is Advanced Polymer¿s marketing partner (2/97)"

Allelix Biopharmaceuticals Inc. (Canada)

Astra AB (Sweden)

US$12

Decision to proceed with Phase III trials of ALX1-11

"The companies agreed in 6/96 to develop ALX1-11 (recombinant human parathyroid hormone) for treating post-menopausal osteoporosis; Astra decided in 9/97 to move the drug into Phase III trials, triggering the US$12M (C$17.1M) payment to Allelix (12/97)"

Alliance Pharmaceutical Corp.

"Hoechst Marion Roussel Inc. (subsidiary of Hoechst AG, Germany)"

10

Milestone; reimbursment of expenses; purchase of product

"The companies signed a development and licensing agreement on LiquiVent (perflubron; for treating acute respiratory failure) in 3/96; the $10M payment includes a $2.5M milestone, a $5M reimbursement for development expenses and a $2.5M purchase of product for use in future clinical trials; the companies have also modified the terms of this agreement (6/97)"

Amylin Pharmaceuticals Inc.

Johnson & Johnson (NYSE:JNJ)

30.6

Debt financing

"Amylin drew down $30.6M from a $57M development loan provided by its partner Johnson & Johnson; this debt financing was part of the original 6/95 agreement between the parties on pramlintide for treating types I and II diabetes; Amylin will use the cash to fund its 50 ost of drug development (now in Phase III clinical trials); the loan has an interest rate of 9%; in conjunction with the loan, Amylin issued 10-year warrants to Johnson & Johnson to buy 1.53M shares of common stock at $12/each (10/97)"

BioCryst Pharmaceuticals Inc.

Torii Pharmaceutical Co. Ltd. (Japan)

1

Milestone in develop- ing oral formulation of BCX-34

BioCryst and Torii entered a research and license agreement in 6/96 on small molecule inhibitors of purine nucleoside phosphorylases (which inhibit proliferation of T cells); BioCryst is developing an oral formulation (5/97)

BioTime Inc.

Abbott Laboratories (NYSE:ABT)

1.4

License fee

BioTime and Abbott established a licensing agreement on BioTime¿s plasma-expanding product Hextend in 4/97 (7/97)

Cell Genesys Inc.

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

1

License agreement on gene-activated EPO

"Cell Genesys licensed gene-activated EPO (erythropoietin) and a 2nd undisclosed protein to Hoechst Marion Roussel in 3/97; Hoechst Marion and Transkaryotic Therapies Inc., who are collaborating on gene-activated EPO, initiated Phase II clinical trials, triggering a milestone payment to Cell Genesys (12/97)"

CoCensys Inc.

Warner-Lambert Co. (NYSE:WLA)

2

Equity investment

"The timing of this $2M equity investment was set by the terms of the firms¿ 10/95 R&D agreement on subtype-selective NMDA receptor antagonists for neurological indications; Warner-Lambert bought 324,465 shares at $6.15 each (3/97)"

Columbia Laboratories Inc.

Wyeth-Ayerst Lab- oratories (division of American Home Pro- ducts Corp.; NYSE:AHP)

1.3

Approval to sell Crinone in Germany

Columbia Laboratories and Wyeth-Ayerst signed a marketing agreement on Crinone progesterone gel for use in infertility treatments in 6/95; Columbia received a $1.25M milestone payment when the product was approved for marketing in Germany (9/97)

Corvas International Inc.

Schering-Plough Corp. (NYSE:SGP)

3

Selection of drug candidate

The companies announced in 12/96 that they had expanded their 12/94 collaboration on orally bioavailable thrombin inhibitors to include coagulation Factor Xa; Schering-Plough has now selected 1 of Corvas¿ inhibitors to develop as a treatment for chronic diseases caused by thrombosis; Corvas got $3M for this milestone event (1/97)

Corvas International Inc.

Schering-Plough Corp. (NYSE:SGP)

3

Payment due under terms of alliance

"The companies agreed in 12/94 to develop oral drugs for preventing and treating chronic cardiovascular disorders, including oral Factor Xa inhibitors (12/97)"

Cytel Corp.

Nextran unit of Baxter Healthcare Corp. (NYSE:BAX)

0.5

Milestone

Cytel got $0.5M following delivery of the initial batch of a bioactive carbohydrate to be used in Nextran¿s xenotransplantation product; this is the 1st milestone in the 10/96 carbohydrate supply agreement between the two firms (1/97)

CytoTherapeutics Inc.

Astra AB (Sweden)

3

Anticipated initiation of Phase II trial

"CytoTherapeutics entered an alliance with Astra in 3/95 to continue clinical development of the former¿s encapsulated bovine adrenal cells for controlling pain (then called CereCRIB; now termed ACTID, or analgesic cell therapy implantable device technology); the product is expected to enter Phase II trials in multiple pain indications, an event that triggered the payment (4/97)"

Diatide Inc.

Nycomed ASA (Norway)

2

NDA for AcuTect accepted by FDA for filing

"The companies agreed in 8/95 to develop and market Diatide¿s Techtide medical imaging products; Diatide submitted an NDA in 8/97 for its thrombus imaging product AcuTect, which the FDA accepted for filing in 9/97 (10/97)"

Epitope Inc.

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

1.5

Vote of confidence¿ in OraSure product

"Epitope and SmithKline signed a worldwide marketing agreement in 2/95 on Epitope¿s OraSure oral specimen collection device for AIDS testing; in 7/97, Epitope reacquired all rights to the product from SmithKline, which is getting out of the over-the-counter market for disease detection diagnostics; SmithKline bought 0.2M shares of Epitope at $7.25 each ($1.45M total) as a vote of confidence in the product (which it will sell during the transition) (8/97)"

GeneMedicine Inc.

Corange Ltd. (Bermuda; parent company of the Boehringer Mannheim Group; Germany)

4.5

Equity and milestone investments for initiation of clinical trial

"GeneMedicine and Corange/Boehringer agreed in 7/95 to collaborate on non-viral gene therapies for cancer; upon FDA¿s approval of the protocol for Phase I clinical trials of GeneMedicine¿s IL-2 gene therapy for head and neck cancer, Corange bought $4M in GeneMedicine stock (0.534M shares at $7.50 each, giving Corange a 10take); Corange also paid $0.5M as milestone for FDA¿s clearance to begin trial (2/97)"

GeneMedicine Inc.

Corange Ltd. (Bermuda; parent company of the Boehringer Mannheim Group; Germany)

1.3

Quarterly R&D payment

"GeneMedicine and Corange entered an R&D collaboration on non-viral gene therapy for cancer in 7/95; under the terms of the agreement, GeneMedicine gets quarterly R&D payments of $1.25M (7/97)"

Gilead Sciences Inc.

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

3

Milestone for completion of Phase I trial on GS4104 (oral)

"Gilead and Hoffmann-La Roche entered a collaboration in 9/96 to develop neuraminidase inhibitors (including GS4104) for viral influenza; upon successful completion of Phase I trial and the start of Phase II trials, Gilead received $3M (5/97)"

Hemosol Inc. (TSE:HML; Canada)

Fresenius AG (Germany)

1.2

Approval to begin Phase II trials of Hemolink

"Hemosol and Fresenius agreed in 6/95 to collaborate on the development, production and marketing of the human blood substitute Hemolink; in 2/97, Canadian regulatory authorities gave Hemosol the approval to begin Phase II trials (sum converted at an exchange rate of C$1.37/US$1) (3/97)"

ImClone Systems Inc.

Merck KGaA (Germany)

1.1

Achievement of pilot-scale manufacturing of BEC-2

"The companies inked the original agreement on therapeutic cancer vaccines, especially BEC-2 for small cell lung cancer and malignant melanoma, in 12/90; the agreement was extended in 5/96; ImClone got $0.5M for achieving pilot-scale manufacturing of BEC-2, which also triggered the 1st in a series of 8 quarterly support payments (about $0.6M each for total of $4.7M) (6/97)"

ImClone Systems Inc.

Merck KGaA (Germany)

1

Achievement of bulk manufacturing of cGMP- grade BEC-2

"The companies inked the original agreement on therapeutic cancer vaccines, especially BEC-2 for small cell lung cancer and malignant melanoma, in 12/90; the agreement was extended in 5/96; ImClone got $1M for achieving manufacturing of bulk GMP-grade BEC-2 (7/97)"

Introgen Therapeutics Inc.*

Rhone-Poulenc Rorer Inc. (NYSE:RPR; subsidiary of Rhone Poulenc Group; France)

5

Research milestone

"Rhone-Poulenc Rorer paid Introgen $5M for progress in the latter¿s p53 in vivo gene therapy program (the subject of a 10/94 collaboration between the parties); in collaboration with RPR Gencell (Rhone- Poulenc Rorer¿s gene therapy division), Introgen currently has several Phase I/II clinical trials in progress (2/97)"

Isis Pharmaceuticals Inc.

Boehringer Ingelheim International GmbH (Germany)

7.9

Second payment on line of credit

Isis and Boehringer Ingelheim entered a wide-ranging collaboration in cell adhesion molecule-targeted drug discovery in 7/95; Isis received $7.9M as its 2nd payment on a $40M line of credit that is part of the collaboration; Isis will use the funds to support its share of the collaboration expenses in 1997 (1/97)

La Jolla Pharmaceutical Co.

Abbott Laboratories (NYSE:ABT)

4

Stock purchase

"La Jolla Pharmaceutical and Abbott signed a worldwide development and marketing agreement on LJP 394 for treating lupus nephritis in 12/96; as part of that agreement, Abbott bought $4M in La Jolla Pharmaceutical stock (0.83M shares at $4.81/each) (9/97)"

Magainin Pharmaceuticals Inc.

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

5

Successful completion of clinical testing of product

The companies signed a development and marketing agreement on Cytolex (broad-spectrum antibiotic for treating diabetic foot ulcers) in 2/97; SmithKline paid $5M on the successful completion of clinical trials of Cytolex as well as its decision that the clinical data are sufficient to support the FDA¿s acceptance of an NDA (6/97)

Microcide Pharmaceuticals Inc.

Pfizer Inc. (NYSE:PFE)

1

1st milestone

"Microcide and Pfizer entered a collaboration in 3/96 to identify the genes that are essential to in vitro bacterial viability and to use them as drug discovery targets; Microcide reached the 1st milestone, related to identifying and sequencing a specific number of these essential genes (2/97)"

Myriad Genetics Inc.

Schering-Plough Corp. (NYSE:SGP)

2

License fee

"The companies signed an agreement in 4/97 to discover genes and develop therapies for prostate and other cancers, including brain cancer; Myriad got a $2M milestone license payment related to advanced findings on the MMAC1 gene (mutated in multiple advanced cancers), which is involved in the progression of brain tumors to fatal cancers (10/97)"

NeoRx Corp.

Schwarz Pharma AG (Germany)

8

Phase I trial data on Biostent

The companies entered a strategic alliance in 4/97 to commercialize Biostent (a combination drug/device for inhibiting restenosis following angioplasty); Schwarz Pharma reviewed the Phase I data on the product and paid $8M total ($4M of which was for 0.7M shares at a 500remium to market) (5/97)

Neurocrine Biosciences Inc.

Janssen Pharmaceutica NV (Belgium; unit of Johnson & Johnson; NYSE:JNJ)

1

Selection of drug development candidate

Neurocrine and Janssen¿s collaboration on small molecule compounds that act as antagonists of corticotropin-releasing factor (for use as drugs for anxiety and depression) dates from 2/95; Janssen selected a lead drug candidate for development (2/97)

North American Vaccine Inc.

Pasteur Merieux-Connaught (member of Rhone-Poulenc Group; France)

6

Milestone on product development

North American Vaccine and Pasteur Merieux-Connaught signed an agreement to jointly develop a conjugate vaccine against meningitis B in 1/96; the milestone-triggering event was not identified (9/97)

NPS Pharmaceuticals Inc.

Kirin Pharmaceutical (division of Kirin Brewery Co. Ltd.; Japan)

2

Initiation of Phase II trial on R-568

The companies agreed in 7/95 to develop calcium receptor agonists and other compounds for treating hyperparathyroidism; Kirin initiated Phase II trials in Japan with drug candidate R-568 (KRN-568; a calcimimetic compound) (12/97)

Pharmacopeia Inc.

Akzo Nobel/Organon NV (the Netherlands)

5

Technology access fee; 2nd equity purchase

Pharmacopeia and Organon formed an R&D collaboration on new drug discovery via combinatorial chemistry in 5/96; the $5M consists of a technology access fee plus the 2nd of 2 equity purchases (6/97)

Protein Polymer Technologies Inc.

Johnson & Johnson Development Corp. (affiliate of Johnson & Johnson; NYSE:JNJ)

4.8

Equity purchase

"Protein Polymer and Ethicon Inc. (a subsid- iary of Johnson & Johnson) agreed in 12/96 to extend their 1994 collaboration on the use of genetically engineered protein poly- mers as tissue adhesives and sealants for wound closure after surgery; as part of that agreement, Johnson & Johnson Develop- ment and other institutional investors bought 1.9M shares of Protein Poly- mer¿s stock at $2.50/share for $4.76M (1/97)"

Sonus Pharmaceuticals Inc.

Abbott Laboratories (NYSE:ABT)

4.4

Initiated Phase III trial of EchoGen

Sonus enrolled the 1st patient in a Phase III trial assessing myocardial perfusion with EchoGen (fluorocarbon-based ultrasound contrast agent); this milestone triggers $4.4M in payments over 2 quarters; in 10/96 the partners expanded their 5/96 alliance on developing EchoGen for use in cardiology and radiology (1/97)

Sonus Pharmaceuticals Inc.

Abbott Laboratories (NYSE:ABT)

1

European Marketing Authoriza- tion appli- cation accepted for filing

The European Medicines Evaluation Agen- cy accepted for filing Sonus¿ application for EchoGen (fluorocarbon-based ultrasound contrast agent); this milestone triggered $1M payment from Abbott (see above) (1/97)

Targeted Genetics

Groupe Fournier

1

Milestone

Targeted Genetics and its subsidiary Rgene Therapeutics Inc. entered an agreement with Groupe Fournier in 6/96 to develop the gene delivery system complexed with the E1A tumor suppressor gene for treating cancer; Targeted Genetics got approval to begin clinical trials in France (7/97)

Transkaryotic Therapies Inc.

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

2.5

Acceptance of cell line for development

"Transkaryotic Therapies and Hoechst Marion Roussel entered a collaboration to develop gene-activated erythropoietin for treating anemia in 1994; the 2nd gene activation collaboration, on an unnamed target protein, has resulted in Hoechst Marion Roussel¿s acceptance of a cell line for development (6/97)"

Unigene Laboratories Inc.

Warner-Lambert Co.(NYSE:WLA)

6

Terms of licensing agreement on oral calcitonin

Unigene and Warner-Lambert¿s Parke-Davis division established a licensing agreement on the development of oral calcitonin for osteoporosis in 6/97; this is the 1st payment under that agreement (8/97)