UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE 13D

(Rule 13d-102)

INFORMATION TO BE INCLUDED IN STATEMENTS FILED PURSUANT

TO RULE 13d-l(a) AND AMENDMENTS THERETO FILED PURSUANT

TO RULE 13d-2(a)

(Amendment No. 3)*

Aprea Therapeutics, Inc.

(Name of Issuer)

Common Stock, par value $0.001 per share

(Title of Class of Securities)

03836J102

(CUSIP Number)

Rebecca Lucia

5AM Venture Management, LLC

501 2nd Street, Suite 350

San Francisco, CA 94107

(415) 993-8565

(Name, Address and Telephone Number of Person
Authorized to Receive Notices and Communications)

October 5, 2020

(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 §§240.13d-1(e), 240.13d-1(f) or 240.13d-1(g), check the following box. ¨

* 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.

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1.	Name of Reporting Persons 5AM Ventures IV, L.P.
2.	Check the Appropriate Box if a Member of a Group (see instructions) (a) (b)			o x(1)
3.	SEC USE ONLY
4.	Source of Funds (see instructions) WC
5.	Check if Disclosure of Legal Proceedings Is Required Pursuant to Item 2(d) or 2(e)				o
6.	Citizenship or Place of Organization Delaware
Number of Shares Beneficially Owned by Each Reporting Person With		7.	Sole Voting Power 0
		8.	Shared Voting Power 1,823,192 shares of common stock (2)
		9.	Sole Dispositive Power 0
		10.	Shared Dispositive Power 1,823,192 shares of common stock (2)
11.	Aggregate Amount Beneficially Owned by Each Reporting Person 1,823,192 shares of common stock (2)
12.	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (see instructions)				o
13.	Percent of Class Represented by Amount in Row 11 8.6% (3)
14.	Type of Reporting Person (see instructions) PN

(1) This Schedule 13D is filed by 5AM Partners IV, LLC (“5AM Partners IV”), 5AM Ventures IV, L.P. (“5AM IV”), 5AM Co-Investors IV, L.P. (“5AM Co-Investors IV”), 5AM Opportunities I, L.P. (“5AM Opportunities”), 5AM Opportunities I (GP), LLC (“5AM Opportunities GP”), Dr. John D. Diekman (“Diekman”), Andrew J. Schwab (“Schwab”) and Dr. Scott M. Rocklage (“Rocklage” and, with 5AM Partners IV, 5AM IV, 5AM Co-Investors IV, 5AM Opportunities, 5AM Opportunities GP, Diekman and Schwab, collectively, the “Reporting Persons”). The Reporting Persons expressly disclaim status as a “group” for purposes of this Schedule 13D.

(2) These shares are held by 5AM IV. Diekman, Schwab and Rocklage, as managing members of 5AM Partners IV, share voting and investment authority over the shares held by 5AM IV.

(3) Percentage based on 21,186,827 shares of Common Stock outstanding as of August 11, 2020 as disclosed in the Issuer’s Form 10-Q filed with the Securities and Exchange Commission on August 11, 2020.

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1.	Name of Reporting Persons 5AM Co-Investors IV, L.P.
2.	Check the Appropriate Box if a Member of a Group (see instructions) (a) (b)			o x(1)
3.	SEC USE ONLY
4.	Source of Funds (see instructions) WC
5.	Check if Disclosure of Legal Proceedings Is Required Pursuant to Item 2(d) or 2(e)				o
6.	Citizenship or Place of Organization Delaware
Number of Shares Beneficially Owned by Each Reporting Person With		7.	Sole Voting Power 0
		8.	Shared Voting Power 75,965 shares of common stock (2)
		9.	Sole Dispositive Power 0
		10.	Shared Dispositive Power 75,965 shares of common stock (2)
11.	Aggregate Amount Beneficially Owned by Each Reporting Person 75,965 shares of common stock (2)
12.	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (see instructions)				o
13.	Percent of Class Represented by Amount in Row 11 0.4% (3)
14.	Type of Reporting Person (see instructions) PN

(1) This Schedule 13D is filed by the Reporting Persons. The Reporting Persons expressly disclaim status as a “group” for purposes of this Schedule 13D.

(2) These shares are held by 5AM Co-Investors IV. Diekman, Schwab and Rocklage, as managing members of 5AM Partners IV, share voting and investment authority over the shares held by 5AM Co-Investors IV.

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1.	Name of Reporting Persons 5AM Partners IV, LLC
2.	Check the Appropriate Box if a Member of a Group (see instructions) (a) (b)			o x(1)
3.	SEC USE ONLY
4.	Source of Funds (see instructions) AF
5.	Check if Disclosure of Legal Proceedings Is Required Pursuant to Item 2(d) or 2(e)				¨
6.	Citizenship or Place of Organization Delaware
Number of Shares Beneficially Owned by Each Reporting Person With		7.	Sole Voting Power 0
		8.	Shared Voting Power 1,899,157 shares of common stock (2)
		9.	Sole Dispositive Power 0
		10.	Shared Dispositive Power 1,899,157 shares of common stock (2)
11.	Aggregate Amount Beneficially Owned by Each Reporting Person 1,899,157 shares of common stock (2)
12.	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (see instructions)				¨
13.	Percent of Class Represented by Amount in Row 11 9.0% (3)
14.	Type of Reporting Person (see instructions) OO

(1) This Schedule 13D is filed by the Reporting Persons. The Reporting Persons expressly disclaim status as a “group” for purposes of this Schedule 13D.

(2) Includes (i) 1,823,192 shares held by 5AM IV; and (ii) 75,965 shares held by 5AM Co-Investors IV. Diekman, Schwab and Rocklage, as managing members of 5AM Partners IV, share voting and investment authority over the shares held by 5AM IV and 5AM Co-Investors IV.

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1.	Name of Reporting Persons 5AM Opportunities I, L.P.
2.	Check the Appropriate Box if a Member of a Group (see instructions) (a) (b)			o x(1)
3.	SEC USE ONLY
4.	Source of Funds (see instructions) WC
5.	Check if Disclosure of Legal Proceedings Is Required Pursuant to Item 2(d) or 2(e)			o
6.	Citizenship or Place of Organization Delaware
Number of Shares Beneficially Owned by Each Reporting Person With		7.	Sole Voting Power 0
		8.	Shared Voting Power 138,497 shares of common stock (2)
		9.	Sole Dispositive Power 0
		10.	Shared Dispositive Power 138,497 shares of common stock (2)
11.	Aggregate Amount Beneficially Owned by Each Reporting Person 138,497 shares of common stock (2)
12.	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (see instructions)			o
13.	Percent of Class Represented by Amount in Row 11 0.7% (3)
14.	Type of Reporting Person (see instructions) PN

(1) This Schedule 13D is filed by the Reporting Persons. The Reporting Persons expressly disclaim status as a “group” for purposes of this Schedule 13D.

(2) These shares are held by 5AM Opportunities. Schwab and Kush Parmar, as managing members of 5AM Opportunities GP, share voting and investment authority over the shares held by 5AM Opportunities.

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1.	Name of Reporting Persons 5AM Opportunities I (GP), LLC
2.	Check the Appropriate Box if a Member of a Group (see instructions) (a) (b)			o x(1)
3.	SEC USE ONLY
4.	Source of Funds (see instructions) AF
5.	Check if Disclosure of Legal Proceedings Is Required Pursuant to Item 2(d) or 2(e)			o
6.	Citizenship or Place of Organization Delaware
Number of Shares Beneficially Owned by Each Reporting Person With		7.	Sole Voting Power 0
		8.	Shared Voting Power 138,497 shares of common stock (2)
		9.	Sole Dispositive Power 0
		10.	Shared Dispositive Power 138,497 shares of common stock (2)
11.	Aggregate Amount Beneficially Owned by Each Reporting Person 138,497 shares of common stock (2)
12.	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (see instructions)			o
13.	Percent of Class Represented by Amount in Row 11 0.7% (3)
14.	Type of Reporting Person (see instructions) OO

(1) This Schedule 13D is filed by the Reporting Persons. The Reporting Persons expressly disclaim status as a “group” for purposes of this Schedule 13D.

(2) Includes 138,497 shares held by 5AM Opportunities. Schwab and Kush Parmar, as managing members of 5AM Opportunities GP, share voting and investment authority over the shares held by 5AM Opportunities.

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1.	Name of Reporting Persons Dr. John D. Diekman
2.	Check the Appropriate Box if a Member of a Group (see instructions) (a) (b)			o x(1)
3.	SEC USE ONLY
4.	Source of Funds (see instructions) AF
5.	Check if Disclosure of Legal Proceedings Is Required Pursuant to Item 2(d) or 2(e)				o
6.	Citizenship or Place of Organization United States
Number of Shares Beneficially Owned by Each Reporting Person With		7.	Sole Voting Power 0
		8.	Shared Voting Power 1,899,157 shares of common stock (2)
		9.	Sole Dispositive Power 0
		10.	Shared Dispositive Power 1,899,157 shares of common stock (2)
11.	Aggregate Amount Beneficially Owned by Each Reporting Person 1,899,157 shares of common stock (2)
12.	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (see instructions)				o
13.	Percent of Class Represented by Amount in Row 11 9.0% (3)
14.	Type of Reporting Person (see instructions) IN

(1) This Schedule 13D is filed by the Reporting Persons. The Reporting Persons expressly disclaim status as a “group” for purposes of this Schedule 13D.

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1.	Name of Reporting Persons Andrew J. Schwab
2.	Check the Appropriate Box if a Member of a Group (see instructions) (a) (b)			o x(1)
3.	SEC USE ONLY
4.	Source of Funds (see instructions) AF
5.	Check if Disclosure of Legal Proceedings Is Required Pursuant to Item 2(d) or 2(e)				o
6.	Citizenship or Place of Organization United States
Number of Shares Beneficially Owned by Each Reporting Person With		7.	Sole Voting Power 0
		8.	Shared Voting Power 2,037,654 shares of common stock (2)
		9.	Sole Dispositive Power 0
		10.	Shared Dispositive Power 2,037,654 shares of common stock (2)
11.	Aggregate Amount Beneficially Owned by Each Reporting Person 2,037,654 shares of common stock (2)
12.	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (see instructions)				o
13.	Percent of Class Represented by Amount in Row 11 9.6% (3)
14.	Type of Reporting Person (see instructions) IN

(1) This Schedule 13D is filed by the Reporting Persons. The Reporting Persons expressly disclaim status as a “group” for purposes of this Schedule 13D.

(2) Includes (i) 1,823,192 shares held by 5AM IV; (ii) 75,965 shares held by 5AM Co-Investors IV; and (iii) 138,497 shares held by 5AM Opportunities. Diekman, Schwab and Rocklage, as managing members of 5AM Partners IV, share voting and investment authority over the shares held by 5AM IV and 5AM Co-Investors IV. Schwab and Kush Parmar, as managing members of 5AM Opportunities GP, share voting and investment authority over the shares held by 5AM Opportunities.

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1.	Name of Reporting Persons Dr. Scott M. Rocklage
2.	Check the Appropriate Box if a Member of a Group (see instructions) (a) (b)			o x(1)
3.	SEC USE ONLY
4.	Source of Funds (see instructions) AF
5.	Check if Disclosure of Legal Proceedings Is Required Pursuant to Item 2(d) or 2(e)				o
6.	Citizenship or Place of Organization United States
Number of Shares Beneficially Owned by Each Reporting Person With		7.	Sole Voting Power 0
		8.	Shared Voting Power 1,899,157 shares of common stock (2)
		9.	Sole Dispositive Power 0
		10.	Shared Dispositive Power 1,899,157 shares of common stock (2)
11.	Aggregate Amount Beneficially Owned by Each Reporting Person 1,899,157 shares of common stock (2)
12.	Check if the Aggregate Amount in Row (11) Excludes Certain Shares (see instructions)				o
13.	Percent of Class Represented by Amount in Row 11 9.0% (3)
14.	Type of Reporting Person (see instructions) IN

(1) This Schedule 13D is filed by the Reporting Persons. The Reporting Persons expressly disclaim status as a “group” for purposes of this Schedule 13D.

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Explanatory Note: This Amendment No. 3 (the “Amendment”) to that statement on Schedule 13D is being filed by 5AM Partners IV, LLC (“5AM Partners IV”), 5AM Ventures IV, L.P. (“5AM IV”), 5AM Co-Investors IV, L.P. (“5AM Co-Investors IV”), 5AM Opportunities I, L.P. (“5AM Opportunities”), 5AM Opportunities I (GP), LLC (“5AM Opportunities GP”), Dr. John D. Diekman (“Diekman”), Andrew J. Schwab (“Schwab”), Dr. Scott M. Rocklage (“Rocklage” and, with 5AM Partners IV, 5AM IV, Co-Investors IV, 5AM Opportunities, 5AM Opportunities GP, Diekman and Schwab, collectively, the “Reporting Persons”) and amends and restates the Schedule 13D filed with the Commission on October 17, 2019, as amended by Amendment No. 1 filed May 22, 2020 and as amended by Amendment No. 2 filed June 11, 2020 (the “Original Schedule 13D”) and relates to shares of Common Stock, $0.001 par value per share of Aprea Therapeutics, Inc., a Delaware corporation (the “Issuer”). This Amendment is being filed by the Reporting Persons to report sales of Common Stock of the Issuer on October 5, 2020. Accordingly, the number of securities beneficially owned by the Reporting Persons has decreased.

Items 4, 5 and 7 of the Original Schedule 13D are hereby amended and supplemented to the extent hereinafter expressly set forth and, except as amended and supplemented hereby, the Original Schedule 13D remains in full force and effect. All capitalized terms used in this Amendment but not defined herein shall have the meanings ascribed thereto in the Original Schedule 13D.

Item 4. Purpose of Transaction

On June 16, 2020, 5AM IV sold an aggregate of 115,357 shares of Common Stock in an open market transaction at a price of $33.30 per share, 5AM Co-Investors IV sold an aggregate of 4,807 shares of Common Stock in an open market transaction at a price of $33.30 per share and 5AM Opportunities sold an aggregate of 19,836 shares of Common Stock in an open market transaction at a price of $33.30 per share.

On October 5, 2020, 5AM Opportunities sold an aggregate of 175,000 shares of Common Stock in an open market transaction at a price of $25.30 per share.

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Item 5. Interest in Securities of the Issuer

(a) — (b). The following information with respect to the ownership of the Common Stock of the Issuer by the persons filing this statement on Schedule 13D is provided as of October 5, 2020:

Reporting Persons	Shares Held Directly	Sole Voting Power	Shared Voting Power(1)	Sole Dispositive Power	Shared Dispositive Power (1)	Beneficial Ownership	Percentage of Class (3)

5AM IV	1,823,192	0	1,823,192	0	1,823,192	1,823,192	8.6	%
5AM Co-Investors IV	75,965	0	75,965	0	75,965	75,965	0.4	%
5AM Partners IV (1)	0	0	1,899,157	0	1,899,157	1,899,157	9.0	%
5AM Opportunities	138,497	0	138,497	0	138,497	138,497	0.7	%
5AM Opportunities GP (2)	0	0	138,497	0	138,497	138,497	0.7	%
Diekman (1)	0	0	1,899,157	0	1,899,157	1,899,157	9.0	%
Schwab (1) (2)	0	0	2,037,654	0	2,037,654	2,037,654	9.6	%
Rocklage (1)	0	0	1,899,157	0	1,899,157	1,899,157	9.0	%

(1) Includes 1,823,192 shares of Common Stock held by 5AM IV and 75,965 shares of Common Stock held by 5AM Co-Investors IV. Diekman, Schwab and Rocklage, as managing members of 5AM Partners IV, share voting and investment authority over the shares held by 5AM IV and 5AM Co-Investors IV.

(2) Includes 138,497 shares of Common Stock held by 5AM Opportunities. Schwab and Parmar, as managing members of 5AM Opportunities GP, share voting and investment authority over the shares held by 5AM Opportunities.

(c) Except as set forth herein, none of the Reporting Persons has effected any transactions in shares of the Issuer’s Common Stock during the last 60 days.

(d) No other person is known to have the right to receive or the power to direct the receipt of dividends from, or any proceeds from the sale of, the shares of Common Stock beneficially owned by any of the Reporting Persons.

(e) Not applicable.

Item 7. Materials to be Filed as Exhibits.

A. Joint Filing Agreement as required by Rule 13d-1(k)(1) under the Securities Exchange Act of 1934, as amended.

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SIGNATURES

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.

Date: October 7, 2020

	5AM Ventures IV, L.P.

	By:	5AM Partners IV, LLC,
		Its General Partner

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	5AM Co-Investors IV, L.P.

	By:	5AM Partners IV, LLC,
		Its General Partner

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	5AM Partners IV, LLC

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	5AM Opportunities I, L.P.

	By:	5AM Opportunities I (GP), LLC,
		Its General Partner

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	5AM Opportunities I (GP), LLC

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	DR. JOHN D. DIEKMAN

	By:	/s/ Dr. John D. Diekman
		Dr. John D. Diekman

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	ANDREW J. SCHWAB

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab

	DR. SCOTT M. ROCKLAGE

	By:	/s/ Dr. Scott M. Rocklage
		Dr. Scott M. Rocklage

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Exhibit 1

Joint Filing Agreement

The undersigned hereby agree that a single Schedule 13D (or any amendment thereto) relating to the Common Stock of Aprea Therapeutics, Inc. shall be filed on behalf of each of the undersigned and that this Agreement shall be filed as an exhibit to such Schedule 13D.

Date: October 7, 2020

	5AM Ventures IV, L.P.

	By:	5AM Partners IV, LLC,
		Its General Partner

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	5AM Co-Investors IV, L.P.

	By:	5AM Partners IV, LLC,
		Its General Partner

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	5AM Partners IV, LLC

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	5AM Opportunities I, L.P.

	By:	5AM Opportunities I (GP), LLC,
		Its General Partner

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

	5AM Opportunities I (GP), LLC

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab
		Managing Member

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	DR. JOHN D. DIEKMAN

	By:	/s/ Dr. John D. Diekman
		Dr. John D. Diekman

	ANDREW J. SCHWAB

	By:	/s/ Andrew J. Schwab
		Andrew J. Schwab

	DR. SCOTT M. ROCKLAGE

	By:	/s/ Dr. Scott M. Rocklage
		Dr. Scott M. Rocklage