ALLPHASE
 Clinical
Research
 
 YM
BIOSCIENCES INC.
 
 PROPOSAL
SUMMARY PR2
 (Detailed)
 
 Brain
Metastases from NSCLC
 
 A
Randomized Phase II, Double-Blind Study Nimotuzumab Plus Whole-
 Brain
Radiation Therapy (WBRT) Compared With WBRT Alone in Patient
 With
Brain Metastases From Non-Small Cell Lung Cancer.
 
 December
16th,
2008
  
 
 MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
 
 1.
Proposal Details
 
 Title:
                  
                  A
      Randomized Phase II, Double-Blind Study Nimotuzumab Plus
      Whole-Brain
      Radiation Therapy (WBRT) Compared With WBRT Alone in PatientWith
      Brain Metastases From Non-Small Cell Lung Cancer.Customer:
                  
                  YM
      BIOSCIENCES INC.MSA
      #:
                  
                  YMB07-MSA-17MAY2007MSA
      Expiry Date:
                  
                  Project
      Completion or TerminationProposal
      No.:
                  
                  YMB08-WO5-15DEC2008-3.0Customer Reference:
                  
                  YMB08-W04Confidentiality:
                  
                  Restricted
      - Commercial Copyright and Reproduction
                    
                    This
      proposal is submitted by Allphase Clinical Research Inc. in response to
      the invitation issued by Ryan Sukhoo MD, Clinical Project Manager, YM
      BIOSCIENCES INC. It may not be used for any other purposes, reproduced in
      whole or in part, nor passed to any organization or person without the
      specific permission in writing of the President, Allphase Clinical
      Research Services Inc.Proposal
      Date:
                  
                  16DEC2008Version:
                  
                  3.0Validity:
                  
                  90
      daysCRO
      Address:
                  
                  Allphase
      Clinical Research Services Inc.
                    1145
      Hunt Club Road, Suite 600
                    Ottawa,
      ON Canada K1V 0Y3
                    P:
      (613) 228-1990 x 100
                    F:
      (6l3) 228-8493
                    C:
      (613) 291-2362
                    Email:
      jsmith@allphaseclinical.comApproved
      by:Jeff
      Smith
                    President
                  
                  Date
  CONFIDENTIAL
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      Date:
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                  WO5
  2.
Requested Services
 
 Project
Management
 
 The role
of the Project Manager is critical to the success of every clinical trial. At
Allphase Clinical Research, our project managers are experienced
professionals trained to deliver superior service to our clients. Their
collaborative approach combined with exceptional organizational and
interpersonal skills creates a responsive, client-driven environment. Our
services include:
 ·
              IND/CTA
      maintenance;
 ·
              Collaborative
      interaction with regulatory authorities and
  IRBs;
 ·
              Investigator
      site selection and feasibility
assessments;
 ·
              Regulatory
      document package design (site
level);
 ·
              Contract
      and budget preparation, negotiation, and
  administration;
 ·
              Investigator
      meeting organization and site
training;
 ·
              CRA
      resourcing, mentoring, and co-monitoring
  support;
 ·
              Monitoring
      report review;
 ·
              SAE
      reporting coordination;
 ·
              Coordination
      of site/ vendor/ client communications;
and
 ·
              Managing
      client expectations for on-time and on-budget
  performance.
 
 Clinical
Monitoring
 
 Our
Clinical Research Associates (CRAs) are appropriately qualified and industry
recognized for their outstanding reputation in customer service, in-depth
knowledge of industry regulations and guidelines, and therapeutic knowledge.
They ensure compliance with protocols, quality standards, data collection
requirements, and regulatory guidelines. The CRAs are regionally located across
North America, reducing travel time and expenses. Our CRAs truly enjoy their
profession, which we feel is ultimately reflected in their interactions with
clients, colleagues, and site staff as they perform their duties:
 ·
              Site
      initiation, routine monitoring, and
close-out;
 ·
              Site
      personnel training, mentoring, and
guidance;
 ·
              Assessing
      protocol compliance and data
integrity;
 ·
              Regulatory
      document review;
 ·
              Pharmacy
      training and drug accountability;
and
 ·
              Ensuring
      GCP, consenting, confidentiality, and safety requirements are
      met.
 
 Operational
Support
 
 Our
Clinical Operations Associates (COAs) fill a crucial supportive role to all
members of the team. COAs work to streamline the process of managing a clinical
trial. A primary function of this role is acting as a central point through
which virtually all clinical documentation is channeled. As documents are
received, they are logged into a tracking system, scanned, and either filed in
our in-house Trial Master File or forwarded to the client using a transmittal
system. We have developed a proprietary process of managing regulatory
documentation that provides our CRAs with a tool to ensure that site regulatory
files accurately represent the Trial Master File, with a minimal amount of
administration. This means that the site regulatory file is kept up to date, and
our client costs are less than organizations that use more conventional
processes.
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                  WO5
  COAs also
compile regulatory and enrolment data from investigative sites, which can then
be posted to a secure, client-specific web site. Clients requesting this
value-added service can access a web portal at their convenience, with a
username and password.
 
 The
Manager of Clinical Operations provides high-level quality control by managing
client expectations, employee workloads, oversee compliance with SOPs and
policies, employee performance evaluations, and providing guidance and support
to the team. This supervision creates an environment of consistency and
high-quality work for our clients.
 
 Quality
Assurance
 
 Allphase
Clinical Research Quality Assurance Team strives to provide thorough coverage
for both our internal and external clients' compliance oversight. Our team
brings practical application of the applicable regulations and guidance's to
your attention through carefully planned audits and detailed reports. The
Allphase QA department is at arms-length to the clinical operations team and
reports directly to the President. Independent audits of clinical
investigational sites, in-house processes and documentation provide an objective assessment of the
quality of the data collected and processed as part of a submission. Our
experienced staff provides a comprehensive Quality Assurance service program
including:
 ·
              Evaluation
      and auditing of our quality
processes:
 o
              Vendor
      qualification and due diligence audits (CROs, central IRBs,
      clinical/diagnostic laboratories, centralized ECG/PFT readers, clinical
      data management, clinical supplies
  distributors);
 o
              Clinical
      investigator site audits;
 o
              Clinical
      data management process audits;
 o
              Clinical
      study report and regulatory submission document
  audits;
 o
              Systems
      audits (pharmacovigilance and drug safety reporting, computer system
      validation documentation compliance, clinical research
      operations).
 ·
              Standard
      Operating Procedure (SOP) and policies
  development:
 o
              Clinical
      research SOP gap analyses and needs
assessment;
 o
              Facilitation
      of SOP/policies development, approval process, distribution and training
      activities;
 o
              Collaborative
      design and writing of customized SOPs and
  policies.
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  Affiliate
Services
  Allphase
Clinical Research is able to offer clients full-service CRO capabilities by
augmenting our in-house services with those of our affiliated partners to
be able to provide:
 ·
              Statistical
      Design and Analysis;
 ·
              Therapeutically
      aligned Medical Monitoring;
 ·
              DSMB;
 ·
              Clinical
      laboratory services;
 ·
              Investigational
      Product Distribution;
 ·
              IVRS;
 ·
              Home
      Health Care network;
 ·
              Ethics
      Review Boards;
 ·
              Translation
      services;
 ·
              Global
      provider network;
 ·
              DocStorage.ca
 
 Operational
Support and Web Portal
 
 Our
Clinical Operations Associates (COAs) fill a crucial supportive role to all
members of the team. COAs work to streamline the process of preparing clinical
documents. COAs assist the Medical Writing team to assemble the necessary
components of clinical documents and manage the communication with third party
publishing groups.
 
 As draft
documents are completed, they call be posted to a secure, client-specific web
site. Clients requesting this value-added service can access a secure
bi-directional web portal at their convenience, with a username and password.
Use of this system allows for efficient review of draft documents and alleviates
the need to transfer large attachments across email servers.
 
 Our
Team is Your Team
 
 All of
our in-house services are provided by full-time employees of
Allphase Clinical Research. This permits us to carefully control the quality of
service that we provide, and ensure uniformity in our means and methods. This,
together with the in-house support infrastructure we have created is the reason
for the reliability our clients have come to expect. As a result, our clients
continue to provide us with repeat business every year.
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  3.
Therapeutic Experience
  Allphase
Clinical Research has conducted studies in a variety of therapeutic areas
including:
 
 Therapeutic
      Area
                              
                              IndicationsOncology
                              
                              Brain
                                Breast
                                Head
      and Neck
                                Ovarian
                                Renal
      Cell Carcinoma
                                Small
      Cell Lung
                                Colorectal
                                Pediatric
      Glioma
                                Bone
      Marrow Transplant
                                Reduction
      of NeurotoxicityAllergy/Respiratory
                              
                              Asthma
                                Chronic
      Obstructive Pulmonary Disease
                                Perennial
      Allergic Rhinitis
                                Seasonal
      Allergic RhinitisCardiovascular
                              
                              Atrial
      Fibrillation
                                Deep
      Vein Thrombosis
                                Intermittent
      Claudication
                                Pulmonary
      Embolism
                                Dyslipidemia
                                Atherosclerosis
                                Venous
      Leg Ulcers
                                HypercholesterolemiaCNS
                              
                              Amytrophic
      Lateral Sclerosis
                                Alzheimer’s
      Disease
                                Depression
                                Multiple
      Sclerosis
                                Smoking
      Cessation
                                Insomnia
                                StrokeEndocrinology
                              
                              Diabetes
                                ObesityInfectious
      Disease
                              
                              Hepatitis
                                HIVOther
                              
                              Alpha-1
      Antitrypsin Deficiency
                                Primary
      Immune Deficiency
                                Post-op
      Pediatric Aggregation Inhibition
                                Thrombotic
      Thrombocytopenic Purpura
                                Dilutional
      Hyponatremia
                                Atopic
      Dermatitis
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  Oncology
Experience
  Therapeutic
      Area
                      
                      Phase
                      
                      #
      of Sites
                      
                      #
      of SubjectsSmall
      Cell Lung Cancer
                      
                      I/II
                      
                      5
                      
                      48Advanced
      Breast Cancer
                      
                      II
                      
                      5
                      
                      30Metastatic
      Renal Cell Carcinoma
                      
                      II
                      
                      1
                      
                      5Metastatic
      Breast Cancer
                      
                      II
                      
                      4
                      
                      37Squamous
      Cell Carcinoma
                      
                      II
                      
                      6
                      
                      20Squamous
      Cell Carcinoma
                      
                      II
                      
                      6
                      
                      10Pediatric
      Brain Tumors
                      
                      I
                      
                      I
                      
                      19Ovarian
      Cancer
                      
                      II
                      
                      7
                      
                      40Colorectal
      Cancer
                      
                      II
                      
                      14
                      
                      61Multiple
      Myeloma
                      
                      IIb
                      
                      10
                      
                      50Multiple
      Myeloma
                      
                      III
                      
                      10
                      
                      50Pediatric
      Glioma
                      
                      II
                      
                      6
                      
                      44
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  4.
Project Team
  YM
BioSciences Inc. has decided to outsource several aspects of their clinical
development plan, and has contacted Allphase Clinical Research Inc. for resource
support and to benefit from our expertise in the conduct of oncology clinical
trials. The selection of an outsourcing partner is a critical step in the
successful execution of any project, as well as integral to the external
perception of the sponsor company.
 
 Allphase
has a proven track record of successfully conducting research trials for our
clients, as demonstrated by the 100%repeat
business our clients provide. Inaddition to
task competence, Allphase also focuses on relationships, both with our
clients and with the investigative site staff. Establishing a positive
environment with future product prescribers is an important adjunct to the
marketing initiatives of our clients.
 
 In order
to meet the objectives of your project, a qualified Project Manager will beresponsible
for the overall execution of the trial. This person will be supported by an
experienced and multi-talented team of CRA's, Regulatory Affairs personnel,
Medical Writers, Drug Safety, Data Management and operational staff. The
proposed team members are noted below however, the availability of proposed
staff is dependent on project initiation timelines.
 
 Project
Management
 
 Wendy
Kerby, RN: Sr. Project Manager (Ottawa)
 
 Ms. Kerby
has over 20 years of research experience primarily in the CRO industry and as a
research nurse/study coordinator at a major Canadian University. Ms. Kerby
offers experience in Clinical Study Monitoring, Project Management, Audit
Preparation, SOP development, CRF development and vendor relations. She has an
excellent knowledge of Good Clinical Practices (GCP), FDA, Health Canada and ICH
guidelines and regulations. Ms. Kerby is a highly motivated individual with a
strong capability for multi-tasking and prioritizing. She has an excellent
working knowledge of the following therapeutic areas: oncology/haematology,
immunology, rheumatology, neurology and infectious diseases. She has also
presented at various Investigator meetings, conducted study specific training
and presented at internal/company meetings.
 
 Ms. Kerby
has over 15 years experience as a bedside nurse and clinic nurse, having worked
in the oncology clinic setting, haematology, paediatrics and emergency. She has
worked as a research nurse/study coordinator in oncology for 10 years, with
emphasis on Lung cancer, Colorectal Cancer, Melanoma, Breast and the various
Haematological disorders, both for industry conducted studies and co-operative
group studies.
 
 The CRO
experience has seen Ms. Kerby in the following roles: CRA, Lead CRA and Project
Manager. She brings over 7 years experience into the project management role and
has managed 4 international oncology studies in colorectal (2), melanoma and
ovarian cancer.
 CONFIDENTIAL
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      Version Code:
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      Date:
                  16DEC2008
                  Work
      Order #:
                  WO5
  Clinical
Research Associates
 
 Karry
Schenk (Ottawa, ON)
 
 Ms.
Schenk has been a CRA for over 10 years and has monitored 7 oncology studies.
Prior to this she worked for 4 years as a study coordinator at a cancer clinic.
Ms. Schenk worked on more than 100 oncology studies during this time, 15 of
which were colorectal studies. She also worked on a part time basis for 1 year
with the NCIC doing randomizations.
 
 Faye
Aspelund (Ottawa, ON)
 
 Ms.
Aspelund has been a CRA for 2.5 years. Prior to this she worked for 15 years as
an oncology study coordinator. Ms. Aspelund worked on more than 200 oncology
studies during this time, 30 of which were colorectal studies.
 
 Heather
Kimber, RN (Toronto, ON)
 
 Ms.
Kimber has a strong background in oncology, including 7 years of direct oncology
patient care in both an inpatient and ambulatory setting. She was an instructor
for the Oncology Certificate Program at Sheridan College and has 10 years of
clinical research coordinator experience. Ms. Kimber successfully completed the
Allphase Center of Excellence (ACE) CRA Training program in June, 2007 and has
been monitoring oncology studies since that time.
 
 Fredy
Perez, MD (Vancouver, BC)
 
 Dr. Perez
obtained his Medical Doctorate in Peru in 2002, followed by a Masters in Disease
Control. Dr. Perez has been a CRA for 4 years and has worked in multiple
therapeutic areas including colorectal and breast cancer. Dr. Perez is a member
of the Society of Clinical Research Associates (SoCRA) and the Clinical Research
Professionals of British Columbia (CRPBC). Dr. Perez' previous work experience
also includes being a clinical research coordinator and some work in Drug Safety
and Pharmacovigilance.
 
 Clinical
Operations Associates
 
 Alison
Conley (Ottawa, ON)
 
 Ms.
Conley is our most senior Clinical Operations Associate with more than five
years of clinical research experience, primarily responsible for organizing
Investigator Meetings. Ms. Conley is an administrative professional who
possesses strong organizational skills and is praised by existing clients for
her proactive, friendly approach. A dedicated project specific COA will also be
assigned to manage the administrative aspect of the project including regulatory
document collection, minutes, document processing and Trial Master File
management.
 
 Litharitza
Vakopoulos (Ottawa, ON)
 
 Ms.
Vakopoulos has been providing Clinical Operations support for over 5 years. She
has thorough knowledge of ICH and local regulatory authority regulations
regarding clinical research and development. Ms. Vakopoulos has been responsible
for supporting study start-up activities, clinical status tracking, and
in-house site management on numerous oncology studies.
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  Compliance
and Quality Assurance
 
 Linda
Kraft, RN, Manager, Compliance and Quality Assurance (Ottawa, ON)
 
 Ms. Kraft
is based in Ottawa and brings with her more than 13years experience in clinical
research including project management and auditing. Mrs. Kraft has several years
of experience in conducting central file assessments, and site and sponsor
audits.
 
 Diane
Motink, MLT; Sr. Compliance and Quality Assurance Specialist (Mississauga,
ON)
 
 Ms.
Motink has 9 years experience in pharmaceutical related quality control roles, 5
of which are as a quality assurance professional.
 
 Consultants
 
 Medical
Monitoring and Biostatistics are the only Allphase managed outsourced functions
anticipated for this project. Client will be consulted regarding the choice of
sub-contractor if and as needed.
 
 Contacts
 
 Technical Contact
                  
                  Administrative
      ContactWendy
      Kirby, RN.,
                  
                  Anne
      GamacheSr.
      Project Manager
                  
                  Project
      AnalystAllphase
      Clinical Research Inc.
                  
                  Allphase
      Clinical Research Inc.1145
      Hunt Club K1V 0Y3
                  
                  1145
      Hunt Club K1V 0Y3Tel:
      613-228-1990 x 117
                  
                  Tel:
      613-228-1990 x 136Fax:
      613-228-8493
                  
                  Fax:
      613-228-8493Cell: 613-808-4768
                  
                  Email: agamache@allphaseclinical.comEmail:
      wkerby@allphaseclinical.com
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  4.
SOPs
  YM
BioSciences Inc. has decided to use the following Allphase SOPs for this
project:
 
 Related
      Area
                        
                        Title
      of SOP
                        
                        Effective DateQuality
      Assurance (QA)QA
      006.01
                        
                        Investigator
      Site Audits
                        
                        03-DEC-2007QA
      008.00
                        
                        Fraud
      or Scientific Misconduct
                        
                        15-JUN-2007Clinical
      Research (CR or CO)CR
      100.00
                        
                        Preparing,
      Maintaining and archiving of the Trial Master File
                        
                        27-MAR-2006CR
      104.00
                        
                        Investigator
      Site Selection
                        
                        27-MAR-2006CO
      105.01
                        
                        Translation
      of Clinical Study Documents
                        
                        07-NOV-2008CO
      106.01
                        
                        Investigator
      Meetings
                        
                        18-SEP-2008CR
      107.00
                        
                        Investigator
      Financial Agreements
                        
                        15-JUN-2006CR
      108.00
                        
                        Site
      Initiation Visit
                        
                        01-JUN-2006CO
      109.03
                        
                        Interim
      Monitoring Visit
                        
                        31-OCT-2007CR
      110.00
                        
                        Close-Out
      Visit
                        
                        10-JUN-2006CO
      111.01
                        
                        Source
      Document versus Case Report Form
                        
                        06-MAY-2008CO
      112.00
                        
                        Source
      Data Verification and Case Report Form Review
                        
                        18-JUL-2008CO
      113.01
                        
                        Protocol
      Deviations
                        
                        11-JUL-2008CO
      114.01
                        
                        Recording
      and Reporting Adverse Events
                        
                        06-AUG-2008CO
      115.01
                        
                        The
      Archiving and Shipping of the Trial Master File
                        
                        09-SEP-2008CO
      118.00
                        
                        Premature
      Termination or Suspension of a Clinical Trial
                        
                        29-JUL-2008CO
      119.00
                        
                        Data
      Clarification
                        
                        03-APR-2008CO
      120.00
                        
                        Investigational
      Product Accountability
                        
                        09-OCT-2008CO
      121.00
                        
                        Site
      Transfer between Clinical Research Associates
                        
                        12-NOV-2008CO
      122.00
                        
                        Monitoring
      Plan
                        
                        24-JUN-2008CO
      123.00
                        
                        Distribution
      and Tracking of Investigator’s Brochure
                        
                        24-JUN-2008CO
      124.00
                        
                        TMF
      Document Retrieval
                        
                        09-SEP-2008CO
      126.00
                        
                        Data
      safety Monitoring Boards
                        
                        19-JAN-2009Scientific
      Affairs (SA)SA
      600.01
                        
                        Clinical
      Study Report
                        
                        19-NOV-2008SA
      601.01
                        
                        Statistical
      Analysis Plan
                        
                        19-NOV-2008Drug
      Safety (DS)
                        
                        Recording
      and Reporting of Serious Adverse Events and Reporting of Safety
      Information Externally
                        
                        10-NOV-2006
 
 To be
determined in discussion with Client
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  5.
Project Summary
  The
following summary outlines the key elements of the study which have been
provided to date. This proposal is based on the accuracy of these items. Should
any facts and/or assumptions be incorrect, Allphase reserves the right to modify
this proposal to reflect any new information.
 
 ProtocolSponsor
                            
                            
                            
                            YM
      BIOSCIENCES INC.Protocol
      Number
                            
                            
                            
                            YMB
      1000-08-0202Protocol
      Version
                            
                            
                            
                            November
      18th,
      2008 - version 1.0Drug
                            
                            
                            
                            Nimotuzumab
      (TheraCIM h-R3) from CIMYMIndication
                            
                            
                            
                            Brain
      Metastases from Non-Small Cell Lung CancerPhase
                            
                            
                            
                            IITitle
                            
                            
                            
                            A
      Randomized Phase II, Double-Blind Study Nimotuzumab Plus Whole- Brain
      Radiation Therapy (WBRT) Compared With WBRT Alone in
      Patient  With Brain Metastases From Non-Small Cell Lung
      Cancer.Short
      Title
                            
                            
                            
                            TBDObjectives
      for Phase II component
                            
                            
                            
                            Primary: Intercranial
      disease progression at 2, 4, and 6 months.
                              Secondary:Overall
      survival (OS); time to neurologic progression (TNP) or death with evidence
      of neurologic progression; OS rate at 6 months; time to intracranial
      disease progression; time to overall progression.Sites
      & Start Up MeetingsNo.
      of Local Investigator Meetings
                            
                            1
                            
                            OttawaLocal
      Investigator Meeting Attendance (hrs)
                            
                            16
                            
                            2
      days; 1 day workshop with coordinatorsPM
                            
                            1
                            
                            No
      = 0; Yes = 1CRA
                            
                            1
                            
                            No
      = 0; Yes = 1Quality
      Assurance (ACE)
                            
                            0
                            
                            No
      = 0; Yes = 1COA
                            
                            1
                            
                            No
      = 0; Yes = 1Medical
      Monitor
                            
                            1
                            
                            No
      = 0; Yes = 1Local
      Kick off Meeting
                            
                            1
                            
                            No
      = 0; Yes = 1PM
                            
                            1
                            
                            No
      = 0; Yes = 1CRA
                            
                            1
                            
                            No
      = 0; Yes = 1COA
                            
                            1
                            
                            No
      = 0; Yes = 1Medical
      Monitor
                            
                            1
                            
                            No
      = 0; Yes = 1Protocol
      Review Process
                            
                            1
                            
                            No
      = 0; Yes = 1PM
                            
                            1
                            
                            No
      = 0; Yes = 1Director
      of Scientific Affairs
                            
                            1
                            
                            No
      = 0; Yes = 1CRA
                            
                            1
                            
                            No
      = 0; Yes = 1COA
                            
                            1
                            
                            No
      = 0; Yes = 1Medical
      Monitor
                            
                            1
                            
                            No
      = 0; Yes = 1Mid
      Study Local Team Meeting
                            
                            1
                            
                            No
      = 0; Yes = 1PM
                            
                            1
                            
                            No
      = 0; Yes = 1CRA
                            
                            1
                            
                            No
      = 0; Yes =
1
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  COA
                      
                      1
                      
                      No
      = 0; Yes = 1Medical
      Monitor
                      
                      1
                      
                      No
      = 0; Yes = 1#
      of Treatment Groups
                      
                      2
                      
                      2:1
      ratioLocal
      or Central IRB
                      
                      Local#
      of Sites to be Managed by Allphase
                      
                      20#
      of Sites to be Monitored by Allphase
                      
                      20Percentage
      of Subjects to be Monitored
                      
                      100Feasibility
      Survey
                      
                      Y
                      
                      Y/N#
      of Sites for Feasibility Survey
                      
                      20
                      
                      YMB
      responsibility - Allphase to Assist#
      of Sites Selection Visits (CRA)
                      
                      0
                      
                      TBD#
      of Sites Selection Visits (PM)
                      
                      0#
      of Sites Initiation Visits (CRA)
                      
                      20#
      of Sites Initiation Visits (PM)
                      
                      4
                      
                      One
      per CRAEst.
      # of Monitoring Hrs/non-evaluable pt.
                      
                      6Est.
      # of Monitoring Hrs/screen failure pt.
                      
                      1
                      
                      Assuming
      minimal data collectionEst.
      # of Monitoring Hrs/Completed CRF
                      
                      20Est.
      # of Hrs/Visit Report
                      
                      5Estimated
      # of Monitoring Hours
                      
                      1769Estimated
      # of Monitoring Days
                      
                      253Estimated
      # of Monitoring Visits
                      
                      177
                      
                      Assume
      30% of visits can be multi-day visits considering both projects (1000-10
      & 1000-08-0202) having many of the same sitesEstimated
      % of 1 day Monitoring Visits
                      
                      70%Estimated
      Monitoring Frequency
                      
                      6
                      
                      WeeksEstimated
      # of CRAs
                      
                      4
                      
                      Regionally
      based in CanadaEstimated
      # of Close-out Visits
                      
                      20SubjectsNumber
      of Subjects Randomized locally
                      
                      88Screen
      Failure Rate
                      
                      10%Drop
      Out Rate (once Randomized)
                      
                      0%#
      of Subjects Evaluable locally
                      
                      88#
      of Subjects Screened locally
                      
                      97Enrolment
      Period
                      
                      52Duration
      of Each Subject
                      
                      52Total
      Study Duration (all subjects)
                      
                      104Project
      Administration#
      PMs for project
                      
                      1
                      
                      No
      = 0; Yes = 1#
      COAs for project
                      
                      1#
      of collaborating CROs
                      
                      0
 CONFIDENTIAL
 Page 13 of
36
  
 MSA#:
                  YMB07-MSA-17MAY2007
                  WO
      Version Code:
                  YMB08-WO5-15DEC2008-3.0Version
      Date:
                  16DEC2008
                  Work
      Order #:
                  WO5
  Total
      Study Duration (PM)
                    
                    122
                    
                    weeksEstimated
      # PM hours/week/site
                    
                    0.5Estimated
      # PM hours/week
                    
                    10Estimated
      # CRA Admin Hrs/week/site
                    
                    0.5Estimated
      # CRA Admin Hrs/week
                    
                    10Estimated
      # COA Admin Hrs/week/site
                    
                    0.75Estimated
      # COA Admin Hrs/week
                    
                    15Estimated
      # Doc Man. Admin Hrs/Site/Week
                    
                    0.5Estimated
      # Doc Man. Admin Hrs/Week
                    
                    10Team
      Teleconferences
                    
                    2
                    
                    1=Weekly;
      2=bi-weekly, 4=monthly#
      of Teleconferences
                    
                    61Estimated
      # Hrs/Teleconference/CRA
                    
                    0.75PM
      Teleconferences (with Sponsor)
                    
                    1
                    
                    1=Weekly;
      2=bi-weekly, 4=monthlyNumber
      of PM Teleconferences (Sponsor)
                    
                    122Estimated
      # Hrs/Teleconference (Sponsor)
                    
                    1PM
      Ad hoc visits/quarter
                    
                    1Estimated
      # of PM Ad-Hoc Visits
                    
                    10Estimated
      # of Co-Visits by PM
                    
                    4Medical
      WritingMedical
      Writing Research and Therapeutic Training
                    
                    0
                    
                    No
      = 0; Yes = 1Regulatory
      AffairsPre
      CTA Meeting with Health Canada
                    
                    0
                    
                    No
      = 0; Yes = 1Submission
      to Health Canada
                    
                    0
                    
                    No
      = 0; Yes = 1Estimated
      # of HC Amendments
                    
                    0SafetyMedical
      Oversight by Allphase
                    
                    1
                    
                    No
      = 0; Yes = 1#
      of subjects for Safety
                    
                    88Estimated
      Percentage of SAEs
                    
                    50%Estimated
      # of SAEs
                    
                    44Estimated
      Percentage of Reportable SAEs
                    
                    20%
                    
                    Percentage
      of SAEs requiring regulatory reportingEstimated
      # of Reportable SAEs
                    
                    9Teleconferences
                    
                    13
                    
                    1=Weekly;
      2=bi-weekly, 4=monthly, 8=bi-monthly, 13=quarterly#
      of Teleconferences with Sponsor
                    
                    9Management
      of DSMB
                    
                    1
                    
                    No
      = 0; Yes = 1
 CONFIDENTIAL
 Page 14 of
36
  
 MSA#:
                  YMB07-MSA-17MAY2007
                  WO
      Version Code:
                  YMB08-WO5-15DEC2008-3.0Version
      Date:
                  16DEC2008
                  Work
      Order #:
                  WO5
  #
      of DSMB meetings
                    
                    3Estimated
      AEs/Randomized Subject
                    
                    10Estimated
      Medical terms for Manual Coding/Subject
                    
                    10Data
      ManagementData
      Management Involvement?
                    
                    0
                    
                    No
      = 0; Yes = 1BioStatisticsBiostatistics
      Involvement?
                    
                    0
                    
                    No
      = 0; Yes = 1Quality
      AssuranceSite
      Audits
                    
                    3TMF
      Audit
                    
                    0Vendor
      ManagementCentral
      Lab Managed by Allphase?
                    
                    0
                    
                    No
      = 0; Yes = Number of labsImaging
      Lab Managed by Allphase?
                    
                    0
                    
                    No
      = 0; Yes = Number if labsInvestigational
      Product Distributor Managed by Allphase?
                    
                    0
                    
                    No
      = 0; Yes = 1SOPAllphase
      SOPs to be used?
                    
                    1
                    
                    No
      = 0; Yes = 1 (expand group)Allphase
      Forms?
                    
                    1
                    
                    No
      = 0; Yes = 1 (expand group)Services
      RequestedRegulatoryYMB
                    
                    CTA
      prep, submission and maintenanceProject
      ManagementYMB
                    
                    Site
      Contract NegotiationACR
                    
                    Site
      Payment FacilitationACR
                    
                    Regulatory
      Document CollectionACR
                    
                    Trial
      Master File Set-up & MaintenanceACR
                    
                    ICF
      Preparation & TranslationACR
                    
                    IRB
      preparations and submissions - central IRB; or assistance with the
      submissions if local IRB.YMB
                    
                    Site
      IdentificationACR
                    
                    Multi-site
      ManagementACR
                    
                    CRA
      ManagementACR
                    
                    Teleconference
      and Project UpdatesYMB
                    
                    Vendor
      Management (if applicable)ACR
                    
                    General
      AdministrationInvestigator
      Meeting - North AmericaACR
                    
                    AttendanceACR
                    
                    Planning
      & ExecutionACR
                    
                    PresentationsACR
                    
                    Travel
      Arrangements for AttendeesClinical
      MonitoringACR
                    
                    Pre-Study
      Visits (new sites only)ACR
                    
                    Site
      Initiation
 CONFIDENTIAL
 Page 15 of
36
  
 MSA#:
                    YMB07-MSA-17MAY2007
                    WO
      Version Code:
                    YMB08-WO5-15DEC2008-3.0Version
      Date:
                    16DEC2008
                    Work
      Order #:
                    WO5
  ACR
                    
                    Interim
      Monitoring & Site managementACR
                    
                    Site
      Close OutSafetyACR
                    
                    Safety
      PlanACR
                    
                    CIOMS/MedWatch
      report prepACR
                    
                    SAE
      alert reporting to authoritiesData
      Management/BiostatisticsYMB
                    
                    CRF
      Design & BuildYMB
                    
                    DM
      System Set Up (include edit checks)YMB
                    
                    Data
      Validation and Review CRFsYMB
                    
                    Data
      QueryYMB
                    
                    Coding
      AE & MedicationsYMB
                    
                    Interim
      Analysis PlanYMB
                    
                    Final
      Analysis PlanYMB
                    
                    Randomization
      ServicesACR
                    
                    Medical
      MonitoringData
      Monitoring CommitteeACR
                    
                    Establish
      Committee and Organize MeetingsMedical
      WritingYMB
                    
                    Protocol
      DevelopmentYMB
                    
                    Interim
      & Final Clinical Study ReportsYMB
                    
                    ManuscriptsQuality
      AssuranceACR
                    
                    GCP
      Investigator/Site/Vendor AuditTBD
                    
                    QA
      Audit of Clinical DatabaseTBD
                    
                    QA
      Audit of Clinical Study
Report
 Project
Timelines
 
 Activity
                  
                  Date
      of CompletionExecuted
      LOI
                  
                  Dec-08Fully
      Executed Contract
                  
                  Dec-08Kick-off
      Meeting
                  
                  Jan-08Site
      Selection
                  
                  Jan-08IRB
      Submissions
                  
                  Jan-09Investigator
      Agreements
                  
                  Jan-09Investigator
      Meeting
                  
                  Feb-09First
      SIV
                  
                  Mar-09First
      Subject First Visit
                  
                  Mar-09Last
      Subject First Visit
                  
                  Mar-10Last
      Subject Last Visit
                  
                  Mar-11Data
      Base Lock
                  
                  May-11Final
      Close-Out Visit
                  
                  Jul-11Final
      Clinical Study Report
                  
                  Jul-11
 CONFIDENTIAL
 Page 16 of
36
  
 MSA#:
                  YMB07-MSA-17MAY2007
                  WO
      Version Code:
                  YMB08-WO5-15DEC2008-3.0Version
      Date:
                  16DEC2008
                  Work
      Order #:
                  WO5
  Start-Up
      Duration
              
              9Enrolment
              
              52Treatment
      period
              
              52Close
      Out (DBL to CSR)
              
              9Total
      Subject Duration
              
              104Total
      Study Duration (PM)
              
              122Data
      Management Duration
              
              125
 
 Roles
and Rates
 
 Allphase
      Role
                              
                              Allphase
      Resource
                              
                              Hourly
      Rate (CDN)DE
                              
                              Data
      Entry Personnel
                              
                              $
                              65DOC
                              
                              Document
      Management
                              
                              $
                              75COA
                              
                              Clinical
      Operations Associate
                              
                              $
                              75CRA
                              
                              Clinical
      Research Associate
                              
                              $
                              90LCRA
                              
                              Lead
      Clinical Research Associate
                              
                              $
                              95DM
                              
                              Data
      Manager
                              
                              $
                              100MW
                              
                              Medical
      Writing
                              
                              $
                              100PM
                              
                              Project
      Manager
                              
                              $
                              100RA
                              
                              Regulatory
      Affairs
                              
                              $
                              100DS
                              
                              Drug
      Safety
                              
                              $
                              100QA
                              
                              Quality
      Assurance Auditor
                              
                              $
                              100DIR
                              
                              Director
      Scientific Affairs
                              
                              $
                              120BIO
                              
                              Biostatistician
                              
                              $
                              130ACE
                              
                              Trainer
                              
                              $
                              150MMD
                              
                              Medical
      Monitor Data Management
                              
                              $
                              200MM
                              
                              Medical
      Monitor
                              
                              $
                              350
 
 Project
Details
 
 List
      of Tasks
                                                    
                                                    YMB
                                                    
                                                    Allphase
                                                    
                                                    ADM
                                                    
                                                    Task Hours
                                                    
                                                    Units
                                                    
                                                    Total Hours
                                                    
                                                    RespPre-Study
      ActivitiesProject
      Feasibility StudyIdentify
      sites
                                                    
                                                    XContact
      sites
                                                    
                                                    XDraft
      CDA for sites
                                                    
                                                    XDevelop
      Feasibility Survey
                                                    
                                                    (X)
                                                    
                                                    X
                                                    
                                                    
                                                    
                                                    4
                                                    
                                                    1
                                                    
                                                    4
                                                    
                                                    PMDistribute
      CDA to sites
                                                    
                                                    XDistribute
      Feasibility to sites
                                                    
                                                    XCollect
      and review CDA/Feasibilities from sites
                                                    
                                                    XReview
      Feasibilities from sites
                                                    
                                                    (X)
                                                    
                                                    X
                                                    
                                                    
                                                    
                                                    0.5
                                                    
                                                    20
                                                    
                                                    10
                                                    
                                                    PMCompile
      Feasibility Report
                                                    
                                                    X
                                                    
                                                    X
                                                    
                                                    
                                                    
                                                    8
                                                    
                                                    1
                                                    
                                                    8
                                                    
                                                    PMProtocol
      Development
                                                    
                                                    XProtocol
      Ammendments (if required)
                                                    
                                                    XCompilation
      & update IB
                                                    
                                                    X
  CONFIDENTIAL
 Page 17 of
36
  
 MSA#:
                  YMB07-MSA-17MAY2007
                  WO
      Version Code:
                  YMB08-WO5-15DEC2008-3.0Version
      Date:
                  16DEC2008
                  Work
      Order #:
                  WO5
 Kick-off
      meeting
                  
                  X
                  
                  XPM
      attendance
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  1
                  
                  8
                  
                  PMPM
      travel time
                  
                  
                  
                  
                  
                  
                  
                  0
                  
                  0
                  
                  0
                  
                  PMCRA
      attendance
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  4
                  
                  32
                  
                  CRACRA
      travel time (average)
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  4
                  
                  32
                  
                  CRACOA
      attendance
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  1
                  
                  8
                  
                  COACOA
      travel time
                  
                  
                  
                  
                  
                  
                  
                  0
                  
                  0
                  
                  0
                  
                  COAMedical
      Monitor attendance
                  
                  
                  
                  
                  
                  
                  
                  4
                  
                  1
                  
                  4
                  
                  MMMedical
      Monitor travel time
                  
                  
                  
                  
                  
                  
                  
                  3
                  
                  1
                  
                  3
                  
                  MMInternational
      Kick-Off Meeting
                  
                  N/AMid
      Study Local Team Meeting
                  
                  X
                  
                  XPM
      attendance
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  1
                  
                  8
                  
                  PMPM
      travel time
                  
                  
                  
                  
                  
                  
                  
                  0
                  
                  0
                  
                  0
                  
                  PMCRA
      attendance
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  4
                  
                  32
                  
                  CRACRA
      travel time (average)
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  4
                  
                  32
                  
                  CRACOA
      attendance
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  1
                  
                  8
                  
                  COACOA
      travel time
                  
                  
                  
                  
                  
                  
                  
                  0
                  
                  0
                  
                  0
                  
                  COAMedical
      Monitor attendance
                  
                  
                  
                  
                  
                  
                  
                  4
                  
                  1
                  
                  4
                  
                  MMMedical
      Monitor travel time
                  
                  
                  
                  
                  
                  
                  
                  3
                  
                  1
                  
                  3
                  
                  MMProtocol
      Review Process
                  
                  (X)
                  
                  XPM
                  
                  
                  
                  
                  
                  
                  
                  4
                  
                  1
                  
                  4
                  
                  PMDirector
      Scientific Affairs
                  
                  
                  
                  
                  
                  
                  
                  4
                  
                  1
                  
                  4
                  
                  DIRCRA
                  
                  
                  
                  
                  
                  
                  
                  4
                  
                  4
                  
                  16
                  
                  CRACOA
                  
                  
                  
                  
                  
                  
                  
                  4
                  
                  1
                  
                  4
                  
                  COAMedical
      Monitor
                  
                  
                  
                  
                  
                  
                  
                  4
                  
                  1
                  
                  4
                  
                  MMRegulatory
      Management – study
                  
                  N/AVendor
      Management
                  
                  N/ALocal
      Investigator MeetingIdentify
      location and conduct preliminary investigation of costs;
      reservations
                  
                  (X)
                  
                  X
                  
                  
                  
                  8
                  
                  1
                  
                  8
                  
                  COAOrganize
      travel & hotel for study team
                  
                  (X)
                  
                  X
                  
                  
                  
                  12
                  
                  1
                  
                  12
                  
                  COAPlan
      and organize IM
                  
                  (X)
                  
                  X
                  
                  
                  
                  40
                  
                  1
                  
                  40
                  
                  PMTeleconferences
      – PM
                  
                  (X)
                  
                  X
                  
                  
                  
                  1
                  
                  5
                  
                  5
                  
                  PMTeleconferences
      – COA
                  
                  (X)
                  
                  X
                  
                  
                  
                  1
                  
                  5
                  
                  5
                  
                  COAPrepare
      agenda
                  
                  (X)
                  
                  X
                  
                  
                  
                  4
                  
                  1
                  
                  4
                  
                  PMPrepare
      presentations
                  
                  (X)
                  
                  X
                  
                  
                  
                  16
                  
                  1
                  
                  16
                  
                  PMDesign
      Investigator Meeting materials
                  
                  (X)
                  
                  X
                  
                  
                  
                  12
                  
                  1
                  
                  12
                  
                  PMPrepare
      Investigator Meeting materials
                  
                  (X)
                  
                  X
                  
                  
                  
                  24
                  
                  1
                  
                  24
                  
                  COAPrepare
      welcome letters, name tags, materials
                  
                  (X)
                  
                  X
                  
                  
                  
                  16
                  
                  1
                  
                  16
                  
                  COAAttendance
      &  presentations at Meeting


CONFIDENTIAL
 Page 18 of
36







MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5




PM
      prep
              
              
              
              X
              
              
              
              2
              
              1
              
              2
              
              PMPM
      travel
              
              
              
              X
              
              
              
              2
              
              1
              
              2
              
              PMPM
      Presentation & Attendance
              
              
              
              X
              
              
              
              16
              
              1
              
              16
              
              PMCRA
      prep
              
              
              
              X
              
              
              
              2
              
              4
              
              8
              
              CRACRA
      travel
              
              
              
              X
              
              
              
              8
              
              4
              
              32
              
              CRACRA
      attendance
              
              
              
              X
              
              
              
              16
              
              4
              
              64
              
              CRAACE
      Trainer prep
              
              
              
              N/A
              
              
              
              
              
              
              
              
              
              QAACE
      Trainer travel
              
              
              
              N/A
              
              
              
              
              
              
              
              
              
              QAACE
      Trainer presentation & attendance
              
              
              
              N/A
              
              
              
              
              
              
              
              
              
              QACOA
      prep & oversight
              
              
              
              X
              
              
              
              24
              
              1
              
              24
              
              COACOA
      travel
              
              
              
              X
              
              
              
              2
              
              1
              
              2
              
              COACOA
      attendance
              
              
              
              X
              
              
              
              16
              
              1
              
              16
              
              COAMedical
      Monitor prep
              
              
              
              X
              
              
              
              2
              
              1
              
              2
              
              MMMedical
      Monitor travel
              
              
              
              X
              
              
              
              2
              
              1
              
              2
              
              MMMedical
      Monitor Presentation & Attendance
              
              
              
              X
              
              
              
              8
              
              1
              
              8
              
              MMEthicsPreparation
      of ICF template
              
              XCustomization
      of ICF (PIPEDA)
              
              
              
              X
              
              
              
              1
              
              20
              
              20
              
              PMPreparation
      of other subject materials
              
              (X)
              
              X
              
              
              
              12
              
              1
              
              12
              
              PMAssist
      sites with submissions
              
              (X)
              
              X
              
              
              
              1
              
              20
              
              20
              
              PMIRB
      approval review & action if needed
              
              (X)
              
              X
              
              
              
              1
              
              20
              
              20
              
              PMTranslation
      of ICF & materials
              
              (X)
              
              X
              
              
              
              6
              
              1
              
              6
              
              PMSubsequent
      ICF revisions (amendments)
              
              (X)
              
              X
              
              
              
              6
              
              1
              
              6
              
              PMIND
      Safety alert reporting to sites
              
              (X)
              
              X
              
              
              
              0.75
              
              13
              
              6.75
              
              PMAnnual
      re-approval documentation
              
              (X)
              
              X
              
              
              
              1
              
              20
              
              20
              
              PMStudy/site
      closure documentation
              
              (X)
              
              X
              
              
              
              2
              
              20
              
              40
              
              PMIRB
      payment facilitation
              
              (X)
              
              X
              
              
              
              0.5
              
              20
              
              10
              
              PMIRB
      payment
              
              (X)
              
              X
              
              
              
              0.5
              
              20
              
              10
              
              PMCRATraining
      – protocol, project & therapy area
              
              
              
              XInitial
      CRA training
              
              
              
              
              
              
              
              8
              
              4
              
              32
              
              CRAPeriodic
      CRA training (i.e. amendments, forms, SOPs, other new
      information)
              
              
              
              
              
              
              
              8
              
              4
              
              32
              
              CRATeam
      Teleconference
              
              
              
              X
              
              
              
              0.8
              
              244
              
              183
              
              CRASite
      Selection Visits
              
              XContact
      sites and confirm date for visitSend
      confirmation letterInterview
      PI and site staff regarding experienceReview
      project requirements and expectationsTour
      facility and assess site


CONFIDENTIAL
 Page 19 of
36












MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





Prepare
      report and make recommendation of site suitabilityPrep
                    
                    
                    
                    
                    
                    
                    
                    1
                    
                    1
                    
                    1
                    
                    CRATravel
                    
                    
                    
                    
                    
                    
                    
                    8
                    
                    1
                    
                    8
                    
                    CRAOn-Site
                    
                    
                    
                    
                    
                    
                    
                    3
                    
                    1
                    
                    3
                    
                    CRAReport
      Writing and Follow-up
                    
                    
                    
                    
                    
                    
                    
                    4
                    
                    1
                    
                    4
                    
                    CRATotal
                    
                    
                    
                    
                    
                    
                    
                    16
                    
                    0
                    
                    0
                    
                    CAASite
      Initiation Visit
                    
                    
                    
                    XContact
      sites and confirm date for visit and provide an agendaSend
      confirmation letterComplete
      Monitors’ Sign-in LogReview
      regulatory documentationReview
      Study protocol and CRF including:Inclusion/exclusion
      criteriaEfficacy
      parameters and measurementStudy
      scheduleComplete/evaluable
      patient definitionsStudy
      medication proceduresLab
      requirementsCRF
      completion instructionsReview
      adverse event reporting, including:Definition
      of AEs and SAEsRequirements
      for documentation collectionProper
      procedures for reporting SAEs to Sponsor and REBFollow-up
      requirementsReview
      Investigational BrochureReview
      communication channelsReview
      requirements for source documentationIRB/site
      responsibilitiesReview
      monitoring scheduleReview
      study site documentationTrain
      study coordinatorsReview
      PI contract and payment schedulePrepare
      study initiation visit reportSend
      site SIV report and ackg. FormPrep
                    
                    
                    
                    
                    
                    
                    
                    1
                    
                    1
                    
                    1
                    
                    CRATravel
                    
                    
                    
                    
                    
                    
                    
                    8
                    
                    1
                    
                    8
                    
                    CRAOn-Site
                    
                    
                    
                    
                    
                    
                    
                    5
                    
                    1
                    
                    5
                    
                    CRAReport
      Writing and Follow-up
                    
                    
                    
                    
                    
                    
                    
                    5
                    
                    1
                    
                    5
                    
                    CRA





CONFIDENTIAL


Page
20 of 36








MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





Sub-Total/site
                  
                  
                  
                  
                  
                  
                  
                  
                  
                  
                  
                  19
                  
                  CRATotal
                  
                  
                  
                  
                  
                  
                  
                  19
                  
                  20
                  
                  380
                  
                  CRAInterim
      Monitoring
                  
                  
                  
                  XSend
      confirmation letterComplete
      Monitors’ Sign-in LogVerify
      proper Informed Consent proceduresMonitor
      in accordance with protocol/ICH/GCP100%
      source document verification vs. CRFAssess
      patient eligibility (protocol inclusion/exclusion/randomization
      criteria)Provide
      site with written query records to be retained with each
    CRFReview
      study-related regulatory documentsReview
      monitoring & discrepancy report queriesSource
      verify data clarification/correction formsReview
      of laboratory dataReview
      and verify SAEs (100% SDV)Verify
      study drug inventory and storageVerify
      proper accountability and destruction of IP and study supplies per
      protocolMaintain
      protocol violation listMonitoring
      of other variables as specifiedPrepare
      monitoring visit reports following each monitoring visitProvide
      monitoring follow-up reports to sites following each visitRegulator
      contacts with sites & TC reportsOngoing
      training of site personnelCRF
      and query managementPrep
                  
                  
                  
                  
                  
                  
                  
                  2
                  
                  1
                  
                  2
                  
                  CRATravel
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  1
                  
                  8
                  
                  CRAOn-Site
                  
                  
                  
                  
                  
                  
                  
                  8
                  
                  1
                  
                  8
                  
                  CRAReport
      Writing and Follow-up
                  
                  
                  
                  
                  
                  
                  
                  5
                  
                  1
                  
                  5
                  
                  CRASub-Total/site
                  
                  
                  
                  
                  
                  
                  
                  
                  
                  
                  
                  23
                  
                  CRATotal
                  
                  
                  
                  
                  
                  
                  
                  23
                  
                  177
                  
                  4073
                  
                  CRAUn-Blinded
      CRA
                  
                  N/AClose
      Out Visit
                  
                  
                  
                  XCOV
      within 6 weeks post data base lockContact
      potential sites, confirm data for visitSend
      confirmation letterComplete
      Monitors’ Sign-in Log





CONFIDENTIAL


Page 21
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MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





Ensure
      site regulatory documentation is complete and accessible future
      auditsEnsure
      that the investigator is aware of his/her responsibilitiesFinancial
      Disclosure documentationEnsure
      that any remaining clinical trial material is removed from the study
      sitePrepare
      COV report following visitProvide
      follow-up report to sitesFollow-up
      with sites to resolve open issuesPrep
                
                
                
                
                
                
                
                2
                
                1
                
                2
                
                CRATravel
                
                
                
                
                
                
                
                8
                
                1
                
                8
                
                CRAOn-Site
                
                
                
                
                
                
                
                8
                
                1
                
                8
                
                CRAReport
      Writing and Follow-up
                
                
                
                
                
                
                
                5
                
                1
                
                5
                
                CRASub-Total/site
                
                
                
                
                
                
                
                
                
                
                
                23
                
                CRATotal
                
                
                
                
                
                
                
                23
                
                20
                
                460
                
                CRASite
      Management/Interaction (1hr/site/week)
                
                
                
                
                
                
                
                10
                
                134
                
                1340
                
                CRALead
      CRA
                
                N/AOverall
      Project ManagementTraining
      – protocol, project & therapy area
                
                
                
                XInitial
      PM training
                
                
                
                
                
                
                
                12
                
                1
                
                12
                
                PMPeriodic
      PM training
                
                
                
                
                
                
                
                8
                
                1
                
                8
                
                PMIn-house
      study managementSelection
      – CDN site
                
                X
                
                
                
                
                
                
                
                
                
                
                
                PMFeasibility
      from admin
                
                X
                
                
                
                
                
                
                
                
                
                
                
                PMConfidential
      Disc. Agreement
                
                X
                
                
                
                
                
                
                
                
                
                
                
                PMCDA
      approval
                
                X
                
                
                
                
                
                
                
                
                
                
                
                PMCRTRA
      template
                
                X
                
                
                
                
                
                
                
                
                
                
                
                PMCTRA
      template approval
                
                X
                
                
                
                
                
                
                
                
                
                
                
                PMCTRA
      negotiation
                
                X
                
                
                
                
                
                
                
                
                
                
                
                PMCTRA
      site sign off
                
                X
                
                
                
                
                
                
                
                
                
                
                
                PMPreparation
      of initial project specific reg pkg
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMReview
      received reg docs:site
      – QUI
                
                
                
                X
                
                
                
                0.25
                
                20
                
                5
                
                PMREBA
                
                
                
                X
                
                
                
                0.25
                
                20
                
                5
                
                PMCTSI
                
                
                
                X
                
                
                
                0.25
                
                20
                
                5
                
                PMConsent
      to Use Personal Data
                
                
                
                N/AProtocol
      signature page
                
                
                
                X
                
                
                
                0.25
                
                20
                
                5
                
                PMFinancial
      Disclosure
                
                
                
                X
                
                
                
                0.25
                
                20
                
                5
                
                PMCV
                
                
                
                X
                
                
                
                0.25
                
                20
                
                5
                
                PMMD
      qualification
                
                
                
                X
                
                
                
                0.25
                
                20
                
                5
                
                PM





CONFIDENTIAL


Page 22 of
36








MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





Internal
      project team meetings – biweekly
                
                
                
                X
                
                
                
                1
                
                61
                
                61
                
                PMSite
      level management
                
                
                
                X
                
                
                
                8
                
                20
                
                160
                
                PMWeekly
      Regular status reports for client
                
                
                
                X
                
                
                
                1
                
                122
                
                122
                
                PMLiaise
      weekly with sponsor
                
                
                
                X
                
                
                
                1
                
                122
                
                122
                
                PMTMF
      set-up and maintenance oversight
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMSite
      budge set-up
                
                XPayment
      calculation (quarterly)
                
                
                
                X
                
                
                
                1
                
                160
                
                160
                
                PMPayment
      tracking
                
                
                
                X
                
                
                
                0.5
                
                160
                
                80
                
                PMPayment
      issuance
                
                
                
                X
                
                
                
                0.25
                
                160
                
                40
                
                PMSOPs
      assignment documentation
                
                
                
                X
                
                
                
                3
                
                1
                
                3
                
                PMResponsibility
      assignment
                
                
                
                X
                
                
                
                1
                
                1
                
                1
                
                PMPreparation
      of Project Plan (1 review)
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMPreparation
      of Monitoring Plan (1 review)
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMPreparation
      of Visit Booklet (1 review)
                
                
                
                X
                
                
                
                12
                
                1
                
                12
                
                PMDevelopment
      of Pharmacy Manual (1 review)
                
                
                
                X
                
                
                
                12
                
                1
                
                12
                
                PMDevelopment
      of SAE Plan
                
                
                
                X
                
                
                
                16
                
                1
                
                16
                
                PMDevelopment
      of Recruitment Plan
                
                
                
                X
                
                
                
                12
                
                1
                
                12
                
                PMReview
      of Monitoring Trip Reports
                
                
                
                X
                
                
                
                1
                
                177
                
                178
                
                PMPrep.
      Of Study specific formsPrep.
      Study specific tracking tools
                
                
                
                X
                
                
                
                12
                
                1
                
                12
                
                PMQoL,
      questionnaires and/or patient diaries, patient (alert)
    cards)
                
                
                
                X
                
                
                
                12
                
                1
                
                12
                
                PMDrug
      Accountability Form
                
                
                
                X
                
                
                
                4
                
                1
                
                4
                
                PMIndividual
      Subject Drug logs
                
                
                
                X
                
                
                
                4
                
                1
                
                4
                
                PMDrug
      Return & Reconciliation Form
                
                
                
                X
                
                
                
                4
                
                1
                
                4
                
                PMClinical
      Re-supplies Form
                
                
                
                X
                
                
                
                1
                
                1
                
                1
                
                PMDrug
      Receipt Form
                
                
                
                X
                
                
                
                1
                
                1
                
                1
                
                PMRelease
      of IP (RIP) Form
                
                X
                
                (X)
                
                
                
                1
                
                1
                
                1
                
                PMDestruction
      of IP (DIP) Form
                
                X
                
                (X)
                
                
                
                1
                
                1
                
                1
                
                PMStudy
      specific tracking tools
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMInvestigational
      Product (IP) and other Clinical Study SuppliesLabeling,
      coding and packing of IP (including provision of sample
      labels)
                
                XComparator
      Procurement
                
                XPreparation
      of written instructions for handling and storage of IP
                
                XRequest
      for import/export approvals for IP
                
                XPreparation
      of custom clearance(s)
                
                XStorage
      of IP oversight
                
                XRequest
      for authorization to release IP oversight
                
                X





CONFIDENTIAL


Page 23
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MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





Authorization
      to distribute drug
                
                XPackaging/labelling
      of Clinical Supplies Oversight
                
                XDistribution
      of Clinical Study Supplies to sites
                
                XTracking
      of IP
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMTracking
      of Clinical Study Supplies
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMOrganization
      of destruction of unused Clinical Study Supplies
                
                
                
                X
                
                
                
                12
                
                1
                
                12
                
                PMStudy
      Completion/Study TerminationNotification
      to national/local authorities of study termination
                
                XFinal
      recon of TMF
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMArchiving
      of Sponsor’s TMF
                
                
                
                X
                
                
                
                8
                
                1
                
                8
                
                PMPM
      – Pre-Study/Specific Task Sub-Total
                
                
                
                
                
                
                
                
                
                
                
                1158
                
                PMLocal
      Management Sub-Total (est. hours/week x # wks)
                
                
                
                
                
                
                
                10
                
                104
                
                1040
                
                PMEx-house
      Project Management
                
                XCo-Initiation/Monitoring/COV
                
                
                
                XPrep
                
                
                
                
                
                
                
                1
                
                1
                
                1
                
                PMTravel
                
                
                
                
                
                
                
                12
                
                1
                
                12
                
                PMOn-Site
      (average)
                
                
                
                
                
                
                
                8
                
                1
                
                8
                
                PMAdmin
                
                
                
                
                
                
                
                3
                
                1
                
                3
                
                PMSub-Total/site
                
                
                
                
                
                
                
                
                
                
                
                24
                
                PMTotal
                
                
                
                
                
                
                
                24
                
                4
                
                96
                
                PMAd
      hoc meetings
                
                
                
                XPrep
                
                
                
                
                
                
                
                1
                
                1
                
                1
                
                PMTravel
                
                
                
                
                
                
                
                12
                
                1
                
                12
                
                PMOn-Site
      (average)
                
                
                
                
                
                
                
                8
                
                1
                
                8
                
                PMAdmin
                
                
                
                
                
                
                
                3
                
                1
                
                3
                
                PMSub-Total/Mtg
                
                
                
                
                
                
                
                
                
                
                
                24
                
                PMTotal
                
                
                
                
                
                
                
                24
                
                12
                
                240
                
                PMAdministration
      – COA & Document ManagementStart
      Up Documentation Activities
                
                (X)
                
                XAssemble
      site reg. packages
                
                
                
                
                
                
                
                1.25
                
                20
                
                25
                
                COACourier
      packages to sites
                
                
                
                
                
                
                
                0.25
                
                20
                
                5
                
                COAInitial
      review of Regulatory Documents
                
                
                
                
                
                
                
                1.5
                
                20
                
                30
                
                COAReceive,
      log, scan & file initial reg docs
                
                
                
                
                
                
                
                1.5
                
                20
                
                30
                
                COAFollow-up
      on reg doc errors & omissions
                
                
                
                
                
                
                
                0.5
                
                15
                
                7.5
                
                COACourier
      – second round
                
                
                
                
                
                
                
                0.25
                
                15
                
                3.75
                
                COASecond
      review of regulatory documents
                
                
                
                
                
                
                
                0.5
                
                15
                
                7.5
                
                COAReceive,
      log, scan & file 2nd
      round reg docs
                
                
                
                
                
                
                
                1
                
                15
                
                15
                
                COA





CONFIDENTIAL


Page 24
of 36








MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





Identify
      Table of Contents for ISF/IHF/GSF
                
                
                
                
                
                
                
                1
                
                1
                
                1
                
                COAAssemple
      PI Site Files (ISF) for TMF
                
                
                
                
                
                
                
                1.5
                
                20
                
                30
                
                COACourier
      site ISF to PI
                
                
                
                
                
                
                
                0.25
                
                20
                
                5
                
                COAAssemble
      In-House site File (IHF) (GSF) for TMF
                
                
                
                
                
                
                
                1
                
                20
                
                20
                
                COACrease
      eTMF folders
                
                
                
                
                
                
                
                8
                
                1
                
                8
                
                COACRF
      related admin
                
                
                
                N/ACDA
      – send to sites; review; send to Client
                
                XCTRA
      – send to sites; review; send to Client
                
                XGeneral
      Admin
                
                
                
                XPost
      tracking tools to web for clientAssist
      with IRB/reg. authority submissionsOngoing
      regulatory doc. tracking /scanningContact
      sites for enrolment updatesHigh
      level site supportAssist
      with query resolutionTC
      minutesCOA
      General Admin Total
                
                
                
                
                
                
                
                15
                
                122
                
                1830
                
                COAGeneral
      –TMF (Document Management)
                
                
                
                XDocument
      receipt & sortingDocument
      review for completenessManagement
      of deficienciesScanning
      & hard copy filinge-naming
      & e-filingMaintenance
      of document tracking toolOngoing
      review of TMF for completenessOngoing
      document retrieval and re-filingFax,
      email or courier docs to CRAs/SponsorReturn
      of Sponsor’s TMFDocument
      Management General TMF Total (hrs/week)
                
                
                
                
                
                
                
                10
                
                122
                
                1220
                
                DOCAllphase
      Center of Excellence (ACE) Training
                
                N/AMedical
      Writing
                
                N/AQuality
      AssuranceFamiliarization
      with client SOPs (if applicable)
                
                
                
                XFamiliarization
      with protocol
                
                
                
                XInspection
      of site regulatory files
                
                
                
                XReview
      and assessment of site SOPs
                
                
                
                XRandom
      sampling of source & CRF data
                
                
                
                XDiscussion
      with site personnel re: processes and findings
                
                
                
                X





CONFIDENTIAL


Page 25 of
36








MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





Inspection
      of client TMF regulatory files
                
                
                
                XReview
      of vendor facilities, SOPs, processes
                
                
                
                XDiscussion
      with vendor personnel re: processes and findings
                
                
                
                XPreparation
      of audit report
                
                
                
                XFollow-up
      resolutions
                
                
                
                XVendor
      Audits
                
                N/ASite
      Audits
                
                
                
                XPrep
                
                
                
                
                
                
                
                8Travel
                
                
                
                
                
                
                
                12On-Site
                
                
                
                
                
                
                
                16Admin/Report
      Writing
                
                
                
                
                
                
                
                12Sub-Total
                
                
                
                
                
                
                
                48
                
                3
                
                144
                
                QATMF
      Audit
                
                
                
                N/APrep
                
                
                
                
                
                
                
                8Travel
                
                
                
                
                
                
                
                8On-Site
                
                
                
                
                
                
                
                32Admin/Report
      Writing
                
                
                
                
                
                
                
                12Sub-Total
                
                
                
                
                
                
                
                60
                
                0
                
                0
                
                QASafetyOverall
      Medical Oversight
                
                (X)
                
                X24/7
      coverage
                
                
                
                
                
                
                
                0.25
                
                104
                
                26
                
                MMConsultation
      with sites
                
                
                
                
                
                
                
                0.25
                
                88
                
                22
                
                MMConsultation
      with Client
                
                
                
                
                
                
                
                1
                
                9
                
                9
                
                MMProtocol
      deviation decision making and management (as required)
                
                
                
                
                
                
                
                0.75
                
                9
                
                6.75
                
                MMSAE
      Trend Analysis
                
                
                
                
                
                
                
                8
                
                1
                
                8
                
                MMLab
      alert review
                
                
                
                
                
                
                
                1
                
                4
                
                4
                
                MMProtocol
      deviation processing and tracking
                
                
                
                
                
                
                
                0.75
                
                88
                
                66
                
                PMAE/SAE
      Database Setup
                
                N/ASAE
      Collection, Processing & Reporting
                
                (X)
                
                XReview
      of SAE Plan
                
                
                
                
                
                
                
                4
                
                1
                
                4
                
                MMSAE
      report receipt, processing & follow-up
                
                
                
                
                
                
                
                3
                
                44
                
                132
                
                DSCIOMs
      generation
                
                
                
                
                
                
                
                3
                
                9
                
                27
                
                DSSubmit
      Alert Reports to Reg. Agencies/IRB/Sponsor
                
                
                
                
                
                
                
                2
                
                9
                
                18
                
                DSSubmit
      SAE Reports to Sites
                
                
                
                
                
                
                
                1.5
                
                9
                
                13.5
                
                DSAnnual
      safety reporting
                
                
                
                
                
                
                
                16
                
                2
                
                32
                
                PMTeleconferences
      with Sponsor
                
                
                
                
                
                
                
                2
                
                9
                
                18
                
                MMSAE
      Medical Evaluation
                
                (X)
                
                X
                
                
                
                
                
                
                
                
                
                MM




CONFIDENTIAL


Page 26 of
36








MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





SAE
      review of report & supporting info
                
                
                
                
                
                
                
                0.75
                
                44
                
                33
                
                MMSAE
      Narrative
                
                
                
                
                
                
                
                0.75
                
                44
                
                33
                
                MMData
      Safety Monitoring BoardFormation
      and Management
                
                (X)
                
                XProvide
      3 suitable board members (2MD; 1 Biostat) & facilitate (3) meetings by
      teleconference
                
                
                
                
                
                
                
                24
                
                1
                
                24
                
                PMOrganize
      DSMB meetings
                
                
                
                
                
                
                
                12
                
                3
                
                36
                
                PMInteract
      with sponsor regarding conclusions
                
                
                
                
                
                
                
                8
                
                3
                
                24
                
                PMImplement
      next steps
                
                
                
                
                
                
                
                8
                
                3
                
                24
                
                PMCharter,
      SOPs, Meeting #1
                
                (X)
                
                XCreation
      of draft & final SOP, Charter, Open & Closed Report format;
      provide support/advice for creating DSMB and defining its duties &
      responsibilities for the project
                
                
                
                
                
                
                
                24
                
                1
                
                24
                
                PMMeeting
      #1 (PM): discussion of protocol, procedures, role & functioning of
      DSMB
                
                
                
                
                
                
                
                6
                
                1
                
                6
                
                PMMeeting
      #1 (COA): Attendance & Minutes
                
                
                
                
                
                
                
                8
                
                1
                
                8
                
                COAMeeting
      #1 (MM): discussion of protocol, procedures, role & functioning of
      DSMB
                
                
                
                
                
                
                
                6
                
                1
                
                6
                
                MMMeeting
      #1 (BIO): discussion of protocol, procedures, role & functioning of
      DSMB
                
                X
                
                
                
                
                
                
                
                
                
                
                
                BIOAdministration
                
                
                
                XDistribute
      meeting materials
                
                
                
                
                
                
                
                2
                
                3
                
                6
                
                COAMM:
      Review of protocol & related changes, SAP, minutes, reports,
      etc.
                
                
                
                
                
                
                
                16
                
                1
                
                16
                
                MMBIO:
      Review of protocol & related changes, SAP, minutes, reports,
      etc.
                
                X
                
                
                
                
                
                
                
                
                
                
                
                BIOBoard
      Member Participation & Evaluation
                
                
                
                XMM x
      2: Meetings #2 (closed) & #3 (open) by teleconference
                
                
                
                
                
                
                
                12
                
                2
                
                24
                
                MMBIO:
      Meetings #2 (closed) & #3(open) by teleconference
                
                X
                
                
                
                
                
                
                
                
                
                
                
                BIOPreparation
      of Open & Closed minutes (non-CRO personnel)
                
                
                
                
                
                
                
                8
                
                2
                
                16
                
                COABIO:
      preparation of Open & Closed reports
                
                X
                
                
                
                
                
                
                
                
                
                
                
                BIODM:
      preparation of database extract for Open & Closed
    reports
                
                X
                
                
                
                
                
                
                
                
                
                
                
                DMData
      Management
                
                N/ABiostatistical
      Services
                
                N/AData
      Management – Licenses and Fees
                
                N/A





CONFIDENTIAL


Page 27 of
36








MSA#:
              YMB07-MSA-17MAY2007
              WO
      Version Code:
              YMB08-WO5-15DEC2008-3.0Version
      Date:
              16DEC2008
              Work
      Order #:
              WO5





6.
Estimate





Based on
the information provided, we have prepared an estimate which we feel is
reasonable at this time. Please be assured that Allphase Clinical
Research strives to economize appropriately whenever possible. Based on the
preceding section of this proposal, the following labour costs have been
estimated, in Canadian dollars. Travel related expenses are to be reimbursed by
the client separately. Allphase reserves the right to revise this estimate if
the assumptions provided herein change. Once executed, revisions to this Work
Order will be documented using a Scope Change process. If the accumulated
Scope Change value exceeds 10% of the estimated labour total, a Change
Order will be processed.





6
a. Summary – Client Template





YM
      BioSciences Inc.
              5045
      Orbitor Drive, Building 11, Suite 400
                Mississauga,
      Ontario, Canada L4W 4Y4
                Telephone:
      905.629.9761
                Facsimile:
      905.629.4959
                Website:
      www.ymbiosciences.com





CRO-Estimated Project Cost
Outline


Executive
Summary





CRO Name:Allphase Clinical
Research Inc.


Project:Palliative
Radiotherapy


Date:10DEC2008





Project
      Start-up/Initiation:
                        
                        CostCRF
      Design
                        
                        Included under DM
      estimateGrant
      Payment Administration
                        
                        
                        28,000.00Critical
      Document Collection/TMF Set-up/QA/Site ID &
Feasibility
                        
                        
                        21,381.25Monitoring
      Plan/CRA manual
                        
                        
                        2,000.00Site
      Binders/Study Procedures (reference) Manual
                        
                        
                        1,200.00Sub-Total:
                        
                        $
                        52,631.25




Investigator
      Meeting:
                        
                        CostInvestigator
      meeting set-up/Coordination
                        
                        
                        12.575.00Investigator
      meeting preparation/Attendance
                        
                        
                        18,710.00Sub-Total:
                        
                        $
                        31,285.00





CONFIDENTIAL


Page 28 of
36


MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
  Clinical
      Site Monitoring and Site Management:
                          
                          CostProject
      team training/Familiarization
                          
                          
                          10,380.00Site
      Selection Visits
                          
                          
                          0.00Site
      Initiation Visits
                          
                          
                          34,200.00Interim
      Site Monitoring Visits
                          
                          
                          366,597.00Interim
      Site Monitoring Visits (follow-up)
                          
                          included in
      aboveSite
      Close-out Visits
                          
                          
                          41,400.00Site
      Interaction (Telephone Contact)
                          
                          
                          93,600.00Query
      Management
                          
                          included in site
      visitsEssential
      Document/Site file Maintenance
                          
                          included in site
      visitsTrial
      Master File reconciliations
                          
                          included in site
      visitsClinical
      Monitoring Oversight (PM)
                          
                          
                          17,800.00Project
      Kick-off meeting
                          
                          
                          7,160.00Mid-Study
      project team meeting
                          
                          
                          7,160.00Teleconferences
      with YM BioSciences
                          
                          
                          28,670.00Internal
      Team Meetings
                          
                          
                          6,100.00Sub-Total:
                          
                          $
                          613,067.00
  Medical
      Management:
                          
                          CostProject
      Team training/Familiarization
                          
                          
                          1,400.00Medical
      Monitoring (includes DSMB involvement)
                          
                          
                          49,212.50Review
      of AE Coding
                          
                          included under DM
      estimateAnnual
      Safety Reporting
                          
                          
                          11,200.00Project
      Kick-off meeting
                          
                          
                          2,450.00Teleconferences
      with YM BioSciences
                          
                          
                          6,300.00Internal
      Team meetings
                          
                          
                          2,450.00Sub-Total:
                          
                          $
                          73,012.50
 
 CONFIDENTIAL
 Page 29 of
36
  
  MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
  Pharmacovigilance:
                        
                        CostProject
      Team Training/Familiarization
                        
                        included in Med Mgmt
      aboveCreate
      SAE Management Plan
                        
                        
                        1,400.00SAE
      Processing
                        
                        
                        27,900.00Safety
      Narratives Writing
                        
                        
                        14,250.00SAE
      Reconciliation
                        
                        Included under DM
      estimateSub-Total:
                        
                        $
                        43,550.00
  Quality
      Assurance Site Audits:
                        
                        CostQA
      Site Audits
                        
                        
                        14,400.00Sub-Total:
                        
                        $
                        14,400.00
  Project
      Management and Administrative Support:
                            
                            CostProject
      Management and Support
                            
                            
                            349,325.00Regulatory
      Document/Site File Maintenance
                            
                            
                            91,500.00Sub-Total:
                            
                            $
                            440,875.00
 Total
      Labour:
                          
                          $
                          1,268,770.75Pass-Through
      Expenses:
                          
                          $
                          286,913.50ACTUAL
      TOTAL ESTIMATED PROJECT COST:
                          
                          $
                          1,555,684.25
  CONFIDENTIAL Page 30 of
36
  
  MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
  6
b. Summary – Allphase Template
 
 Service
                                                                                                                                  
                                                                                                                                  Resp.
                                                                                                                                  
                                                                                                                                  Approx.
                                                                                                                                    # hours
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  Hourly
                                                                                                                                    Rate
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  TOTALSProject
      Management (PM)Pre-Study
      Activities
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  1,200
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  120,000Local
      Investigator’s Meeting
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  97
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  9,700Ethics
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  170.75
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  17,075Co-Initiation/IMV/COV
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  96
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  9,600Ad
      hoc meetings
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  240
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  24,000Safety
      - SAE
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  80
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  7,950Safety
      – DSMB
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  138
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  13,800Local
      Management
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  1,040
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  104,000Sub-Total
                                                                                                                                  
                                                                                                                                  PM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  3,061
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  306,125Scientific
      AffairsPre-Study
      Activities
                                                                                                                                  
                                                                                                                                  DIR
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  4
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  120
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  480Sub-Total
                                                                                                                                  
                                                                                                                                  DIR
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  4
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  120
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  480Clinical
      Monitoring (CRA)Pre-Study
      Activities
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  144
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  12,960Local
      Investigator’s Meeting
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  104
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  9,360Teleconferences
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  183
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  16,470Training
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  64
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  5,760Site
      Selection Visits
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  0
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  0Initiation
      Visits
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  380
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  34,200Interim
      Monitoring
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  4073
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  366,597Close-Out
      Visit
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  460
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  41,400Site
      Management/Interaction
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  1040
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  93,600Sub-Total
                                                                                                                                  
                                                                                                                                  CRA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  6448
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  90
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  580,347Clinical
      Operations Associate (COA)Pre-Study
      & Specific Tasks
                                                                                                                                  
                                                                                                                                  COA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  208
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  75
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  15,581Local
      Investigator’s Meeting
                                                                                                                                  
                                                                                                                                  COA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  107
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  75
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  8,025DSMB
                                                                                                                                  
                                                                                                                                  COA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  30
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  75
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  2,250General
                                                                                                                                  
                                                                                                                                  COA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  1,830
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  75
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  137,250Sub-Total
                                                                                                                                  
                                                                                                                                  COA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  2175
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  75
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  163,106Document
      Management Associate (DOC)General
      TMF Maintenance
                                                                                                                                  
                                                                                                                                  DOC
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  1220
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  75
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  91,500Sub-Total
                                                                                                                                  
                                                                                                                                  DOC
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  1220
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  75
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  91,500Quality
      Assurance (QA)Site
      Audits
                                                                                                                                  
                                                                                                                                  QA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  144
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  14,400TMF
      Audit
                                                                                                                                  
                                                                                                                                  QA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  0
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  0Sub-Total
                                                                                                                                  
                                                                                                                                  QA
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  144
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  14,400Drug
      Safety - ManagementDrug
      Safety
                                                                                                                                  
                                                                                                                                  DS
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  177
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  17,700Sub-Total
                                                                                                                                  
                                                                                                                                  DS
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  177
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  100
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  17,700Medical
      MonitoringPre-Study
      Activities
                                                                                                                                  
                                                                                                                                  MM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  18
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  350
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  6,300Local
      Investigator’s Meeting
                                                                                                                                  
                                                                                                                                  MM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  12
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  350
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  4,200Medical
      Monitoring
                                                                                                                                  
                                                                                                                                  MM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  196
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  350
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  68,513DSMB
                                                                                                                                  
                                                                                                                                  MM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  46
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  350
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  16,100Sub-Total
                                                                                                                                  
                                                                                                                                  MM
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  272
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  350
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  95,113Estimated
      Project Operational – Sub-Total
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  1,268,771Estimated
      Project Pass-Through Costs – Sub-Total
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  286,914Estimated
      Project - Total
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  1,555,684Estimated
      Project – Total/patient (Labour only)
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  14,418Estimated
      Project – Total/patient (Labour and pass-through)
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  $
                                                                                                                                  17,678
  CONFIDENTIAL
 Page 31 of
36
  
 
 MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
  7.
Estimated Pass-Through Expenses
  TOTALS
      (CDN)Pass-Through
      Expenses
                    
                    
                    
                    
                    Unit
      Cost
                    
                    
                    #
      Units
                    
                    
                    Total
      CostTravel
      Expenses (1 Day Trip)
                    
                    
                    75
                    %
                    
                    
                    200.00
                    
                    
                    
                    190
                    
                    
                    $
                    38,000Travel
      Expenses (2 Day Trip)
                    
                    
                    25
                    %
                    
                    
                    800.00
                    
                    
                    
                    63
                    
                    
                    $
                    50,400Meal
      Expenses - day trip
                    
                    per
      day
                    
                    
                    
                    30.00
                    
                    
                    
                    190
                    
                    
                    $
                    5,700Monitor
      Overnight Expenses (ie. Hotel)
                    
                    per
      trip
                    
                    
                    
                    200.00
                    
                    
                    
                    126
                    
                    
                    $
                    25,200Meal
      Expenses - overnight
                    
                    
                    
                    
                    
                    
                    60.00
                    
                    
                    
                    126
                    
                    
                    $
                    7,560Quality
      Assurance / Site Audit
                    
                    per
      trip
                    
                    
                    
                    1,500.00
                    
                    
                    
                    3
                    
                    
                    $
                    4,500Allphase
      & Client Meeting Expenses
                    
                    per
      person
                    
                    
                    
                    600.00
                    
                    
                    
                    10
                    
                    
                    $
                    6,000Miscellaneous
      Expenses (consumables* and communication costs) = $120 pp/month (active
      period)/CRA
                    
                    per
      month
                    
                    
                    
                    120.00
                    
                    
                    
                    97
                    
                    
                    $
                    11,640Miscellaneous
      Expenses (consumables* and communication costs) = $120 pp/month for the
      entire study duration: 1PM & 1 COA
                    
                    per
      month
                    
                    
                    
                    120.00
                    
                    
                    
                    57
                    
                    
                    $
                    6,840CRF
      Printing
                    
                    per
      CRF
                    
                    
                    
                    50.00
                    
                    
                    
                    0
                    
                    
                    $
                    0Diaries
      in French and English
                    
                    
                    
                    
                    
                    TBDTranslation
                    
                    
                    
                    
                    
                    TBDTeleconferences
                    
                    per
      conf.
                    
                    
                    
                    25.00
                    
                    
                    
                    61.00
                    
                    
                    $
                    1,525Mailing
                    
                    per
      letter
                    
                    
                    
                    2.00
                    
                    
                    
                    293.00
                    
                    
                    $
                    586Courier
                    
                    per
      package
                    
                    
                    
                    25.00
                    
                    
                    
                    122.00
                    
                    
                    $
                    3,050Finance
      Couriers (expenses)
                    
                    per
      package
                    
                    
                    
                    25.00
                    
                    
                    
                    30.50
                    
                    
                    $
                    763Newsletters
                    
                    per
      newsletter
                    
                    
                    
                    2.00
                    
                    
                    
                    0
                    
                    
                    $
                    0TMF
      Regulatory Binders
                    
                    per
      site
                    
                    
                    
                    50.00
                    
                    
                    
                    20
                    
                    
                    $
                    1,000Regulatory
      Binders
                    
                    per
      site
                    
                    
                    
                    50.00
                    
                    
                    
                    20
                    
                    
                    $
                    1,000Study
      Reference Binders
                    
                    per
      site
                    
                    
                    
                    50.00
                    
                    
                    
                    20
                    
                    
                    $
                    1,000Investigator
      Grants
                    
                    per
      patient
                    
                    
                    TBD
                    
                    
                    
                    88Ethics
      Committee/IRB Fees
                    
                    per
      site
                    
                    
                    TBD
                    
                    
                    
                    0Insurance
                    
                    per
      site
                    
                    
                    TBD
                    
                    
                    
                    0Advertising
                    
                    per
      site
                    
                    
                    TBD
                    
                    
                    
                    0Pharmacy
      Set up fees
                    
                    per
      site
                    
                    
                    TBD
                    
                    
                    
                    0
 
 CONFIDENTIAL
 Page 32 of
36
  
 
 MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
 
 Sub-Total:
                                      
                                      
                                      $
                                      164,764Local
      Investigator’s MeetingInvestigator
      Meeting Airfare - site staff (PI business, CRC economy)
                                      
                                      
                                      per
      site
                                      
                                      
                                      
                                      1,950.00
                                      
                                      
                                      
                                      40
                                      
                                      
                                      $
                                      78,000Investigator
      Meeting Airfare - Allphase staff (all economy)
                                      
                                      
                                      per
      person
                                      
                                      
                                      
                                      900.00
                                      
                                      
                                      
                                      3
                                      
                                      
                                      $
                                      2,700Investigator
      Meeting Hotel - site staff (3 nights)
                                      
                                      
                                      per
      person
                                      
                                      
                                      
                                      750.00
                                      
                                      
                                      
                                      40
                                      
                                      
                                      $
                                      30,000Investigator
      Meeting Hotel - Allphase staff (3 nights)
                                      
                                      
                                      per
      person
                                      
                                      
                                      
                                      750.00
                                      
                                      
                                      
                                      3
                                      
                                      
                                      $
                                      2,250Transportation
      and meals
                                      
                                      
                                      per
      person
                                      
                                      
                                      
                                      200.00
                                      
                                      
                                      
                                      46
                                      
                                      
                                      $
                                      9,200Sub-Total:
                                      
                                      
                                      $
                                      122,150Total
                                      
                                      
                                      $
                                      286,914
  Note:
*Consumable volume limited to 500 B&W and 100 colour copies/prints per
month. Excess will be billed at $0.05 per page for B&W; $0.25 per page for
colour.
 
 CONFIDENTIAL
 Page 33 of
36
  
 
 MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
  8.
Payment Schedule and Terms
  A deposit
of 15% ($190,316 CDN) of
the estimated project total is to be paid upon initiation of this contract.
Detailed invoices will be submitted to Client monthly.
 
 ·
              Monthly
      labour invoices will be issued
 ·
              Expense
      invoices to be issued once original receipts have been collected from
      personnel.
 ·
              Expenses
      related to courier, teleconferencing, and communication & consumables
      will be summarized on expense invoices. Original documentation will not be
      provided but is available for review for an additional fee (labour
      required to anonymize).
 ·
              Applicable
      taxes on labor will be indicated on
invoice.
 ·
              Payment
      terms are 30 days from receipt of
invoice.
 ·
              2%
      per month financing fee may be applied to outstanding balance
      owing.
 ·
              Sponsor
      authorization will be obtained if budget exceeds 10% of
      estimate.
 ·
              The
      Client acknowledges that upon execution of the full Work Order, Allphase
      will dedicate personnel to this Project, on a full time or part time basis
      as appropriate. If after 90 days following the date of execution of this
      Work Order (exclusive of the letter of Intent provisions) the project is
      delayed for greater than 30 days for reasons beyond the control of
      Allphase (e.g. regulatory hold), if Client wishes to retain the assigned
      project team, Client agrees to pay Allphase its direct costs per assigned
      employee. This value will be calculated based on the average number of
      hours billed per individual over the preceding 3 months. This will be a
      daily calculation starting on day 31 post written notification of the
      effective date of the delay. If billable work continues during the delay
      period and the value of this work is at least equal to Allphase direct
      costs, then no additional fee will be levied. Alternately, Allphase may
      re-assign personnel to other Projects, or Client and Allphase may
      negotiate alternate arrangements to minimize the economic impact on both
      Parties.
 
 9.
Standard Practices
  Allphase
Clinical Research will manage the project using industry best practice and will
endeavor to perform the work at or below cost and schedule. Please be assured
that Allphase strives to economize appropriately whenever possible. The client
will be consulted regarding the possibility of deviating from the scope of work
defined within this proposal.
 
 Allphase
Standard Operating Procedures (SOP) or client SOPs can be used for this
project.
 
 Allphase
Clinical Research is an insured and incorporated company.
 
 CONFIDENTIAL
 Page 34 of
36
  
 
 MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
  10.
Client Signatures
  The
details as described in the version on the Work Order referenced in the header
of this document are acceptable. Any significant change in the terms or
requirements of this Work Order will be managed in accordance with section 2.2
of the above referenced Master Services Agreement.
 
 IN
WITNESS WHEREOF, this Agreement has been executed by the Parties hereto through
their duly authorized officers on the date(s) set forth below.
 
 Agreed
and accepted
 
 YM
BioSciences Inc.
 
 Signature:
                    
                    
                    Signature:Date:
      December 24, 2008
                    
                    Date:
      January 5, 2009Name/Title:
      David Allan/Chairman & CEO
                    
                    Name/Title:
      Jeff Smith/PresidentI
      have the authority to bind the corporation.
                    
                    I
      have the authority to bind the
corporation.
  If
the details of this Work Order require further refining and the parties wish to
initiate work on the project prior to finalizing the Work Order, the Letter of
Intent of section 11of this Work Order may be executed.
 
 CONFIDENTIAL
 Page 35 of
36
  
 
 MSA#:
                YMB07-MSA-17MAY2007
                WO
      Version Code:
                YMB08-WO5-15DEC2008-3.0Version
      Date:
                16DEC2008
                Work
      Order #:
                WO5
  11.
Letter of Intent
  Further
to contact regarding the "A Randomized, Phase II, Double-Blind Study Nimotuzumab
Plus Whole-Brain Radiation Therapy (WBRT) Compared With WBRT Alone in Patient
With Brian Metastases From Non-Small Cell Lung Cancer.” Study, YM BioSciences
(YMB) confirms the intent to place a contract with ALLPHASE Clinical Research
Inc. (ALLPHASE) for clinical services in relation to this project.
 
 As the
above referenced Work Order for this project is being negotiated between YMB and
ALLPHASE, YMB authorises ALLPHASE to begin the necessary preparations for the
project upon written approval of individual tasks.
 
 YMB will
prepay 15% equal to $190,316 Canadian dollars of
the estimated project total under this Letter of Intent. It is understood that
ALLPHASE will not make any financial commitments extending beyond the above
mentioned value, before a signed Work Order has been executed by the parties.
The prepaid amount under this Letter of Intent will be reconciled against
subsequent payments for this study as agreed in the final contract.
 
 ALLPHASE
agrees that all information disclosed under this Letter of Intent is
confidential and property of YMB and agrees not to disclose or use such
information without prior written approval of YMB.
 
 In the
event that no final contract can be executed between YMB and ALLPHASE by 31
January 2009, ALLPHASE shall remit YMB the amount already paid having deducted
any fees or expenses already incurred by ALLPHASE at the time of such decision.
YMB shall have the right to audit ALLPHASE records regarding this
project.
 
 This
Letter of intent is to be signed by the parties.
 
 Agreed
      and accepted
                    
                    Agreed
      and acceptedYM
      BioSciences Inc.
                    
                    ALLPHASE
      Clinical Research Inc.Date:
      December 24, 2008
                    
                    Date:
      January 5, 2009Signature:
                    
                    
                    Signature:Name/Title:
      David Allan/Chairman & CEO
                    
                    Name/Title:
      Jeff Smith/President
                      I
      have the authority to bind the
corporation.
 
 Date:
 
 Signature:Name/Title:
  We have
the authority to bind the corporation.
 
 CONFIDENTIAL
 Page 36 of
36