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UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549

FORM 40-F

(Check One)

[   ]  Registration statement pursuant to Section 12 of
the Securities Exchange Act of 1934 or

[X]  Annual report pursuant to section 13(a) or 15(d) of
the Securities Exchange Act of 1934

For the fiscal year ended December 31, 2015

Commission file number1-36596

TRILLIUM THERAPEUTICS INC.(Exact name of registrant as specified in its charter)

|Ontario, Canada                    | 2834                         | Not applicable                        
|---------------------------------- | ---------------------------- | --------------------------------------
|(Province or other jurisdiction of | (Primary Standard Industrial | (I.R.S. Employer                      
|incorporation or organization)     | Classification Code Number   | Identification Number (if applicable))
|(if applicable))                  

96 Skyway Avenue, Toronto, Ontario, Canada M9W 4Y9
Telephone: (416) 595-0627(Address and Telephone Number of
Registrants Principal Executive Offices)

Puglisi & Associates, 850 Library Avenue, Suite 204,
Newark, Delaware 19711 Telephone: (302) 738-6680(Name,
Address (Including Zip Code) and Telephone Number (Including Area Code) of
Agent For Service in the United States)

Securities registered or to be registered pursuant to Section
12(b) of the Act.

|Title of each class | Name of each exchange on which
      registered
|------------------- | -----------------------------------------------
|Common Shares       | The NASDAQ Stock Market LLC                    

Securities registered or to be
registered pursuant to Section 12(g) of the Act. None

Securities for
which there is a reporting obligation pursuant to Section 15(d) of the Act.
None

For annual reports, indicate by check mark the information filed
with this Form:

|[X]  Annual Information Form | [X]  Audited Annual Financial
      Statements
|---------------------------- | ----------------------------------------------

Indicate the number of outstanding shares of each of the
issuers classes of capital or common stock as of the close of the period
covered by the annual report: 7,796,137 common shares

Indicate by check mark whether the registrant: (1) has filed
all reports required to be filed by Section 13 or 15(d) of the Securities
Exchange Act of 1934 (the Exchange Act) during the preceding 12 months (or for
such shorter period that the registrant was required to file such reports); and
(2) has been subject to such filing requirements for the past 90 days.

Yes [X]       No [   ]

Indicate by check mark whether the registrant has submitted
electronically and posted on its corporate Web site, if any, every Interactive
Data File required to be submitted and posted pursuant to Rule 405 of Regulation
S-T (s.232.405 of this chapter) during the preceding 12 months (or for such
shorter period that the registrant was required to submit and post such files).

Yes  [   ]       No  [   ]

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FORM 40-F

Principal Documents

The following documents, filed as Exhibits 99.1, 99.2 and 99.3
to this Annual Report on Form 40-F, are hereby incorporated by reference into
this Annual Report on Form 40-F:

| | (a) | Annual Information Form for the fiscal year ended
      December 31, 2015;                                                                                                                                                       
| | --- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
| |     |                                                                                                                                                                                                                                  
| | (b) | Managements Discussion and Analysis for the years ended
      December 31, 2015 and 2014; and                                                                                                                                   
| |     |                                                                                                                                                                                                                                  
| | (c) | Audited Consolidated Financial Statements for the years
      ended December 31, 2015 and 2014, prepared under International Financial
      Reporting Standards as issued by the International Accounting Standards
      Board.

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ADDITIONAL DISCLOSURE

Certifications and Disclosure Regarding Controls and
Procedures.

|(a) | Certifications. See Exhibits 99.4, 99.5, 99.6 and
      99.7 to this Annual Report on Form 40-F.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
|--- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
|(b) | Disclosure Controls and Procedures. As of the end
      of Trillium Therapeutics Inc.s (Trillium or the Company) fiscal year
      ended December 31, 2015, an evaluation of the effectiveness of Trilliums
      disclosure controls and procedures (as such term is defined in Rules
      13a-15(e) and 15d-15(e) under the Exchange Act) was carried out by the
      management of Trillium, with the participation of the President and Chief
      Executive Officer (CEO) and the Chief Financial Officer (CFO) of
      Trillium. Based upon that evaluation, the CEO and CFO have concluded that
      as of the end of that fiscal year, Trilliums disclosure controls and
      procedures were effective to ensure that information required to be
      disclosed by Trillium in reports that it files or submits under the
      Securities Exchange Act of 1934, as amended, is (i) recorded, processed,
      summarized and reported within the time periods specified in Securities
      and Exchange Commission (the Commission) rules and forms and (ii)
      accumulated and communicated to the management of Trillium, including the
      CEO and CFO, to allow timely decisions regarding required
    disclosure.
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
|    | It should be noted that while the CEO and CFO believe
      that Trilliums disclosure controls and procedures provide a reasonable
      level of assurance that they are effective, they do not expect that
      Trilliums disclosure controls and procedures or internal control over
      financial reporting will prevent all errors and fraud. A control system,
      no matter how well conceived or operated, can provide only reasonable, not
      absolute, assurance that the objectives of the control system are
    met.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
|(c) | Managements Annual Report on Internal Control Over
      Financial Reporting.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
|    | Management is responsible for establishing and
      maintaining adequate internal control over Trilliums financial reporting.
      Trilliums internal control system was designed to provide reasonable
      assurance that all transactions are accurately recorded, that transactions
      are recorded as necessary to permit preparation of financial statements in
      accordance with generally accepted accounting principles, and that
      Trilliums assets are safeguarded.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
|    | Management has assessed the effectiveness of Trilliums
      internal control over financial reporting as at December 31, 2015. In
      making its assessment, management used the Committee of Sponsoring
      Organizations of the Treadway Commission (COSO) framework in Internal
      Control  Integrated Framework (2013) to evaluate the effectiveness of
      Trilliums internal control over financial reporting. Based on this
      assessment, management has concluded that Trilliums internal control over
      financial reporting was effective as of December 31,
  2015.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        

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|(d) | Attestation Report of the Registered Public Accounting
      Firm.                                                                                                                                                                                                                                                                                                                                                                                                                                                 
|--- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
|    | This annual report does not include an attestation report
      of the Companys independent registered public accounting firm regarding
      internal control over financial reporting because emerging growth
      companies are exempt from this requirement for so long as they remain
      emerging growth companies. Therefore, managements report on internal
      control over financial reporting is not subject to attestation by the
      Companys independent registered public accounting firm.
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
|(e) | Changes in Internal Control Over Financial
      Reporting. The required disclosure is included under the heading
      Disclosure Controls and Internal Controls Over Financial Reporting in
      Trilliums Managements Discussion and Analysis for the years ended
      December 31, 2015 and 2014, filed as Exhibit 99.2 to this Annual Report on
      Form 40-F.                                                                                                                                        

Notices Pursuant to Regulation BTR.

None.

Audit Committee Financial Expert.

Trilliums board of directors has determined that Luke Beshar,
a member of Trilliums audit committee, qualifies as an audit committee
financial expert (as such term is defined in Form 40-F) and is independent as
that term is defined in the rules of the Nasdaq Stock Market.

Code of Business Conduct.

Trillium has adopted a Code of Business Conduct and Ethics,
which qualifies as a code as ethics within the meaning of Form 40-F, that is
applicable to each of Trilliums directors, officers and employees, including
its principal executive officer, principal financial officer, principal
accounting officer or controller and persons performing similar functions.

The Code of Business Conduct and Ethics is available for
viewing on Trilliums website at www.trilliumtherapeutics.com, and is
available in print, without charge, to any shareholder who requests a copy of
it. Requests for copies of the Code of Business Conduct and Ethics should be
made by contacting: James Parsons, Chief Financial Officer, by phone at (416)
595-0627 or by e-mail to info@trilliumtherapeutics.com.

Since the date on which Trillium became subject to the
reporting requirements of Section 13(a) or 15(d) of the Exchange Act, there have
not been any amendments to, or waivers, including implicit waivers, granted
from, any provision of the Code of Business Conduct and Ethics.

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If any amendment to the Code of Ethics is made, or if any
waiver from the provisions thereof is granted, Trillium may elect to disclose
the information about such amendment or waiver required by Form 40-F to be
disclosed, by posting such disclosure on its website, which may be accessed at
www.trilliumtherapeutics.com.

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Principal Accountant Fees and Services.

The required disclosure is included under the heading Audit
Committee Information  External Auditors Service Fees (By Category) in
Trilliums Annual Information Form for the year ended December 31, 2015, filed
as Exhibit 99.1 to this Annual Report on Form 40-F.

Pre-Approval Policies and Procedures.

|(a) | The audit committee of Trilliums board of directors has
      adopted an Auditor Services Pre-Approval Policy (the "Policy") with
      respect to the pre-approval of audit and permitted non-audit services to
      be provided by Ernst & Young LLP, Trilliums independent auditor.
      Pursuant to the Policy, the audit committee on an annual basis may approve
      the provision of a specified list of audit and permitted non-audit
      services that the audit committee believes to be typical, reoccurring or
      otherwise likely to be provided by the external auditor during the then
      current fiscal year. All pre-approvals granted under this Policy shall be
      sufficiently detailed as to the particular services being provided that it
      will not be necessary for management of Trillium to exercise any
      discretion in determining whether a particular service has been
      pre-approved.
|--- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
|    | In addition, pursuant to the Policy the audit committee
      has delegated its pre- approval authority to the Chair of the audit
      committee for services where the aggregate fees are estimated to be less
      than or equal to Cdn. $50,000. The Chair of the audit committee is required to report any
      such granted pre-approvals to the audit committee at its next scheduled
      meeting. The audit committee shall not delegate to management the audit
      committee's responsibilities for pre-approving audit and non-audit
      services to be performed by the external auditor.                                                                                                                                                                                                                                                                                                                                     
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
|    | Pursuant to the Policy, there is an exception to the
      pre-approval requirements for permitted non-audit services, provided all
      such services were not recognized at the time of the engagement to be
      non-audit services and, once recognized, are promptly brought to the
      attention of the audit committee and approved prior to the completion of
      the audit. The aggregate amount of all services approved in this manner
      may not constitute more than five percent of the total fees paid to the
      external auditor during the fiscal year in which the services are
      provided.                                                                                                                                                                                                                                                                                                                     
|    |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
|(b) | Of the fees reported in this Annual Report on Form 40-F
      under the heading Principal Accountant Fees and Services, none of the
      fees billed by Ernst & Young LLP were approved by Trilliums audit
      committee pursuant to the de minimusexception provided by Section
      (c)(7)(i)(C) of Rule 2-01 of Regulation S- X.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        

Off-Balance Sheet Arrangements.

Trillium does not have any off-balance sheet arrangements that
have, or are reasonably likely to have, a current or future effect on its
financial condition, revenues or expenses, results of operations, liquidity,
capital expenditures or capital resources that are material to investors.

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Tabular Disclosure of Contractual Obligations.

The required disclosure is included under the heading
Contractual Obligations and Contingencies in Trilliums Managements
Discussion and Analysis for the years ended December 31, 2015 and 2014, filed as
Exhibit 99.2 to this Annual Report on Form 40-F.

Identification of the Audit Committee.

Trillium has a separately-designated standing audit committee
established in accordance with Section 3(a)(58)(A) of the Exchange Act. The
members of the audit committee are: Luke Beshar, Henry Friesen and Robert
Kirkman.

Mine Safety Disclosure.

Not applicable.

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Disclosure Pursuant to the Requirements of the Nasdaq Stock
Market.

As a Canadian corporation listed on the NASDAQ Stock Market, we
are not required to comply with most of the NASDAQ corporate governance
standards, so long as we comply with Canadian corporate governance practices. In
order to claim such an exemption, however, we must disclose the significant
differences between our corporate governance practices and those required to be
followed by U.S. domestic issuers under NASDAQs corporate governance standards.

Our corporate governance practices meet or exceed all
applicable Canadian requirements. They also incorporate some best practices
derived from the NASDAQ rules and comply with applicable rules adopted by the
Securities and Exchange Commission to give effect to the provisions of the
United States Sarbanes-Oxley Act of 2002.

We expect that further information about our corporate
governance practices will be included in our Information Circulars in respect of
future annual meetings of shareholders.

The following is a summary of the significant ways in which our
corporate governance practices differ from those required to be followed by U.S.
domestic issuers under NASDAQs corporate governance standards. Except as
described in this summary, we are in compliance with the NASDAQ corporate
governance standards in all significant respects.

Shareholder Approval

Section 5635 of the NASDAQ Marketplace Rules requires
shareholder approval to be obtained in connection with the undertaking of
certain actions. The circumstances under which shareholder approval is required
under the NASDAQ Marketplace Rules are not identical to the circumstances under
which shareholder approval is required under Canadian and TSX requirements. For
example, but without limitation, Section 5635 requires shareholder approval of
most equity compensation plans and material revisions to such plans. This
requirement covers plans that provide for the delivery of both newly issued and
treasury securities. The TSX rules provide that only the creation of or certain
material amendments to equity compensation plans that provide for new issuances
of securities are subject to shareholder approval. We follow the TSX rules with
respect to the requirements for shareholder approval of potential transactions,
including, without limitation, shareholder approval of equity compensation plans
and material revisions to such plans.

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UNDERTAKING AND CONSENT TO SERVICE OF PROCESS

|A. | Undertaking.
|-- | ------------

Trillium undertakes to make
available, in person or by telephone, representatives to respond to inquiries
made by the Commission staff, and to furnish promptly, when requested to do so
by the Commission staff, information relating to: the securities registered
pursuant to Form 40-F; the securities in relation to which the obligation to
file an annual report on Form 40-F arises; or transactions in said securities.

|B. | Consent to Service of
Process.
|-- | ------------------------------

Trillium has previously filed a
Form F-X in connection with the class of securities in relation to which the
obligation to file this report arises.

Any change to the name or address
of the agent for service of process of Trillium shall be communicated promptly
to the Commission by an amendment to the Form F-X referencing the file number of
Trillium.

SIGNATURES

Pursuant to the requirements of
the Exchange Act, Trillium Therapeutics Inc. certifies that it meets all of the
requirements for filing on Form 40-F and has duly caused this annual report to
be signed on its behalf by the undersigned, thereunto duly authorized, on March
9, 2016.

| | Trillium Therapeutics Inc.    
| | ------------------------------
| |                               
| |                               
| |                               
| | By: /s/ James Parsons         
| | Name: James Parsons           
| | Title: Chief Financial Officer

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EXHIBIT INDEX

|Exhibit | Description                                                                                                                                                                                                                     
|------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
|        |                                                                                                                                                                                                                                 
|99.1    | Annual Information Form for the fiscal year ended
      December 31, 2015                                                                                                                                                       
|        |                                                                                                                                                                                                                                 
|99.2    | Managements Discussion and Analysis for the years ended
      December 31, 2015 and 2014                                                                                                                                       
|        |                                                                                                                                                                                                                                 
|99.3    | Audited Consolidated Financial Statements for the years
      ended December 31, 2015 and 2014, prepared under International Financial
      Reporting Standards as issued by the International Accounting Standards
      Board
|        |                                                                                                                                                                                                                                 
|99.4    | Certification of President & Chief Executive Officer
      pursuant to Rule 13a-14(a) or 15d-14 of the Securities Exchange Act of
      1934                                                                                    
|        |                                                                                                                                                                                                                                 
|99.5    | Certification of Chief Financial Officer pursuant to Rule
      13a-14(a) or 15d-14 of the Securities Exchange Act of 1934                                                                                                      
|        |                                                                                                                                                                                                                                 
|99.6    | Certification of Chief Executive Officer pursuant to 18
      U.S.C. Section 1350                                                                                                                                               
|        |                                                                                                                                                                                                                                 
|99.7    | Certification of Chief Financial Officer pursuant to 18
      U.S.C. Section 1350                                                                                                                                               
|        |                                                                                                                                                                                                                                 
|99.8    | Consent of Ernst & Young LLP                                                                                                                                                                                                    

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