Aquinox Pharmaceuticals Inc (AQXP): Baker Bros. Advisors Pushes Stake to Over 45%

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

SCHEDULE 13D

Under the Securities Exchange Act of
1934

(Amendment No. 6)

Aquinox Pharmaceuticals, Inc.

(Name of Issuer)

Common Stock, par value $0.000001 per
share

(Title of Class of Securities)

03842B101

(CUSIP number)

Alexandra A. Toohey

Chief Financial Officer

Baker Bros. Advisors LP

667 Madison Avenue, 21^st Floor

New York, NY 10065

(212) 339-5690

(Name,
address and telephone number of person authorized to receive notices and communications)

September 19, 2016

(Date of event which requires filing of this statement)

If the filing person has previously filed a statement on Schedule
13G to report the acquisition that is the subject of this Schedule 13D, and is filing this schedule because of Rule 13d-1(e),
13d-1(f) or 13d-1(g), check the following box. x

(Continued on the following pages)

Note: Schedules filed in paper format shall include a
signed original and five copies of the schedule, including all exhibits. See Rule 13d-7 for other parties to whom copies are to
be sent.

*The remainder of this cover page shall be filled out for a
reporting person’s initial filing on this form with respect to the subject class of securities, and for any subsequent amendment
containing information which would alter disclosures provided in a prior cover page.

The information required on the remainder of this cover page
shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (“Act”)
or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however,
see the Notes).

Amendment No. 6 to Schedule 13D

This Amendment No. 6 to Schedule 13D amends and supplements
the previously filed Schedule 13D filed by Baker Bros. Advisors LP (the “Adviser”), Baker Bros. Advisors (GP) LLC (the
“Adviser GP”), Julian C. Baker and Felix J. Baker (collectively the “Reporting Persons”). Except as supplemented
herein, such statements, as heretofore amended and supplemented, remain in full force and effect. Information given in response
to each item shall be deemed incorporated by reference in all other items, as applicable. Each capitalized term used but not defined
herein has the meaning ascribed to such term in the Schedule 13D, as amended.

Item 3.    Source and Amount of Funds or Other Consideration.

Item 3 of Schedule 13D is supplemented as follows:

The disclosure in Item 4 below is incorporated herein by reference.

The disclosure regarding purchases in Item 5(c) below is incorporated
herein by reference.

Item 4.    Purpose of the Transaction.

Item 4 of Schedule 13D is supplemented and superseded, as the
case may be, as follows:

The disclosure regarding the purchases in Item 5(c) below is
incorporated herein by reference.

On September 19, 2016, Aquinox Pharmaceuticals, Inc. (“the
Issuer”) entered into an underwriting agreement (the “Underwriting Agreement”) with Leerink Partners LLC, as
representatives of the several underwriters listed on Schedule A thereto (the “Underwriters”), related to a public
offering (the “Offering”) of 5,350,000 shares of the Issuer’s Common Stock at a price to the public of $12.25
per share. In addition, the Issuer granted the Underwriters an option exercisable for 30 days from the date of the Underwriting
Agreement to purchase, at the public offering price less any underwriting discounts and commissions, up to an additional 802,500
shares of Common Stock to cover overallotments, if any. The Offering is expected to close on September 23, 2016.

Pursuant to the Offering, on September 20, 2016, 667, L.P. (“667”)
and Baker Brothers Life Sciences, L.P. (“Life Sciences”, and together with 667, the “Funds”) purchased
294,707 shares and 2,476,348 shares, respectively of the Issuer’s Common Stock at the offering price of $12.25 per share.
The Funds purchased the shares of the Issuer’s Common Stock with their working capital.

The Funds hold securities of the Issuer for passive investment
purposes. The Reporting Persons or their affiliates have had and may continue to have discussions with management of the Issuer
regarding financing. The Reporting Persons may acquire additional securities of the Issuer, including shares of Common Stock, in
such financings or by means of open market purchases, privately negotiated purchases, or otherwise. The Reporting Persons or their
affiliates may purchase additional securities or dispose of securities in varying amounts and at varying times depending upon the
Reporting Persons’ continuing assessments of pertinent factors, including the availability of shares of Common Stock or other
securities for purchase at particular price levels, the business prospects of the Issuer, other business investment opportunities,
economic conditions, stock market conditions, money market conditions, the attitudes and actions of the board of directors and
management of the Issuer, the availability and nature of opportunities to dispose of shares of the Issuer and other plans and requirements
of the particular entities. Depending upon their assessments of the above factors, the Reporting Persons or their affiliates may
change their present intentions as stated above. The Reporting Persons may discuss items of mutual interest with the Issuer, which
could include items in subparagraphs (a) through (j) of Item 4 of Schedule 13D.

Except as otherwise disclosed herein, at the present time, the
Reporting Persons do not have any plans or proposals with respect to any extraordinary corporate transaction involving the Issuer
including, without limitation, those matters described in subparagraphs (a) through (j) of Item 4 of Schedule 13D.

Item 5.    Interest in Securities of
the Issuer.

Item 5 of this Schedule 13D is hereby amended and restated in
its entirety as follows:

(a) and (b) Items 7 through 11 and 13 of each of the cover pages
of this Amendment No. 6 are incorporated herein by reference. Set forth below is the aggregate number and percentage of shares
of Common Stock directly held, as of the date hereof, by each of the following based upon 23,365,137 shares of Common Stock that
will be outstanding following the Offering, as disclosed in the Issuer’s Prospectus filed with the SEC on September 20, 2016.
Such percentage figures were calculated in accordance with Rule 13d-3 under the Securities Exchange Act of 1934 (the “Exchange
Act”).

Pursuant to management agreements, as amended, among the Adviser,
the Funds, and their respective general partners, the Adviser has complete and unlimited discretion and authority with respect
to the Funds’ investments and voting power over investments.

The Adviser GP, Felix J. Baker and Julian C. Baker as principals
of the Adviser GP, and the Adviser may be deemed to be beneficial owners of securities of the Issuer directly held by the Funds,
and may be deemed to have the power to vote or direct the vote of and the power to dispose or direct the disposition of such securities.

The Reporting Persons disclaim beneficial ownership of the securities
of the Issuer held by each of the Funds, and this Amendment No. 6 shall not be deemed an admission that the Reporting Persons are
the beneficial owners of such securities for purposes of Section 13(d) or for any other purpose, except to the extent that any
such Reporting Persons actually exercises voting or dispositive power with respect to such securities.

(c)
The disclosure regarding the purchase of common stock of the Issuer in the Offering described in Item 4 is incorporated by reference
herein. The following transaction in the Issuer’s Common Stock was effected by the Fund noted below during the sixty
days preceding the filing of this statement using working capital of the applicable purchasing Fund. The purchase transaction was
effected in the open market directly with a broker-dealer. Except as disclosed herein or in any previous amendments to this Schedule
13D, none of the Reporting Persons or their affiliates has effected any other transactions in securities of the Issuer during the
past 60 days.

(d) Certain securities of the Issuer are held directly
by 667, L.P., a limited partnership the sole general partner of which is Baker Biotech Capital, L.P., a limited partnership the
sole general partner of which is Baker Biotech Capital (GP), LLC. Julian C. Baker and Felix J. Baker are the controlling members
of Baker Biotech Capital (GP), LLC.

Certain securities of the Issuer are held directly by Baker
Brothers Life Sciences, L.P., a limited partnership the sole general partner of which is Baker Brothers Life Sciences Capital,
L.P., a limited partnership the sole general partner of which is Baker Brothers Life Sciences Capital (GP), LLC. Julian C. Baker
and Felix J. Baker are the controlling members of Baker Brothers Life Sciences Capital (GP), LLC.

(e) Not applicable.

Item 6.    Contracts, Arrangements, Understandings or Relationships
with Respect to the Securities of the Issuer.

Item 6 of this Schedule 13D is hereby supplemented and amended,
as the case may be, as follows:

On September 19, 2016 the Issuer entered
into a registration rights agreement (the “Registration Rights Agreement”) with the Funds. Under the Registration Rights
Agreement, the Issuer agreed that, if at any time and from time to time after December 19, 2016, the Funds demand that the Issuer
register shares of common stock directly held by them for resale under the Securities Act of 1933, as amended, the Issuer would
be obligated to effect such registration. The Issuer’s registration obligations under the Registration Rights Agreement cover
all shares of common stock now held or later acquired by the Funds, including shares of common stock issued or issuable upon the
exercise or conversion of any other securities , will continue in effect for up to ten years as long as shares of common stock
held by the Funds remain Registrable Securities (as defined in the Registration Rights Agreement), and include the Issuer’s
obligation to facilitate certain underwritten public offerings of common stock by the Funds in the future, including one underwritten
public offering per calendar year and a total of no more than three total underwritten public offerings. The Funds will bear all
expenses incurred in effecting any registration pursuant to the Registration Rights Agreement.

The foregoing description of the Registration
Rights Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Registration
Rights Agreement, which is incorporated by reference as Exhibit 99.1, and is incorporated herein by reference.

Item 7.    Material to be Filed as Exhibits.

SIGNATURE

After reasonable inquiry and to the best of my knowledge and
belief, I certify that the information set forth in this statement is true, complete and correct.

September 21, 2016