Document:

Exhibit 10.6

 

EMPLOYMENT AGREEMENT

 

THIS AGREEMENT
made as of the 12th day of September, 2005

 

BETWEEN:

 

OncoGenex, Inc., a Corporation incorporated under the laws of Washington and having an
office at Seattle, Washington

 

(together with any subsidiaries hereinafter referred to as the “Company”)

 

OF THE FIRST PART

 

AND:

 

Cindy Jacobs,
an individual, domiciled at [***] Washington

 

(hereinafter referred to as the “Employee”)

 

OF THE SECOND PART

 

WHEREAS the
Company is a research and development company engaged in clinical research of
novel therapeutics for cancer;

 

AND WHEREAS the
Company and the Employee wish to enter into this Employment Agreement under the
terms and conditions herein;

 

AND WHEREAS
during the course of the Employee’s employment with the Company, the Employee
will be introduced to, have contact with, and her services may be solicited by,
one or more of the clients of the Company;

 

AND WHEREAS
the Employee will acquire knowledge, experience and expertise, as well as
detailed knowledge of the Company’s confidential customer and supplier lists
and information, marketing techniques, price lists, trade secrets and other
property which is and shall be the property of the Company, and the disclosure,
loss or, unauthorized use of which would substantially harm the business of the
Company;

 

NOW THEREFORE THIS AGREEMENT WITNESSES that for good and valuable consideration,
the receipt and sufficiency of which are hereby acknowledged, the parties
hereto hereby agree as follows:

 

ARTICLE 1

EMPLOYMENT RELATIONSHIP

 

1.1                                The terms of employment under this Agreement
are not intended to create, and should not be construed as creating, a contract
for employment. All employees are employed on an at-will basis. At-will
employment means that either the Company or the employee can terminate the
employment relationship at any time, with or without prior notice, for any
reason not otherwise prohibited by law. Any representation to the contrary is
not binding on the Company unless it is in writing and is signed by the President
of the Company. This Agreement shall be effective on September 12, 2005 (the “Effective Date”).

 

*Certain information in
this exhibit has been omitted as confidential, as indicated by [***]. This
information has been filed separately with the Commission.

 

 

ARTICLE 2

DUTIES AND RESPONSIBILITIES

 

2.1                                 The Employee shall serve the Company as an
Employee initially in the position of Executive VP and Chief Medical Officer
and initially reporting to the President.

 

2.2                                 The Employee shall undertake and perform the
following duties and responsibilities:

 

(a)                      participate in the overall strategic
orientation of the Company;

 

(b)                     contribute significantly to the
identification and selection of future therapeutic opportunities;

 

(c)                      provide leadership, establish strategy and
implement drug development and regulatory affairs efforts. Clinical development
will encompass full therapeutic responsibility from Phase I-Phase IV including
Medical Communications, Pharmacovigilance and Safety;

 

(d)                     ensure project goals and timelines are met by
working with the clinical team, clients, co-development partners, CROs and
principal investigators, and design and prepare clinical trial protocols,
conduct data analysis, and review and modify development programs as necessary;

 

(e)                      provide leadership to establish the essential
conditions for determining the safety, efficacy, medical usefulness, and
eventual marketability of the Company’s and clients’ drug candidates;

 

(f)                        provide medical guidance and direction to the
Company’s and clients’ clinical development programs;

 

(g)                     establish relationships with thought leaders,
consultants and key clinicians across the varied segments of interest to ensure
that the Company and clients have a clear understanding of clinicians’ needs
and requirements as well as medical practice patterns, and to encourage support
of the Company’s and clients’ clinical programs;

 

(h)                     provide key medical/scientific input into
regulatory submissions;

 

(i)                         manage cross-functional collaborations, both
internal and external to the Company including representing the Company as an
expert liaison to academic specialists;

 

(j)                         travel as necessary, consistent with project
needs; and

 

(k)                      perform such other duties and
responsibilities as may be assigned or vested in her by the Employee’s
supervisor from time to time and which are consistent with the duties and
responsibilities of an executive vice president and chief medical officer, and
such duties, responsibilities, or assignments as are necessary for adjustment
to changes in the Company’s business.

 

2.3                                In accordance with the other terms of this
Agreement, the Employee agrees during the continuance of her employment, to
devote her entire working time, services, skill and

 

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ability
to such employment and to serve at all times with loyalty and honesty in the
best interests of the Company. Prior written consent from the President must be
obtained if the Employee wishes to engage in activities with for-profit and
charitable or non-profit organizations during normal working hours.

 

ARTICLE 3 

BASE COMPENSATION

 

3.1                                 In consideration of the services provided by
the Employee hereunder, the Company shall, as of the Effective Date, pay to the Employee an annual base salary in
the amount of three hundred twenty thousand US dollars (US$320,000) as
increased from time to time in accordance with Article 3.2 (“Base Salary”), payable semi-monthly or such other manner as
may be agreeable to the parties hereto and in compliance with any applicable
legislation.

 

3.2                                 Such Base Salary shall be reviewed by the
Employee’s supervisor and may be further reviewed by the Compensation Committee
of the Board every twelve (12) months based on the Employee’s performance,
corporate cash flow, achievement of corporate objectives and in accordance with
Company policies. Any recommended increase may require approval by the Board.

 

3.3                                 The Employee shall be eligible to participate
in any bonus plans (“Bonus”) offered
by the Company to its Employees in accordance with the terms thereof as
established by the Board and as amended from time to time. Initially, the
Employee shall be eligible for a Bonus of up to 30% of the Base Salary. The
Bonus shall be based on annual corporate objectives as established by the Board
and annual personal objectives as established by the Employee’s supervisor,
each of which shall be communicated to the Employee annually by December 31 in
the year preceding the year in which the milestones pertain and attached hereto
as Appendix A. At the same time, the allocation of bonus potential between
corporate and personal objectives for the upcoming year will be communicated to
the Employee.

 

ARTICLE 4 

INCENTIVE COMPENSATION

 

4.1                                 The Employee shall participate in the share
option plan of OncoGenex Technologies Inc. (the “Plan”)
as set forth in Appendix B attached hereto and in accordance with its terms as
amended from time to time.

 

4.2                                 The exercise of any Options shall at all
times be subject to obtaining any applicable regulatory or legal approval.

 

ARTICLE 5

BENEFITS

 

5.1           Group Insurance and Pension

 

The Employee shall be
eligible on the Effective Date for
any group medical, dental, insurance and pension programs applicable to the
employees of the Company.

 

5.2           Vacation

 

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The Employee shall be
entitled to 20 Business Days (as defined in
Article 10) of annual paid vacation during each year with your vacation
entitlement in the first year after the Effective Date accruing monthly from
the Effective Date. Unused vacation may not be carried over for more than
twelve months after the completion of each fiscal year.

 

5.3                                Expenses

 

The
Employee shall be reimbursed for all out-of-pocket expenses incurred on behalf
of the Company within 15 days of receipt by the Company of an expense report
together with original receipts in respect of such expenses.

 

ARTICLE 6 

TERMINATION OF EMPLOYMENT

 

6.1                                The Employee acknowledges and agrees that,
during the first 3 months of employment, (the “Probationary
Period”), starting on the Effective
Date, she is employed on a probationary basis. During the
Probationary Period, this Agreement may be terminated by the Company at any
time, with or without notice. If the Company terminates the employment of the
Employee during the Probationary Period, the “Date
of Termination” shall mean the last day on which the Employee works
for the Company. Employee further understands and agrees that completion of the
Probationary Period does not guarantee continued employment and does not change
the at-will nature of the employment relationship.

 

6.2                                 For Cause. Company will have the right to immediately terminate Employee’s
services and this Agreement for Cause. “Cause”
means:  any breach of this Agreement by
Employee, including, without limitation, breach of Employee’s covenants in
Articles 7, 8 and 9; any failure to perform assigned job responsibilities that
continues unremedied for a period of thirty (30) days after written notice to
Employee by the Company; conviction of a felony or misdemeanor or failure to
contest prosecution for a felony or misdemeanor;  the Company’s reasonable belief that Employee
engaged in a violation of any statute, rule, regulation, or Company policy, any
of which in the judgment of the Company is harmful to the Company or to the
Company’s reputation; the Company’s reasonable belief that Employee engaged in
unethical practices, dishonesty or disloyalty; or the Company’s failure to
obtain or lack of funding sufficient to support Employee’s position. Upon
termination for Cause, Employee will have no rights to any unvested benefits or
any other compensation or payments except as stated in this Article 6.2 and Employee shall only be entitled to
such benefits or payments if both OncoGenex and Employee sign (and then
Employee does not rescind, as may be permitted by law) a mutual general release
of claims in a form mutually acceptable to both parties. In the event the
Employee is terminated for Cause pursuant to this Article 6.2, the “Date of Termination” shall mean the last day on which the
Employee works for the Company.

 

6.3                                 Without Cause. After the Probationary Period, the Company
may terminate Employee’s employment under this Agreement without cause and
without advance notice; provided, however, that OncoGenex will
continue to provide, as severance pay, the Employee’s Base Salary in cash (less
statutory withholdings) at the rate in effect on Date of Termination for a
period of twelve months following the Date of Termination. Upon termination
without cause, Employee will have no rights to any unvested benefits or any
other compensation or payments except as stated in this Article 6.3 and Employee shall only be entitled to
such benefits and payment if both OncoGenex and Employee sign (and then
Employee does not rescind, as may be permitted by law) a mutual general

 

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release of claims in a form mutually acceptable to
both parties. In the event the Employee is terminated without cause pursuant to
this Article 6.3, the “Date of Termination”
shall mean the last day on which the Employee works for the Company.

 

6.4                                Termination by
Employee. The Employee may terminate her employment
under this Agreement for any reason, provided that Employee gives the Company
at least thirty (30) days’ notice in writing (the “Notice
Period”). Upon provision of thirty (30) days’ notice of Employee’s
decision to voluntarily terminate her employment under this Agreement for any
reason, Employee shall be paid (i) her salary through the Date of Termination,
(ii) for any unused vacation time, and (iii) for any unreimbursed business
expenses that are subject to reimbursement under the Company’s then current
policy on business expenses. If the Employee terminates her employment pursuant
to this Article 6.4, the Company may request that the Employee cease duties
prior to the expiry of the Notice Period. The Company shall, in such event, pay
to the Employee an amount equal to the difference between what the Employee
would have received had the employment of the Employee been continued for the
Notice Period and the amount actually paid by the Company to the Employee
during the Notice Period. In the event the Employee provides such notice to the
Company, the “Date of Termination” shall mean
the last day on which the Employee works for the Company.

 

ARTICLE 7 

NON-COMPETITION AND NON-SOLICITATION

 

7.1                                 As used in this Agreement, the following
words and phrases are defined as follows:

 

(a)                                  “UBC Licenses”
means the licenses entered into by the University of British Columbia and OncoGenex
Technologies Inc. effective November 1, 2001, September 1, 2002 and April 5,
2005 which define the terms under which OncoGenex Technologies Inc. has
acquired an exclusive license to certain technology. It is understood that
OncoGenex Technologies Inc. has granted the Company a limited right to use
certain technology licensed under the UBC Licenses solely for the Company to
perform work for OncoGenex Technologies Inc.

 

(b)                                 “Technology”
means all ideas, concepts, business and trade names, trademarks, know-how,
trade secrets, inventions, improvements, devices, methods, processes and
discoveries, whether patentable or not, and whether or not reduced to writing
or other tangible form or to actual or constructive practice which either:  (i) are part
of the technology licensed to OncoGenex Technologies Inc. under the UBC
Licenses; or (ii) are otherwise developed or acquired on behalf of or by the
Company, including but not limited to the technology licensed to the Company by
its clients for work to be performed for such clients persuant to research
contracts.

 

(c)                                  “Business” means
the research and development of the Technology and such other business plans as
approved by the Board from time to time and which are in effect on the Date of
Termination of this Agreement.

 

7.2                                Employee understands and agrees that during
her employment with the Company, she will not, within Canada, the United States
or Europe, without the written consent of the Company:

 

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(a)                                  own or
have any interest directly in, save and except for an interest of less than 5%
in a publicly traded company;

 

(b)                                 act as an
officer, director, agent, employee or consultant of; or

 

(c)                                  assist in
any way or in any capacity,

 

any person, firm, association, syndicate,
partnership, joint venture, collaboration, corporation or other entity that is
engaged in a business that is substantially similar to or that competes with
the Business.

 

7.3                                 Employee further understands and agrees that
or a period of twelve (12) months following termination of her employment with
the Company, she will not, within Canada or the State of Washington, without
the prior written approval of the Company:

 

(a)                                  act as an
officer, director, agent, employee or consultant of; or

 

(b)                                 assist in
any way or in any capacity,

 

any
person, firm, association, syndicate, partnership, joint venture,
collaboration, corporation or other entity that is engaged in a business that
is substantially similar to or that competes with the Business. Following the
expiration of this twelve-month period, Employee shall continue to be obligated
under Article 8 “Confidentiality” of this Agreement.

 

7.4                                The Employee will not, during her employment
and for a period of twelve (12) months from the Date of
Termination of her employment with the Company:

 

(a)                                  directly
or indirectly, either personally, through an agent or by letters, circulars or
advertisements, contact for the purpose of solicitation or actually solicit any
person, firm, association, syndicate, joint venture, collaboration,
corporation, or business entity who/which is or was a customer of the Company
on or at any time within the 12 months before the Date of
Termination, or who was scheduled to become a customer of the
Company within twelve months prior to the Date of Termination;

 

(b)                                 induce or
attempt to induce any person:

 

(i)                                    who was an
employee of the Company or a client of the Company at the Date of Termination;
or

 

(ii)                                 who has
been, during the twelve months before the Date of Termination, an employee of
the Company or a client of the Company;

 

to leave the employ
of the Company or the client, as the case may be, whether to join the Employee
in a similar enterprise or otherwise; or

 

(c)                                  either
directly or indirectly, solicit, divert or take away any staff, temporary
personnel, trade, or business from the Company or a client, or otherwise
compete for accounts or personnel which become known to her through her
relationship with the Company and agrees not to influence or attempt to
influence any of the Company’s customers, suppliers, or resellers or personnel

 

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not to do business
with the Company or take any action which may be reasonably foreseen to result
in harm to the Company.

 

ARTICLE 8 

CONFIDENTIALITY

 

8.1                                Delivery of Records. Any and all computer code, data,
notes, diagrams, reports, notebook pages, memoranda, and like materials,
including confidential information and trade secrets as defined in Article 8.2
below, received from or developed for the Company and any copies or excerpts
thereof shall remain the property of the Company. Upon the termination of the
Employee’s employment with the Company, or at any time during her employment at
the request of the Company, the Employee shall deliver to the Company all such
materials and other property belonging to the Company or developed in
connection with the Business.

 

7.2                                Confidential Information and Trade
Secrets. Employee
acknowledges that during her employment with the Company, she is and will
continue to be exposed to confidential information and trade secrets of both
the Company and its clients, all of which are essential to the Company’s
business and the continued confidentiality of which is critical to the Company’s
economic well-being. Such confidential information and trade secrets include,
but are not limited to:  financial
information, business plans, prospects, inside information (including
information regarding financial performance, earnings, existing products,
existing techniques, new products, new techniques and business strategies),
proprietary processes and know-how, client lists, personnel information
(including, without limitation, skills and              compensation),
product development information, and information regarding possible
acquisitions or sales of businesses or facilities. Such confidential
information does not include any information that has become part of the public
domain by means other than her breach of this Agreement. Employee agrees not to
use or disclose, at any time during her employment or at any time thereafter,
any such confidential or trade secret information to any third party for any
reason, except as authorized and necessary to perform her job.

 

8.3                                The Employee agrees that the confidential
information is and will remain the exclusive property of the Company. The
Employee also agrees that the confidential information:

 

(a)                                  constitutes a proprietary right
which the Company is entitled to protect; and

 

(b)                                 constitutes information and
knowledge not generally known to the trade.

 

8.4                                For purposes of the copyright laws
of the United States of America, to the extent, if any, that such laws are
applicable to any confidential information, it shall be considered a work made
for hire and the Company shall be considered the author thereof.

 

ARTICLE 9

INTELLECTUAL PROPERTY

 

9.1                                Employee agrees that she will promptly
disclose to the Company in writing and in full and enabling detail all
inventions, designs, processes and protectable works (collectively, “Inventions”) that she hereafter may create during the term
of her employment that pertain to the Technology or Business of the Company or
its clients, or that are created by her during working hours or by using any
resource of the Company,

 

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including training, tools,
equipment, facilities, or services. She agrees that all such Inventions and
copyrights shall be the exclusive property of the Company or its designee. She
agrees that she will assist the Company or its designee in any and all efforts
to protect such Inventions. She understands that this Agreement does not apply
to inventions and copyrights for which no equipment, supplies, facility or
trade secret information of the Company or its clients were used and that were
developed entirely on her own time, unless (a) the inventions or copyrights
relate (i) directly to the Technology or Business of the Company or its
clients, or (ii) to the Company’s actual or demonstrably anticipated research
or development, or (b) the inventions or copyrights result from any work
performed by her for the Company.

 

9.2                                Employee hereby waives, to the extent
permitted by law, the benefits of any provision of law known as droit moral or
any similar law in any country of the world, including without limitation, 17 U.S.C.
§ 106A, and agrees not to permit or prosecute any action or lawsuit on the
ground that an Invention as used by OncoGenex in any way constitutes an
infringement of any of Employee’s “droit moral” or are in any way a defamation
or mutilation thereof or that any such use contains unauthorized variations,
alterations, modifications, changes or translations of such Invention.

 

ARTICLE 10

MISCELLANEOUS

 

10.1                          This Agreement shall be the whole and
complete agreement between the parties hereto with respect to the employment of
the Employee; it replaces and supersedes any and all previous verbal or written
agreements that may have been entered into between the parties hereto. This
Agreement may not be amended or modified except by written amendment signed
between the parties hereto.

 

10.2                          In the event that any part of this Agreement
shall be determined at any time to be invalid, such provisions shall be deemed
severable and deleted herefrom and the remainder of this Agreement shall
constitute the whole agreement of the parties hereto and shall, except as
hereinbefore provided, continue in full force and effect.

 

10.3                          The Employee hereby confirms that she is not
a party to any agreement or under any other obligation to anyone, including any
former employer, nor does the Employee have any other interest which is
inconsistent with or in conflict with or which would prevent, limit or impair
the Employee’s performance of any obligations hereunder which the Employee has
not disclosed in writing to the Company. The Employee acknowledges that the
Company is not requesting the Employee disclose any confidential information
which the Employee may have obtained from a former employer.

 

10.4                          The Employee acknowledges that a breach by
the Employee of any of the covenants contained in Articles 7, 8, and 9 of this
Agreement shall result in damages to the Company and that the Company could not
be adequately compensated for such damages by a monetary award. Accordingly, in
the event of any such breach, in addition to all other remedies available to
the Company at law or in equity, the Company shall be entitled as a matter of
right to apply to a court of competent jurisdiction for such relief by way of
restraining order, temporary or permanent injunction, decree or otherwise, as
may be appropriate to ensure compliance with the provisions of this Agreement.

 

8

 

10.5                          The Employee acknowledges that the
restrictions contained in Articles 7, 8, and 9 are reasonable and valid and the
Employee hereby waives all defences to the strict enforcement thereof by the
Company.

 

10.6                          The Employee acknowledges that the provisions
of Articles 7, 8, 9 and 10 shall survive the termination of this Agreement.

 

10.7                          This Agreement shall enure to the benefit of
and be binding upon the parties hereto, their respective successors, heirs,
representatives, administrators and the assigns of the Company. The Employee
shall not assign or transfer this Agreement or any of her rights or obligations
hereunder.

 

10.8         Any
amount payable under this Agreement shall be paid in United States currency.

 

10.9                          This Agreement shall be governed by and
construed according to the laws of the State of Washington, and both parties
hereto hereby agree that the Courts of the State of Washington and the United
States District Court of Western Washington have exclusive jurisdiction in any
dispute, action, cause or action or otherwise that may arise from this
Agreement.

 

10.10                    Any notice
or other communication or writing required or permitted to be given under this
Agreement or for the purposes of this Agreement shall be in writing and shall
be sufficiently given if delivered personally, or if transmitted by facsimile
transmission (with original to follow by mail) or other form of recorded communication,
tested prior to transmission, to:

 

(a)                                  if to the Company:

 

Attention:                                         President

c/o:                                                                            Suite 400
– 1001 West Broadway

Vancouver, British Columbia

CANADA,
V6H 4B1

Telephone:                                    604-736-3678

Facsimile:                                            604-736-3687

 

(b)                                 if to the Employee:

Cindy Jacobs

[***]

 

or to such other address as
the party to whom such notice is to be given shall have last notified the party
giving the same in the manner provided in this Article. Any notice so delivered
shall be deemed to have been given and received on the day it is so delivered
at such address, provided that such day is not a Business Day then the notice
shall be deemed to have been given and received on the Business Day next
following the day it is so delivered. Any notice so transmitted by facsimile
transmission or other form of recorded communication shall be deemed to have
been given and received on the day of its confirmed transmission (as confirmed
by the transmitting medium), provided that if such day is not a Business Day
then the notice shall be deemed to have been given and received on the Business
Day next following such day. “Business Day”
means any day

 

9

 

that
is not a Saturday, Sunday or civic or statutory holiday in the State of
Washington or the United States;

 

10.12                    No amendment or waiver of any provision of
this Agreement shall be binding on any party unless consented to in writing by
such party and approved by the Board in the case of the Company. No waiver of
any provision of this Agreement shall constitute a waiver of any other
provision nor shall any waiver constitute a continuing waiver unless otherwise
provided.

 

10.13                    Employee acknowledges that
she has had the opportunity to consult legal counsel in regard to this
Agreement, that she has read and understands this Agreement, that she is fully
aware of its legal effect, and that she has entered into it freely and
voluntarily based on her own judgment and not on any representations or
promises other than those contained in this Agreement.

 

IN WITNESS WHEREOF this Agreement has been executed this 12th day of September, 2005 by
the parties hereto.

 

	
  SIGNED,
  SEALED AND DELIVERED

  	
  )

  	
   

  
	
  in
  the presence of

  	
  )

  	
   

  
	
   

  	
  )

  	
   

  
	
   

  	
  )

  	
   

  
	
   

  	
   

  	
  )

  	
  /s/
  Cindy A. Jacobs

  	
   

  
	
  Witness

  	
  )

  	
  CINDY
  JACOBS

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  ONCOGENEX,
  INC.

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  /s/
  Scott Cormack

  	
   

  
						

 

10

 

APPENDIX A

 

ONCOGENEX, INC.

 

Bonus Plan – Milestones

 

Medium
Term Corporate Objectives:

 

Recognizing
that our primary objective, above all else, is to get effective cancer
therapies to patients as quickly as possible, and that by doing so all
stakeholders will benefit, the Company is striving to achieve the following
value-creating milestones before the end of [***]:

 

1.               Complete at least 4 phase II
clinical studies in which OGX-011 is combined with different therapeutic agents
in various stages and types of malignancies, in order to (1) demonstrate that OGX-011 has a broad market
opportunity across a variety of solid tumours (2) provide sufficient proof of
efficacy to justify advancing OGX-011 into at least one phase III clinical
study in [***], and (3) to justify an accelerated regulatory strategy if the
data supports an early filing. To meet this objective, all patients in all
trials must be accrued by the end of [***], such that the data has sufficient
time to mature after last-treatment in the last patient. Data integrity is also
of primary importance, as our clinical data must stand up to scrutiny by
regulatory agencies as well as investors and potential partners for OGX-011.

 

2.               Sign a [***] or [***] agreement in respect of [***] which will help ensure a
broad-based product development and registration strategy and rapid
commercialization of [***], and which provides significant economic return to
OncoGenex Technologies’ investors over the ongoing development and potential
commercialization of [***].

 

3.               Continue to build OncoGenex
Technologies’ product pipeline. This objective will be met in part by advancing OGX-427 into phase I
clinical development in [***]. Data from this trial must be available by [***]
to justify advancing this product into phase II clinical studies. In addition,
OncoGenex Technologies will continue to assess in-licensing opportunities and
to advance its existing product candidates through pre-clinical research in order
to ensure a steady pipeline of near-term clinical candidates.

 

4.               Build the financial resources and
opportunities of the company
such that (1) the above objectives can be met without undue interruption or
delay and (2) OncoGenex Technologies will be able to secure a significant
equity financing in [***] that will allow the OncoGenex Technologies to finance
the ongoing development and commercialization of its products.

 

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Short
Term (balance of 2005) Corporate Objectives:

 

Any Bonus paid for the 2005 fiscal year will be
pro-rated for actual time employed by the Company, and will be allocated to the
achievement of particular milestones and overall performance as follows:

 

(a)          Up
to 60% of Bonus based on achievement of OncoGenex Technologies Inc.’s 2005
Corporate Objectives:

 

1.               Launch the phase II clinical
development of OGX-011, and focus on strategies to accelerate patient accrual. We will measure our success by our ability to
meet the following targets:

 

i.                  OGX-011-02: 
complete patient accrual by [***], and select phase II dose and regimen
for OGX-011-03 and OGX-011-06 by [***].

 

ii.               OGX-011-03:  If
this trial is conducted by [***] as originally planned, we will treat first
patient by [***]; have at least [***] clinical sites open for accrual by [***];
accrue at least [***] patients by [***]; and accrue a total of [***] patients
by [***] (assuming [***] patients in the total trial). Target last patient
enrolment date: [***]. If this trial is conducted by [***], all target dates
will shift 4 months later.

 

iii.            OGX-011-04: treat
first patient by [***]; complete accrual of first stage of the two stage design
(25 patients) by [***]; reach go/no go decision on second stage by [***].

 

iv.           OGX-011-05:  accrue last patient of phase I trial by
[***]; treat first patient of phase II trial by [***]; open first US site by
[***]; accrue at least 10 patients on phase II trial by [***]; accrue at least
40 patients in total (phase II trial only) by [***]. Target last patient
enrolment date: [***].

 

v.              OGX-011-06: treat
first patient by [***]; accrue 3 patients by [***]; accrue a total of 12
patients by [***]; accrue a total of 24 patients by [***]. Target last patient
enrolment date: [***].

 

vi.           OGX-011-07: This
trial will only proceed if OGX-011-03 is conducted by [***], in which case we
will finalize study design by [***]; file regulatory applications with each of
the FDA and TPD by [***]; and have two sites open for accrual by [***].

 

2.               Garner significant interest from
potential partners for [***]
by [***], as measured by the:

 

i.                  Completion of comprehensive, face-to-face
scientific presentations in respect of the pre-clinical and clinical data for
[***] with no less than [***] potential commercial partners; or

 

ii.               Signing of at least 2 material transfer
agreements with potential commercial partners, in order that such third parties
can evaluate the compound in their own labs.

 

12

 

3.               Strengthen the pipeline of
additional product candidates
by:

 

i.                  Prepare OGX-427 for phase I clinical studies
(to start in [***]), as measured by the following targets:

 

1.               Sign a license agreement with UBC in respect
of the underlying intellectual property by [***].

 

2.               Complete manufacturing of API by [***] and of
toxicology drug product lots by [***].

 

3.               Initiate IND-enabling pharmacokinetic and
toxicology (pk/tox) studies (as measured by first administration of drug
product in animals) for OGX-427 by [***].

 

4.               Complete clinical protocol for at least one
phase I clinical study of OGX-427 by [***], subject to any final adjustments
upon receipt of pk/tox data.

 

ii.               Completing
additional pre-clinical pharmacology of OGX-427 in other tumour models by
[***].

 

iii.            Expanding
the pre-clinical pharmacological data in support of advancing OGX-225 into
clinical development.

 

iv.           Assessing,
and as appropriate acquiring, additional pre-clinical product candidates which
have demonstrated in vivo efficacy and some evidence, through analysis of human
tumour tissue or otherwise, of relevance of the target in human disease. Preference
may be given to potential products which
would diversify the development risk by broadening the therapeutic approach to
treating cancer.

 

4.               Complete an equity financing
sufficient to fund the medium term (3 year) corporate objectives by [***].

 

5.               Facilitate meeting all of our 3
year corporate objectives by increasing public awareness of OncoGenex
Technologies among potential investors, underwriters, collaborators,
development partners, clinical investigators and patients, through:

 

i.                  strategic use of media relations and press
releases;

 

ii.               participation
in targeted scientific, business development and/or investor conferences;

 

iii.            creation
of, or participation in, patient and/or clinician outreach and education
opportunities; and

 

iv.           general community involvement / networking.

 

13

 

(b)          Up
to 40% of Bonus based on OncoGenex, Inc.’s achievement of the following 2005
Objectives:

 

1.              OGX-011-01:  Review SAS datasets and analyze data internally; initiate data analyses
for writing corporate study report; plan for integration into future Integrated
Safety Summary (ISS); review PK/PD data for integration into corporate study
report; develop a standardized Draft 0 “Clinical Study Report” template for
future reports while drafting the OGX-011-01 Clinical Study Report; update
Investigator Brochure and other corporate documents, as appropriate.

 

2.              OGX-011-02:  Review SAS datasets and analyze data internally; initiate data analyses
for writing corporate study report; plan for integration into future Integrated
Safety Summary (ISS); review PK/PD data and develop timeline for OGX-011-02
Final study report; update any Grade 3 or 4 AE safety data for Investigator
Brochure and other corporate documents, as appropriate.

 

3.              OGX-011-03  and OGX-011-06:  Improve [***] communication; finalize process for specific trial
updates and enrollment/AE tracking; coordinate timing of SAS data transfers
with [***].

 

4.              OGX-011-04:  Develop in-house database/data management; coordinate CRF retrieval and
input into database; finalize planning for safety review/reporting (including
narrative writing); finalize data management plan

 

5.              OGX-011-05:  Coordinate/plan for Phase 2 ongoing safety data review/interim analysis
for DMC; complete Phase 2 clinical monitoring plan; schedule Phase 1 safety
review with Data Safety Monitoring Committee per Charter [***]; initiate
Regulatory strategy for [***] indication for possible accelerated approval by
FDA (Discuss similar strategy for Canadian approval); complete literature
search on clinical outcomes for historical control strategy.

 

6.              OGX-011-07:  Develop study design and protocol with Advisory input; draft protocol;
coordinate Advisory meeting for input/finalization of protocol; identify
sites/PI’s and plan for CRA support based on site selections; prepare for a
Data Safety Monitoring Committee and draft Charter; draft general clinical
monitoring plan including SAE reporting and trial tracking/data management
plan.

 

7.              OGX-427:   Initiate a proposed clinical
development plan and Clinical/Regulatory strategy: Coordinate Advisor Panel
input.

 

14

 

APPENDIX B

 

ONCOGENEX TECHNOLOGIES INC.

STOCK OPTION PLAN

OPTION AGREEMENT

 

This Option Agreement is entered into between OncoGenex
Technologies Inc. (“the Company”) and the Optionee named below pursuant to the
Company Stock Option Plan as amended (the “Plan”), a copy of which is attached
hereto, and confirms that:

 

1.                                       on September 12, 2005
(the “Grant Date”);

 

2.                                       Cindy Jacobs (the “Optionee”);

 

3.                                       was granted the option
(the “Option”) to purchase 125,000 common shares (the “Option Shares”) of the
Company;

 

4.                                       for the price (the “Option
Price”) of Cdn. $0.95 per share;

 

5.                                       which shall be
exercisable (“Vested”) in whole or in part in the following amounts on or after
the following dates:

 

i)                                         31,250 shares on
December 12, 2005; and

ii)                                      31,250 shares upon each
anniversary of the Grant Date.

 

6.                                       terminating on the
September 12, 2012 (the “Expiry Date”);

 

all on the terms and subject to the conditions set out
in the Plan. For greater certainty, once Option Shares have become Vested, they
continue to be exercisable until the termination or cancellation thereof as
provided in this Option Agreement and the Plan.

 

By signing this Option Agreement, the Optionee
acknowledges that the Optionee has read and understands the Plan and agrees to
the terms and conditions of the Plan and this Option Agreement.

 

In order to exercise this Option, the Optionee must
deliver to the Company a notice of exercise in the form attached hereto as
Exhibit No. 1, duly completed and executed together with a certified cheque for
payment for all Option Shares in respect of which the Option is exercised.

 

IN WITNESS WHEREOF the parties hereto have executed this Option
Agreement as of the 12th day of September, 2005.

 

	
  SIGNED,
  SEALED AND DELIVERED

  	
  )

  	
   

  
	
  in
  the presence of

  	
  )

  	
   

  
	
   

  	
  )

  	
   

  
	
   

  	
   

  	
  )

  	
  /s/
  Cindy A. Jacobs

  	
   

  
	
  Witness

  	
  )

  	
  OPTIONEE

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ONCOGENEX
  TECHNOLOGIES INC.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  /s/
  Scott Cormack

  	
   

  
					

 

15

 

EXHIBIT NO. 1 TO OPTION AGREEMENT

 

EXERCISE FORM

TO:                        OncoGenex Technologies Inc.

400 – 1001 West
Broadway

Vancouver, British
Columbia V6H 4B1

Telephone:            604-736-3678

Facsimile:               604-736-3687

Attention:              Scott
Cormack

 

I, the undersigned holder of the attached Option
Agreement with OncoGenex Technologies Inc. (the “Company”), hereby exercise my
Option and agree to acquire                        
common shares of the Company (the “Acquired Shares”) and enclose a certified
cheque in the amount of $                        
representing the exercise price (Option Price multiplied by number of shares
being acquired) for the Acquired Shares.

 

I hereby request that the Company issue the Acquired
Shares to me under the OncoGenex Technologies Inc. Stock Option Plan and
irrevocably direct that the Acquired Shares be issued registered in the
following name and address and delivered as follows:

 

	
  Name in Full

  	
   

  	
  Registered Address

  	
   

  	
  Delivery Address

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  

 

(PLEASE PRINT IN FULL THE NAME IN WHICH CERTIFICATES ARE
TO BE ISSUED.)

 

	
  DATED this           
  day of                                  ,
                  .

  
	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  Signature of Optionee

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  Name of Optionee

  	
   

  

 

16Exhibit 10.10

COLLABORATION AND CO-DEVELOPMENT AGREEMENT

THIS
COLLABORATION AND CO-DEVELOPMENT AGREEMENT (“Agreement”) is
made and entered into effective as of November 16, 2001 (the “Effective Date”),
by and among ONCOGENEX TECHNOLOGIES INC., having offices at Suite 400, 609 – 14th
Street N.W., Calgary, Alberta T2N 2A1 (“OncoGenex”) and ISIS PHARMACEUTICALS,
INC., having principal offices at 2292 Faraday Avenue, Carlsbad CA 92008
(“Isis”). OncoGenex and Isis each may be referred to herein individually as a
“Party,” or collectively as the “Parties.”

WHEREAS,
Isis and OncoGenex wish to establish a relationship to co-develop and
commercialize an antisense compound targeted to Clusterin, 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 have entered into this collaboration (the
“Collaboration”) to jointly develop and commercialize the Product 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 Collaboration Activities in accordance with this Agreement, and in
accordance with the Initial Project Plan and any future Project Plans. Each
Party will perform, or cause to be performed, its Collaboration Activities in
good scientific manner, and in compliance in all material respects with all
Applicable Law and will use best efforts to (a) research, develop, manufacture,
file for Regulatory Approval and commercialize the Product,  (b) perform the work of each Project Plan
with the view to achieving the objectives of such Project Plan efficiently and
expeditiously by allocating sufficient time, effort, equipment and skilled
personnel to complete such activities successfully and promptly, and (c)
cooperate fully with the other Party to achieve the goals of the Collaboration.

2.2.2                     Collaboration
Exclusivity.  During the Term of this
Agreement, neither Party will engage, on behalf of itself or any other party,
in the development or commercialization of antisense compounds targeted to Clusterin
other than as provided in this Agreement.

*Certain information in this exhibit has been omitted
as confidential, as indicated by [***]. This information has been filed
separately with the Commission.

1

Section 2.3            Initial
Project Plan.

 

2.3.1       Goals
of Initial Project Plan. The Initial Project Plan will be
directed to completing Trial 1 and Trial 2, as set forth in Appendix 2.3.1. The
Parties’ responsibilities for Collaboration Activities for the Initial Project
Plan are set forth in Appendix 2.3.1. Collaboration Activities for the Initial
Project Plan will be funded as set forth in Appendix 2.3.1.

 

2.3.2       Changes
to Initial Project Plan. Any changes to the Initial Project
Plan requiring the performance of additional activities will require the prior
written approval of both Parties and will be funded 65% by OncoGenex and 35% by
Isis, unless otherwise agreed by the Parties. Any such changes to the Initial
Project Plan will include a budget covering any additional activities.

 

2.3.3       Licensing
of Product. The Product will not be sublicensed to any Third
Party prior to completion of the Initial Project Plan, without mutual agreement
of the Parties in writing.

 

2.3.4       Discontinued
Performance by OncoGenex. If OncoGenex elects during
performance of the Initial Project Plan to discontinue its participation in the
Collaboration, Isis may continue the development and commercialization of the
Product independently of OncoGenex. Upon discontinuation of performance of the
Initial Project Plan by OncoGenex, Isis will retain any licenses granted in
Section 4.1, including the right to sublicense as provided in that section. Isis
will pay OncoGenex a royalty equal to [***] of Net Sales of the Product for the
life of the Product. In addition, Isis will pay OncoGenex any applicable Third
Party Payments. OncoGenex will transfer to Isis all information relating to the
Product as may be necessary to enable Isis to practice the licenses granted in
Section 4.1, including, but not limited to, summaries of clinical trials,
rights to all foreign-equivalent INDs and NDAs filed with respect to the
Product in such country and all drug dossiers and master files with respect
thereto. OncoGenex will have no further expense obligations under this
Agreement.

 

2.3.5       Discontinued
Performance by Isis. If Isis elects during performance of the
Initial Project Plan to discontinue its participation in the Collaboration,
OncoGenex may continue the development and commercialization of the Product
independently of Isis. Upon discontinuation of performance of the Initial
Project Plan by Isis, OncoGenex will retain any licenses granted in Section
4.1, including the right to sublicense as provided in that section. OncoGenex
will pay Isis a royalty equal to [***] of Net Sales of the Product for the life
of the Product. In addition, OncoGenex will pay Isis any applicable Third Party
Payments. Isis will transfer to OncoGenex all information relating to the
Product as may be necessary to enable OncoGenex to practice the licenses
granted in Section 4.1, including, but not limited to, summaries of clinical
trials, rights to all foreign-equivalent INDs and NDAs filed with respect to
the Product in such country and all drug dossiers and master files with respect
thereto. Isis will have no further expense obligations under this Agreement.

 

2

Section 2.4            Future
Collaboration Activities.

 

2.4.1       Proportionate
Share. After completion of the Initial Project Plan, the
Proportionate Share of OncoGenex and Isis will be 65% and 35%, respectively.

 

2.4.2       Future
Project Plans. Ninety days prior to estimated completion of
the Initial Project Plan, and 90 days prior to estimated completion of each
subsequent Project Plan, the Operating Committee will establish a new Project
Plan for the next stage of development of the Product. Upon written acceptance
of a new Project Plan by each of the Parties, such Project Plan will be
appended to this Agreement. Each new Project Plan will include a budget for the
Collaboration Activities to complete such Project Plan, and provisions for the
Parties to fund the Collaboration Activities according to their Proportionate
Share.

 

2.4.3       Third
Party or Unilateral Product Development. If the Parties
cannot agree to the terms of a new Project Plan, the Parties will negotiate in
good faith for one Party to unilaterally develop the Product, or will agree to
jointly sub-license the Product to a Third Party. If the Parties cannot reach
agreement regarding the principal terms for unilateral development or
sub-licensing of the Product within 120 days of beginning negotiations, the
Parties will refer the matter to dispute resolution according to the procedures
set forth in Section 12.6.

 

2.4.4       Licensing
of Product.

 

(a)           No
Third Party negotiations will be undertaken in respect of the Product by either
Party unless agreed to by each of the Parties. The Party that introduces the
Third Party to such negotiations will continue as the negotiating lead.

 

(b)           Net
Licensing Revenue received as a result of a licensing or other collaboration
agreement with a Third Party will be shared by the Parties  in accordance with Article 5.

 

2.4.5       Manufacturing
of the Product. With respect to clinical and commercial
supplies of the Product for the performance of future Project Plans, the
Operating Committee will use its best efforts to enter into a supply agreement
with the supplier that is best able to meet the Parties’ requirements, taking
into consideration such factors as price, timing, quality, capacity, quantity,
reliability and reputation. Such supplier may be either a Third Party or one of
the Parties.

 

ARTICLE
3 - 

OPERATION OF THE COLLABORATION

 

Section 3.1            Operating  Committee.

 

3.1.1       Formation
of Operating  Committee. The Parties will
establish a joint committee (the “OperatingCommittee”),
which will oversee the Collaboration and development and commercialization
activities as described hereunder. Each of OncoGenex and Isis will appoint 2
representatives with the requisite experience and 

 

3

seniority to
enable them to fulfill the obligations of the OperatingCommittee
with respect to the Collaboration. Additional representatives of each Party
will be free to attend the Operating Committee meetings, but not to vote. From
time to time, OncoGenex and Isis each may substitute any of its representatives
to the OperatingCommittee with notice to the
other Party and to the members of the OperatingCommittee.
Each Party will ensure that each member of the OperatingCommittee
is bound by the obligations of confidence in accordance with Article 6.

 

3.1.2       Operating
Committee Responsibilities. The OperatingCommittee
will, in addition to its other responsibilities described in this Agreement:
(a) periodically review the Project Plan from a strategic and scientific
perspective, and present opinions to the Parties; (b) make changes to Project
Plans as it deems necessary to accomplish the purpose of the Collaboration,
and, recommend to the Parties allocation of responsibilities for Collaboration
Activities between OncoGenex and Isis necessary to implement the Project Plans,
taking into consideration the Parties’ relevant expertise and available
resources and relevant Project Plans and budgets; (c) prioritize for the
Parties the research, development, manufacturing and commercialization
activities with respect to the Product; (d) attempt to resolve any
disagreements between the Parties with respect to the research conducted under
the Collaboration; (e) monitor, at least on a quarterly basis, Collaboration
Activities conducted and expenses incurred sufficient to insure that progress
and expense contribution are in accordance with Project Plan; and (f) take such
other actions as are set forth in this Agreement or as the Parties may mutually
agree.

 

3.1.3       Procedural
Rules for the Operating  Committee.

 

(a)           Generally. Except
as explicitly set forth in this Agreement, the Operating Committee will
establish its own procedural rules for its operation.

 

(b)           Voting. The
Operating Committee will take action by unanimous agreement of the members of
the Operating Committee. In the event that unanimous agreement cannot be
achieved within 20 days, the matter will be resolved according to the
procedures set forth in Section 3.2.

 

Section 3.2            Dispute
Resolution. Any dispute that may arise relating to the terms of this
Agreement or the activities of the Parties hereunder will be brought to the
attention of the Operating Committee, which will attempt in good faith to
achieve a resolution. Either Party may convene a special meeting of the
Operating Committee for the purpose of resolving disputes. If the Operating
Committee is unable to resolve such a dispute within 20 days of the first
presentation of such dispute to the Operating Committee, such dispute will be
referred to the Chief Executive Officers of each of the Parties (or their
respective designees) who will use their good faith efforts to mutually agree
upon the resolution of the dispute. If any dispute is not resolved by the Chief
Executive Officers of the Parties (or their designees) within 30 days after
such dispute is referred to them, then either Party will have the right, with
respect to a Party’s interpretation of, or performance under, this Agreement,
to arbitrate such dispute in accordance with Section 12.6.

 

4

ARTICLE 4 - 

GRANT OF RIGHTS

 

Section 4.1            License
Grants for Collaboration Activities.

 

4.1.1       Isis
Grant. Subject to the terms and conditions of this Agreement,
Isis hereby grants to OncoGenex (a) a co-exclusive (with Isis), worldwide,
fully-paid, royalty-free license, under the Joint Patents and Product-Specific
Technology Patents, and (b) a non-exclusive, worldwide, royalty-free
license under the Isis Core Technology Patents, both licenses solely to
develop, make, have made, use, sell, offer for sale, have sold and import the
Product. The license granted hereunder will be sublicensable only in connection
with a license of the Product to a Third Party in accordance with the terms of
this Agreement.

 

4.1.2       OncoGenex
Grant. Subject to the terms and conditions of this Agreement,
including without limitation Section 4.2, OncoGenex hereby grants to Isis a
co-exclusive (with OncoGenex), worldwide, fully-paid, royalty-free license, or
sub-license, as the case may be, under the OncoGenex Product Patents, the Joint
Patents, and the Product-Specific Technology Patents, solely to develop, make,
have made, use, sell, offer for sale, have sold and import the Product. The license
granted hereunder will be sublicensable only in connection with a license of
the Product to a Third Party in accordance with the terms of this Agreement.

 

4.1.3       Isis Manufacturing Patents. Isis
will grant to OncoGenex or to a Third Party manufacturer pursuant to Section
2.4.5 a non-exclusive, worldwide, fully-paid, royalty-free license, under the
Isis Manufacturing Patents to make or have made the Product only upon a
determination by the Operating Committee to have OncoGenex or such Third Party
manufacture the Product; or upon discontinuance of performance by Isis and
unilateral development of the Product by OncoGenex under Section 2.3.5; or upon
unilateral development of the Product by OncoGenex  or a Third Party sublicensee under Section
2.4.3; or upon unilateral development of the Product by OncoGenex if Isis is
found to be in breach of this Agreement in accordance with Article 9 hereof.

 

4.1.4       Improvements.
If any Improvement that is not Product-Specific Technology is
made during the Collaboration, the Parties will negotiate in good faith
regarding the use of any such Improvement in the Collaboration. If the Parties
agree to terms under which such Improvement will be used in the Collaboration,
the Party owning the Improvement will grant to the other Party a license under
the Improvement solely to develop, make, have made, use, sell, offer for sale,
have sold and import the Product. The license granted hereunder will be
sublicensable only in connection with a license of the Product to a Third Party
in accordance with the terms of this Agreement.

 

Section 4.2            Pre-Existing
Grants.  The Parties further
acknowledge and agree that  pursuant to
the ARC Pharmaceuticals co-development letter of intent, OncoGenex has or
intends to grant an exclusive license under the OncoGenex Product Patents to
develop and commercialize a topical/intratumoral antisense compound designed to
interact with Clusterin and the Parties acknowledge that OncoGenex is free to
do so 

 

5

without breach of
this Agreement. No rights to Isis Patent Rights, Joint Technology, or
Product-Specific Technology may be granted, expressed or implied, by OncoGenex
to ARC Pharmaceuticals.

 

ARTICLE
5 -

FINANCIAL PROVISIONS

 

Section 5.1            Payment
by OncoGenex. OncoGenex will pay $500,000 (US) to Isis within 30 days of
the Effective Date. Such payment will be for approximately [***] of Product to
support the IND-directed toxicology and PK studies. All other expenses incurred
by Isis in respect of Isis’ Collaboration Activities as set forth in the
Initial Project Plan shall be borne solely by Isis.

 

Section 5.2            Licenses
from Third Parties.

 

5.2.1       Third
Party Payments. OncoGenex acknowledges that Isis entered into
a license agreement with [***] and a license agreement with [***] under which
Isis is obligated to pay royalties and milestones on the Product. Isis
acknowledges that OncoGenex entered into a license agreement with University of
British Columbia dated November 1, 2001, under which OncoGenex is obligated to
make payments with respect to the Product. The Third Party Payments identified
in this Section 5.2.1 will be determined in accordance with the terms of the
referenced license agreements. In the event that either Party negotiates
reduced royalties or milestones with these Third Party licensors, the royalties
and milestones due under the original license agreements will still be paid to
Isis or OncoGenex as the case may be.

 

Section 5.3            Product
Licensing Revenue Allocation. Licensing Revenue will be allocated as
follows: first, each Party will receive any Third Party Payments owing to its
licensors in respect of the Product, then each Party will receive its
Proportionate Share of the Net Licensing Revenue. In the event that one Party
receives all Licensing Revenue, then such receiving Party will distribute the
Licensing Revenue to the non-receiving Party in accordance with the immediately
preceding sentence within 15 days after receipt of such Licensing Revenue.

 

Section 5.4            Sharing
of Third Party Payments. During the Initial Project Plan, each Party will
be responsible for any Third Party Payments owing to its licensors.Following completion of the Initial Project Plan, any Third
Party Payments owing in respect of the Product will be shared by the Parties
according to their Proportionate Share.

 

Section 5.5            Revenue
Sharing on Direct Sales. The Party marketing the Product will: first,
subtract expenses from Revenues received from the Product; second, pay or
distribute Third Party Payments; and third, distribute the remaining Revenue to
the Parties according to their Proportionate Shares. The Party marketing the
Product will distribute Revenue within 30 days after the end of each calendar
quarter. In the event that expenses from marketing the Product are greater than
Revenues received, the Parties will

 

6

Section 5.6            divide
such expenses that are in excess of Revenues, according to their Proportionate
Shares.

 

Section 5.7            Payment
Method. Any amounts due to a Party hereunder will be paid in Canadian
dollars if paid to OncoGenex, and in U.S. dollars if paid to Isis, 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 two percent
(2%), or the maximum rate permitted by law, whichever is lower, calculated on
the number of days such payment is delinquent, compounded monthly.

 

Section 5.8            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, or for the purchase of Canadian
dollars as published by the Royal Bank of Canada, 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 5.9            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 5.10         Records
Retention; Audit.

 

5.10.1     Regulatory
Records. With respect to the subject matter of this
Agreement, each Party will maintain, or cause to be maintained, records of its
respective research, development, manufacturing and commercialization
activities, including all Regulatory Documentation, in sufficient detail and in
good scientific manner appropriate for patent and regulatory purposes, which
will be complete and accurate and will fully and properly reflect all work done
and results achieved in the performance of such activities. All Regulatory
Documentation will be retained for a period as may be required by Applicable
Law. Each Party will have the right, during normal business hours and upon
reasonable notice, to inspect and copy any such records.

 

5.10.2     Record
Retention. Each Party will maintain (and will ensure that its
sublicensees will maintain) complete and accurate books, records and accounts
that 

 

7

fairly reflect (a)
their respective costs and expenses reimbursable or otherwise shared by the
Parties hereunder (collectively, the “Collaboration Expenses”), and (b) Revenue
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.

 

5.10.3     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
Collaboration Expenses or Revenues, as applicable, for any calendar quarter or
calendar year ending not more than 24 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 5% from the reported results, in which case the audited Party shall
bear the cost of the audit. The requesting Party will have the right to audit
previous years, if such years have not been previously audited, if the audit
reveals a variance of more than 5% from the reported results. The requesting
Party will bear the cost of such previous year audits unless such audits reveal
a variance of more than 5%. The results of such accounting firm shall be final
and binding upon the Parties, absent manifest error.

 

5.10.4     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 additional payments, with interest from the
date originally due at the rate of 1% per month, within 60 days after the date
on which such accounting firm’s written report is delivered to such Party.

 

5.10.5     Confidentiality.
The auditing Party will treat all information subject to
review under this Section 5.9 in accordance with the confidentiality provisions
of Article 6 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
6 - 

CONFIDENTIALITY

 

Section 6.1            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.

 

8

6.1.1       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 required in connection with any filing,
application or request for Regulatory Approval; 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 6; 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 6.

 

Section 6.2            Press
Releases. Press releases or other similar public communication by either
Party relating to this Agreement, will be approved in advance by the other
Party, which approval will not be 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.

 

9

Section 6.3            Publications.
The Parties acknowledge that scientific lead-time is a key element of the
value of the research and development activities under the Collaboration and
further agree that scientific publications must be strictly monitored to
prevent any adverse effect from premature publication or disclosure of results
of the research or development activities hereunder. At least 45 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 30
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 or the taking
of such measures to establish and preserve proprietary rights in the
information in the material being submitted for publication or presentation. The
Parties recognize that it may not be practical under all circumstances to
comply with the above notice requirements for review of publications and
presentations. Each Party will reasonably review proposed publications and
presentations submitted by the other Party as promptly as possible and will not
unreasonably withhold its consent to such publications or presentations that
have been submitted for review with less than the required notice period.

 

ARTICLE
7 - 

INTELLECTUAL PROPERTY

 

Section 7.1            Intellectual
Property Ownership.

 

7.1.1       Ownership
of Intellectual Property. Ownership of inventions conceived
or reduced to practice as part of the Collaboration will be determined in
accordance with the rules of inventorship under United States patent laws. Isis
will own all inventions conceived of and reduced to practice as part of the
Collaboration solely by its employees and agents, and all Patents claiming such
inventions. OncoGenex will own all inventions conceived of and reduced to
practice as part of the Collaboration solely by its employees and agents, and
all Patents claiming such inventions. All inventions conceived of and reduced
to practice jointly by employees or agents of Isis and employees or agents of
OncoGenex, and all Patents claiming such inventions, will be owned jointly by
Isis and OncoGenex. 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.

 

7.1.2       Ownership
of Regulatory Documentation. All Regulatory Approvals with
respect to the Product will be owned by OncoGenex for the duration of the
Collaboration. If the Collaboration terminates, or if one Party discontinues 

 

10

performance
according to the terms of this Agreement, all Regulatory Approvals will remain
with the Party that has retained the rights to the Product.

 

Section 7.2            Prosecution
of Patents.

 

7.2.1       Isis
Rights. Isis will, subject to Section 7.2.3 and Section
7.2.5, have the sole right, at its cost and expense and at its sole discretion,
to obtain, prosecute and maintain throughout the world the Isis Patent Rights.
OncoGenex shall reimburse Isis for its Proportionate Share of the reasonable
out-of-pocket costs incurred to obtain, prosecute and maintain throughout the
world, any Product-Specific Technology Patents Controlled by Isis. Isis will
keep OncoGenex informed of all Product-Specific Technology Patent applications
and registrations to be filed by Isis, and OncoGenex shall have the right to
comment on such applications within the timeframes of the patent filing process
and deadlines. Notwithstanding the foregoing, if OncoGenex is unilaterally
developing and commercializing the Product in accordance with Section 2.3.5,
Section 2.4.3, or Article 9, OncoGenex will have the first right to file,
prosecute and maintain any Product-Specific Technology Patents at its expense. If
OncoGenex elects not to (a) pursue the filing, prosecution or maintenance of a
Product-Specific Technology Patent in a particular country, (b) take any other
action with respect to Product-Specific Technology in a particular country that
is necessary or reasonably useful to establish or preserve rights thereto, then
in each such case OncoGenex will so notify Isis promptly in writing and in good
time to enable Isis to meet any deadlines by which an action must be taken to
establish or preserve any rights in such Product-Specific Technology in such
country, and Isis will have the right, but not the obligation, to pursue the
filing or registration, or support the continued prosecution or maintenance, of
such Product-Specific Technology Patents, at its expense in such country.

 

7.2.2       OncoGenex
Rights. OncoGenex will, subject to Section 7.2.3 and Section
7.2.5, have the sole right and at its sole discretion, to obtain, prosecute and
maintain throughout the world the OncoGenex Patent Rights. Isis shall reimburse
OncoGenex for its Proportionate Share of the reasonable out-of-pocket costs
incurred to obtain, prosecute and maintain throughout the world, any OncoGenex
Product Patents and Product-Specific Technology Patents Controlled by
OncoGenex. OncoGenex will keep Isis informed of all OncoGenex Product Patent
and Product-Specific Technology Patent applications and registrations to be
filed by Oncogenex, 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 2.3.4, Section 2.4.3, or Article 9, Isis
will have the first right to file, prosecute and maintain any Product-Specific
Technology Patents at its expense. If Isis elects not to (a) pursue the filing,
prosecution or maintenance of a Product-Specific Technology Patents in a
particular country, (b) take any other action with respect to Product-Specific
Technology in a particular country that is necessary or reasonably useful to
establish or preserve rights thereto, then in each such case Isis will so
notify OncoGenex promptly in writing and in good time to enable OncoGenex to
meet any deadlines by which an action must be taken to establish or preserve
any rights in such Product-Specific Technology in such country, and OncoGenex
will have the right, but not the obligation, to pursue the filing or
registration, 

 

11

or support the
continued prosecution or maintenance, of such Product-Specific Technology
Patents, at its expense in such country. Upon unilateral development and commercialization
by Isis, the Parties will negotiate for Isis to have the right to control the
prosecution of the OncoGenex Product Patents. At a minimum, Isis will have the
right to comment on the prosecution of the OncoGenex Product Patents, and to
request countries for foreign filings related thereto. OncoGenex will keep Isis
informed of all prosecution matters regarding OncoGenex Product Patents
promptly to allow Isis sufficient time to comment within the timeframes of the
patent prosecution process and deadlines.

 

7.2.3       Filing
of Joint Patents. Subject to Section 7.2.5, 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 the
responsible Party’s expenses as follows: 
i) Proportionate Share of such expenses if the Joint Patent is a
Product-Specific Technology Patent, or ii) equal sharing of such expenses if
the Joint Patent is not a Product-Specific Technology Patent. 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. Not withstanding
the foregoing, if one Party is unilaterally developing and commercializing the
Product in accordance with Section 2.3.4, section 2.3.5, or Section 2.4.3, or
Article 9, the Party continuing with the development and commercialization of
the Product (for purposes of this Section only, the “Continuing Party”) will
have the first right to file, prosecute and maintain any Joint Patents to
Product-Specific Technology at its expense. If the Continuing Party elects not
(a) to pursue the filing, prosecution or maintenance of such a Joint Patent in
a particular country, (b) to take any other action with respect to such Joint
Patent in a particular country that is necessary or reasonably useful to
establish or preserve rights thereto, then in each such case the Continuing
Party will so notify the other Party promptly in writing and in good time to
enable such Party to meet any deadlines by which an action must be taken to
establish or preserve any rights in such Joint Technology in such country, and
such Party will have the right, but not the obligation, to pursue the filing or
registration, or support the continued prosecution or maintenance, of such
Patent, at its expense in such country.

 

7.2.4       Cooperation.
Each Party will cooperate fully 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.

 

12

7.2.5       Patent
Filings. OncoGenex covenants not to file any patent
application with respect to the Product disclosing or claiming any information
disclosed or claimed in the Isis Patent Rights, without Isis’s prior written
consent. Isis covenants not to file any patent application disclosing or
claiming any information disclosed or claimed in the OncoGenex Patent Rights
without OncoGenex’s prior written consent.

 

Section 7.3            Enforcement
of Patents

 

7.3.1       Rights
and Procedures. If Isis or OncoGenex determines that any
Technology 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 and provide such other Party with any evidence of such
infringement that is reasonably available.

 

(a)           Joint Patents. With
respect to infringement of a Joint Patent, the Party responsible for filing,
prosecution and maintenance of such Joint Patent under Section 7.2.3 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 Right 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 such action. Notwithstanding the foregoing, if the infringement
is likely to have a material adverse effect on the Parties’ 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 in the reasonable costs incurred relating to
the removal of any such infringement on a Proportionate Share basis.

 

(b)           Product-Specific Technology Patents. With
respect to Product-Specific Technology Patents, the Party owning such Patents
will have the first right, but not the obligation, to remove such infringement,
provided, however, that the other Party will reimburse the owner of such Patent
for its Proportionate Share of the reasonable costs incurred by such owner
relating to the removal of any such infringement. In the event the Party owning
the Product-Specific Technology Patent 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 the other Party in writing of its intent not to take such steps, and
such infringement is likely to have a material adverse effect on the Product,
the other Party will have the right to do so at its expense, and the Party
owning the Product-Specific Technology Patent will have the right, at its own
expense, to be represented in any such action.

 

(c)           Isis Patent Rights and OncoGenex
Patent Rights. With respect to Isis Patent Rights or
OncoGenex Patent Rights, and subject to Section 7.3.1(b), the 

 

13

owner of such Patents
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, and the other Party will
have the right, at its own expense, to be represented in any such action. Notwithstanding
the foregoing, if the infringement is likely to have a material adverse effect
on the Parties’ development or commercialization of the Product, the Parties
will meet to determine whether to defend against such infringement based on the
Patents of one Party, and if the Parties mutually agree to proceed in defending
such infringement based on the Patent rights of either Party, the Party owning
the Patent will remove the infringement using commercially appropriate steps,
and the Parties will share in the reasonable costs incurred relating to the
removal of any such infringement on a Proportionate Share basis. Upon
unilateral development and commercialization by Isis, the Parties will
negotiate for Isis to have the right, at Isis’ own expense, to remove infringement
of the OncoGenex Product Patents. At a minimum, OncoGenex will keep Isis
informed regarding infringement actions brought by OncoGenex on the OncoGenex
Product Patents, and Isis will have the right to comment on such infringement
actions.

 

(d)           Cooperation. The
Party not enforcing the applicable Patent will provide reasonable assistance to
the other Party, including providing access to relevant documents and other
evidence, making its employees available at reasonable business hours, and
joining the action to the extent necessary to allow the enforcing Party to
maintain the action.

 

7.3.2       Recovery.
Any amounts recovered by either or both Parties in connection
with or as a result of any action contemplated by  Section 7.3.1, whether by settlement or
judgment, will be used to reimburse the Parties for their reasonable costs and
expenses in making such recovery (which amounts will be allocated pro rata if
insufficient to cover the totality of such expenses), with any remainder being
divided between the Parties according to their proportionate expenditures in
the litigation; provided, however, that to the extent that any award is
attributable to loss of sales of the Product, the award will first be used to
reimburse the Parties for their reasonable costs and expenses in making such
recovery, and any remainder will be allocated according to the Parties’
Proportionate Shares.

 

Section 7.4            Potential
Third Party Rights.

 

7.4.1       Third
Party Licenses. If the Parties determine that a license to a
Third Party Patent is necessary to develop, manufacture, and/or commercialize
the Product, the Parties will use Commercially Reasonable Efforts to obtain a
license from such Third Party; provided, however, that Isis will have the first
right to seek any such license necessary to practice the Isis Patent Rights and
will use Commercially Reasonable Efforts to obtain such a license in its own
name from such Third Party in such country, under which Isis will, to the
extent permissible under such license, grant a sublicense to OncoGenex as
necessary for OncoGenex to develop, make, have made, use, sell, offer for sale,
have sold and import the Product. If Isis declines to seek a license for which
it has the first right, OncoGenex may seek to obtain such a license, under
which OncoGenex will, to the extent permissible under such license, grant a
sublicense to Isis as necessary 

 

14

for Isis to
develop, make, have made, use, sell, offer for sale, have sold and import the
Product.

 

7.4.2       Third
Party Litigation. In the event that a Third Party institutes
a patent infringement suit (including any suit alleging the invalidity or
unenforceability of the Patents of a Party) against either Party or both
Parties during the Term of this Agreement, alleging that any of the activities
hereunder infringes one or more patent or other intellectual property rights
held by such Third Party (an “Infringement Suit”), the Parties will cooperate
with one another in defending such suit. Isis will have the sole right to
control any defense of any such claim involving alleged infringement of Third
Party rights by Isis’ activities at its own expense and by counsel of its own
choice, and OncoGenex will have the right, at its own expense, to be
represented in any such action by counsel of its own choice. OncoGenex will
have the sole right to control any defense of any such claim involving alleged
infringement of Third Party rights by OncoGenex’s activities at its own expense
and by counsel of its own choice, and Isis will have the right, at its own
expense, to be represented in any such action by counsel of its own choice ;
provided, however, that, where such Infringement Suit relates to the
development and commercialization of the Product, the Party controlling such
Infringement Suit will keep the other Party reasonably informed of developments
in any such Infringement Suit.

 

Section 7.5            Validity
and Enforceability of Parties’ Technology. The Parties agree that during
the Term of this Agreement, and for 5 years thereafter, neither Party will
bring any action in a court of law, or otherwise challenge the validity or
enforceability of the other Party’s Technology.

 

ARTICLE
8 - 

TERM AND TERMINATION

 

Section 8.1            Term.
The term of this Agreement (the “Term”) will commence upon the Effective
Date and will continue in effect until such time as the Product is no longer
being developed or commercialized hereunder, or unless terminated at an earlier
date in accordance with the terms and conditions set forth in this Article 8.

 

Section 8.2            Termination
Upon Insolvency. Either Party may terminate this Agreement if, at any time,
the other Party files in any court or agency pursuant to any statute or
regulation of any state, country or jurisdiction, a petition in bankruptcy or
insolvency or for reorganization or for an arrangement or for the appointment
of a receiver or trustee of that Party or of its assets, or if such other Party
proposes a written agreement of composition or extension of its debts, or if
such other Party will be served with an involuntary petition against it, filed
in any insolvency proceeding, and such petition will not be dismissed within 60
days after the filing thereof, or if such other Party will propose or be a
party to any dissolution or liquidation, or if such other Party will make an
assignment for the benefit of its creditors.

 

Section 8.3            Rights
in Bankruptcy. All rights and licenses granted under or pursuant to this
Agreement by Isis or OncoGenex are, and will otherwise be deemed to be, for
purposes of Section 365(n) of the United States Bankruptcy Code, licenses of 

 

15

rights to
“intellectual property” as defined under Section 101 of the United States
Bankruptcy Code. The Parties agree that the Parties, as licensees of such
rights under this Agreement, will retain and may fully exercise all of their
rights and elections under the United States Bankruptcy Code. The Parties
further agree that, in the event of the commencement of a bankruptcy proceeding
by or against a Party under the United States Bankruptcy Code, the Party hereto
that is not a Party to such proceeding will be entitled to a complete duplicate
of (or complete access to, as appropriate) any such intellectual property and
all embodiments of such intellectual property, which, if not already in the
non-subject Party’s possession, will be promptly delivered to it (a) upon any
such commencement of a bankruptcy proceeding upon the non-subject Party’s
written request therefor, unless the Party subject to such proceeding elects to
continue to perform all of its obligations under this Agreement or (b) if not
delivered under clause (a) above, following the rejection of this Agreement by
or on behalf of the Party subject to such proceeding upon written request therefor
by the non-subject Party.

 

Section 8.4            Consequences
of Expiration or Termination.

 

8.4.1       Licenses.
Upon expiration of the Term of this Agreement in accordance
with Section 8.1 and payment of all amounts owed pursuant to this Agreement,
the licenses granted by Isis to OncoGenex, and by OncoGenex to Isis, hereunder
will terminate.

 

8.4.2       Return
of Information and Materials. Upon expiration of this
Agreement pursuant to Section 8.1 or upon termination of this Agreement in its
entirety by either Party pursuant to this Article 8, each Party, at the request
of the other Party, will return all data, files, records and other materials in
its possession or control relating to such other Party’s Technology, or
containing or comprising such other Party’s Information and Inventions or other
Confidential Information and, in each case, to which the returning Party does
not retain rights hereunder (except one copy of which may be retained for
archival purposes).

 

Section 8.5            Accrued
Rights; Surviving Obligations.

 

8.5.1       Accrued
Rights. Termination or expiration of this Agreement for any
reason will be without prejudice to any rights or financial compensation that
will have accrued to the benefit of a Party prior to such termination or
expiration. Such termination or expiration will not relieve a Party from
obligations that are expressly indicated to survive the termination or
expiration of this Agreement.

 

8.5.2       Survival.
Articles 5, 6, 10, 11 and 12 and Sections 7.1, 7.2.3, 7.3.1(a), 7.3.1(d),
7.2.4, 7.2.5, 7.3.2, and 7.5 of this Agreement and this Section 8.5 will
survive expiration or termination of this Agreement for any reason.

 

16

ARTICLE
9 -

MATERIAL BREACH OF THIS AGREEMENT

 

Section 9.1            Material
Breach. Failure by a Party to comply with any of its material obligations
contained herein will entitle the Party not in default to give to the
defaulting Party notice specifying the nature of the material breach, requiring
the defaulting Party to make good or otherwise cure such default, and stating
its intention to trigger the provisions of Section 9.2 if such default is not
cured. If such default is not cured within 90 days after the receipt of such
notice (or, if such default cannot be cured within such 90-day period, if the
Party in default does not commence actions to cure such default within such
period and thereafter diligently continue such actions or if such default is
not otherwise cured within 90 days after the receipt of such notice), the Party
not in default will be entitled, without prejudice to any of its other rights
conferred on it by this Agreement, and in addition to any other remedies
available to it under Section 12.6 as remedy for the breach, to continue to
develop or commercialize the Product independently of the defaulting Party in
accordance with Section 9.2 hereof; provided, however, that in the event of a
good faith dispute with respect to the existence of a material breach, the
90-day cure period will be stayed until such time as the dispute is resolved
pursuant to Section 12.6 hereof.

 

Section 9.2            Consequences
of Material Breach. If a Party has not remedied the material breach within
the time period allowed in accordance with Section 9.1, then the Party not in
default may elect, by notice to the defaulting Party, to continue to develop or
commercialize the Product independently of the defaulting Party in accordance
with this section.

 

9.2.1       Material
Breach During Performance of Initial Project Plan. If an
uncured material breach has occurred on or before the completion of the Initial
Project Plan, and such material breach remains uncured under the terms of
Section 9.1, the defaulting Party will be deemed to have elected to discontinue
its participation in the Collaboration in accordance with the terms of Section
2.3.4, in the case of OncoGenex, or Section 2.3.5, in the case of Isis, and the
terms of such section will apply to the Parties.

 

9.2.2       Material
Breach After Performance of Initial Project Plan. If an
uncured material breach has occurred at any point after the Initial Project
Plan has been completed, the defaulting Party will be deemed to have elected to
discontinue its participation in the Collaboration, and the Party not in
default may continue development or commercialization of the Product independently
of the defaulting Party. Upon such discontinuation of performance by the
defaulting Party, the Party not in default shall retain any licenses granted to
it in Section 4.1, including the right to sublicense. The Party not in default
will pay the defaulting Party a royalty as agreed by the parties or as
established by arbitrator in accordance with Section 12.6.3. The defaulting
Party will transfer to the non-defaulting Party all information relating to the
Product as may be necessary to enable the non-defaulting Party to practice the
licenses granted in Section 4.1, including, but not limited to, summaries of
clinical trials, rights to all foreign-equivalent INDs and NDAs filed with
respect to the Product in such country and all drug dossiers and master files
with respect thereto. The defaulting Party will have no future expense
obligations under this Agreement.

 

17

ARTICLE
10 - 

INDEMNIFICATION AND INSURANCE

 

Section 10.1         Indemnification
of Isis. OncoGenex will indemnify Isis, and their respective directors,
officers, employees and agents, and defend and hold each of them harmless, from
and against any and all losses, damages, liabilities, costs and expenses
(including reasonable attorneys’ fees and expenses) but only to the extent
arising from or occuring as a result of any and all liability suits,
investigations, claims or demands by a Third Party (collectively, “Losses”)
arising from or occurring as a result of or in connection with (a) any material
breach by OncoGenex of this Agreement, or (b) the gross negligence or willful
misconduct on the part of OncoGenex or its licensees or sublicensees in
performing any activity contemplated by this Agreement, except for those Losses
for which Isis has an obligation to indemnify OncoGenex pursuant to Section
10.2, as to which Losses each Party will indemnify the other to the extent of
their respective liability for the Losses.

 

Section 10.2         Indemnification
of OncoGenex. Isis will indemnify OncoGenex,  and their respective directors, officers,
employees and agents, and defend and save each of them harmless, from and
against any and all Losses arising from or occurring as a result of or in
connection with (a) any material breach by Isis of this Agreement, or (b) the
gross negligence or willful misconduct on the part of Isis or its licensees or
sublicensees in performing any activity contemplated by this Agreement, except
for those Losses for which OncoGenex has an obligation to indemnify Isis
pursuant to Section 10.1, as to which Losses each Party will indemnify the
other to the extent of their respective liability for the Losses.

 

Section 10.3         Indemnification
Procedure.

 

10.3.1     Notice
of Claim. The indemnified Party will give the indemnifying
Party prompt written notice (an “Indemnification Claim Notice”) of any claim
upon which such indemnified Party intends to base a request for indemnification
under Section 10.1 or Section 10.2, but in no event will the indemnifying Party
be liable for any losses that result from any delay in providing such notice. Each
Indemnification Claim Notice must contain a description of the claim and the
nature and amount of such loss (to the extent that the nature and amount of
such loss are known at such time). The indemnified Party will furnish promptly
to the indemnifying Party copies of all papers and official documents received
in respect of any claim or losses. All indemnification claims in respect of a
Party, its Affiliates or their respective directors, officers, employees and
agents (collectively, the “Indemnitees” and each an “Indemnitee”) will be made
solely by such Party to this Agreement (the “Indemnified Party”).

 

10.3.2     Third
Party Claims. The obligations of an indemnifying Party under
this Article 10 with respect to losses arising from claims of any Third Party
that are subject to indemnification as provided for in Section 10.1 or 10.2 (a
“Third Party Claim”) will be governed by and be contingent upon the following
additional terms and conditions:

 

18

(a)           Control of Defense. At
its option, the indemnifying Party may assume the defense of any Third Party
Claim by giving written notice to the Indemnified Party within 30 days after
the indemnifying Party’s receipt of an Indemnification Claim Notice. The
assumption of the defense of a Third Party Claim by the indemnifying Party will
not be construed as an acknowledgment that the indemnifying Party is liable to
indemnify any Indemnitee in respect of the Third Party Claim, nor will it constitute
a waiver by the indemnifying Party of any defenses it may assert against any
Indemnitee’s claim for indemnification. Upon assuming the defense of a Third
Party Claim, the indemnifying Party may appoint as lead counsel in the defense
of the Third Party Claim any legal counsel selected by the indemnifying Party. In
the event the indemnifying Party assumes the defense of a Third Party Claim,
the Indemnified Party will immediately deliver to the indemnifying Party all
original notices and documents (including court papers) received by any
Indemnitee in connection with the Third Party Claim. Should the indemnifying
Party assume the defense of a Third Party Claim, the indemnifying Party will
not be liable to the Indemnified Party or any other Indemnitee for any legal
expenses subsequently incurred by such Indemnified Party or other Indemnitee in
connection with the analysis, defense or settlement of the Third Party Claim. In
the event that it is ultimately determined that the indemnifying Party is not
obligated to indemnify, defend or hold harmless an Indemnitee from and against
the Third Party Claim, the Indemnified Party will reimburse the indemnifying
Party for any and all costs and expenses (including attorneys’ fees and costs
of suit) and any Losses incurred by the indemnifying Party in its defense of
the Third Party Claim with respect to such Indemnitee.

 

(b)           Right to Participate in Defense.
Without limiting Section 10.3.2(a), any Indemnitee will be entitled to
participate in, but not control, the defense of such Third Party Claim and to
employ counsel of its choice for such purpose; provided, however,
that such employment will be at the Indemnitee’s own expense unless (i) the
employment thereof has been specifically authorized by the indemnifying Party in
writing, or (ii) the indemnifying Party has failed to assume the defense and
employ counsel in accordance with Section 10.3.2(a) (in which case the
Indemnified Party will control the defense).

 

(c)           Settlement. With
respect to any Losses relating solely to the payment of money damages in
connection with a Third Party Claim and that will not result in the
Indemnitee’s becoming subject to injunctive or other relief or otherwise
adversely affect the business of the Indemnitee in any manner, and as to which
the indemnifying Party will have acknowledged in writing the obligation to
indemnify the Indemnitee hereunder, the indemnifying Party will have the sole
right to consent to the entry of any judgment, enter into any settlement or
otherwise dispose of such loss, on such terms as the indemnifying Party, in its
sole discretion, will deem appropriate. With respect to all other losses in
connection with Third Party Claims, where the indemnifying Party has assumed
the defense of the Third Party Claim in accordance with Section 10.3.2(a), the
indemnifying Party will have authority to consent to the entry of any judgment,
enter into any settlement or otherwise dispose of such loss provided it obtains
the prior written consent of the Indemnified Party (which consent will not be
unreasonably withheld or delayed). The indemnifying Party will not be liable
for any 

 

19

settlement or other
disposition of a loss by an Indemnitee that is reached without the written
consent of the indemnifying Party. Regardless of whether the indemnifying Party
chooses to defend or prosecute any Third Party Claim, no Indemnitee will admit
any liability with respect to, or settle, compromise or discharge, any Third
Party Claim without the prior written consent of the indemnifying Party.

 

(d)           Cooperation. Regardless
of whether the indemnifying Party chooses to defend or prosecute any Third
Party Claim, the Indemnified Party will, and will cause each other Indemnitee
to, cooperate in the defense or prosecution thereof and will furnish such
records, information and testimony, provide such witnesses and attend such
conferences, discovery proceedings, hearings, trials and appeals as may be
reasonably requested in connection therewith. Such cooperation will include
access during normal business hours afforded to the indemnifying Party to, and
reasonable retention by the Indemnified Party of, records and information that
are reasonably relevant to such Third Party Claim, and making Indemnitees and
other employees and agents available on a mutually convenient basis to provide
additional information and explanation of any material provided hereunder, and
the indemnifying Party will reimburse the Indemnified Party for all its
reasonable out-of-pocket expenses in connection therewith.

 

(e)           Expenses. Except as
provided above, the reasonable and verifiable costs and expenses, including
fees and disbursements of counsel, incurred by the Indemnified Party in
connection with any claim will be reimbursed on a calendar quarter basis by the
indemnifying Party, without prejudice to the indemnifying Party’s right to
contest the Indemnified Party’s right to indemnification and subject to refund
in the event the indemnifying Party is ultimately held not to be obligated to
indemnify the Indemnified Party.

 

Section 10.4         Insurance.
Each Party will have and maintain such types and amounts of liability
insurance as is normal and customary in the industry generally for parties
similarly situated, and will upon request provide the other Party with a
certificate of insurance. Each party will promptly notify the other Party of
any material change in insurance coverage or lapse in coverage in that regard.

 

ARTICLE
11 - 

REPRESENTATIONS AND WARRANTIES

 

Section 11.1         Representations,
Warranties and Covenants. Each Party hereby represents, warrants and
covenants to the other Party as of the Effective Date as follows:

 

11.1.1     Corporate
Authority. Such Party (a) has the power and authority and the
legal right to enter into this Agreement and perform its obligations hereunder,
and (b) has taken all necessary action on its part required to authorize the
execution and delivery of this Agreement and the performance of its obligations
hereunder. This Agreement has been duly executed and delivered on behalf of
such Party and constitutes a legal, valid and binding obligation of such Party
and is enforceable against it in accordance with its terms subject to the
effects of bankruptcy, insolvency or other laws of 

 

20

general
application affecting the enforcement of creditor rights and judicial
principles affecting the availability of specific performance and general
principles of equity, whether enforceability is considered a proceeding at law
or equity.

 

11.1.2     Litigation.
Such Party is not aware of any pending or threatened
litigation (and has not received any communication) that alleges that such
Party’s activities related to this Agreement have violated, or that by
conducting the activities as contemplated herein such Party would violate, any
of the intellectual property rights of any other party.

 

11.1.3     Consents, Approvals, etc. All
necessary consents, approvals and authorizations of all Regulatory Authorities
and other parties required to be obtained by such Party in connection with the
execution and delivery of this Agreement and the performance of its obligations
hereunder have been obtained.

 

11.1.4     Conflicts.
The execution and delivery of this Agreement and the
performance of such Party’s obligations hereunder (a) do not conflict with or
violate any requirement of Applicable Law or any provision of the articles of
incorporation, bylaws or any similar instrument of such Party, as applicable,
in any material way, and (b) do not conflict with, violate, or breach or
constitute a default or require any consent under, any contractual obligation
or court or administrative order by which such Party is bound.

 

11.1.5     Debarment.
No such Party nor any of its Affiliates has been debarred or
is subject to debarment and neither such Party nor any of its Affiliates will
use in any capacity, in connection with the services to be performed under this
Agreement, any party who has been debarred pursuant to Section 306 of the
Federal Food, Drug, and Cosmetic Act, as amended, or who is the subject of a
conviction described in such section. Each Party will inform the other Party in
writing immediately if it or any party who is performing services hereunder is
debarred or is the subject of a conviction described in Section 306, or if any
action, suit, claim, investigation or legal or administrative proceeding is
pending or, to such Party’s knowledge, is threatened, relating to the debarment
or conviction of such Party or any party performing services hereunder.

 

Section 11.2         Additional
Representations and Warranties of Isis. Isis represents and warrants to
OncoGenex that Isis is a corporation duly organized, validly existing and in
good standing under the laws of the State of Delaware, and has full corporate
power and authority and the legal right to own and operate its property and
assets and to carry on its business as it is now being conducted and as it is
contemplated to be conducted by this Agreement. Isis further represents and
warrants to OncoGenex that any Product Isis provides to OncoGenex for
pre-clinical and clinical use will be in compliance with FDA regulatory
requirements for use in humans.

 

Section 11.3         Additional
Representations and Warranties of OncoGenex. OncoGenex represents and
warrants to Isis that OncoGenex is a corporation duly organized, validly
existing and in good standing under the laws of Canada, and has full corporate
power and authority and the legal right to own and operate its property and 

 

21

assets and to
carry on its business as it is now being conducted and as it is contemplated to
be conducted by this Agreement.

 

Section 11.4         DISCLAIMER
OF WARRANTY. EXCEPT FOR THE EXPRESS WARRANTIES SET
FORTH IN SECTIONS 11.1, 11.2 AND 11.3, ONCOGENEX AND ISIS MAKE NO
REPRESENTATIONS AND GRANT NO WARRANTIES, EXPRESS OR IMPLIED, EITHER IN FACT OR
BY OPERATION OF LAW, BY STATUTE OR OTHERWISE, AND ONCOGENEX AND ISIS EACH
SPECIFICALLY DISCLAIM ANY OTHER WARRANTIES, WHETHER WRITTEN OR ORAL, OR EXPRESS
OR IMPLIED, INCLUDING ANY WARRANTY OF QUALITY, MERCHANTABILITY OR FITNESS FOR A
PARTICULAR USE OR PURPOSE OR ANY WARRANTY AS TO THE VALIDITY OF ANY PATENTS OR
THE NON-INFRINGEMENT OF ANY INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES.

 

ARTICLE
12 - 

MISCELLANEOUS

 

Section 12.1         Force
Majeure. Neither Party will be held liable or responsible to the other
Party or be deemed to have defaulted under or breached this Agreement for
failure or delay in fulfilling or performing any term of this Agreement when
such failure or delay is caused by or results from events beyond the reasonable
control of the non-performing Party, including fires, floods, embargoes,
shortages, epidemics, quarantines, war, acts of war (whether war be declared or
not), insurrections, riots, civil commotion, strikes, lockouts or other labor
disturbances, acts of God or acts, omissions or delays in acting by any
governmental authority. The non-performing Party will notify the other Party of
such force majeure within ten (10) days after such occurrence by giving written
notice to the other Party stating the nature of the event, its anticipated
duration, and any action being taken to avoid or minimize its effect. The
suspension of performance will be of no greater scope and no longer duration
than is necessary and the non-performing Party will use Commercially Reasonable
Efforts to remedy its inability to perform; provided, however,
that in the event the suspension of performance continues for one-hundred and
eighty (180) days after the date of the occurrence, the Parties will meet to
discuss in good faith how to proceed in order to accomplish the goals of the
Collaboration outlined in this Agreement.

 

Section 12.2         Subcontractors.
Each Party will have the right, subject to the prior written consent of the
Operating Committee, such consent not to be unreasonably withheld or delayed,
to subcontract any of its research, development, manufacture and/or
commercialization activities to a Third Party, provided that it furnishes the
other Party with advanced written notice thereof, which notice will specify the
work to be subcontracted, and obtains a written undertaking from the
subcontractor that it will be subject to the applicable terms and conditions of
this Agreement, including the provisions of Article 6. If a Party wishes to
subcontract any of its research, development, manufacturing or
commercialization activities to a Third Party and the Operating  Committee consents, the other Party may
submit a bid to the subcontracting Party to perform such work. The
subcontracting Party will use Commercially Reasonable Efforts 

 

22

to enter into an
agreement with the bidder that is best able to meet the Collaboration’s
requirements, taking into consideration such factors as price, timing, quality,
capacity, quantity, reliability and reputation, provided that such bidder is
reasonably acceptable to the Operating 
Committee. Unless the Parties agree otherwise, the subcontracting Party
will remain solely liable for the performance of its research, development,
manufacture or commercialization activities by its subcontractor; and further,
the subcontracting Party  will remain
solely responsible for all costs and expenses associated with its use of
subcontractor(s).

 

Section 12.3         Assignment.
Without the prior written consent of the other Party hereto, neither Party
will sell, transfer, assign, delegate, pledge or otherwise dispose of, whether
voluntarily, involuntarily, by operation of law or otherwise, this Agreement or
any of its rights or duties hereunder; provided, however, that either Party
hereto may assign or transfer this Agreement or any of its rights or
obligations hereunder without the consent of the other Party to any Third Party
with which it has merged or consolidated, or to which it has transfered all or
substantially all of its assets to which this Agreement relates if in any such
event the Third Party assignee or surviving entity assumes in writing all of
the assigning Party’s obligations under this Agreement. Any purported assignment
or transfer in violation of this Section will be void ab initio and
of no force or effect.

 

Section 12.4         Severability.
If any provision of this Agreement is held to be illegal, invalid or
unenforceable by a court of competent jurisdiction, such adjudication shall not
affect or impair, in whole or in part, the validity, enforceability, or
legality of any remaining portions of this Agreement. All remaining portions
shall remain in full force and effect as if the original Agreement had been
executed without the invalidated, unenforceable or illegal part.

 

Section 12.5         Governing
Law.

 

This Agreement will be
governed by and construed in accordance with the laws of the Province of
British Columbia without reference to any rules of conflicts of laws.

 

Section 12.6         Dispute Resolution.

 

12.6.1     General. The
Parties will negotiate in good faith and use reasonable efforts to settle any
dispute, controversy or claim arising from or related to this Agreement or the
breach thereof in accordance with Section 3.2 hereof. If the Parties do not
fully settle, and a Party wishes to pursue the matter, each such dispute,
controversy or claim will be finally resolved by binding arbitration in
accordance with the Commercial Arbitration Rules of the American Arbitration
Association (“AAA”), and judgment on the arbitration award may be entered in
any court having jurisdiction thereof. The arbitration will be conducted by a
panel of three persons experienced in the pharmaceutical business: within 30
days after initiation of arbitration, each party will select one person to act
as arbitrator and the two party-selected arbitrators will select a third
arbitrator within 30 days of their appointment. If the arbitrators selected by
the parties are unable or fail to agree upon the third arbitrator, the third
arbitrator will be appointed by the AAA. No individual shall be
appointed to arbitrate a dispute pursuant to 

 

23

this Agreement
unless he or she agrees in writing to be bound by the provisions of this
Section 12.6. The place of arbitration will
be Seattle, Washington. Either Party may apply to the arbitrators for interim
injunctive relief until the arbitration award is rendered or the controversy is
otherwise resolved.

 

12.6.2     Disputes Regarding Unilateral Development or Sublicensing Terms.
If the Parties cannot
agree on the terms under which one Party unilaterally, or a Third Party
sublicensee, can develop and commercialize the Product in accordance with
Section 2.4.3, the arbitrators will set a fair value for any disputed terms,
taking into consideration valuation factors including but not limited to: the
Proportionate Share of the Parties; stage of development of the Product
including the clinical trials which have been completed and which would need to
be completed before approval by the Regulatory Authority; the requirement for additional Third Party licenses for the
commercialization of the Product;  market potentialfor
the Product including the size of the target market(s), the availability,
effectiveness and cost of alternative treatments, and the life of the Patents
relating to the Product; likelihood of the Product receiving Regulatory
Approval; 
and, the time and resources required to receive Regulatory
Approval and begin marketing of the Product.

 

12.6.3     Disputes Regarding Material Breach. If the Parties are in dispute as to whether one
party is in material breach of this Agreement, then the arbitrators will first
determine if material breach has in fact occurred, and if so, will as part of
the same arbitration, determine a royalty to be paid by the non-defaulting
Party to the defaulting Party if the non-defaulting Party elects to
unilaterally develop and commercialize the Product, taking into consideration
the factors set forth in Section 12.6.2, and will award damages to the
non-defaulting Party, in the form of off-set royalties or otherwise, to account
for the damages to the non-defaulting Party from the breach, and to account for
the defaulting Party’s contribution to the Product in view of the breach.

 

12.6.4     Costs and Expenses. Except as expressly provided herein, each Party will bear its own costs
and expenses and attorneys’ fees and an equal share of the arbitrators’ and any
administrative fees of arbitration. Notwithstanding the foregoing, if a Party
has been found to be in material breach of this Agreement, the defaulting Party
will be responsible for both Parties’ costs and expenses (including the costs
of the arbitrators and any administrative fees of arbitration) and the reasonable
attorneys’ fees of the non-defaulting Party.

 

12.6.5     Procedure. Except
to the extent necessary to confirm an award or as may be required by law,
neither a Party nor an arbitrator may disclose the existence, content, or
results of an arbitration without the prior written consent of both Parties. In
no event will an arbitration be initiated after the date when commencement of a
legal or equitable proceeding based on the dispute, controversy or claim would
be barred by the applicable Province of British Columbia statute of
limitations.

 

12.6.6     Speedy Resolution. The Parties intend, and shall take all reasonable action as is
necessary or desirable to ensure, that there be a speedy resolution 

 

24

to
any dispute which becomes the subject of arbitration, and the arbitrators shall
conduct the arbitration so as to resolve the dispute as expeditiously as
possible.

 

12.6.7     Awards.
All awards shall be in writing and shall state reasons. Executed
copies of all awards shall be delivered by the arbitrators to the Parties as
soon as is reasonably possible. All awards of the arbitrators shall be final
and binding on the Parties, and there shall be no appeal of any such award
whatsoever. The Parties undertake to satisfy any award without delay.

 

Section 12.7         Notices.
All notices or other communications that are required or permitted
hereunder will be in writing and delivered personally with acknowledgement of
receipt, sent by facsimile (and promptly confirmed by personal delivery,
registered or certified mail or overnight courier as provided herein), sent by
nationally-recognized overnight courier or sent by registered or certified
mail, postage prepaid, return receipt requested, addressed as follows:

 

If to OncoGenex, to:

 

OncoGenex Technologies Inc.

Suite
400, 609 – 14th Street N.W.

Calgary,
Alberta T2N 2A1

Attention:
Scott D. Cormack, President

Facsimile:
403-283-6753

 

with a
copy to:

 

Dr.
Martin Gleave

D-9
2733 Heather Street

Vancouver,
British Columbia V5Z 3J5

Facsimile:
604-875-5604

 

If to Isis, to:

 

Isis Pharmaceuticals, Inc.

2292
Faraday Avenue

Carlsbad,
California 92008

Attention:
Executive Vice President

Facsimile:
( 760) 603-4650

 

with a
copy to:

 

Attention:  General Counsel

Facsimile:
(760) 603-2707

 

25

or to such other address
as the Party to whom notice is to be given may have furnished to the other
Party in writing in accordance herewith. Any such communication will be deemed
to have been given (i) when delivered, if personally delivered or sent by
facsimile on a Business Day, (ii) on the Business Day after dispatch, if sent
by nationally-recognized overnight courier, and (iii) on the third business day
following the date of mailing, if sent by mail. It is understood and agreed
that this Section 12.7 is not intended to govern the day-to-day business
communications necessary between the Parties in performing their duties, in due
course, under the terms of this Agreement.

 

Section 12.8         Entire
Agreement; Modifications. This Agreement sets forth and constitutes the
entire agreement and understanding between the Parties with respect to the
subject matter hereof and all prior agreements, understanding, promises and
representations, whether written or oral, with respect thereto are superseded
hereby. Each Party confirms that it is not relying on any representations or
warranties of the other Party except as specifically set forth herein. No
amendment, modification, release or discharge will be binding upon the Parties
unless in writing and duly executed by authorized representatives of both
Parties.

 

Section 12.9         Relationship
of the Parties. It is expressly agreed that the Parties will be independent
contractors of one another and that the relationship between the Parties will not
constitute a partnership, joint venture or agency. Neither Party nor the
Operating  Committee will have the
authority to make any statements, representations or commitments of any kind,
or to take any action, which will be binding on the other, without the prior
written consent of the other to do so. All persons employed by a Party will be
employees of such Party and not of the other Party and all costs and
obligations incurred by reason of any such employment will be for the account
and expense of such Party.

 

Section 12.10       Waiver.
Any term or condition of this Agreement may be waived at any time by the
Party that is entitled to the benefit thereof, but no such waiver will be
effective unless set forth in a written instrument duly executed by or on behalf
of the Party waiving such term or condition. The waiver by either Party hereto
of any right hereunder or of the failure to perform or of a breach by the other
Party will not be deemed a waiver of any other right hereunder or of any other
breach or failure by said other Party whether of a similar nature or otherwise.

 

Section 12.11       Counterparts.
This Agreement may be executed in two (2) or more counterparts, each of
which will be deemed an original, but all of which together will constitute one
and the same instrument.

 

Section 12.12       No
Benefit to Third Parties. The representations, warranties, covenants and
agreements set forth in this Agreement are for the sole benefit of the Parties
hereto and their successors and permitted assigns, and they will not be
construed as conferring any rights on any other parties.

 

Section 12.13       Further
Assurance. Each Party will duly execute and deliver, or cause to be duly
executed and delivered, such further instruments and do and cause to be 

 

26

done such further
acts and things, including the filing of such assignments, agreements,
documents and instruments, as may be necessary or as the other Party may
reasonably request in connection with this Agreement or to carry out more
effectively the provisions and purposes, or to better assure and confirm unto
such other Party its rights and remedies under this Agreement.

 

Section 12.14       References.
Unless otherwise specified, (a) references in this Agreement to any
Article, Section, Schedule or Exhibit will mean references to such Article,
Section, Schedule or Exhibit of this Agreement, (b) references in any section
to any clause are references to such clause of such section, and (c) references
to any agreement, instrument or other document in this Agreement refer to such
agreement, instrument or other document as originally executed or, if
subsequently varied, replaced or supplemented from time to time, as so varied,
replaced or supplemented and in effect at the relevant time of reference
thereto.

 

Section 12.15       Construction.
Except where the context otherwise requires, wherever used, the singular
will include the plural, the plural the singular, the use of any gender will be
applicable to all genders and the word “or” is used in the inclusive sense
(and/or). The captions of this Agreement are for convenience of reference only
and in no way define, describe, extend or limit the scope or intent of this
Agreement or the intent of any provision contained in this Agreement. The term
“including” as used herein will mean including, without limiting the generality
of any description preceding such term. The language of this Agreement will be
deemed to be the language mutually chosen by the Parties and no rule of strict
construction will be applied against either Party hereto. Appendices to this
Agreement, or added hereto according to the terms of this Agreement, are made
part of this Agreement.

 

The remainder of this page
intentionally left blank.

 

27

IN
WITNESS WHEREOF, the Parties hereto have caused this
Agreement to be executed by their duly authorized representatives as of the
date first above written.

 

	
  ONCOGENEX TECHNOLOGIES INC.

  	
  ISIS PHARMACEUTICALS,
  INC.

  
	
   

  	
   

  
	
   

  	
   

  
	
  Per:

  	
  /s/
  Scott Cormack

  	
   

  	
  Per:

  	
  /s/
  B. Lynne Parshall

  	
   

  
	
   

  	
   

  
	
  Scott
  D. Cormack,

  	
  B.
  Lynne Parshall

  
	
  President
  & CEO

  	
  Executive
  Vice President and

  
	
   

  	
  CFO

  
						

 

28

 

APPENDIX
A

 

Definitions

 

 “Affiliate” of a party means
any other party that, directly or indirectly, through one or more
intermediaries, controls, is controlled by, or is under common control with
such first party. For purposes of this definition only, “control” and, with
correlative meanings, the terms “controlled by” and “under common control with”
will mean (a) the possession, directly or indirectly, of the power to direct
the management or policies of a party, whether through the ownership of voting
securities or by contract relating to voting rights or corporate governance,
and (b) the ownership, directly or indirectly, of more than fifty percent (50%)
of the voting securities or other ownership interest of a party; provided that,
if local law restricts foreign ownership, control will be established by direct
or indirect ownership of the maximum ownership percentage that may, under such
local law, be owned by foreign interests.

 

“Applicable Law”
means the applicable laws, rules, and regulations, including any rules,
regulations, guidelines, or other requirements of the Regulatory Authorities,
that may be in effect from time to time.

 

“Business Day” means any day,
other than Saturday, Sunday or any statutory holiday in the Province of British
Columbia or the United States.

 

“Calendar Year” means each
successive period of 12 months commencing on January 1 and ending on December
31.

 

“Clusterin” means the gene
target which is also referred to as Testosterone Repressed Prostatic Message -2
(TRPM-2), and Sulphated Glycoprotein-2 (SGP-2).

 

“Collaboration Activities”
means the responsibilities of the Parties under this Agreement to research,
develop, manufacture, and commercialize the Product.

 

“Commercially Reasonable Efforts”
means, with respect to the research, development, manufacture or
commercialization of the Product, efforts and resources commonly used in the
biotechnology industry for products of similar commercial potential at a
similar stage in its lifecycle, taking into consideration their safety and
efficacy, cost to develop, priority in relation to other products under
development by the other Party, the competitiveness of alternative products,
proprietary position, the likelihood of regulatory approval, profitability, and
all other relevant factors.

 

“Confidential
Information” means all information and know-how and any
tangible embodiments thereof provided by or on behalf of one Party to the other
Party either in connection with the discussions and negotiations pertaining to
this Agreement or in the course of performing this Agreement, including data;
knowledge; practices; processes; ideas; research plans; engineering designs and
drawings; research data; manufacturing processes and techniques; scientific,
manufacturing, marketing and 

 

business plans;
and financial and personnel matters relating to the disclosing Party or to its
present or future products, sales, suppliers, customers, employees, investors
or business. For purposes of this Agreement, notwithstanding the Party that
disclosed such information or know-how, all information or know-how of
OncoGenex shall be Confidential Information of OncoGenex, and all information
and know-how of Isis shall be Confidential Information of Isis.

 

Notwithstanding
the foregoing, information or know-how of a Party shall not be deemed
Confidential Information for purposes of this Agreement if such information or
know-how:

 

(a)           was already known
to the receiving Party, other than under an obligation of confidentiality or
non-use, at the time of disclosure to such receiving Party;

 

(b)           was generally
available or known to parties reasonably skilled in the field to which such
information or know-how pertains, or was otherwise part of the public domain,
at the time of its disclosure to, or, with respect to know-how, discovery or
development by, such receiving Party;

 

(c)           became generally
available or known to parties reasonably skilled in the field to which such
information or know-how pertains, or otherwise became part of the public
domain, after its disclosure to such receiving Party through no fault of the
recieving Party;

 

(d)           was disclosed to
such receiving Party, other than under an obligation of confidentiality or
non-use, by a Third Party who had no obligation to the Party that Controls such
information and know-how not to disclose such information or know-how to
others; or

 

(e)           was independently
discovered or developed prior to disclosure by such receiving Party, as
evidenced by their written records, without the use of Confidential Information
belonging to the Party that Controls such information and know-how.

 

Specific aspects or
details of Confidential Information shall not be deemed to be within the public
domain or in the possession of a Party merely because the Confidential
Information is embraced by more general information in the public domain or in
the possession of such Party. Further, any combination of Confidential
Information shall not be considered to be in the public domain or in the
possession of a Party merely because individual elements of such Confidential
Information are in the public domain or in the possession of such Party unless the
combination and its principles are in the public domain or in the possession of
such Party.

 

“Control”
means, with respect to any Patent or other intellectual property right,
possession of the right (whether by ownership, license or otherwise), to assign,
or grant a license, sublicense or other right to or under, such Patent or right
as provided for herein without violating the terms of any agreement or other
arrangement with any Third Party.

 

A-2

“FDA” means the
United States Food and Drug Administration and any successor agency thereto.

 

“FTE” means the
equivalent of the work of one employee full time for one year (consisting of at
least a total of [***] per year (excluding vacations and holidays) of work on
or directly related to the Collaboration), carried out by an Isis employee or
Third Party mutually agreed upon by the Parties. For the purposes of Appendix
2.3.1, the FTE rate will be (i) [***] per FTE for any of the following
activities: drug substance manufacturing; analytical chemistry; process
chemistry; formulation; raw material ordering and handling; quality control; or
manufacturing technology transfer; and (ii) [***] per FTE for any of the
following activities:  toxicology;
pharmacokinetics/metabolism; regulatory; clinical development; or data
management. These FTE rates will be adjusted upward on a Calendar Year basis
commencing January 1, 2002 (and on January 1 of each year thereafter during the
Term of this Agreement) by a factor which reflects changes in the Consumer
Price Index for San Diego, California as reported on that date in each
applicable year during the Term of the Agreement when compared to the
comparable statistic for that date in the preceding year.

 

“GAAP” means
generally accepted accounting principles of the United States consistently
applied.

 

“Improvement”
means any enhancement or improvement
(whether or not patentable) to the Isis Core Technology Patents, Isis
Manufacturing Patents, or the OncoGenex Product Patents, that is made by either party during the Term of
this Agreement.

 

“IND” means an
investigational new drug application filed with the FDA or TPD for
authorization to commence human clinical trials, and its equivalent in other
countries or regulatory jurisdictions.

 

“Initial Project Plan”
means the first Project Plan of the Collaboration, as set forth in Section 2.3.

 

“Isis
Core Technology Patents” means Patents Controlled by Isis on
the Effective Date that are necessary for the development and commercialization
of the Product, but not including the Isis Manufacturing Patents.

 

                “Isis Manufacturing Patents”
means Patents Controlled by Isis on the Effective Date that claim the practice
of the Isis Standard Chemistry Manufacturing Process.

 

“Isis
Patent Rights” means any Patents owned or Controlled by Isis.

 

“Isis
Standard Chemistry” means “2 ́MOE Gapmers” or an antisense
phosphorothioate oligonucleotide of 15-30 nucleotides wherein all of the
backbone linkages are modified by adding a sulfur at the non-bridging oxygen (phosphorothioate)
and a stretch of at least 10 consecutive nucleotides remain unmodified (deoxy
sugars) and

 

A-3

 the remaining nucleotides contain an O ́-methyl
O ́-ethyl substitution at the 2 ́ position (MOE).

 

“Isis
Standard Chemistry Manufacturing Process” means the
manufacturing process used by Isis as of the Effective Date to manufacture
products comprising Isis Standard Chemistry, represented by the batch record
for [***]  Manufacturing for this purpose
includes synthesis, purification and analysis.

 

“Joint
Patents” means all Patents that claim or disclose Joint
Technology.

 

“Joint Technology”
means any and all (a) inventions conceived, discovered, developed or
otherwise made (as determined in accordance with the rules of inventorship
under United States patent laws to establish authorship, inventorship or
ownership), jointly by employees or agents of Isis and employees or agents of
OncoGenex  or, to the extent permitted,
by one Party and a sublicensee of the other Party or both Parties (as the case
may be), in connection with the work conducted under this Agreement, whether or
not patented or patentable.

 

 “Licensing Revenue” means
all revenues, receipts, monies, and the fair market value of all other consideration
directly or indirectly collected or received whether by way of cash, or credit
or any barter, benefit, advantage, or concession received by a Party pursuant
to each sublicense agreement relating to the Product including, without
limitation, license fees, royalties, milestone payments and the fair market
value of equities received, as determined on the date of receipt thereof.

 

“Net Sales”
means the gross invoice price of the Product sold by either Party and
sublicensees to a Third Party which is not a sublicensee of the selling party
(unless such sublicensee is the end user of the Product, in which case the
amount billed therefor shall be deemed to be the amount that would be billed to
a Third Party in an arm’s-length transaction) for sales of such Product to such
end users less the following items, as allocable to such Product (if not
previously deducted from the amount invoiced): (i) trade discounts,
credits or allowances, (ii) credits or allowances additionally granted
upon returns, rejections or recalls (except where any such recall arises out of
the Party or its sublicensee’s gross negligence, willful misconduct or fraud),
(iii) freight, shipping and insurance charges, (iv) taxes, duties or
other governmental tariffs (other than income taxes) and (v) government
mandated rebates.

 

“Net Licensing Revenue” means
the amount equal to any Licensing Revenue less Third Party Payments.

 

“OncoGenex Patent Rights”
means any Patents owned or Controlled by OncoGenex.

 

“OncoGenex Product Patents” means
Patents Controlled by OncoGenex on the Effective Date that claim an antisense
inhibitor of Clusterin or a method of using an antisense inhibitor of
Clusterin.

 

A-4

“OGX-011” means an antisense inhibitor of Clusterin
having the sequence [***] with
phosphorothioate linkages throughout and in which bases [***] and [***] contain
2’-O-methoxyethyl sugar modifications, also referred to as ISIS 112989.

 

“Patents” shall
include (x) all U.S. patents and patent applications, (y) any substitutions,
divisions, continuations, continuations-in-part, reissues, renewals,
registrations, confirmations, re-examinations, extensions, supplementary
protection certificates and the like, and any provisional applications, of any
such patents or patent applications, and (z) any foreign or international
equivalent of any of the foregoing.

 

“Product” means
an intravenous or subcutaneous pharmaceutical preparation, excluding
encapsulation technology controlled by Isis, containing as the sole active pharmaceutical
ingredientOGX-011. For clarity, the product may be used in
association with other products such as chemotherapy, hormone ablation therapy
and radiation therapy and the immediately
preceding sentence does not limit such intended use.

 

“Product-Specific Technology”
means any discovery, device, process, formulation, or Improvement, whether or
not patented or patentable, which is made solely by Isis or OncoGenex, or
jointly by Isis and OncoGenex, during the Term of this Agreement, and the
application of which has utility only with respect to the Product.

 

“Product-Specific Technology
Patents” means all Patents that disclose or claim
Product-Specific Technology.

 

“Project Plan”
means any development plan for Collaboration Activities subsequent to the
Initial Project Plan, including the costs associated with such development plan
and the proposed distribution of such costs between the Parties.

 

 “Proportionate Share” means
the relative ownership of the Product and relative sharing of expenses and revenue
with respect to the Product between the Parties in relation to each other.

 

“Regulatory Approval”
means any and all approvals (including pricing and reimbursement approvals),
licenses, registrations or authorizations of any Regulatory Authority, necessary
for the development and commercialization of the Product in a country,
including any (a) approval for the Product (including any INDs, and supplements
and amendments thereto); (b) pre- and post-approval marketing authorizations
(including any prerequisite manufacturing approval or authorization related
thereto); (c) labeling approval; and (d) technical, medical and scientific
licenses.

 

“Regulatory Authority”
means any applicable government entities regulating or otherwise exercising
authority with respect to the development and commercialization of the Product.

 

“Regulatory Documentation”
means all applications, registrations, licenses, authorizations and approvals
(including all Regulatory Approvals), all correspondence submitted to or
received from Regulatory Authorities (including minutes and official contact
reports relating to any communications with any Regulatory Authority), all 

 

A-5

supporting documents and all clinical studies and
tests, including the manufacturing batch records, relating to the Product, and
all data contained in any of the foregoing, including all regulatory drug
lists, advertising and promotion documents, adverse event files and complaint
files.

 

“Revenue” means
all revenues, receipts, monies, and the fair market value of all other
consideration directly or indirectly collected or received whether by way of
cash or credit or any barter, benefit, advantage, or concession received by any
Party relating to the sale or any other exploitation of the Product.

 

“Technology”means
Isis Patent Rights, the OncoGenex Patent Rights, the Product-Specific
Technology Patents, Joint Patents and/or the Joint Technology, as applicable.

 

“Third Party”
means any party other than Isis or OncoGenex.

 

“Third Party Payments”
means royalties, milestones, and other payments owing to Third Parties,
including payments as set forth in Section 5.2.1.

 

“TPD” means the
Therapeutics Products Directorate, Health Products and Food Branch, Health
Canada, and any successor agency thereto.

 

A-6

APPENDIX
2.3.1

INITIAL
PROJECT PLAN

 

Isis Initial Project Plan
Responsibilities.

 

1)              In consideration for the payment by OncoGenex to
Isis as set forth in Section 5.1, Isis shall provide the Product in
amounts adequate to support the IND-directed toxicology and PK studies. Isis
will provide, at its own cost and expenses, additional Product in amounts
adequate to support Trial 1 and Trial 2 as set forth below. The Product will be
provided to OncoGenex in vial-form, and in compliance with FDA regulatory
requirements for use in humans, including compliance with requirements for
sterility, pyrogenicity and stability.

 

2)              Isis shall perform or provide at its own cost and
expense, the following:

 

(a)          development
of analytical methods required for the conduct and completion of IND-directed
animal toxicology and pharmacokinetic studies.

 

(b)         conduct and complete the IND-directed animal
toxicology and pharmacokinetic (“PK”) studies, and provide OncoGenex with the
reports and data from these studies for inclusion in an IND in Canada, to be
filed by OncoGenex. The studies to be
conducted are as follows:

 

1.               [***]
toxicity study in [***] with a [***] recovery period including pharmacokinetic
analysis of tissue and plasma exposure; and,

 

2.               [***]
toxicity study in [***] with a [***] recovery period including pharmacokinetic
analysis of tissue and plasma exposure; and,

 

3.               [***]
study with radiolabelled OGX-011 in [***]; and,

 

4.               [***]
assay; and,

 

5.               [***]
assay for [***].

 

(c)          provide the analytical
methods for use in Trial 1 and Trial 2, or cooperate with OncoGenex in the
development of such methods.

 

(d)         prepare the CMC section
of the IND and provide, as is necessary for regulatory approval, data and
information related to the use of Isis Standard Chemistry and Isis Standard
Chemistry Manufacturing Process.

 

(e)          participate in Pre-IND
meetings, review and provide comment on regulatory submissions prepared by
OncoGenex, including the IND submission, and participate in the development of
clinical trial design.

(f)            Upon determination by
the Operating Committee and the agreement of the Parties, Isis will provide
services to assist OncoGenex in its responsibilities as set forth below.

 

OncoGenex Initial Project Plan
Responsibilities.

 

OncoGenex shall provide
or perform, at its cost and expense, the following:

 

(a)          prepare and file the IND
in Canada, with support from Isis as described in Isis’s Initial Project Plan
Responsibilities.

 

(b)         conduct Trial 1 and Trial
2 as set forth below.

 

(c)          conduct all [***]
pharmacology studies to establish efficacy of the Product in [***] models as
may be required to satisfy regulatory authorities and the initiation of  Trial 1 and Trial 2.

 

Funding for Initial Project Plan.

 

(a)          OncoGenex is responsible
for all costs associated with completing OncoGenex’s responsibilities as set
forth above.

 

(b)         Isis is responsible for
all costs associated with completing Isis’s responsibilities as set forth
above.

 

Should Isis provide services
to assist OncoGenex in performance of OncoGenex’s responsibilities, and such
services are beyond the scope agreed to by the Parties under Isis’
responsibilities above, OncoGenex will reimburse Isis in full at the applicable
FTE defined in Appendix A. Isis will invoice OncoGenex within 30 days after the
end of each calendar quarter for such service. OncoGenex will pay invoices
within 30 days of receipt.

 

Filing of the IND.

 

The Parties will use
Commercially Reasonable Efforts to file the IND on or before June 1, 2002.

 

G-2

TRIAL 1
AND TRIAL 2

 

Trial#1 (OGX-011-01) - Phase
I/IIa pharmacokinetic and pharmacodynamic study in men with localized prostate
cancer combining weekly MOE clusterin ASO’s (OGX-011) with 4 weeks of
neoadjuvant hormone therapy (nilutamide plus suprefact) prior to radical
prostatectomy

 

Primary Objective:

 

To assess the safety and
tolerability of once weekly OGX-011

 

Secondary Objectives:

 

•                  To
assess the pharmacokinetics of once weekly OGX-011 by determining levels of
OGX-011 in both serum (HPLC) and tissue (CGE) OGX-011

•                  To
assess the pharmacodynamics of once weekly OGX-011 by measuring effects of
OGX-011 on clusterin levels (using western analysis) in prostate tissues,
compared to tissue bank of untreated and 
NHT-treated  controls.

 

Patient Eligibility:

 

•                  Histologically
confirmed adenocarcinoma of the prostate

•                  Potential
candidate for radical prostatectomy

 

Sample size and Treatment
Schedule:

 

•                  Approximately
25 patients, 7 doses each

•                  3
patients per dose schedule 50mg, 100 mg, and 6 pts at 200 mg and 400mg of
OGX-011 (surgery within 5 days of last dose)

•                  Interm
analysis will determine whether higher doses are necessary (ie up to 600 or 800
mg). Once optimal dose determined, then 3 additional pts will be treated with 5
doses and surgery 2 weeks after last dose (this will provide tissue
pharmacokinetic and pharmacodynamic data that will guide future scheduling)

 

Drug requirement:

 

•                  Approximately
50-75 grams OGX-011 dosed

•                  Approximately
[***]of suprefact and nilutamide to be provided [***].

 

Timeline and Trial Sites:

 

•                  Estimated
to start mid-2002

•                  Goal:
complete accrual  in 9 months

•                  Location
– Vancouver (consideration being given to running as an [***] trial at 2 sites
– Vancouver and [***] – [***]with [***][med onc and [***] of [***] site] and
[***] [urology].

 

G-3

Trial#2 (OGX-011-02)  - A Phase I/II Study of Custerin ASOs
(OGX-011) with Docetaxel in Patients with Hormone Refractory Prostate Cancer

 

Primary Objective:

 

To determine the toxicity
and maximum tolerated dose of OGX-011 administered once weekly intravenously in
combination with weekly docetaxel.

 

Secondary Objectives:

 

•                  To
determine the pharmacologic alterations of OGX-011 and weekly docetaxel when
administered in combination

•                  To
preliminarily determine whether OGX-011 and docetaxel in combination induce
objective and/or PSA responses in HRPC

•                  To
measure evidence of OGX-011 effect on patient clusterin serum levels and
clusterin expression in accessible tumors.

 

Patient Eligibility:

 

•                  Histological
or cytological evidence of advanced prostate cancer with rising PSA and
castrate levels of testosterone

•                  Radiologic
or clinical evidence of metastatic or locally recurrent disease.

 

Sample size and Treatment
Schedule:

 

•                  Clusterin
ASO (OGX-011) administered intravenously on days 1, 3, and 5, then weekly for a
total of 3 weeks out of 4, 5 weeks out of 6, or 6 weeks out of 8. The precise
treatment schedule will be determined by mutual agreement of the parties.

•                  Docetaxel
administered IV bolus weekly for 3 weeks out of 4, 5 weeks out of 6, or 6 weeks
out of 8, schedule to be determined by mutual agreement of the parties.

•                  3
patients per dose level in Phase 1 portion. Dose levels to be determined by
mutual agreement of the parties

•                  6
more patients on max tolerated dose (probably [***]), additional 24 pts for
phase II component

 

Drug Requirement:

 

•                  Estimated
200-250 grams of OGX-011 drug product dosed.

•                  [***]
provided by [***].

 

Timeline and Trial Sites:

 

•                  Targeted
to start concurrently with study OGX-011-01, pending regulatory approval.

•                  Goal
to complete patient accrual  in 1 yr,

•                  2-3
sites (Vancouver and [***], maybe [***] in [***])

 

G-4

PROJECT
PLAN-2

 

PROJECT
PLAN-2 is made pursuant to Section 2.4.2 of the Collaboration
and Co-Development Agreement dated November 16, 2001 (the “Agreement”), by and
between ONCOGENEX TECHNOLOGIES INC., having offices at Room 550, 2660 Oak
Street, Vancouver, B.C., V6H 3Z6, and ISIS PHARMACEUTICALS, INC., having
principal offices at 2292 Faraday Avenue, Carlsbad, CA, 92008. Capitalized
terms used in Project Plan-2 and not otherwise defined herein have the meanings
set forth in the Agreement.

 

WHEREAS,
the Agreement provides that the Parties can mutually agree in writing to append
to the Agreement an additional Project Plan, herein referred to as Project
Plan-2, for the continued development of the Product; and

 

WHEREAS,
the Parties wish to append Project Plan-2 to the Agreement, effective the 18th
day of December, 2003;

 

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

 

ARTICLE
1 – SCOPE OF PROJECT PLAN-2

 

Section 1.1            Scope of Project Plan-2  Project
Plan-2 covers 3 phase II clinical trials of OGX-011, referred to by the Parties as CS4, CS5 and CS6 and as
more particularly described below. Far clarity, the clinical trials
contained in Project Plan-2 are, in addition to those clinical
studies (referred to by the Parties as CS1, CS2 and CS3) described in the
Initial Project Plan.

 

Section 1.2            Project Plan Budgets 
For so long as any of CS4, CS5 Or CS6 are being conducted by
the Parties, the Operating Committee will develop and the Parties will agree to
a project plan budget (the “Project Plan Budget”) for each new Calendar Year by
December 1 of the preceding year, which will include all anticipated clinical,
non-clinical and Product manufacturing costs related to CS4, CS-5 and CS6, as
applicable. The Project Plan Budget for 2004 has been agreed to by the Parties
and is appended hereto as Schedule 1. Each new Project Plan Budget for
subsequent years will also be appended to Schedule 1 upon approval of same by
each of the Parties, at which time it will be deemed to be the Project Plan Budget for the purposes
hereof.

 

Section 1.3            Additional Clinical Studies  The Parties agree to
conduct the following clinical studies of OGX-011 in accordance with the terms
of Project Plan-2, the attached Schedules and the Agreement.

 

1.3.1       A
Phase II Pre-Surgery Study in Patients with Localized Prostate Cancer. The
Parties are aware that certain clinicians have received grant funding to pay
for a phase 11 pre-surgery study in patients with prostate cancer (“CS4”), The
Parties will only be required to provide Product to the trial and to share
certain nominal expenditures detailed in the 

 

1

Project Plan Budget. The Parties intend that CS4 will
be conducted in accordance with the protocol summary attached hereto Schedule 2
and the Project Plan Budget.

 

1.3.2       A
Phase I/II Study in Patients
with Stage IIIB/IV Non-Small Cell Lung Cancer. The Parties
intend that a phase I/II study for non-small cell lung cancer (“CS5”) will be
conducted in accordance with the protocol summary attached hereto as Schedule 3
and the Project Plan Budget.

 

1.3.3       A
Phase II Study in Patients with Locally Advanced or Metastatic Breast Cancer. The
Parties intend that a phase II study for patients with locally advanced or
metastatic breast cancer (“CS6”) will be conducted in accordance with the
protocol summary attached hereto as Schedule 4 and the Project Plan Budget.

 

ARTICLE
2 – COLLABORATION ACTIVITIES

 

Section 2.1            Collaboration Activities for
Additional Clinical Studies. For each of CS4, CS5 and CS6, the Parties will be responsible for
performing the Collaboration Activities contained in this Article 2 in
accordance with the terms of the Agreement.

 

2.1.1       Isis
shall be responsible for performing, or having performed, the following
Collaboration Activities:

 

(a)                                  as
necessary, provide OncoGenex with the reports and data from the IND-directed
animal toxicology and pharmacokinetic studies conducted by Isis under the
Initial Project Plan for inclusion in each IND to be filed by OncoGenex;

 

(b)                                 provide
technology transfer necessary for OncoGenex to assume responsibility for
fill/finish manufacturing:

 

(c)                                  prepare the CMC section of the IND(s)
and related Regulatory Documentation, and provide as necessary For Regulator
Approval, data and information related to the use of Isis Standard Chemistry
and Isis Standard Chemistry Manufacturing Process for all Product manufactured
in whole or in part by Isis;

 

(d)                                 review
and provide comment on items listed in 2.1.2,(a)l, 2.1.2(a)2, and 2.1.2(b);

 

(e)                                  as
necessary, participate in meetings with Regulatory Authorities, review and
provide comment on regulatory submissions prepared by OncoGenex, including the
IND submission(s), and participate in the development of clinical trial design;
and

 

(f)                                    assist
with the review and interpretation of clinical data generated.

 

2.1.2       OncoGenex
shall be responsible for performing, or having performed, the following
Collaboration Activities:

 

2

(a)                                  prepare
the (1) clinical trial protocols, (2) investigators brochure and (3) related
clinical study documents as necessary for initiating and managing the clinical
studies;

 

(b)                                 prepare
and file the IND(s) in the jurisdiction(s) listed in the attached Schedules or
as otherwise determined by the Operating Committee, with support by Isis as
described in Section 2.1.1;

 

(c)                                  conduct
the clinical studies in accordance with the IND and Project Plan Budget, as
amended if so required by the regulatory authorities in the applicable
jurisdictions;

 

(d)                                 hire
and manage any contract research organizations necessary to perform the
clinical studies in accordance with the Schedules hereto and the IND(s); and,

 

(e)                                  analyze
clinical trial data.

 

ARTICLE
3 – CLINICAL TRIALS SUPPLIES

 

Section 3.1            Manufacturing Product for Additional Clinical
Studies. The Parties will supply the Product necessary to
conduct CS4, CS5 and CS6 in accordance with the protocol summaries attached
hereto and the INDs to be filed in respect thereof. The Parties acknowledge
that a portion of the Product required for these trials has already been
manufactured by Isis and Third Party contractors, and each Party has committed
to pay their Proportionate Share thereof as evidenced by OncoGenex’ purchase
order number 001 issued to Isis on December 3, 2003. The Parties further
acknowledge that additional Product will be required to complete the clinical
studies under Project Plan-2, and in accordance with Section 2.4.5 of the
Agreement, the Operating Committee will determine the appropriate suppliers,
amount and timing of delivery of such Product, and each Party will be
responsible for its Proportionate Share of the costs of manufacturing such
Product. The Parties acknowledge and agree that, following the planned delivery
of Product scheduled for January 2005, Isis will cease being responsible for
managing the fill/finish portion of the manufacturing process. During 2004 and
2005, the Parties will work together to such responsibility to OncoGenex in an
efficient manner, and the Parties agree that no costs for any technology
transfer or transfer of associated know-how will be charged to OncoGenex, by
Isis in return for OncoGenex agreeing to assume such responsibility. The
Parties will use Commercially Reasonable Efforts to ensure that sufficient
Product is available when required so as not to cause a delay in patient
accrual or treatment for CS4, CS5 and CS6.

 

ARTICLE
4 – COST SHARING AND REIMBURSEMENT

 

Section 4.1            Internal (FTE) Costs. Except as provided in the Project Plan Budget, each Party will be
responsible for its own costs and expenses of performing its own costs and
expenses of performing its respective Collaboration Activities.

 

Section 4.2            Out of Scope Work - Should either Party desire that the
other Party perform work that is beyond the scope of Section 2.1 or the Agreement,
then the Parties may 

 

3

agree to enter a consulting agreement, the form of
which will be negotiated, under which one Party will perform specified work for
the other Party on terms defined therein.

 

Section 4.3            Maintaining Costs within Budget  The Parties will use
Commercially Reasonable Efforts to maintain total Third Party expenses for CS4,
CS5 and CS6 within the Project Plan Budget. Pursuant to Section 3.1.2 of the
Agreement, the Operating Committee will regularly review progress against
Project Plan-2 and the Project Plan Budget, and recommend or make any changes
it deems necessary. If the Operating Committee reasonably expects such changes
to increase the overall Project Plan Budget by more than 10%, then the
Operating Committee must submit for approval by the Parties a revised Project
Plan Budget, which once approved will be appended to this Project Plan-2 as
Schedule 1. Similarly, any such change which would modify the Collaboration
Activities of either Party as described in Article 2 hereof, must be agreed to
in writing by the Parties prior to committing to such modification.

 

Section 4.4            Reimbursement of External Costs. The Parties will be responsible for
paying their Proportionate Share of all external expenses necessary to conduct
CS4, CS5 and CS6 as detailed in each
Project Plan Budget. The
Parties acknowledge and agree that, to the extent permitted by law, the Parties
will share in any discounts, credits, rebates or allowances attributable to Project Plan-2 (including those
arising from any provincial research institute programs, but specifically
excluding any tax credits and refunds received under any scientific research
and experimental development (SR&ED) tax credit program or any other tax
filing of either Party), by their Proportionate Share, even it such discounts,
credits, rebates or allowances arise after the Parties have paid their respective invoices
described below. At the end of each calendar quarter in which Third Party costs
related to Project Plan are
incurred, each Party will provide to the other a detailed of the other Party’s
Proportionate Share of the expenses
incurred pursuant to Project Plan-2. A net payment will be made by the Party owing the larger amount. Payment
will be made within 30 days of receipt of invoices by both parties. All other
matters related to payments will be
made in accordance with Article 5 of the Agreement.

 

ARTICLE
5 – GENERAL

 

Section 5.1            Agreement is in full force and affect Except as provided in Project Plan-2, the
Agreement remains in all other respects unamended and in full force and effect
between the Parties. In the event of a conflict between this Protect Plan 2 and
the Agreement, this Project Plan 2 will govern.

 

Section 5.2            References  Unless otherwise
specified, references in Project Plan-2 to any Article, Section or Schedule
will mean references to such Article, Section or Schedule of Project Plan-2.

 

Section 5.3            Construction  Pursuant to Section 12.15 of the
Agreement, Project Plan-2 is hereby added as an Appendix to and made part of
the Agreement.

 

4

IN WITNESS WHEREOF the Parties hereto have caused
Project Plan-2 to be executed by their duly authorized representatives as of
the date first above written.

 

 

	
  ONCOGENEX TECHNOLOGIES INC. 

  	
  ISIS PHARMACEUTICALS, INC.

  
	
   

  	
   

  
	
   

  	
   

  
	
  Per:

  	
  /s/ Scott Cormack

  	
   

  	
  Per: 

  	
  /s/ B. Lynne Parshall

  	
   

  
	
   

  	
   

  
	
  Scott D. Cormack 

  	
  B. Lynne Parshall

  
	
  President & CEO

  	
  Executive Vice President & CFO

  
						

 

5

Schedule
1

Project
Plan Budget

FX
Assumption    $1.00 US =                             $1.30 Cdn

External Pre-Clinical and Clinical Costs, Excluding
Manufacturing

 

	
   

  	
   

  	
   

  	
   

  	
  CS4

  	
   

  	
  CS5

  	
   

  	
  CS6

  	
   

  
	
  (US$ estimates)

  	
   

  	
  TOTAL

  	
   

  	
  PC-Pre Surg.

  	
   

  	
  NSCLC

  	
   

  	
  Breast Cancer

  	
   

  
	
  PRE-CLINICAL COSTS

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  in-vitro/in-vivo costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Other

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Total Pre-Clinical Costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  CLINICAL COSTS

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Number of Patients

  	
   

  	
   

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  Number of Sites

  	
   

  	
   

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  Regulatory submissions

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Ethics Review Boards

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  CRO Costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Monitoring Travel Costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Patient Care Costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Routine Clinical Labs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Clinical PK Assays:OGX-011

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
   

  	
   

  
	
  Clinical PK Assays:Chemos

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
   

  	
   

  
	
  Consulting (outside experts)

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Drug Shipping to Sites

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Less: Grant Reimbursement

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
   

  	
   

  	
  $

  	
   

  	
   

  
	
  Total Clinical Costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  CLINICAL COST ALLOCATION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Upfront Clinical Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Regulatory Submissions

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Ethics Review Boards

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  CRO upfront work fees

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Consulting

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Sub-Total: Upfront Clinical Costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Per Patient Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Patients accrued in 2004

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  Percent of All Pts to be Accrued

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  Total Variable Clinical Costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Per Patient Costs in 2004

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  Costs allocated to 2004

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  OTHER 2004 COSTS

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Labeling/Packaging/Storage

  	
   

  	
  $

  	
  [***]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Travel (Steering Committees)

  	
   

  	
  $

  	
  [***]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total Other Costs

  	
   

  	
  $

  	
  [***]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  TOTAL COSTS 2004

  	
   

  	
  $

  	
  [***]

  	
   

  	
  excluding Manufacturing

  	
   

  	
   

  	
   

  
	
  ONCOGENEX COST (65%)

  	
   

  	
  $

  	
  [***]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  ISIS COST (35%)

  	
   

  	
  $

  	
  [***]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  

 

Notes:

Budget
does not include manufacturing of second batch, finished in 2003 and delivered,
under PO001, in Jan 2004.

Budget
does not include manufacturing of batch 3, scheduled for production in 2004 for
delivery in Q1/05.

[***]
grant has been secured by the investigators on CS4, therefore nearly all costs
of this study are covered.

CRO
costs include costs for pre-study site preparation, site initiation,
management, monitoring and close out, SAE reporting to OncoGenex, data entry
and clean up, database management, limited biostatistics, and final report
writing.

Patient
care costs for CS4 are estimated at [***] per patient, but are covered by the
[***].

Patient
care costs for CS5 are estimated at [***] for PI and [***] in PII.

Patient
care costs for CS6 are estimated at [***] per patient.

Routine
clinical labs are estimated at [***] per patient, and cover additional patient
care costs.

“Total
Variable Clinical Costs” = Total Clinical Costs – Upfront Clinical Costs.

“Per
Patient Costs in 2004” are the Total Variable Clinical Costs * Percent of All
Pts to be Accrued

 

6

Schedule 2

CS4 Protocol
Summary

 

CS
4:  Phase II Clinical Study of OGX-011
Combined with Hormone Ablation Therapy (Pre-Surgery) in Localized Prostate
Cancer Patients

 

This
is the phase II continuation of CS1, and is intended to provide additional
pharmacokinetic and pharmacodynamic reformation related to the ability of
OGX-011 to be taken up in therapeutic concentrations by cancerous tissue, and
to down-regulate the target (Clusterin) in cancerous tissue. Patients will be
treated for longer periods of time (13 weeks rather than 4 weeks in CS1) at a
fixed dose level (established from CS1); the study may also attempt to establish tissue half-life by
extending the duration between treatment and surgery date (to be determined).

 

	
  Funding Status:

  	
   

  	
  Fully Funded: [***]

  
	
   

  	
   

  	
   

  
	
  Study Sponsor:

  	
   

  	
  OncoGenex

  
	
   

  	
   

  	
   

  
	
  Study Site:

  	
   

  	
  British Columbia Cancer
  Agency/Prostate Centre at VGH

  
	
   

  	
   

  	
   

  
	
  Principal Investigator:

  	
   

  	
  Kim Chi, MD, British
  Columbia Cancer Agency

  
	
   

  	
   

  	
   

  
	
  # of Patients:

  	
   

  	
  up to 25

  
	
   

  	
   

  	
   

  
	
  Patient Population:

  	
   

  	
  Patients with localized
  prostate cancer intending to undergo radical prostatectomy

  
	
   

  	
   

  	
   

  
	
  Intended Outcome:

  	
   

  	
  Primary: tissue
  pharmacokinetics and pharmacodynamics Secondary: pathologic response rates

  
	
   

  	
   

  	
   

  
	
  Treatment Protocol:

  	
   

  	
  1 week loading dose (days 1, 3, 5) followed by weekly (starting day
  8) administration of QGX-011 for a total of 13 weeks; plus hormone ablation
  therapy for entire 13 week period; each 13 week period equals 1 cycle;
  maximum 1 cycle, followed by radical prostatectomy within 1 week of last
  treatment.

  
	
   

  	
   

  	
   

  
	
  Drug Usage:

  	
   

  	
  All patients on the
  trial will receive a total of 15 doses. Assuming dosage at 640 mg and 25
  patients, CS 4 will use [***] ([***] vials), or [***] of finished product, before wastage.

  
	
   

  	
   

  	
   

  
	
  Third Party Support:

  	
   

  	
  Intended – [***] ([***])

  

 

7

Schedule
3

CS5 Protocol Summary

 

CS 5: 
Phase I/II Clinical Study of OGX-011 in Combination with Gemzar
and Cisplatin) in Patients with Advanced NSCLC

 

This study will combine a
phase I limited dose escalation to establish safety in combination with Gemzar
and Cisplatin, and then a phase H component for first line treatment in
patients with Stage lllb/IV NSCLC. Gem/Cis is one of 4 approved first line
treatments for patients with advanced NSCLC.

 

	
  Funding Status:

  	
   

  	
  No grant funding

  
	
   

  	
   

  	
   

  
	
  Study Sponsor:

  	
   

  	
  OncoGenex

  
	
   

  	
   

  	
   

  
	
  Study Site{s}:

  	
   

  	
  a total of 10-12 sites
  located in Canada and the United States (participating sites to be
  determined)

  
	
   

  	
   

  	
   

  
	
  Principal lnvestigator:

  	
   

  	
  [***], MD, BCCA

  
	
   

  	
   

  	
   

  
	
  # of Patients:

  	
   

  	
  up to 85 (9 - 15 pts to
  small Phase I dose escalation; balance in PII)

  
	
   

  	
   

  	
   

  
	
  Patient Population:

  	
   

  	
  Stage IIIb/IV Non-Small
  Cell Lung Cancer patients

  
	
   

  	
   

  	
   

  
	
  Intended Outcome:

  	
   

  	
  Phase I component:
  Safety; recommended dose with Gemzar/Cis.

  Phase H component: Primary: objective response rates;
Secondary: progression-free
  survival; overall survival; safety and tolerability.

  
	
   

  	
   

  	
   

  
	
  Treatment Protocol:

  	
   

  	
  1 week loading dose
  (days -7, -5, -3), then weekly (starting day 1) administration of OGX-011 for
  3 weeks; plus weekly Gemzar at 1250
  mg/m2 for 2 weeks of 3 weeks and cisplatin once (coincident with first
  Gemzar), for 3 week cycles, starting day 1. Patients would be eligible for a
  maximum 6 cycles.

  
	
   

  	
   

  	
   

  
	
  Drug Usage:

  	
   

  	
  Assuming 15 pts in
  Phase I (dose escalation), 70 its
  treated in Phase 11 at 640 mg, [***]
  of patients go a maximum of [***]
  cycles (balance go only [***]
  cycles), CS 5 will use [***]
  vials ([***] vials), or [***] of finished product, before
  wastage.

  
	
   

  	
   

  	
   

  
	
  Third Party Support:

  	
   

  	
  Intended - [***] in locations where [***] is not on [***].

  

 

8

Schedule 4

CS6 Protocol Summary

 

CS 6:  Phase II Clinical Study of OGX-011 in
Combination with TAXOTERE in
Patients with Advanced / Metastatic Breast Cancer

 

This study will follow
completion of CS2, and will combine OGX-011 with Taxotere to treat patents with
advanced/metastatic breast cancer who have failed prior anthracycline-based
chemotherapy.

 

	
  Funding Status:

  	
   

  	
  No grant funding.

  
	
   

  	
   

  	
   

  
	
  Study Sponsor:

  	
   

  	
  OncoGenex

  
	
   

  	
   

  	
   

  
	
  Study Site(s,):

  	
   

  	
  8-10 NCIC affiliated sites located in Canada; US
  sites may be added if deemed necessary to reach accrual goals

  
	
   

  	
   

  	
   

  
	
  Principal Investigator;

  	
   

  	
  Dr. Stephen Chia, MD, BCCA

  
	
   

  	
   

  	
   

  
	
  # of Patients:

  	
   

  	
  up to 50

  
	
   

  	
   

  	
   

  
	
  Patient Population:

  	
   

  	
  Advanced / Metastatic Breast Cancer patients who
  have failed at least one prior anthracycline-based chemotherapy. Patients may
  be required to have primary tumor tissue available for analysis.

  
	
   

  	
   

  	
   

  
	
  Intended Outcome:

  	
   

  	
  Primary: objective response rates; Secondary:
  progression-free survival; overall survival: overall safety and tolerability.

  
	
   

  	
   

  	
   

  
	
  Treatment Protocol:

  	
   

  	
  1 week loading dose (days -7, -5, -3), then weekly
  (starting day 1) administration of CGX-011 for 3 weeks plus Taxotere on day
  1. Each [***] week period
  equals one cycle. Patients would be eligible for a maximum of [***] cycles. Patients may be
  required to have tumor biopsies after treatment.

  
	
   

  	
   

  	
   

  
	
  Drug Usage:

  	
   

  	
  Assuming 50 pts treated at 640 mg, all patients go a
  maximum of [***], CS 6 will
  use [***] ([***] vials), or [***] of finished product, before
  wastage.

  
	
   

  	
   

  	
   

  
	
  Third Party Support:

  	
   

  	
  Intended — [***]
  for [***].

  

 

9

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