13G Filing: Palo Alto Investors and Epizyme Inc. (NASDAQ:EPZM)

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

SCHEDULE 13G

Under the Securities Exchange Act of 1934
(Amendment No. 2)

Epizyme, Inc.

(Name of Issuer)

Common Stock

(Title of Class of Securities)

29428V104

(CUSIP Number)

March 23, 2017

(Date of Event Which Requires Filing of this
Statement)

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

[X] Rule 13d-1(b)

[ ] Rule 13d-1(c)

[ ] Rule 13d-1(d)

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).

Potential persons who are to respond to the collection of information
contained in this form are not required to respond unless the form displays a currently valid OMB control number.

1.

Names of Reporting Persons. Patrick Lee, MD

2. Check the Appropriate Box if
a Member of a Group (See Instructions)

(a)

(b) ___X___

3. SEC Use Only

4. Citizenship or Place of Organization
U.S.A.

Number of Shares Beneficially Owned by Each Reporting Person With:	5. Sole Voting Power 0
	6. Shared Voting Power 4,699,675
	7. Sole Dispositive Power 0
	8. Shared Dispositive Power 4,699,675

9. Aggregate Amount Beneficially
Owned by Each Reporting Person 4,699,675

10. Check if the Aggregate Amount
in Row (9) Excludes Certain Shares (See
Instructions) ______

11. Percent of Class Represented
by Amount in Row (9) 8.07%

12. Type of Reporting Person (See
Instructions) IN, HC

1.

Names of Reporting Persons. Anthony Joonkyoo Yun, MD

2. Check the Appropriate Box if
a Member of a Group (See Instructions)

(a)

(b) X

3. SEC Use Only

4. Citizenship or Place of Organization
U.S.A.

Number of Shares Beneficially Owned by Each Reporting Person With:	5. Sole Voting Power 0
	6. Shared Voting Power 4,699,675
	7. Sole Dispositive Power 0
	8. Shared Dispositive Power 4,699,675

9. Aggregate Amount Beneficially
Owned by Each Reporting Person 4,699,675

10.

Check if the Aggregate Amount in Row (9) Excludes Certain Shares (See Instructions)

11. Percent of Class Represented
by Amount in Row (9) 8.07%

12. Type of Reporting Person (See
Instructions) IN, HC

1.

Names of Reporting Persons. Palo Alto Investors, LLC

2. Check the Appropriate Box if
a Member of a Group (See Instructions)

(a)

(b) ___X__

3. SEC Use Only

4. Citizenship or Place of Organization
California

Number of Shares Beneficially Owned by Each Reporting Person With:	5. Sole Voting Power 0
	6. Shared Voting Power 4,699,675
	7. Sole Dispositive Power 0
	8. Shared Dispositive Power 4,699,675

9. Aggregate Amount Beneficially
Owned by Each Reporting Person 4,699,675

10. Check if the Aggregate Amount
in Row (9) Excludes Certain Shares (See
Instructions) ______

11. Percent of Class Represented
by Amount in Row (9) 8.07%

12. Type of Reporting Person (See
Instructions) OO, IA

1.

Names of Reporting Persons. Palo Alto Healthcare Master Fund II, L.P.

2. Check the Appropriate Box if
a Member of a Group (See Instructions)

(a)

(b) X

3. SEC Use Only

4. Citizenship or Place of Organization
Cayman Islands

Number of Shares Beneficially Owned by Each Reporting Person With:	5. Sole Voting Power 0
	6. Shared Voting Power 2,948,996
	7. Sole Dispositive Power 0
	8. Shared Dispositive Power 2,948,996

9. Aggregate Amount Beneficially
Owned by Each Reporting Person 2,948,996

10. Check if the Aggregate Amount
in Row (9) Excludes Certain Shares (See
Instructions) ______

11. Percent of Class Represented
by Amount in Row (9) 5.06%

12. Type of Reporting Person (See
Instructions) PN

Item 1.

(a) Name of Issuer

Epizyme, Inc.

(b) Address of Issuer’s Principal
Executive Offices

400 Technology Square, 4th Floor, Cambridge, MA 02139

Item 2.

(a) The names of the persons filing
this statement are:

Palo Alto Investors, LLC (“PAI”)
Palo Alto Healthcare Master Fund II, L.P.
Patrick Lee, MD
Anthony Joonkyoo Yun, MD

(collectively, the “Filers”).

(b)

The principal business office of the Filers is located at: 470 University Avenue, Palo Alto, CA 94301

(c)

For citizenship of Filers, see Item 4 of the cover sheet for each Filer.

(d)

This statement relates to shares of Common Stock of the Issuer (the “Stock”).

(e) The CUSIP number of the Issuer is: 29428V104

 

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

(a) [ ] Broker or dealer registered
under section 15 of the Act (15 U.S.C. 78o).

(b) [ ] Bank as defined in section
3(a)(6) of the Act (15 U.S.C. 78c).

(c) [ ] Insurance company as
defined in section 3(a)(19) of the Act (15 U.S.C. 78c).

(d) [ ] Investment company registered
under section 8 of the Investment Company Act of 1940 (15 U.S.C. 80a-8).

(e) [ x ] An investment
adviser in accordance with section 240.13d-1(b)(1)(ii)(E) (as to PAI).

(f) [ ] An employee benefit plan
or endowment fund in accordance with section 240.13d-1(b)(1)(ii)(F).

(g) [ x ] A parent holding
company or control person in accordance with 240.13d-1(b)(1)(ii)(G) (as to Dr. Lee and Dr. Yun).

(h) [ ] A savings association
as defined in section 3(b) of the Federal Deposit Insurance Act (12 U.S.C. 1813).

(i) [ ] A church plan that is
excluded from the definition of an investment company under section 3(c)(14) of the Investment Company Act of 1940 (15 U.S.C. 80a-3).

(j) [ ] A non-U.S. institution
in accordance with §240.13d-1(b)(ii)(J).

(k) [ ] Group, in accordance
with Rule 13d-1(b)(1)(ii)(K).

If filing as a non-U.S. institution
in accordance with §240.13d-1(b)(1)(ii)(J), please specify the type of institution _______________________________________________________________.

Item 4. Ownership.

See Items 5-9 and 11 of the cover page for each Filer.

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

 

If this statement is being filed to report the fact that as of the
date hereof the reporting person has ceased to be the beneficial owner of more than five percent of the class of securities, check
the following [ ].

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

 

PAI is a registered investment adviser and is the general partner
and investment adviser of investment limited partnerships, and is the investment adviser to Healthcare Master II and other investment funds. PAI’s
clients have the right to receive or the power to direct the receipt of dividends from, or the proceeds from the sale of, the Stock.
No individual client other than Healthcare Master II separately holds more than five percent of the outstanding Stock.

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

 

Not applicable.

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

Dr. Lee and Dr. Yun co-manage PAI. The Filers are filing this Schedule
13G jointly, but not as members of a group, and each of them expressly disclaims membership in a group. Each Filer disclaims beneficial
ownership of the Stock except to the extent of that Filer’s pecuniary interest therein.

Item 9. Notice of Dissolution
of Group.

Not applicable.

Item 10. Certification of PAI LLC, Dr. Lee, Dr. Yun, Healthcare Master II.

By signing below I certify that, to the best of my knowledge and
belief, the securities referred to above were acquired and are held in the ordinary course of business and 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.

Exhibits

Exhibit A Joint Filing Agreement.

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.

Dated: April 3, 2017

PALO ALTO INVESTORS, LLC By: /s/Angela Nguyen-Dinh, Chief Compliance Officer
PALO ALTO HEALTHCARE MASTER FUND II, L.P.   By: Palo Alto Investors, LLC, General Partner By: /s/ Angela Nguyen-Dinh, Chief Compliance Officer
/s/ Patrick Lee, MD	/s/ Anthony Joonkyoo Yun, MD

EXHIBIT A

AGREEMENT REGARDING JOINT FILING

OF STATEMENT ON SCHEDULE 13D OR 13G

The undersigned agree to file jointly with
the Securities and Exchange Commission (the “SEC”) any and all statements on Schedule 13D or Schedule 13G (and any amendments
or supplements thereto) required under section 13(d) of the Securities Exchange Act of 1934, as amended, in connection with purchases
and sales by the undersigned of the securities of any issuer until such time as the undersigned file with the SEC a statement terminating
this Agreement Regarding Joint Filing of Statement on Schedule 13D or 13G. For that purpose, the undersigned hereby constitute
and appoint Palo Alto Investors, LLC, a California limited liability company, as their true and lawful agent and attorney-in-fact,
with full power and authority for and on behalf of the undersigned to prepare or cause to be prepared, sign, file with the SEC
and furnish to any other person all certificates, instruments, agreements and documents necessary to comply with section 13(d)
and section 16(a) of the Securities Exchange Act of 1934, as amended, in connection with said purchases and sales, and to do and
perform every act necessary and proper to be done incident to the exercise of the foregoing power, as fully as the undersigned
might or could do if personally present, until such time as the undersigned file with the SEC a statement terminating this Agreement
Regarding Joint Filing of Statement on Schedule 13D or 13G.

Dated: April 3, 2017

PALO ALTO INVESTORS, LLC By: /s/Angela Nguyen-Dinh, Chief Compliance Officer
PALO ALTO HEALTHCARE MASTER FUND II, L.P.   By: Palo Alto Investors, LLC, General Partner By: /s/ Angela Nguyen-Dinh, Chief Compliance Officer
/s/ Patrick Lee, MD	/s/ Anthony Joonkyoo Yun, MD