COLLABORATION AND LICENSE AGREEMENT

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CONFIDENTIAL TREATMENT REQUESTED
UNDER 17 C.F.R. §§ 200.80(b)4, AND 240.24

Exhibit 10.58

COLLABORATION AND LICENSE AGREEMENT

         THIS COLLABORATION AND LICENSE AGREEMENT ("Agreement") is made and entered into effective as of February 10, 2005 (the "Effective Date"), by and among Sarissa, Inc., having principal offices at 121 Timber Drive, London, ON, N6K4A2, Canada ("Sarissa") and Isis Pharmaceuticals, Inc., having principal offices at 2292 Faraday Avenue, Carlsbad CA 92008 ("Isis"). Sarissa and Isis each may be referred to herein individually as a "Party," or collectively as the "Parties."

         WHEREAS , Isis and Sarissa wish to collaborate in the identification of a lead TS ASO targeted to inhibit Thymidylate Synthase ("TS"), using Isis' proprietary MOE chemistry, on the terms set forth below;

         NOW, THEREFORE, the Parties do hereby agree as follows:

ARTICLE 1—DEFINITIONS

        Capitalized terms used in this Agreement and not otherwise defined herein have the meanings set forth in Appendix 1.

ARTICLE 2—
SCOPE OF COLLABORATION; COLLABORATION ACTIVITIES

         Section 2.1      Scope of Collaboration.     The Parties wish to collaborate to identify TS ASOs (the "Collaboration"), according to the Project Plan attached hereto as Appendix 2.1 and made part of this Agreement. Following the completion of the Project Plan, Sarissa will be solely responsible for the continued development and commercialization of any Products subject to royalty and milestone payments to be paid to Isis as set forth in this Agreement.

         Section 2.2      Collaboration Activities.     

         2.2.1 General.     The Parties will use Commercially Reasonable Efforts to conduct their respective responsibilities outlined in the Project Plan.

         Section 2.3      Selecting TS ASOs.     

         2.3.1 Selection of First TS ASO.     From the TS ASOs generated under the Project Plan or from TS ASOs generated by Isis prior to the Effective Date, Sarissa will select one TS ASO for use in a Product to take into IND enabling toxicology for purposes of evaluating such Product in human clinical trials. Sarissa may replace the selected TS ASO with any other TS ASO generated under the Project Plan or generated by Isis prior to the Effective Date, and for no additional cost (except the cost of new or additional active pharmaceutical ingredient for such new TS ASO supplied to Sarissa), upon written notice to Isis.

         2.3.2 Selection of Additional TS ASOs.     If, in addition to the TS ASOs selected in Section 2.3.1, Sarissa elects to select one or more additional TS ASOs generated under the Project Plan or generated by Isis prior to the Effective Date, for use in a Product to take into human clinical trials, Sarissa will so notify Isis and will pay Isis the payment set forth in Section 4.2. Notwithstanding the foregoing, Sarissa will not be required to pay the fee under Section 4.2 for additional TS ASOs, so long as Sarissa uses such additional TS ASOs as part of a Tandem that includes a TS ASO selected under Section 2.3.1.

         2.3.3 Responsibilities Following Completion of the Project Plan.     Following the completion of the Project Plan, Sarissa will be solely responsible for further development and commercialization of the Product, including but not limited to:

        (a)   Contracting for the manufacturing of all drug needed for toxicology studies and clinical trials, as described in Section 2.4.

        (b)   Coordinating all aspects of animal pharmacology and toxicology studies needed for IND filing.

        (c)   Conducting clinical trials.

        (d)   Negotiating any and all sublicensing agreements with Third Parties for the ongoing development and/or marketing of the Product.

If requested by Sarissa in order to facilitate further development and commercialization of the Product, the Parties will mutually agree to a consulting agreement under which Isis will provide consulting in addition to the hours set forth in the Project Plan.

         Section 2.4      Manufacturing of Product.     

         2.4.1  Isis will have the first right to manufacture the Product, on mutually agreeable, commercially reasonable terms and conditions, and pursuant to a supply agreement to be agreed to by the Parties containing standard terms. If Isis is unable or unwilling to manufacture the Product, or if the Parties cannot reach agreement on the terms and conditions within [***] days of a request for transfer pricing quote by Sarissa, Sarissa may (i) have the Product manufactured by a manufacturer already licensed under Isis' proprietary manufacturing and analytical technology; or (ii) have the Product manufactured using a process not covered by Isis' proprietary manufacturing and analytical technology.

ARTICLE 3—
GRANT OF RIGHTS

         Section 3.1      License Grant for Collaboration Activities.     

         3.1.1 Isis Grant.     Subject to the terms and conditions of this Agreement (including but not limited to Article 4 and Section 9.2), Isis hereby grants to Sarissa an exclusive, worldwide license (a) under the Isis Product-Specific Technology Patents and the Joint Patents to any Product-Specific Technology and (b) under the Isis Core Technology Patents, in each case solely to develop, make, have made, use, sell, offer for sale, have sold and import Products. The licenses granted to Sarissa are sublicensable only in connection with a license of Products to a Third Party for the continued development and commercialization of Products in accordance with the terms of this Agreement.

         3.1.2 Sarissa Grant.     Subject to the terms and conditions of this Agreement, Sarissa hereby grants to Isis a non-exclusive, non-transferable, limited license or sublicense, as the case may be, under the Sarissa Product-Specific Technology Patents, solely to perform Isis' responsibilities in the Project Plan.

         3.1.3 Additional Chemistry.     Should Sarissa notify Isis in writing that Sarissa wishes to collaborate to create additional antisense products targeting TS and incorporating other Isis proprietary chemistry, such as PNA or modified siRNA, then Isis and Sarissa will negotiate in good faith an additional license to these chemistries, including an appropriate allocation of Third Party financial obligations.

         3.1.4 Conditions to Licenses.     Notwithstanding the foregoing, if (i) Sarissa does not complete its first Qualified Financing by the [***]-month anniversary of the Effective Date or (ii) Sarissa

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fails to use Commercially Reasonable Efforts to develop and commercialize Products, any licenses granted to Sarissa under this Article 3 will automatically terminate and a Discontinuance will be deemed to have occurred.

ARTICLE 4—FINANCIAL PROVISIONS

         Section 4.1      Up-Front Payment by Sarissa.     Sarissa will pay an up-front license fee of $1,000,000 (U.S.) to Isis, payable in Sarissa's sole discretion either (i) in cash or (ii) by convertible promissory note. The Note will be issued in accordance with the Note Purchase Agreement executed concurrently herewith.

         Section 4.2      Payment for Additional TS ASOs.     If Sarissa elects to select an TS ASO for use in an additional Product as set forth in Section 2.3.2, Sarissa will pay Isis an up-front fee of $1,000,000 (U.S.) for each TS ASO selected. Such up-front fee may be paid in cash or equity securities of Sarissa at Sarissa's discretion, provided that any equity securities so issued to Isis will be issued at the same per-share price and will be of the same class with the same rights and preferences as the equity securities issued in Sarissa's most recent Qualified Financing. Notwithstanding the foregoing, (i) if Sarissa's most recent Qualified Financing occurred more than [***] months prior to the date such up-front fee becomes due, Isis in its sole discretion can elect to be paid in cash only and (ii) in no event will Isis be required to take equity in excess of 18% of all shares of Sarissa, fully diluted as converted. In addition to the up-front fee, Sarissa will pay to Isis the milestone payments and royalty payments detailed in Article 4 hereof as and when such milestone payments and royalty payments are due for a Product containing such TS ASO. All milestone payments and royalty payments for such Product will be in addition to all milestone payments and royalty payments required to be made for any other Product being developed or commercialized by Sarissa.

         Section 4.3      Milestone Payments by Sarissa.     Sarissa will pay to Isis the relevant milestone payment not more than 30 days after achievement, by Sarissa or a sublicensee, of each of the applicable events in the first primary indication for each Product developed hereunder; provided however that additional milestone payments will be reduced by [***]% when a Product meets the same milestone in an additional indication once that milestone payment has already been paid for the first primary indication, as follows:

         Section 4.4      Royalty Payments by Sarissa.     In consideration of Isis' collaborative efforts and the licenses granted hereunder, Sarissa will pay Isis a royalty of [***]% of Net Sales of the Product. Sarissa will pay such royalties for the Term of the Agreement.

         Section 4.5      Third Party Payments.     In addition to the royalty set forth in Section 4.4, Sarissa will pay to Isis a royalty of [***]% of Net Sales of Product, pursuant to a license agreement with [***], dated [***], and a royalty of [***]% of Net Sales of Product pursuant to a license agreement with [***] dated [***]. In the event that Isis negotiates reduced royalties with these Third Party licensors, the royalties due hereunder will still be paid to Isis. Notwithstanding the foregoing, the Parties agree that if the Isis Patent Rights licensed by Isis from [***] and/or [***] and sublicensed under this Agreement cease to have any Valid Claims during the term of this Agreement, then Sarissa will no longer be responsible for paying the royalties flowing through to [***] and/or [***], as applicable, and the total royalty payable will be reduced accordingly. Isis will promptly advise Sarissa in writing regarding any

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changes to its licenses with [***] or [***] that would materially affect the respective royalties under such agreements.

         Section 4.6      Timing of Royalty Payments.     The royalties will become due and payable within 60 days of each respective Royalty Due Date and shall be calculated in respect of the Net Sales in the 3 month period immediately preceding the applicable Royalty Due Date.

         Section 4.7      Payment Method.     Any amounts due to a Party under this Agreement will be paid in U.S. dollars, by wire transfer in immediately available funds to an account designated by the receiving Party. Any payments or portions thereof due hereunder which are not paid on the date such payments are due under this Agreement will bear interest at a rate equal to the lesser of the prime rate as published in The Wall Street Journal , Eastern Edition, on the first day of each calendar quarter in which such payments are overdue, plus 6%, or the maximum rate permitted by law, whichever is lower, calculated on the number of days such payment is delinquent, compounded monthly.

         Section 4.8      Currency; Foreign Payments.     If any currency conversion will be required in connection with any payment hereunder, such conversion will be made by using the exchange rate for the purchase of U.S. dollars as published in The Wall Street Journal , Eastern Edition, on the last business day of the calendar quarter to which such payments relate. If at any time legal restrictions prevent the prompt remittance of any payments in any jurisdiction, the applicable Party may notify the other and make such payments by depositing the amount thereof in local currency in a bank account or other depository in such country in the name of the receiving Party or its designee, and such Party will have no further obligations under this Agreement with respect thereto.

         Section 4.9      Taxes.     A Party may deduct from any amounts it is required to pay to the other Party pursuant to this Agreement an amount equal to that withheld for or due on account of any taxes (other than taxes imposed on or measured by net income) or similar governmental charge imposed on the receiving Party by a jurisdiction of the paying Party ("Withholding Taxes"). The paying Party will provide the receiving Party a certificate evidencing payment of any Withholding Taxes hereunder within 30 days of such payment and will reasonably assist the receiving Party, at the receiving Party's expense, to obtain the benefit of any applicable tax treaty.

         Section 4.10      Records Retention; Audit.     

         4.10.1 Record Retention.     Each Party will maintain (and will ensure that its sublicensees will maintain) complete and accurate books, records and accounts that fairly reflect Net Sales with respect to the Product, in each case in sufficient detail to confirm the accuracy of any payments required hereunder and in accordance with GAAP, which books, records and accounts will be retained by such party until the later of (i) 3 years after the end of the period to which such books, records and accounts pertain, and (ii) the expiration of the applicable tax statute of limitations (or any extensions thereof), or for such longer period as may be required by Applicable Law.

         4.10.2 Audit.     Each Party will have the right to have an independent certified public accounting firm of nationally recognized standing, reasonably acceptable to the audited Party, have access during normal business hours, and upon reasonable prior written notice, to such of the records of the other Party (and its sublicensees) as may be reasonably necessary to verify the accuracy of Net Sales, as applicable, for any calendar quarter or calendar year ending not more than [***] months prior to the date of such request; provided, however , that neither Party will have the right to conduct more than one such audit in any Calendar Year except as provided below. The requesting Party shall bear the cost of such audit unless the audit reveals a variance of more than [***]% from the reported results, in which case the audited Party shall bear the cost of the audit.

         4.10.3 Payment of Additional Amounts.     If, based on the results of such audit, additional payments are owed by the audited Party under this Agreement, the audited Party will make such

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additional payments, with interest as set forth in Section 4.7, within 60 days after the date on which such accounting firm's written report is delivered to such Party.

         4.10.4 Confidentiality.     The auditing Party will treat all information subject to review under this Section 4.10 in accordance with the confidentiality provisions of Article 5 and will cause its accounting firm to enter into a reasonably acceptable confidentiality agreement with the audited Party obligating such firm to maintain all such financial information in confidence pursuant to such confidentiality agreement.

ARTICLE 5—
CONFIDENTIALITY

         Section 5.1      Disclosure and Use Restriction.     Except as expressly provided herein, the Parties agree that, for the Term and for five (5) years thereafter, each Party will keep completely confidential and will not publish, submit for publication or otherwise disclose, and will not use for any purpose except for the purposes contemplated by this Agreement, any Confidential Information received from the other Party.

         5.1.1 Authorized Disclosure.     Each Party may disclose Confidential Information of the other Party to the extent that such disclosure is:

         (a)    made in response to a valid order of a court of competent jurisdiction; provided, however , that such Party will first have given notice to such other Party and given such other Party a reasonable opportunity to quash such order and to obtain a protective order requiring that the Confidential Information and documents that are the subject of such order be held in confidence by such court or agency or, if disclosed, be used only for the purposes for which the order was issued; and provided further that if a disclosure order is not quashed or a protective order is not obtained, the Confidential Information disclosed in response to such court or governmental order will be limited to that information which is legally required to be disclosed in response to such court or governmental order;

         (b)    otherwise required by law; provided, however , that the disclosing Party will provide such other Party with notice of such disclosure in advance thereof to the extent practicable;

         (c)    made by such Party to the Regulatory Authorities as necessary for the development or commercialization of a Product in a country, as required in connection with any filing, application or request for Regulatory Approval or as required by applicable securities laws and regulations; provided, however, that reasonable measures will be taken to assure confidential treatment of such information;

         (d)    made by such Party, in connection with the performance of this Agreement, to permitted sublicensees, licensors, directors, officers, employees, consultants, representatives or agents, each of whom prior to disclosure must be bound by obligations of confidentiality and non-use at least equivalent in scope to those set forth in this Article 5; or

         (e)    made by such Party to existing or potential acquirers; existing or potential pharmaceutical collaborators (to the extent contemplated hereunder); investment bankers; existing or potential investors, merger candidates, partners, venture capital firms or other financial institutions or investors for purposes of obtaining financing; or, bona fide strategic potential partners; each of whom prior to disclosure must be bound by obligations of confidentiality and non-use at least equivalent in scope to those set forth in this Article 5.

         Section 5.2      Press Releases.     Press releases or other similar public communication by either Party relating to this Agreement, unless relating solely to a Product being developed by the Party making the communication, will be approved in advance by the other Party, which approval will not be

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unreasonably withheld or delayed, except for those communications required by Applicable Law, disclosures of information for which consent has previously been obtained, and information of a similar nature to that which has been previously disclosed publicly with respect to this Agreement, each of which will not require advance approval, but will be provided to the other Party as soon as practicable after the release or communication thereof.

         Section 5.3      Publications.     At least [***] days prior to submission of any material related to the research or development activities hereunder for publication or presentation, the submitting Party will provide to the other Party a draft of such material for its review and comment. The receiving Party will provide any comments to the submitting Party within [***] days of receipt of such materials. No publication or presentation with respect to the research or development activities hereunder will be made unless and until the other Party's comments on the proposed publication or presentation have been addressed and changes have been received and agreed upon and any information determined by the other Party to be Confidential Information has been removed. If requested in writing by the other Party, the submitting Party will withhold material from submission for publication or presentation for a reasonable time to allow for the filing of a patent application.

ARTICLE 6—
INTELLECTUAL PROPERTY

         Section 6.1      Intellectual Property Ownership.     

         6.1.1 Ownership of Intellectual Property.     Isis will own all inventions made (as determined under United States patent laws) solely by its employees and agents, and all Patents claiming such inventions. Sarissa will own all inventions made (as determined under United States patent laws) solely by its employees and agents, and all Patents claiming such inventions. All inventions made (as determined under United States patent laws) jointly by employees or agents of Isis and employees or agents of Sarissa ("Joint Technology"), and all Patents claiming such inventions, will be owned jointly by Isis and Sarissa. During the Term of this Agreement, each Party shall promptly disclose in writing to the other Party on an ongoing basis, and prior to filing any Patent, any Joint Technology or Product-Specific Technology invented as part of the Collaboration. In addition, promptly after executing this Agreement, the Parties will each disclose to each other the current status of all Product-Specific Technology Patents Controlled by such Party and licensed under this Agreement.

         6.1.2 Ownership of Regulatory Documentation.     Unless and until Isis sends an Election Notice pursuant to Article 9 of this Agreement, all Regulatory Documentation with respect to a Product will be owned by Sarissa, or its sublicensee, if applicable. If Sarissa discontinues development of such Product and Isis sends an Election Notice in accordance with Section 9.2, all Regulatory Documentation with respect to such Product will be transferred to Isis. In the event that this Agreement terminates pursuant to Section 9.2, all Regulatory Documentation will remain with the Party that first secured such Regulatory Documentation.

         Section 6.2      Prosecution of Patents.     

         6.2.1 Solely Owned Patents.     With the exception of Product-Specific Technology Patents, as set forth in 6.2.2, each Party will have the sole right, at its cost and expense and at its sole discretion, to obtain, prosecute and maintain throughout the world any Patents solely owned or Controlled by such Party.

         6.2.2 Product-Specific Technology Patents.     Sarissa will have the sole right and at its sole discretion, to obtain, prosecute and maintain throughout the world the Product-Specific Technology Patents. Sarissa shall reimburse Isis for all of Isis' reasonable out-of-pocket costs incurred prior to and after entering into this Agreement to obtain, prosecute and maintain throughout the world,

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any Product-Specific Technology Patents Controlled by Isis, provided however that Sarissa will not be required to make any such reimbursements for expenses incurred by Isis after the occurrence of the Discontinuance, as and when Sarissa issues such notice. As of December 31, 2004, these out-of-pocket costs where approximately $[***] Sarissa will keep Isis informed of all Isis Product Specific Technology Patent applications and registrations to be filed by Sarissa, and Isis shall have the right to comment on such applications within the timeframes of the patent filing process and deadlines. Notwithstanding the foregoing, if Isis is unilaterally developing and commercializing the Product in accordance with Section 9.2, Isis will have the first right to file, prosecute and maintain any Product-Specific Technology Patents at its expense.

         6.2.3 Filing of Joint Patents.     The Parties will cooperate with one another with respect to the filing, prosecution and maintenance of all Joint Patents. The Parties will designate one of the Parties to be responsible for, and to initially bear the expense of, the preparation, filing, prosecution, and maintenance of a Joint Patent, provided that the responsible Party will be entitled to reimbursement by the other Party of an equal share of the responsible Party's expenses. The Parties agree that for all Joint Patents for Product-Specific Technology, Sarissa will be deemed to be the responsible Party for the purposes of this Section 6.2.3, and will bear all expenses for the preparation, filing, prosecution and maintenance of such Patents. With the exception of Joint Patent to Product-Specific Technology, which will be as set forth in Section 6.2.2, the responsible Party will consult with the other Party as to the preparation, filing, prosecution, and maintenance of such Joint Patent reasonably prior to any deadline or action with the U.S. Patent & Trademark Office or any foreign patent office, and will furnish to the other Party copies of all relevant documents reasonably in advance of such consultation. For the life of the Joint Patents, the Parties will mutually agree upon all Joint Patent filings. Notwithstanding the foregoing, if Isis is unilaterally developing and commercializing the Product in accordance with Section 9.2, Isis will have the first right to file, prosecute and maintain any Joint Patents to Product-Specific Technology at its expense.

         6.2.4 Cooperation.     Each Party will cooperate reasonably in the preparation, filing, prosecution, and maintenance of the other Party's Patents, the Product-Specific Technology Patents and the Joint Patents. Such cooperation includes (a) promptly executing all papers and instruments and requiring employees to execute such papers and instruments as reasonable and appropriate so as to enable such other Party, to file, prosecute, and maintain its Patents in any country; and (b) promptly informing such other Party of matters that may affect the preparation, filing, prosecution, or maintenance of any such Patents.

         Section 6.3      Enforcement of Patents     

         6.3.1 Rights and Procedures.     If Isis or Sarissa determines that any Patent licensed hereunder is being infringed by a Third Party's activities and that such infringement could affect the exercise by the Parties of their respective rights and obligations under this Agreement, it will promptly notify the other Party in writing.

        (a)    Joint Patents.     With respect to infringement of a Joint Patent that is not a Product-Specific Technology Patent, the Party responsible for filing, prosecution and maintenance of such Joint Patent under Section 6.2.3 will have the first right to bring and control any action or proceeding with respect to such Joint Patent, and will bear all expenses thereof, and the other Party will have the right, at its own expense, to be represented in any such action; provided, however, that if the Party with the first right to bring and control actions and proceedings with respect to such Joint Patent fails to bring an action or proceeding within ninety (90) days following notice of such infringement, or earlier notifies the other Party in writing of its intent not to take such steps, the other Party will have the right to do so at its expense, and the first Party will have the right, at its own expense, to be represented in any

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such action. Notwithstanding the foregoing, if the infringement is likely to have a material adverse effect on the development or commercialization of the Product, the Parties will meet to determine whether to defend against such infringement based on the Joint Patents, and if the Parties mutually agree to proceed in defending such infringement based on the Joint Patents, the Parties will share (on a pre-determined basis as agreed to by the Parties) in the reasonable costs incurred relating to the removal of any such infringement.

        (b)    Product-Specific Technology Patents.     With respect to Product-Specific Technology Patents, Sarissa will have the first right, at Sarissa's expense, but not the obligation, to remove such infringement. In the event that Sarissa fails to take commercially appropriate steps to remove any infringement of any such Product-Specific Technology Patent within ninety (90) days following notice of such infringement, or earlier notifies Isis in writing of its intent not to take such steps, and such infringement is likely to have a material adverse effect on the Product, Isis will have the right to do so at its expense, and Sarissa will have the right, at its own expense, to be represented in any such action. If Isis is unilaterally developing and commercializing the Product pursuant to Section 9.2, Isis will have the right, at Isis's own expense, to remove infringement of the Product-Specific Technology Patents.

        (c)    Isis Patent Rights.     Except as set forth in Sections 6.3.1(a) and (b) above, with respect to the Isis Patent Rights, Isis will have the sole right, but not the obligation, at its own expense, to remove such infringement using commercially appropriate steps, including the filing of an infringement suit or taking other similar action. Notwithstanding the foregoing, if the infringement is likely to have a mat