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. 7)*

Karyopharm Therapeutics Inc.
(Name of Issuer)

Common Stock
(Title of Class of Securities)

48576U106
(CUSIP Number)

December 31, 2022
(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 9 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

5,655,676

7.
SOLE DISPOSITIVE POWER

0

8.
SHARED DISPOSITIVE POWER

5,655,676

9.
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON

5,655,676

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


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

5.00%

12.
TYPE OF REPORTING PERSON (see instructions)

IN, HC







CUSIP No. 48576U106

13G

Page 3 of 9 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

5,655,676

7.
SOLE DISPOSITIVE POWER

0

8.
SHARED DISPOSITIVE POWER

5,655,676

9.
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON

5,655,676

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


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

5.00%

12.
TYPE OF REPORTING PERSON (see instructions)

IN, HC


CUSIP No. 48576U106

13G

Page 4 of 9 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

5,655,676

7.
SOLE DISPOSITIVE POWER

0

8.
SHARED DISPOSITIVE POWER

5,655,676
9.
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON

5,655,676

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


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

5.00%

12.
TYPE OF REPORTING PERSON (see instructions)

OO, IA

CUSIP No. 48576U106

13G

Page 5 of 9 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

5,655,676

7.
SOLE DISPOSITIVE POWER

0

8.
SHARED DISPOSITIVE POWER

5,655,676

9.
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON

0

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


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

5.00%

12.
TYPE OF REPORTING PERSON (see instructions)

OO, IA







CUSIP No. 48576U106

13G

Page 6 of 9 Pages

Item 1.

(a)
Name of Issuer

Karyopharm Therapeutics Inc.




(b)
Address of Issuer's 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 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)
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);





(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. 29428V104

13G

Page 7 of 9 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. 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.

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 Filer's pecuniary interest therein.

Item 9. Notice of Dissolution of Group.

N/A




CUSIP No. 29428V104

13G

Page 8 of 9 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, 2023


PALO ALTO INVESTORS LP

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

PAI LLC

By: /s/ Patrick Lee, MD


/s/ Anthony Joonkyoo Yun, MD





CUSIP No. 29428V104

13G

Page 9 of 9 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, 2023


PALO ALTO INVESTORS LP

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

PAI LLC

By: /s/ Patrick Lee, MD

/s/ Anthony Joonkyoo Yun, MD