Phase 1B. The goals of Track 2, phase 1B are similar to those of Track 1 phase 1B. In addition to examining the interaction of other Track 2 assays, Track 2 phase 1B will require examining interactions with Track 1 assays. Track 2, phase 1B should last 6 months. Following establishment of Track 2 assays and the acquisition of data regarding the interaction of both Track 1 and Track 2 assays, a working protocol will be assembled for all chosen assays. *** As described for Phase 2 of Track 1 *** lines will be tested in Phase 2 of Track 2. *** of these line will be Pfizer-supplied KO lines on a *** and *** will be *** from an outsource breeder. One of the *** cohorts will be just *** mice and one will be a *** with ***. As with Phase 2 of Track 1, delivery to Xenogen Cranbury will be made for one of the *** lines, at 1-week intervals for *** weeks at the start of phase 2. In this case, *** KO mice and *** will be supplied or for the *** mice a cohort of *** mice will be supplied *** of which will serve as untreated controls and another *** which will serve to be treated with validation reagents as outlined in Appendix 1. Xenogen Cranbury should complete a full phenotypic protocol on each line within *** months after receiving a given KO line. ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇ ▇ will last approximately *** months. We anticipate that following Phase 2, as we proceed to full scale production phenotyping, the number of *** may be reduced. These decisions will be made on an assay by assay basis, following discussions with the associated TA and scientists at Xenogen. ***. The cost of phenotypic analysis using all Track I and Track II Assays under this Research Plan is at a rate of *** per Transgenic Mouse Line. *** *** CONFIDENTIAL TREATMENT REQUESTED *** CONFIDENTIAL TREATMENT REQUESTED *** CONFIDENTIAL TREATMENT REQUESTED December 11, 2003 Xenogen Biosciences ▇ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: Mr. ▇▇▇ ▇▇▇▇▇▇ Dear ▇▇. ▇▇▇▇▇▇, I am writing to confirm that the parties have agreed that additional research activities will be carried out under the Collaborative Research Agreement dated December 28, 2000 (“2000 Agreement”). Accordingly, the Research Plan will be amended pursuant to Sections 1.16 and 13.4 of the 2000 Agreement to include the activities described in the attached document, which will be appended to the 2000 Agreement as Exhibit C, and Section 1.13 is hereby amended by revising the second sentence to read, “as Exhibits A and C.” The amount and payment schedule of fees payable to Xenogen Cranbury for these additional research activities, pursuant to Section 3.1(h) of the 2000 Agreement, are set out in Exhibit C, and Section 3.1(h) is amended by adding the following sentence, “Exhibit C describes certain additional work to be performed by Xenogen Cranbury under the Research Program, and that Exhibit contains the separate price and payment terms for that work.” Section 3.1(g) shall be replaced in full with the following sentence, “At Pfizer’s option, it may extend this Agreement for three successive one-year periods by providing 90 days’ prior written notice to Xenogen Cranbury.” The work to be undertaken during such intended periods and the fees payable for such work will be as set out in Exhibit C. All other terms and conditions of the 2000 Agreement shall remain unchanged and in full force and effect. If the foregoing reflects your mutual understanding, please have the appropriate official at Xenogen Cranbury sign both copies of this Letter and return one original to ▇▇▇▇▇ ▇. ▇▇▇▇▇ at the above address, and it shall become a binding amendment to the 2000 Agreement. Sincerely, /s/ ▇▇▇▇ ▇▇▇▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇▇▇, President, PGRD By: /s/ ▇▇▇ ▇▇▇▇▇▇ Name: ▇▇▇ ▇▇▇▇▇▇ Title: V. P. Business Development Date: 12.26.03 Research Plan Summary The objective of this collaborative research project is to implement, a comprehensive mouse phenotyping protocol. The phenotyping will be carried out using a previously established comprehensive protocol of *** (see below) which therapeutic areas scientists have deemed as useful in making go/no go decisions on whether a new gene represents a potential therapeutic target. ***. We aimed to include as many therapeutic areas as possible in this program. This four-year program is intended for implementing the comprehensive phenotyping protocol on approximately *** knockout mouse lines/year. Pfizer-derived knockout lines, as well as third party-derived lines will be phenotyped. The *** assays will be carried out over a period of *** weeks and data will be deposited into the phenotype pfinder database in a previously established “real-time” manner for each assay as it is completed. The first year (2004) of this collaboration Pfizer will contribute *** lines to be phenotyped, *** KO and *** WT animals will be sent to Xenogen for comprehensive phenotyping, an additional *** lines are currently breeding at Xenogen and will be incorporated into the protocol to complete the *** lines for testing in 2004. A similar model will be followed during the following 3 years of the collaboration. The following assays will be carried out in the comprehensive protocol: *** ***
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Phase 1B. The goals of Track 2, phase 1B are similar to those of Track 1 phase 1B. In addition to examining the interaction of other Track 2 assays, Track 2 phase 1B will require examining interactions with Track 1 assays. Track 2, phase 1B should last for 6 months. Following establishment of Track 2 assays and the acquisition of data regarding the interaction of both Track 1 and Track 2 assays, a working protocol will be assembled for all chosen assays. *** *. As described for Phase 2 of Track 1 *** lines will be tested in Phase 2 of Track 2. *** of these line lines will be Pfizer-supplied KO lines on a *** and *** will be *** from an outsource breeder. One of the *** cohorts will be just *** mice and one will be a *** with ***. As with Phase 2 of Track 1, delivery to Xenogen Cranbury will be made for one of the *** lines, at 1-week intervals for *** weeks weeks, at the start of phase 2. In this case, *** KO mice and *** controls will be supplied or for the *** mice a cohort of *** mice will be supplied *** of which will serve as untreated controls and another *** which will serve to be treated with validation reagents as outlined in Appendix 1. Xenogen Cranbury should complete a full phenotypic protocol on each line within *** months after receiving a given KO line. ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇ ▇ will last approximately *** months. We anticipate that following Phase 2, as we proceed to full scale production phenotyping, the number of *** may be reduced. These decisions will be made on an assay by assay basis, following discussions with the associated TA and scientists at Xenogen. ***. The cost of phenotypic analysis using all Track I and Track II Assays under this Research Plan is at a rate of *** per Transgenic Mouse Line. *** *** CONFIDENTIAL TREATMENT REQUESTED *** CONFIDENTIAL TREATMENT REQUESTED *** CONFIDENTIAL TREATMENT REQUESTED December 11September 29, 2003 Xenogen Biosciences ▇ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: Mr. ▇▇▇ ▇▇▇▇▇▇ Dear ▇▇. ▇▇▇▇▇▇, I am writing to confirm that the parties have agreed that additional research activities will be carried out under the Collaborative Research Agreement dated December 28September 30, 2000 2001 (“2000 2001 Agreement”). Accordingly, the Research Plan will be amended pursuant to Sections 1.16 1.13 and 13.4 of the 2000 2001 Agreement to include the activities described in the attached document, which will be appended to the 2000 2001 Agreement as Exhibit C, and Section 1.13 is hereby amended by revising the second sentence to read, “as Exhibits A and C.” The amount and payment schedule of fees payable to Xenogen Cranbury for these additional research activities, pursuant to Section 3.1(h3.1(d) of the 2000 2001 Agreement, are set out in Exhibit C, and Section 3.1(h3.1(d) is amended by adding the following sentence, “Exhibit C describes certain additional work to be performed by Xenogen Cranbury under the Research Program, and that Exhibit contains the separate price and payment terms for that work.” Section 3.1(g) shall be replaced in full with the following sentence, “At Pfizer’s option, it may extend this Agreement for three successive one-year periods by providing 90 days’ prior written notice to Xenogen Cranbury.” The work to be undertaken during such intended periods and the fees payable for such work will be as set out in Exhibit C. All other terms and conditions of the 2000 2001 Agreement shall remain unchanged and in full force and effect. If the foregoing reflects your mutual understanding, please have the appropriate official at Xenogen Cranbury sign both copies of this Letter and return one original to ▇▇▇▇▇ ▇. ▇▇▇▇▇ at the above address, and it shall become a binding amendment to the 2000 2001 Agreement. Sincerely, /s/ ▇▇▇▇ ▇▇. ▇▇▇▇▇▇▇ ▇▇▇▇ ▇▇. ▇▇▇▇▇▇▇, President, PGRD Ph.D. By: /s/ ▇▇▇ ▇▇▇▇▇▇ Name: Name ▇▇▇ ▇▇▇▇▇▇ Title: V. P. Title V.P., Business Development Date: 12.26.03 Research Plan Summary The objective of this collaborative research project is to implement, a comprehensive mouse phenotyping protocol. The phenotyping will be carried out using a previously established comprehensive protocol of *** (see below) which therapeutic areas scientists have deemed as useful in making go/no go decisions on whether a new gene represents a potential therapeutic target. ***. We aimed to include as many therapeutic areas as possible in this program. This four-year program is intended for implementing the comprehensive phenotyping protocol on approximately *** knockout mouse lines/year. Pfizer-derived knockout lines, as well as third party-derived lines will be phenotyped. The *** assays will be carried out over a period of *** weeks and data will be deposited into the phenotype pfinder database in a previously established “real-time” manner for each assay as it is completed. The first year (2004) of this collaboration Pfizer will contribute *** lines to be phenotyped, *** KO and *** WT animals will be sent to Xenogen for comprehensive phenotyping, an additional *** lines are currently breeding at Xenogen and will be incorporated into the protocol to complete the *** lines for testing in 2004. A similar model will be followed during the following 3 years of the collaboration. The following assays will be carried out in the comprehensive protocol: *** ***Date 9.30.03
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