AMGEN
Vectibix • Panitumumab • ABX-EGF (formerly known as clone E7.6.3) Affiliate(s):
Japan Tobacco
The XenoMouse technology platform, used to generate ABX-EGF, was originally developed by Xenotech LP, an equally owned limited partnership formed in 1991 by Cell Genesys and JT America, Japan Tobacco's (JT)USA subsidiary. When Cell Genesys created Abgenix in 1996 as a wholly owned subsidiary, Cell Genesys assigned its interest in Xenotech to Abgenix, and in December 1999, Abgenix became sole owner of the XenoMouse technology platform by acquiring all of JT America's interest in Xenotech. Abgenix paid $47 million to JT America for its 50% interest as well as $10 million as compensation to JT to relinquish certain option and license rights to which it was entitled. JT obtained a research license to use XenoMouse technology and options to license the technology for a small number of antigen targets each year. Abgenix will also provide JT with licenses to related technology, obtaining $10 million in return. JT also retains options to, or licenses on, several antigen targets it previously nominated under the Xenotech structure. For all antibody products generated using XenoMouse technology and developed by JT, JT will make license fee payments to Abgenix as well as royalty payments on any product sales. JT and its subsidiaries are estimated to have invested more than $40 million in the creation of the XenoMouse technology; however, JT's emphasis will now be on generating antibody products for its pharmaceutical division to market itself rather than on creating a royalty based income stream. Lonza Biologics (terminated 6/03)
In June 2003, Abgenix terminated the Agreement with Lonza based on expansion of its own manufacturing capability.
In July 2001, Abgenix and Lonza entered into an agreement giving Abgenix right to enter into exclusive negotiations with Lonza for an additional manufacturing supply agreement for Lonza to make available to Abgenix, for a period of up to 5 years, extendable for an additional 2-year period, approximately 25% of the annual capacity of a cell culture production suite for large scale manufacturing of products that was under construction. The exclusive negotiation period was extended to expire no earlier than June 30, 2002. Financial terms of the agreements were not disclosed.
In November 2000, Abgenix and Lonza Biologics entered into a manufacturing supply agreement for Lonza to make available exclusively to Abgenix, for a period of 5 years, a cell-culture production suite, with associated purification capacity, within Lonza's UK facility. The agreement included an option to extend the initial 5-year term. This dedicated cell culture production suite became available to Abgenix in the third quarter of 2001. Abgenix gained access to production capacity, and scheduling flexibility, Lonza retained responsibility for, and control over, the facility's employees, and its operation. Current as of: November 25, 2007 | Approved (9/06) and launched (10/06) USA - colorectal cancer expressing the epidermal growth factor receptor (EGFr), metastatic, refractory, third line - colorectal cancer, metastatic, refractory to fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy regimens, third line, expressing EGFr with non-mutated K-ras |
BAYER
Nexavar • Sorafenib tosylate • 4-[4-[[4-Chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide; C21H16ClF3N4O3 • BAY 43-9006 Affiliate(s):
Onyx Pharmaceuticals
Sorafenib is being co-developed by Bayer Pharmaceuticals and Onyx Pharmaceuticals. The co-development collaboration calls for Onyx to fund 50% of the development and marketing costs for sorafenib worldwide, except in Japan. In return, Onyx has a 50/50 profit share in the USA, where the companies plan to co-promote the product if approved. In all other countries (except Japan) Bayer has exclusive marketing rights and Onyx's profit share is less than 50%. In Japan, Bayer will fund product development and Onyx will receive a royalty.
In September 2002, initiation of the phase II clinical program earned Onyx a $5 million loan milestone payment.
In April 1996, the agreement was amended to allow, that during the research term, Onyx and Bayer, to propose additional cancer research targets or programs outside of ras for inclusion, by mutual agreement, in the research collaboration. No additional targets have been proposed by either party during the period ended December 31, 1996. In addition, Bayer agreed that the research collaboration would continue for its full five-year scheduled term (through January 1999), subject only to termination for breach or in the event of the acquisition of Onyx. The agreement provides for Bayer to pay Onyx an aggregate of $25.0 million to fund research efforts over the five-year research term, of which $5.2 million was recorded by the Company as revenue in 1996, $5.2 million in 1995, and $5.5 million in 1994. In addition, Bayer made a $13.5 million equity investment in Onyx in 1994. Under the agreement, compounds that demonstrate the required level of activity in collaboration assays, as established by the Joint R&D Committee (JRDC), are subject to exclusive rights under the collaboration. Bayer will funds all preclinical work necessary to determine which compounds to take into clinical development and to obtain approval for conducting clinical trials. The parties will share equally all costs of developing each product worldwide (excluding Japan), subject to each party's right to elect not to pay such costs. Under the agreement, Bayer shall make substantial payments to Onyx, based on achievement of development milestones, which are subject to repayment by Onyx out of its share of marketing profits and royalties, subject to certain annual limitations.
Bayer shall market the products worldwide (excluding Japan), and Onyx has the option to co-promote such products in the USA, provided that Onyx share equally all costs of development in which case its expenses would be paid out of product sales. Onyx and Bayer will share equally the profits or losses from jointly developed commercialized products. Bayer has the sole and exclusive right to develop and market these compounds as royalty bearing products in Japan, and will bear all related development expenses. Furthermore, Bayer has the sole and exclusive right to develop and market any compounds active against Bayer-proposed targets as royalty bearing products. In addition, either party may independently develop a compound as a royalty bearing product if the JRDC declined such party's proposal to select the compound for joint development.
In February 1994, Onyx entered into a collaboration with Bayer relating to the ras program. Onyx is responsible for conducting research on the ras signaling pathways, identifying leads for drug screening and developing drug discovery assays. Bayer will screen its compound libraries, synthesized analogs of identified leads and conduct preclinical and clinical trials. In addition, Bayer will fund Onyx' research. Chiron
When Onyx was established in April 1992, Chiron transfered to Onyx the drug discovery program, primarily in the field of ras research, being conducted at Chiron by Dr. Frank McCormick, the scientific founder of Onyx, and his research team. As part of such transaction, Chiron and Onyx executed a Technology Transfer Agreement dated April 24, 1992, pursuant to which Chiron consented to the transfer of such research program, including the research team, and its trade secrets and materials used in this research. Chiron also granted a license to Onyx under certain patent rights held by Chiron useful in such research. As part of such agreement Chiron agreed not to re-establish a research program in this field for a period of three years. In May 1994, in connection with the formation of the collaboration between Bayer and Onyx, the Transfer Agreement was amended to make Onyx the sole licensee under one of the research assays transferred from Chiron until January 1, 1999, in consideration of which the covenant against Chiron re-establishing its research program in the field was eliminated.
In addition, through April 2007, Chiron has an option to obtain a royalty-bearing license with respect to diagnostic and vaccine products, developed by Onyx in this field. Such license would be exclusive unless an arbitrator determines that Chiron does not have the ability to commercialize the product in question so as to provide Onyx with a reasonable return, in which case such license will be co-exclusive. If Chiron does not exercise such option rights with respect to a particular product, then prior to the completion of phase II clinical trials of the product, the Onyx may seek a third party licensee of the product in question, subject to a right of first refusal in favor of Chiron, and after the completion of phase II clinical trials, the option rights of Chiron expire.
The Transfer Agreement also provides that Onyx may propose collaborations to Chiron in the field of gene therapy. Such proposal would require that Onyx disclose to Chiron the material information known to Onyx regarding the program in question, and also propose a set of terms. If such a proposal is made, and Onyx and Chiron do not reach agreement within 60 days after the proposal by Onyx, then Onyx may, within 120 days thereafter, enter into an agreement regarding such program with a third party on terms no more favorable taken as a whole, to the third party than the terms which Onyx offered to Chiron. Chiron has advised Onyx that it believes the foregoing provision, in the context of other provisions of the Transfer Agreement, imposes an obligation on Onyx to offer gene therapy programs to Chiron pursuant to this mechanism before it licenses any such program to a third party. The Company does not agree that such provision imposes an obligation on Onyx to make such proposals. However, Chiron has agreed that this provision does not apply to the p53 program for therapeutic applications.
In addition, Chiron agreed to fund the Company's research and operating activities up to a maximum of $3.95 million. As of December 31, 1993, all such amounts were earned and paid to Onyx. Chiron also made equity investments in Onyx totaling $402,000 in 1992. Current as of: November 20, 2007 | Approved and launched (12/05) USA; approved Switzerland, Chile, Brazil, Korea, Argentina, approved (4/06) Mexico; as of November 2007, Nexavar had been approved in over 60 countries worldwide - kidney cancer, advanced, refractory Approved and launched (3/06) Switzerlend; approved (7/06) EU - renal cell carcinoma (RCC), advanced, refractory to interferon (IFN)-alpha or interleukin (IL)-2-based therapy or not suitable for such therapy - hepatocellular carcinoma (HCC), advanced, inoperable, first line
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GENENTECH
Avastin • Bevacizumab • rhuMAb-VEGF •
NSC-704865 Affiliate(s):
ImmunoGen
See description for Herceptin. Roche
In June 2003, Roche obtained the rights for Avastin in all countries outside of the USA, under an existing agreement with Genentech. Genentech retains all marketing rights for Avastin within the USA. Protein Design Labs
Genentech exercised a license for Avastin in the first quarter of 2004, for which PDL received and recognized a fee in excess of $1.0 million. PDL will recognize royalties under that license commencing in the second quarter of 2004. Lonza Group
In November 2006, Genentech entered into an agreement with Lonza Group for Lonza to purchase Genentech's manufacturing facility in Porrino, Spain for $150 million. Concurrently, Genentech will enter into a supply agreement for the manufacture of certain Genentech products at Lonza's facility currently under construction in Singapore, with Genentech also receiving the right to exercise an exclusive option to purchase the Lonza Singapore facility. Under the terms of the agreement, Lonza will acquire from Genentech the FDA-licensed Porrino facility, which has 40,000 liters of biologic manufacturing capacity and is currently dedicated to the production of Genentech's Avastin. Lonza will continue to produce Avastin for Genentech at Porrino under the terms of a supply agreement. Under the terms of a concurrent agreement, Genentech plans to purchase Avastin and other oncology products from Lonza's planned 80,000-liter Singapore facility, and Genentech may opt to purchase the facility in the future. FDA licensure for producing Avastin at the Lonza plant in Singapore is expected in 2010. The terms of the option to purchase the facility allow Genentech to acquire the facility during the period from 2007 to 2012 for a purchase price of $290 million, plus an additional $70 million in milestone payments if certain performance milestones are met. Current as of: November 19, 2007 | Approved and launched (2/04) USA; approved (04) Israel, Switzerland; approved and launched (1/05) EU; launched (3/05) UK; approved (4/07) Japan - colorectal cancer, advanced, metastatic, first line (combination) Approved (6/06) USA - colorectal cancer, relapsed, metastatic, second line Approved (10/06) USA - non-small cell lung cancer (nsclc), non-squamous, inoperable, locally advanced, recurrent or metastatic, in combination with carboplatin and paclitaxel chemotherapy, first line
Approved and launched (3/07) EU - breast cancer, chemotherapy naive, first line, locally recurrent or metastatic, in combination with taxane chemotherapy
Approved (8/07) EU - non-small cell lung cancer (nsclc), non-squamous, inoperable, locally advanced, recurrent or metastatic, in combination with platinum-based chemotherapy, first line
- renal cell carcinoma (RCC), metastatic, in combination with interferon (IFN) alpha, first line
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IMCLONE SYSTEMS
Erbitux • Cetuximab • IMC-C225 Affiliate(s):
University of California San Diego
The University of California San Diego granted ImClone an exclusive worldwide license in April 1993 to a USA patent covering MAb that bind to EGFr. sanofi aventis
In June 1994, Aventis Pharmaceuticals granted ImClone an exclusive worldwide license to pending patent applications covering use of anti-EGFr MAbs in combination with specific chemotherapeutic regimens. Merck KGaA
In October 2007, ImClone Systems and Bristol-Myers Squibb entered into an agreement with Merck KGaA for the co-development and co-commercialization of Erbitux (cetuximab) in Japan. Under the terms of the agreement, ImClone Systems, Bristol-Myers Squibb and Merck KGaA will collaborate on a joint effort to develop and, following regulatory approval, market Erbtux in Japan for the treatment of epidermal growth factor receptor (EGFr)-expressing metastatic colorectal cancer, as well as for the treatment of any other malignancies the parties agree to pursue. Bristol-Myers Squibb and Merck KGaA will use their respective sales forces in Japan, and the three companies will share profits/losses realized as a result of the agreement. Merck Serono Japan will distribute the product and record the sales for the collaboration. The terms of this new agreement provide that Merck KGaA will receive 50% of the profit/loss from sales in Japan, and ImClone Systems and BMS will each receive 25%. The sharing of profit/loss reflects the co-exclusive rights to Erbitux in Japan, previously granted by ImClone Systems to Merck KGaA and Bristol-Myers Squibb. In addition to its percentage of profits, ImClone Systems will receive from Merck KGaA a royalty equal to 4.75% of total net sales in Japan.
In July 2006, ImClone Systems and Merck KGaA entered into agreements amending and supplementing the 1998 development and license agreement covering Erbitux and certain other work in the field of epidermal growth factor receptor (EGFr)-targeted monoclonal antibodies (MAb). As part of the agreements, ImClone consented to Merck's sublicense of certain intellectual property rights relating to the development and commercialization of an anti-EGFr antibody to Takeda Pharmaceutical Company. Merck and Takeda signed an alliance in September 2005 for the development and commercialization of matuzumab (EMD72000), a humanized EGFr-targeting MAb. In consideration for ImClone Systems' consent, Merck agreed to pay ImClone Systems €2.5 million upon execution of the agreements and a further €5 million upon ImClone Systems' written consent to the sublicense. In addition, Merck agreed to increase its fixed royalty to 9.5% for all sales of Erbitux outside the USA and Canada, effective July 1, 2006. The agreements also promote freedom to operate in the development and commercialization of matuzumab outside the USA and Canada, and of IMC-11F8, a fully human EGFr-targeted IgG1 MAb being developed by ImClone Systems, within the USA and Canada, through the granting of certain reciprocal rights, including the sharing of confidential technical information. The agreements do not extend to key intellectual property rights in the USA and Canada, where ImClone Systems and its partner Bristol-Myers Squibb continue to hold exclusive licenses to key patents covering certain uses of EGFr-targeted MAb.
In August 2004, ImClone Systems received a cash payment of $5 million as a result of its achieving a milestone in its license agreement with Merck KGaA, for development of Erbitux outside of North America. The milestone relates to the European Commission approval of Erbitux for the treatment of patients with metastatic, epidermal growth factor receptor (EGFr)-expressing colorectal cancer after failure of irinotecan-including cytotoxic therapy. Upon payment, ImClone Systems issued 58,807 shares of ImClone Systems' common stock to Merck KGaA, representing the sale of these shares at a 10% premium to market value as provided in the license agreement.
In June 2003, ImClone Systems received a $3 million payment from Merck KGaA for achieving a clinical development milestone under the companies' license agreement for Erbitux. Upon payment, ImClone Systems issued 150,007 shares of its common stock to Merck KGaA, representing sale of these shares at a 10% premium to market value as provided in the license agreement.
In May 2003, ImClone received a $6 million payment from Merck KGaA for achieving a manufacturing-related milestone under the companies' license agreement for Erbitux. Upon payment, ImClone Systems issued 334,471 shares of ImClone Systems' common stock to Merck KGaA, representing sale of these shares at a 10% premium to market value as provided in the license agreement. The milestone relates to Merck KGaA's receipt in April 2003 of an import license from the German state regulatory authority (the Regierungspraesidium Darmstadt), that allows Merck KGaA to import Erbitux supply manufactured at ImClone' manufacturing facilities in Somerville, NJ directly into Germany. In order to secure the import license and the subsequent milestone payment, ImClone's manufacturing facilities went through an inspection by a team of European regulators that included members of the Regierungspraesidium Darmstadt and the Paul Ehrlich Institute.
In March 2000, ImClone received a $2 million milestone payment from Merck relating to the expansion into France of a phase II trial of the combination of IMC-C225 and cisplatin in the treatment of patients with refractory advanced squamous cell head and neck cancer.
In January 2000, ImClone received a $4 million payment from Merck as a result of ImClone's preparation and delivery of a regulatory decument to Merck supporting submission for approval of a phase II trial in Spain of IMC-C225 in combination with cisplatin in the treatment of patients with refractory advanced head and neck cancer.
In December 1999, a $6 million milestone payment was triggered based on receipt by Merck of a letter of scientific advice from the European Agency for the Evaluation of Medical Products, a prerequisite for the initiation of a European trial center, as well as trial center initiation in Spain and treatment of the first patient with IMC-C225, combined with radiation therapy in a phase III trial of patients with advanced head and neck cancer.
In March 1999, ImClone Systems received a $5 million milestone payment from Merck, based on the successful completion of a meeting with the FDA allowing ImClone to initiate a phase III clinical trial of IMC-C225 in combination with radiation therapy in the treatment of patients with advanced squamous cell head and neck cancer. In May 1999, the FDA approved initiation of a second phase III trial of IMC-C225 in combination with cisplatin, resulting in a $3 million milestone payment from Merck.
In December 1998, Merck KGaA and ImClone initiated a collaboration under which Merck has received the exclusive license to develop and commercialize IMC-C225 outside North America (excluding Japan); ImClone retains North American rights, and both companies will co-develop the product in Japan. The collaboration agreement calls for ImClone to receive up-front fees, early cash-based milestones, latter equity-based milestones, and a $30 million credit line to support ImClone's build-out of a commercial manufacturing facility for IMC-C225. Merck will purchase IMC-C225 from ImClone for clinical trials and commercialization in its territory, and will pay royalties to ImClone on sales of IMC-C225 outside of North America. Bristol-Myers Squibb
In October 2007, ImClone Systems and Bristol-Myers Squibb entered into an agreement with Merck KGaA for the co-development and co-commercialization of Erbitux (cetuximab) in Japan (see Merck KGaA entry above).
The terms of this new agreement provide that Merck KGaA will receive 50% of the profit/loss from sales in Japan, and ImClone Systems and BMS will each receive 25%. The sharing of profit/loss reflects the co-exclusive rights to Erbitux in Japan, previously granted by ImClone Systems to Merck KGaA and Bristol-Myers Squibb. In addition to its percentage of profits, ImClone Systems will receive from Merck KGaA a royalty equal to 4.75% of total net sales in Japan.
In July 2007, ImClone Systems and Bristol-Myers Squibb amended the terms of their agreement for the co-development and co-promotion of Erbitux (cetuximab) in North America. Under this amendment, the companies have jointly agreed to expand the investment in the ongoing clinical development plan for Erbitux by up to several hundred million dollars. Development costs, up to a threshold value, will be the sole responsibility of Bristol-Myers Squibb; costs in excess of this threshold will be shared by both companies according to a pre-determined ratio. With this additional funding, the companies will seek to add numerous phase II and phase III clinical trials that will further explore the activity of Erbitux in a wide variety of therapeutic settings. The companies intend to use the results of these trials to support new registrational opportunities for Erbitux. The comprehensive clinical program will supplement the significant body of clinical data existing for Erbitux in colorectal and head and neck cancer by exploring the use of Erbitux in additional tumor types including brain, breast, bladder, gastric, lung, pancreatic and prostate cancer. The companies intend to use pharmacogenomic markers and other screening technologies to enhance patient outcomes, which may further differentiate Erbitux from other commercially available antibodies. This new commitment to Erbitux represents one of the largest and broadest cancer-focused development programs for any antibody.
In April 2006, ImClone Systems received a $250 million milestone payment under its commercial agreement with Bristol-Myers Squibb. The cash payment was triggered by FDA's approval of Erbitux (cetuximab) for use in the treatment of squamous cell carcinoma of the head and neck on March 1, 2006. Erbitux, which received a priority review, is the first drug approved to treat head and neck cancer in 45 years. The $250 million milestone payment is the final such payment under the commercial agreement. Total milestone payments received to date under the agreement are $900 million.
In March 5, 2003, ImClone Systems received a $60 million cash payment from Bristol-Myers Squibb as part of the companies' amended commercialization agreement for Erbitux.
In March 2002, the commercial agreement with ImClone to co-develop and co-promote Erbitux was revised to reduce the total remaining payments to $700 million from $800 million. Under the new agreement, BMS paid ImClone $140 million in the first quarter of 2002. Also, under the agreement, BMS will pay ImClone $60 million in March 2003 and an aggregate of $500 million upon the achievement of two milestones. Also under the agreement, the company will pay ImClone a distribution fee based on a flat rate of 39% of product revenues in North America.
In October 2001, Bristol-Myers Squibb accepted for purchase 14,392,003 shares of common stock of ImClone Systems tendered in its offer, which expired at midnight Eastern time on Friday, October 26, 2001. The shares accepted represent approximately 19.9% of the approximately 72 million ImClone Systems shares outstanding just prior to the commencement of offer. The completion of the tender offer is part of a strategic agreement between Bristol-Myers Squibb and ImClone to codevelop and copromote IMC-C225 in the USA, Canada, and Japan.
In September 2001, Bristol-Myers Squibb reached an agreement with ImClone Systems to codevelop and copromote IMC-C225 in the USA, Canada, and Japan. The transaction comprises a commercial agreement for the c-development and copromotion of IMC-C225, as well as the acquisition of an equity stake in ImClone. Under the terms of the commercial agreement, BMS will pay ImClone a total of $1 billion in three cash payments for the achievement of the following milestones, one upon the signing of the agreement, one upon the completion of the BLA submission with the FDA, and one upon the marketing approval of IMC-C225 by the FDA. In addition, ImClone will receive a significant share of product revenues. The term of the commercial agreement runs through at least 2018. Genentech
In January 2005, ImClone Systems signed license agreements with Genentech and Centocor for the rights to patents relating to various aspects of antibody technology [USA Patent #4,816,567, #6,331,415, and #5,807,715) and use of antibodies targeting EGFr (#5,770,195). These licenses relate to Erbitux and IMC-11F8. Centocor
See Genentech affiliation description. Current as of: November 29, 2007 | Approved and launched (12/03) Switzerland - colorectal cancer, metastatic, refractory to irinotecan-based treatment, in combination with irinotecan Approved and launched (2/04) USA; approved (6/04) Switzerland, the 25 member states of the newly expanded European Union, Iceland and Norway; approved (04) Chile, Argentina, Mexico; as of April 2006, Erbitux obtained market authorization to treat colorectal cancer in 53 countries, including Switzerland, the USA, Mexico, Argentina, Chile, Iceland, Norway, the European Union, Peru, Australia, Croatia, Israel, Bulgaria, Panama, Guatemala, Colombia, Singapore, Hong Kong, South Korea, Canada, Ecuador, Malaysia, the Philippines, Taiwan, China, India, Lebanon, Venezuela and Nicaragua for the use in combination with irinotecan in patients with EGFr-expressing metastatic colorectal cancer who have failed prior irinotecan therapy. In the USA, Argentina, Chile, Mexico, Peru, Singapore, Australia, Panama, Colombia, Guatemala, Hong Kong, Canada, Ecuador, the Philippines, Lebanon, Venezuela and Nicaragua Erbitux is also approved for single agent use. - colorectal cancer, metastatic, refractory to irinotecan, EGFr expressing (combination or single agent), second line or third line Approved and launched (12/05) Switzerland; approved and launched (3/06) USA; approved and launched (4/06) EU (25 countries, Norway and Iceland); approved (06) Argentina, Colombia - head and neck cancer, advanced, in combination with radiotherapy, first line
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