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

SCHEDULE 13G

INFORMATION TO BE INCLUDED IN STATEMENTS FILED PURSUANT
TO RULE 13d-1(b), (c), AND (d) AND AMENDMENTS THERETO FILED
PURSUANT TO RULE 13d-2(b)

(AMENDMENT NO. 4)*

Karyopharm Therapeutics Inc.
(Name of Issuer)

Common Stock
(Title of Class of Securities)

48576U106
(CUSIP Number)

December 31, 2019
(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 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).


CUSIP No. 48576U106

13G

Page 2 of 10 Pages

1.
NAMES OF REPORTING PERSONS OR
I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)

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
USA


NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH
5.
SOLE VOTING POWER

 0

6.
SHARED VOTING POWER

4,595,001

7.
SOLE DISPOSITIVE POWER

 0

8.
SHARED DISPOSITIVE POWER

 4,595,001

9.
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON

 4,595,001

10.
CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES
(see instructions) [  ]


11.
PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)

 7.32%

12.
TYPE OF REPORTING PERSON (see instructions)

 IN, HC







CUSIP No. 48576U106

13G

Page 3 of 10 Pages

1.
NAMES OF REPORTING PERSONS OR
I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)

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
 USA


NUMBER OF SHARES BENEFICIALLY OWNED BY EACH REPORTING PERSON WITH
5.
SOLE VOTING POWER

 0

6.
SHARED VOTING POWER

4,595,001

7.
SOLE DISPOSITIVE POWER

 0

8.
SHARED DISPOSITIVE POWER

 4,595,001

9.
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON

4,595,001

10.
CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES
(see instructions) [  ]


11.
PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)

7.32%

12.
TYPE OF REPORTING PERSON (see instructions)

 IN, HC









CUSIP No. 48576U106

13G

Page 4 of 10 Pages

1.
NAMES OF REPORTING PERSONS OR
I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)

Palo Alto Investors LP

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

4,595,001

7.
SOLE DISPOSITIVE POWER

 0

8.
SHARED DISPOSITIVE POWER

 4,595,001

9.
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON

 4,595,001

10.
CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES
(see instructions) [  ]


11.
PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)

 7.32%

12.
TYPE OF REPORTING PERSON (see instructions)

 OO, IA







CUSIP No. 48576U106

13G

Page 5 of 10 Pages

1.
NAMES OF REPORTING PERSONS OR
I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)

PAI 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

4,595,001

7.
SOLE DISPOSITIVE POWER

 0

8.
SHARED DISPOSITIVE POWER

 4,595,001

9.
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON

 4,595,001

10.
CHECK IF THE AGGREGATE AMOUNT IN ROW (9) EXCLUDES CERTAIN SHARES
(see instructions) [  ]


11.
PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (9)

 7.32%

12.
TYPE OF REPORTING PERSON (see instructions)

 OO, IA







CUSIP No. 48576U106

13G

Page 6 of 10 Pages

Item 1.

(a)
Name of Issuer

Karyopharm Therapeutics Inc.




(b)
Address of Issuers Principal
Executive Offices

85 Wells Avenue, 2nd Floor, Newton, MA 02459

Item 2.

(a)
Name of Person Filing

Palo Alto Investors LP (PAI)
PAI LLC (PAI GP)
Patrick Lee, MD
Anthony Joonkyoo Yun, MD
(collectively, the "Filers").




(b)
The address of the principal place of the Filers:

470 University Avenue, Palo Alto, CA 94301





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





(d)
Title of Class of Securities

Common Stock




(e)
CUSIP Number

48576U106

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:


(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
240.13d-1(b)(1)(ii)(E); (as to PAI)











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







CUSIP No. 48576U106

13G

Page 7 of 10 Pages



(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 associations 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)
[  ]
Group, in accordance with
240.13d-1(b)(1)(ii)(J).



CUSIP No. 48576U106

13G

Page 8 of 10 Pages

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.

N/A

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

PAI is a registered investment adviser and investment
adviser of investment limited partnerships, and is
the investment adviser to other investment funds.
PAI GP is the general partner of investment limited
partnerships. PAIs 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.

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

N/A

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 Filers pecuniary
interest therein.


Item 9. Notice of Dissolution of Group.

N/A




CUSIP No. 48576U106

13G

Page 9 of 10 Pages

Item 10. Certification.

By signing below I 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.

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: February 14, 2020

PALO ALTO INVESTORS LP

By: /s/ Angela Nguyen-Dinh, Chief Compliance Officer

PAI LLC

By: /s/ Patrick Lee, MD

/s/ Patrick Lee, MD


/s/ Anthony Joonkyoo Yun, MD


CUSIP No. 48576U106

13G

Page 10 of 10 Pages

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, LP, a California
limited partnership, 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: February 14, 2020


PALO ALTO INVESTORS LP

By: /s/ Angela Nguyen-Dinh, Chief Compliance Officer

PAI LLC

By: /s/ Patrick Lee, MD

/s/ Patrick Lee, MD

/s/ Anthony Joonkyoo Yun, MD