Ardelyx (ARDX): RA Capital Management Boosts Stake to 7.7%

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

SCHEDULE 13G

Under the Securities Exchange Act of
1934

(Amendment No. __)*

ARDELYX, INC.

 (Name of Issuer)

Common Stock, par value $0.0001 per share

(Title of Class of Securities)

039697107

(CUSIP Number)

July 18, 2016

(Date of Event Which Requires Filing of
this Statement)

Check the appropriate box to designate the rule pursuant to
which this Schedule is filed:

*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 the disclosures provided in a prior cover page.

The information required in 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).

¹ The reporting person is the beneficial owner of
3,457,718 shares of Common Stock, as well as warrants to acquire 168,225 shares of Common Stock, which together would constitute
approximately 7.7% of the issuer’s Common Stock if the warrants were exercised in full, following the issuance of 168,225
shares of Common Stock in respect of the fully-exercised warrants. The percentage calculation assumes that there are currently
47,230,378 outstanding shares of the Issuer, based on the Issuer’s 10-Q as filed with the Securities and Exchange Commission
(“SEC”) on May 9, 2016 and the Issuer’s 8-K as filed with the SEC on July 20, 2016.

² The reporting person is the beneficial owner of
3,457,718 shares of Common Stock, as well as warrants to acquire 168,225 shares of Common Stock, which together would constitute
approximately 7.7% of the issuer’s Common Stock if the warrants were exercised in full, following the issuance of 168,225
shares of Common Stock in respect of the fully-exercised warrants. The percentage calculation assumes that there are currently
47,230,378 outstanding shares of the Issuer, based on the Issuer’s 10-Q as filed with the SEC on May 9, 2016 and the Issuer’s
8-K as filed with the SEC on July 20, 2016.

³ The reporting person is the beneficial owner of
2,314,024 shares of Common Stock, as well as warrants to acquire 137,944 shares of Common Stock, which together would constitute
approximately 7.7% of the issuer’s Common Stock if the warrants were exercised in full, following the issuance of 137,944
shares of Common Stock in respect of the fully-exercised warrants. The percentage calculation assumes that there are currently
47,230,378 outstanding shares of the Issuer, based on the Issuer’s 10-Q as filed with the SEC on May 9, 2016 and the Issuer’s
8-K as filed with the SEC on July 20, 2016.

Item 1.

(a)           Name of Issuer: ARDELYX,
INC. (the “Issuer”).

(b)           Address of the Issuer’s Principal Executive
Offices: 34175 Ardenwood Blvd., Suite 200, Fremont, CA 94555.

Item 2.

(a)           Name of Person
Filing: This joint statement on Schedule 13G is being filed by Peter Kolchinsky, RA Capital Management, LLC (“Capital”),
and RA Capital Healthcare Fund, L.P. (the “Fund”). Mr. Kolchinsky, Capital and the Fund are collectively referred to
herein as the “Reporting Persons.” Capital is the general partner of the Fund and serves
as investment adviser for a separately managed account (the “Account”). Mr. Kolchinsky is the manager of Capital. As
the investment adviser to the Fund and the Account, Capital may be deemed a beneficial owner, for purposes of Section 13(d) of
the Securities Exchange Act of 1934 (the “Act”), of any securities of the Issuer owned by the Fund or the Account.
As the manager of Capital, Mr. Kolchinsky may be deemed a beneficial owner, for purposes of Section 13(d) of the Act, of any securities
of the Issuer beneficially owned by Capital. Capital is a registered investment adviser within the meaning of Rule 13d-1(b)(1)(ii)(E)
and Rule 16a-1(a)(v), and Mr. Kolchinsky is a parent or control person of Capital within the meaning of Rule 13d-1(b)(1)(ii)(G)
and Rule 16a-1(a)(1)(vii). Capital and Mr. Kolchinsky disclaim beneficial ownership of the securities reported in this Schedule
13G Statement (the “Statement”) other than for the purpose of determining their obligations under Section 13(d) of
the Act, and neither the filing of the Statement nor the filing of this Amendment shall not be deemed an admission that either
Capital or Mr. Kolchinsky is or was the beneficial owner of such securities for any other purpose.

(b)           Address of
Principal Business Office: The principal business office of the Reporting Persons is c/o RA Capital Management, LLC, 20 Park
Plaza, Suite 1200, Boston, MA 02116.

(c)           Citizenship:
Capital is a Massachusetts limited liability company. The Fund is a Delaware limited partnership. Mr. Kolchinsky is a United
States citizen.

(d)           Title and Class
of Securities: Common stock (“Common Stock”) of the Issuer.

(e)           CUSIP Number:
039697107

Item 3.           If this statement is filed
pursuant to §§240.13d-1(b) or 240.13d-2(b) or (c), check whether the person filing is a:

Not applicable.

Item 4.           Ownership:

Item 5.           Ownership of Five Percent
or Less of a Class:

Not applicable.

Item 6.           Ownership
of More than Five Percent on Behalf of Another Person:

Not applicable.

Item 7.           Identification and Classification
of the Subsidiary Which Acquired the Security Being Reported on By the Parent Holding Company or Control Person:

Not applicable.

Item 8.           Identification and Classification
of Members of the Group:

Not applicable.

Item 9.           Notice of Dissolution of
Group:

Not applicable.

Item 10.         Certification:

By signing below I hereby certify that,
to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of
or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held
in connection with or as a participant in any transaction having that purpose or effect.

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.