Pasteur Merieux Connaught (unit of Rhone-Poulenc Group; France)
0.15
Results of Phase Ia clinical trial on vaccine for ear infections
The companies signed a licensing agreement in 12/94 on Antex s recombinant Haemophilus influenzae (nontypeable) vaccine for treating inner ear infections (otitis media) in infants and children and upper respiratory disorders in the elderly; due to encouraging results of Phase Ia trial in adults, Antex received its 2nd milestone payment (1/98)
ArQule Inc.
Wyeth-Ayerst Pharmaceuticals (division of American Home Products Corp.; NYSE:AHP)
2
Equity
The companies signed a broad drug discovery agreement in 7/97; the $2M equity investment is in accordance with the terms of that agreement (6/98)
Atrix Laboratories Inc.
Block Drug Corp. (NASDAQ:BLOCA)
7
Approvable letter on Atridox
The companies entered an agreement in 12/96 for Block Drug to market Atridox in North America; the FDA sent Atrix an approvable letter for Atridox for treating periodontal disease, triggering the $7M milestone payment (4/98)
Atrix Laboratories Inc.
Block Drug Corp. (NASDAQ:BLOCA)
5
FDA approval of Atridox
The companies entered an agreement in 12/96 for Block Drug to market Atridox in North America; the FDA approved the product on 9/8/98 for treating periodontal disease, triggering the milestone payment (9/98)
Atrix Laboratories Inc.
Block Drug Corp. (NASDAQ:BLOCA)
5
First product shipment
The companies entered an agreement in 12/96 for Block Drug to market Atridox for treating periodontal disease in North America; Block began the 1st shipment of product to dentists, triggering the $5M milestone payment (10/98)
Axiom Biotechnologies Inc.*
Cadus Pharmaceutical Corp.
2
Equity
The companies signed a licensing agreement on Axiom s high-throughput pharmacological screening system (HT-PS) in 5/97; Cadus received the 1st HT-PS system, triggering its purchase of $2M in Axiom preferred stock (giving Cadus a total of 30% ownership) (6/98)
Cadus Pharmaceutical Corp.
SmithKline Beecham plc (NYSE:SBH; U.K.)
2
Technology development fee
The companies signed a functional genomics collaboration in 2/97; Cadus got a scheduled $2M technology development fee as part of that collaboration (3/98)
Cadus Pharmaceutical Corp.
SmithKline Beecham plc (NYSE:SBH; U.K.)
5
Equity
Cadus exercised its option to issue and sell $5M in common stock (0.66M shares at $7.56/each) to SmithKline Beecham; Cadus acquired the option as part of its 2/97 collaboration with SmithKline on functional genomics (5/98)
Cell Genesys Inc.
Hoechst Marion Roussel Inc. (subsidiary of Hoechst AG; Germany)
2
Initiation of Phase III trial of gene-activated EPO
The companies signed a licensing agreement in 2/97 on Cell Genesys gene-activated erythro-poietin (EPO) and a 2nd undisclosed protein; Hoechst Marion Roussel initiated a Phase III clinical trial of the product (which it is developing with Transkaryotic Therapies Inc.), triggering the milestone payment (9/98)
Cor Therapeutics Inc.
Schering-Plough Corp. (NYSE:SGP)
8
Acceptance for review by European Union of marketing application on Integrilin
The companies signed a collaboration on Integrilin in 4/95; the European Medicines Evaluation Agency accepted for review the marketing application on Integrilin, triggering the $8M milestone payment (2/98)
Cor Therapeutics Inc.
Schering-Plough Corp. (NYSE:SGP)
24
FDA approval of Integrilin
The companies signed an agreement to develop and market Integrilin (a small molecule synthetic compound that inhibits the GPIIb/ IIIa receptor that mediates platelet aggregation) in 4/95; the FDA approved the drug 5/19/98 for treating patients with acute coronary syndromes and as an adjunct to percutaneous coronary intervention; Cor received a $24M milestone payment for the approval (6/98)
Corvas International Inc.
Pfizer Inc. (NYSE:PFE)
1
Initiation of clinical trial
In 2/97, Pfizer exercised its option under a 10/95 agreement between the 2 companies to license and develop neutrophil inhibitor factor as a stroke therapy; Pfizer has started a Phase I trial, triggering the milestone payment (2/98)
Corvas International Inc.
Schering-Plough Corp. (NYSE:SGP)
1
Initiation of Phase I clinical trial
The companies signed an R&D agreement on oral anti-thrombotic drugs for treating chronic cardiovascular disorders in 12/94; Schering-Plough started Phase I trials of a drug candidate, triggering the milestone payment (6/98)
Cytogen Corp.
The DuPont Merck Pharmaceutical Co.
3.8
Termination of agreement on Quadramet
The companies signed a licensing and marketing agreement on Quadramet (Samarium 153 EDTMP) for treating bone pain from cancer that has spread to the bone in 12/94; that agreement was terminated and Cytogen received a $3.8M payment from DuPont Merck (6/98)
Diatide Inc.
Nycomed Amersham plc (U.K.)
2
Submission of NDA for NeoTect
The companies signed a marketing agreement in 8/95 that covers Diatide s TechTides (peptide-based imaging agents); Diatide submitted an NDA for NeoTect (a lung cancer imaging product) in 6/98, for which it received the $2M milestone payment (8/98)
Diatide Inc.
Nycomed Amersham plc (U.K.)
2
FDA approval of AcuTect
The companies signed a marketing agreement in 8/95 that covers Diatide s TechTides (peptide-based imaging agents); FDA approved AcuTect on 9/15/98 for imaging venous thrombosis, triggering the payment (9/98)
GelTex Pharmaceuticals Inc.
Genzyme Corp.
15
FDA approval of Renagel Capsules
The companies formed a joint venture for marketing Renagel in 6/97; FDA approved the phosphate binder for reducing serum phosphorus in end-stage renal disease on 11/2/98, triggering the milestone payment (11/98)
GeneMedicine Inc.
Corange International Ltd. (Bermuda)
5.3
Scheduled payments (equity; R&D) per terms of alliance
The companies signed a collaboration on gene medicines for treating various cancers in 7/95; Corange bought $4M in GeneMedicine stock (0.53M shares at $7.50 each) and paid a $1.25M quarterly R&D payment (2/98)
Gensia Sicor Inc.
SangStat Medical Corp.
2.5
Commercial supply agreement on bulk cyclosporine
The companies signed a supply agreement in 4/97 for Gensia Sicor s commercial-scale production of bulk cyclosporine; SangStat bought $2.5M in Gensia Sicor stock in connection with the agreement (1/98)
Genzyme Transgenics Corp.
SMI Genzyme Ltd. (joint venture between Genzyme Transgenics and Sumitomo Metals; Japan)
2
Audit of production facility for rhATIII
SMI Genzyme was formed in 1990 to develop recombinant human antithrombin III (rhATIII) in milk of transgenic goats; SMI paid $2M as milestone on successful independent audit of the commercial-scale production facility (1/98)
Geron Corp.
Pharmacia & Upjohn Inc. (NYSE:PNU; U.K.)
4
Stock purchase
The companies signed a definitive agreement on anticancer drugs that inhibit telomerase in 3/97; as part of that agreement, Pharmacia & Upjohn bought $4M of Geron s common stock (premium to market) (3/98)
Guilford Pharmaceuticals Inc.
Amgen Inc.
1
Initiation of toxicology study on NIL-A
The companies signed a major collaboration in 8/97 to develop Guilford s FKBP-neuro-immunophilin ligands; a toxicology study of the lead compound NIL-A (for treating Parkinson s disease) was initiated, triggering the milestone payment (9/98)
The Immune Response Corp.
Agouron Pharmaceuticals Inc.
5
Quarterly payment
The companies entered an agreement in 6/98 to collaborate on the final development and commercialization of the immune-based therapy Remune for treating HIV infection; this is the 1st in a series of quarterly payments Agouron will make to Immune Response; it consists of $3M for R&D and $2M for the purchase of 0.13M shares of unregistered common stock (10/98)
Immunex Corp.
Wyeth-Ayerst Laboratories (division of American Home Products Corp.; NYSE:AHP)
20
Submission of BLA for Enbrel
The companies signed a broad marketing agreement on Enbrel in 9/97; Immunex completed its submission of the BLA on Enbrel (soluble tumor necrosis factor receptor) for treating active rheumatoid arthritis, trigger-a $20M milestone payment (5/98)
IntraBiotics Pharmaceuticals Inc.*
Pharmacia & Upjohn Inc. (NYSE: PNU; U.K.)
1
Completion of Phase I trial of Protegrin IB-367
The companies entered an agreement in 10/97 to develop and market the topical antimicrobial compound IB-367 (synthetic peptide based on natural host defense peptide protegrin) for treating oral mucositis; IntraBiotics completed the Phase I trial, triggering a $1M milestone (12/98)
Isis Pharmaceuticals Inc.
CIBA Vision Corp. (division of Novartis AG; Switzerland)
5
Submission of NDA on fomivirsen (a.k.a. Vitravene)
The companies entered an agreement in 7/97 for CIBA Vision to market fomivirsen worldwide; the partners jointly submitted an NDA for the antisense drug (for treating AIDS-related cytomegalovirus retinitis), triggering the $5M milestone payment (4/98)
Isis Pharmaceuticals Inc.
Ciba Vision Corp. (division of Novartis AG; Switzerland)
7.5
FDA approval of Vitravene
The companies entered an agreement in 7/97 for Ciba Vision to market Vitravene worldwide; FDA approved the product on 8/27/98 for treating cytomegalovirus retinitis in AIDS patients, triggering the milestone payment (9/98)
La Jolla Pharmaceutical Co.
Abbott Laboratories (NYSE:ABT)
4
Terms of alliance
The companies entered an agreement in 12/96 to develop and market LJP 394 for treating lupus nephritis; per terms of the agreement, Abbott bought 1.54M shares of La Jolla stock for $4M (11/98)
Medarex Inc.
Eisai Co. Ltd. (Japan)
0.8
Manufacturing and development progress on MDX-CD4
The companies signed an agreement in 10/97 to develop fully human monoclonal antibodies via Medarex s HuMAb-mouse technology; the $0.75M milestone was achieved for progress on the 1st antibody, MDX-CD4, for treating rheumatoid arthritis and other autoimmune diseases (9/98)
Medarex Inc.
Merck KGaA (Germany)
1.2
Clinical progress of MDX-477
The companies signed an agreement to collaborate on the development of Medarex s MDX-477 bispecific antibody for certain cancers in 4/94; the product is now entering Phase II trials in head and neck cancer, triggering a $1.2M equity investment (0.192M shares of Medarex common stock) by Merck KGaA (8/98)
Medarex Inc.
Xenotech LP (joint venture between Cell Genesys Inc., its subsidiary Abgenix Inc. and Japan Tobacco Inc.)
7.5
Issuance of European patent on Medarex s HuMAb-Mouse technology
GenPharm International Inc., which has since been acquired by Medarex, entered into a cross-licensing agreement on human monoclonal antibody technology with Xenotech in 3/97; GenPharm (Medarex) was due 2 milestones of $7.5M each as part of the agreement, including when Gen-Pharm s patent on HuMAb-mouse technology issued (1/98)
Medarex Inc.
Xenotech LP (joint venture between Cell Genesys Inc., its subsidiary Abgenix Inc. and Japan Tobacco Inc.)
7.5
Terms of crosslicensing agreement
The parties entered a cross-licensing agreement on all issued and related patent applications on the generation of fully human antibodies in genetically modified mice in 3/97; this is 2nd of two $7.5M payments (11/98)
MedImmune Inc.
Abbott Laboratories (NYSE:ABT)
15
FDA approval of Synagis
The companies signed a worldwide marketing agreement on Synagis in 12/97; the FDA approved the product (a humanized monoclonal antibody to respiratory syncytial virus; RSV) for preventing the disease in high-risk infants and children on 6/19/98; Abbott paid MedImmune a $15M milestone on FDA approval (6/98)
NeoRx Corp.
Janssen Pharmaceutica NV (Belgium; unit of Johnson & Johnson; NYSE:JNJ)
7
Janssen decided to initiate Phase II trials of Avicidin
The companies formed a strategic alliance in 8/97 to develop NeoRx s Avicidin radioimmunotherapy product for cancer; Janssen decided to take the product into Phase II trials in lung, colon and prostate cancer once FDA clearance obtained; NeoRx got $7M for this milestone (1/98)
NovaDx International Inc. (VSE:NVN)
Metra Biosystems Inc.
0.55
First commercial sales of blood test for arthritis
The companies signed a licensing and development agreement in 1/96 on NovaDx s Chondrex blood test for arthritis; Metra is now marketing the test and has completed beta testing; Metra bought 2.57M special warrants of NovaDx at US$0.214 each for total of US$0.55M; each special warrant is convertible into 1 common share of NovaDx (prices converted at rate of C$1.43/ US$1) (1/98)
NPS Pharmaceuticals Inc.
SmithKline Beecham plc (NYSE:SBH; U.K.)
1.8
Terms of alliance
The companies entered an agreement in 12/93 on orally active small-molecule drugs that act on calcium receptors for treating osteoporosis; the agreement was extended in 12/97; as per those terms, SmithKline is to buy equity in NPS on an annual basis; it bought 0.2M shares at $8.87 each for a total investment of $1.8M (11/98)
Organogenesis Inc.
Novartis Pharma AG (Switzerland)
3.8
Milestone payment
Organogenesis signed a licensing agreement on Apligraf with Sandoz Ltd. (which is now Novartis) in 1/96; Novartis paid $0.75M in research support and bought $3M in new Organogenesis equity under the terms of that agreement (3/98)
Organogenesis Inc.
Novartis Pharma AG (Switzerland)
7.7
FDA approval of Apligraf
Organogenesis signed a licensing agreement on Apligraf with Sandoz Ltd. (which is now Novartis) in 1/96; upon FDA approval of Apligraf, Novartis bought $6M in Organogenesis equity and paid an additional $1.7M in research/milestones (together with the $3.75M that Organogenesis got in 3/98, total payments related to product approval equal $11.5M) (5/98)
Pharmacopeia Inc.
Daiichi Pharmaceutical Co. Ltd. (Japan)
3
Research milestone
The companies entered a research collaboration on use of combinatorial chemistry and high-throughput screening for drug discovery in 4/96; Pharmacopeia achieved a key preclinical milestone, for which Daiichi invested $3M in Pharmacopeia equity (1/98)
Protein Design Labs Inc.
Toagosei Co. Ltd. (Japan)
2
Equity investment
The companies entered an agreement in 9/96 for Protein Design Labs to humanize one of Toagosei s antibodies; Toagosei bought $2M in Protein Design Labs equity (0.045M shares at $44.875 each) in 4Q:97 (2/98)
Regeneron Pharmaceuticals Inc.
The Procter & Gamble Co. (NYSE:PG)
5
Preclinical development of Axokine
The companies signed a broad-based discovery collaboration in 5/97, and expanded that agreement in 9/97 to include Regeneron s Axokine (2nd generation ciliary neurotrophic factor) for treating obesity associated with diabetes; Regeneron received a $5M milestone for progress in the preclinical development of Axokine (7/98)
Regeneron Pharmaceuticals Inc.
Sumitomo Pharmaceuticals Co. Ltd. (Japan)
5
License agreement for BDNF in Japan
The companies signed an R&D agreement to develop Regeneron s brain-derived neurotrophic factor (BDNF) in Japan in 6/94; in 8/98, Sumitomo licensed the product for use in Japan, paying Regeneron $5M as the initial fee (8/98)
RiboGene Inc.
Abbott Laboratories (NYSE:ABT)
4
IPO
The companies entered a collaboration on antifungal drugs in 4/96; as part of that agreement, Abbott agreed to buy stock in RiboGene concurrently with its IPO at the same price/share in a private placement; although Abbott terminated the collaboration effective 4/8/98, it still bought $4M concurrent with RiboGene s IPO (0.57M shares at $7/each), giving it a 12.72% stake (5/98)
Ribozyme Pharmaceuticals Inc.
Schering AG (Germany)
2.5
Completion of 1st phase of collaboration
The companies entered a collaboration on use of ribozymes to validate a broad range of therapeutic targets in 4/97; Ribozyme has successfully completed the 1st phase of the collaboration, triggering a $2.5M equity investment from Schering Berlin Venture Corp. (an affiliate of Schering AG) (5/98)
Sugen Inc.
ASTA Medica AG (Germany)
0.5
Joint decision to proceed with clinical development of Pan-HER cancer program
The companies formed a strategic alliance in 12/95 to develop oncology products based on cell signal transduction targets HER-2 and Raf; the joint decision to proceed with clinical development triggered ASTA s purchase of $0.5M of Sugen s stock (at $26.75/share) (1/98)
Transkaryotic Therapies Inc.
Hoechst Marion Roussel Inc. (unit of Hoechst AG; Germany)
2.5
Hoechst Marion initiated Phase III trial of GA-EPO
The companies signed an agreement in 1994 to develop gene-activated drugs; Hoechst Marion initiated Phase III trials of GA-EPO (erythro-poietin), triggering the $2.5M milestone (9/98)
Trega Biosciences Inc.
Novartis Pharma AG (Switzerland)
7
Terms of alliance
The companies entered an agreement in 5/98 on orally active small molecules for treating diseases mediated by the melanocortin-4 receptor pathway; as part of that agreement, Trega had the option of getting an equity investment from Novartis; Novartis bought 1.9M shares of Trega at $3.75 each for $7M total (11/98)
Trega Biosciences Inc.
Parke-Davis (division of Warner-Lambert Co.; NYSE:WLA)
1.5
Identification of series of lead compounds
The companies entered a collaboration in 5/97 to use Trega s combinatorial chemistry libraries to identify compounds active against a Parke-Davis biological target; a series of lead compounds has been identified; Warner-Lambert will buy $1.5M in Trega common stock, the timing and pricing of which will be determined by Trega over the next 2 years (2/98)
Unigene Laboratories Inc.
Parke-Davis (division of Warner-Lambert Co.; NYSE:WLA)
2
Developmental benchmark
The companies signed a licensing agreement on Unigene s oral calcitonin for treating osteoporosis in 7/97; Unigene got a $2M milestone payment for achieving a developmental benchmark for this product (2/98)
Unigene Laboratories Inc.
Parke-Davis (division of Warner-Lambert Co.; NYSE:WLA)
3
Achievement of developmental benchmark on calcitonin
The companies signed a licensing agreement on Unigene s oral calcitonin for treating osteoporosis in 7/97; Unigene got a $3M milestone for achieving a developmental benchmark; it expects to initiate a pilot human study in the U.K. this year (9/98)
U.S. Bioscience Inc.
Alza Corp.
5
Clinical development milestone
The companies entered a U.S. marketing and distribution agreement for Ethyol in 12/95; U.S. Bioscience received $5M for achieving a clinical development milestone in connection with its Phase III trial of Ethyol in head and neck cancer (2/98)
Vertex Pharmaceuticals Inc.
Glaxo Wellcome plc (NYSE:GLX; U.K.)
3
Glaxo submitted NDA on Agenerase
The companies signed a collaboration to develop HIV protease inhibitors in 12/93; Glaxo submitted an NDA to FDA on Vertex s drug Agenerase (amprenavir), triggering a $3M milestone payment to Vertex (10/98)
Vertex Pharmaceuticals Inc.
Kissei Pharmaceutical Co. Ltd. (Japan)
2
Selection of lead drug development candidate
The companies signed an agreement in 9/97 to develop orally active inhibitors of Vertex s p58 mitogen-activated protein kinase for treating inflammatory and neurological disorders; the companies selected a lead drug development candidate (VX-745), triggering a $2M milestone payment (7/98)
Xenova Group plc
Parke-Davis (division of Warner-Lambert Co.; NYSE:WLA)
1.7
Achievement of pilot phase of R&D collaboration
The companies signed a drug discovery agreement in 10/96, which uses Xenova s natural product drug discovery technology, QTC; the 1st QTC compounds were delivered to Parke-Davis in late 1997 and a number of them tested positive against targets; Warner-Lambert paid US$1.66M for 0.46M new common shares of Xenova, raising its equity stake to 3% (prices converted at a rate of 0.6/US$1) (3/98)
Zonagen Inc.
Schering-Plough Corp. (NYSE:SGP)
5
Completion of clinical program on Vasomax
The companies signed a worldwide marketing agreement on Vasomax (immediate-release oral formulation of phentolamine mesylate) for treating male erectile dysfunction in 11/97; Zonagen received an accelerated milestone payment of $5M, marking the completion of the clinical program in support of an NDA submission (6/98)
Zonagen Inc.
Schering-Plough Corp. (NYSE:SGP)
5
FDA accepted Vasomax NDA for filing
The companies signed a worldwide marketing agreement on Vasomax (immediate-release oral formulation of phentolamine mesylate) for treating male erectile dysfunction in 11/97; the FDA accepted for filing the NDA on Vasomax, triggering the milestone (9/98)