13D Filing: James E. Flynn and Proteon Therapeutics Inc (PRTO)

SECURITIES
AND EXCHANGE COMMISSION

Washington,
D.C. 20549

SCHEDULE
13D

[Rule 13d-101]

INFORMATION TO BE INCLUDED IN STATEMENTS FILED PURSUANT TO §
24.13d-1(a) AND AMENDMENTS THERETO FILED PURSUANT TO § 240.13D-2(a)

(Amendment No. 1)*

Proteon
Therapeutics, Inc.

(Name
of Issuer)

Common
Stock

(Title
of Class of Securities)

74371L109

(CUSIP
Number)

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

August
2, 2017

(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 ☐.

Note: Schedules
filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See § 240.13d-7
for other parties to whom copies are to be sent.

(Continued on following
pages)
(Page 1 of 21 Pages)

* 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).

SCHEDULE 13D

SCHEDULE 13D

SCHEDULE 13D

SCHEDULE 13D

SCHEDULE 13D

(1) Comprised of shares of common stock issuable upon conversion
of shares of the Issuer’s Series A Convertible Preferred Stock (“Series A Convertible Preferred Stock”).

(2) The provisions of the Series A Convertible Preferred Stock
beneficially owned by the reporting person restrict the conversion of such securities to the extent that, upon such conversion,
the number of shares of the Issuer’s common stock then beneficially owned by the holder and its affiliates and any other
person or entities with which such holder would constitute a Section 13(d) “group” would exceed 9.985% of the total
number of shares of the Issuer’s common stock then outstanding (the “Ownership Cap”). Accordingly, notwithstanding
the number of shares reported, the reporting person disclaims beneficial ownership of the shares of common stock issuable upon
conversion of such preferred stock to the extent that upon such conversion the number of shares beneficially owned by all reporting
persons hereunder, in the aggregate, would exceed the Ownership Cap.

SCHEDULE 13D

(3) Comprised of shares of common stock held by Deerfield Special
Situations Fund, L.P., Deerfield Partners, L.P. and Deerfield International Master Fund, L.P., of which Deerfield Mgmt, L.P. is
the general partner.

SCHEDULE 13D

(4) Comprised of shares of Common Stock held by Deerfield Private
Design Fund III, L.P., of which Deerfield Mgmt III, L.P. is the general partner.

SCHEDULE 13D

(5) Comprised of shares of common stock issuable upon conversion
of shares of the Issuer’s Series A Convertible Preferred Stock held by Deerfield Private Design Fund IV, L.P., of which Deerfield
Mgmt IV, L.P. is the general partner.

(6) See footnote 2.

SCHEDULE 13D

(7) Comprised of (i) an aggregate of 1,224,899 shares of common
stock held by Deerfield Private Design Fund III, L.P., Deerfield Special Situations Fund, L.P., Deerfield Partners, L.P. and Deerfield
International Master Fund, L.P., and (ii) 16,082,018 shares of common stock issuable upon conversion of shares of the Issuer’s
Series A Convertible Preferred Stock held by Deerfield Private Design Fund IV, L.P. Deerfield Management Company, L.P. is the investment
manager of Deerfield Private Design Fund III, L.P., Deerfield Special Situations Fund, L.P., Deerfield Partners, L.P., Deerfield
International Master Fund, L.P. and Deerfield Private Design Fund IV, L.P.

(8) See footnote 2.

SCHEDULE 13D

(9) Comprised of (i) an aggregate of 1,224,899 shares of common
stock held by Deerfield Private Design Fund III, L.P., Deerfield Special Situations Fund, L.P., Deerfield Partners, L.P. and Deerfield
International Master Fund, L.P., and (ii) 16,082,018 shares of common stock issuable upon conversion of shares of the Issuer’s
Series A Convertible Preferred Stock held by Deerfield Private Design Fund IV, L.P. James E. Flynn is the sole member of the general
partner of each of Deerfield Mgmt, L.P., Deerfield Mgmt III, L.P., Deerfield Mgmt IV, L.P. and Deerfield Management Company, L.P.
Deerfield Management Company, L.P. is the investment manager of Deerfield Special Situations Fund, L.P., Deerfield Private Design
Fund III, L.P., Deerfield Private Design Fund IV, L.P., Deerfield Partners, L.P. and Deerfield International Master Fund, L.P.
Deerfield Mgmt III, L.P is the general partner of Deerfield Private Design Fund III, L.P. Deerfield Mgmt IV, L.P. is the general
partner of Deerfield Private Design Fund IV, L.P. Deerfield Mgmt, L.P. is the general partner of each of Deerfield Special Situations
Fund, L.P., Deerfield Partners, L.P. and Deerfield International Master Fund, L.P.

(10) See footnote 2.

Page 11 of 21

This Amendment No.
1 (this “Amendment”) to Schedule 13D is filed by (i) Deerfield Mgmt, L.P. (“Deerfield Mgmt”),
(ii) Deerfield Management Company, L.P. (“Deerfield Management”), (iii) Deerfield Mgmt III, L.P. (“Deerfield
Mgmt III”), (iv) Deerfield Special Situations Fund, L.P. (“Deerfield Special Situations Fund”), (v)
Deerfield Partners, L.P. (“Deerfield Partners”), (vi) Deerfield International Master Fund, L.P. (“Deerfield
International Master Fund”), (vii) Deerfield Private Design Fund III, L.P. (“Deerfield Private Design Fund III”),
(viii) Deerfield Private Design Fund IV, L.P. (“Deerfield Private Design Fund IV”), (ix) Deerfield Mgmt, L.P.
(“Deerfield Mgmt IV”) and (x) James E. Flynn (“Flynn” and, collectively with Deerfield Mgmt,
Deerfield Management, Deerfield Mgmt III, Deerfield Special Situations Fund, Deerfield Partners, Deerfield International Master
Fund, Deerfield Private Design Fund III, Deerfield Private Design Fund IV and Deerfield Mgmt IV, the “Reporting Persons”),
with respect to the securities of Proteon Therapeutics, Inc. (as amended, the “Schedule 13D”). Deerfield Special
Situations Fund, Deerfield Partners, Deerfield International Master Fund, Deerfield Private Design Fund III and Deerfield Private
Design Fund IV are collectively referred to herein as the “Funds”. The primary purpose of this Amendment is
to report (a) the consummation of the transactions contemplated by the Purchase Agreement (as defined in the Schedule 13D) and
(b) the addition of Deerfield Private Design Fund IV and Deerfield Mgmt IV as reporting persons due to Deerfield Private Design
Fund IV’s acquisition of 16,000 shares of the Issuer’s Series A Convertible Preferred Stock.

Capitalized terms used herein but not
otherwise defined herein shall have the meanings ascribed to them in the Schedule 13D.

Items 2(a) and (b) of the Schedule 13D
are hereby amended and restated as follows:

Item 2(c) of the Schedule 13D is hereby
amended by adding the following:

Item 2(f) of the Schedule 13D is hereby
amended and restated as follows:

Page 1 of 21

The Reporting Persons have entered into a Joint Filing Agreement,
a copy of which is attached hereto as Exhibit 99.9.

Item 3 of the Schedule 13D is hereby
amended by adding the following:

As previously reported
in Item 4 of the Schedule 13D, on June 22, 2017, Deerfield Private Design Fund IV, the Company and the other Investors entered
into the Purchase Agreement, a copy of which has been filed as Exhibit 10.20 to the Company’s Form 8-K filed with the Securities
and Exchange Commission on June 23, 2017, and is incorporated by reference as Exhibit 99.7 hereto. On August 2, 2017, pursuant
to the Purchase Agreement, Deerfield Private Design Fund IV purchased 16,000 Preferred Shares for an aggregate purchase price of
$16.0 million. Such Preferred Shares are initially convertible into an aggregate of 16,082,018 shares (“Series A Conversion
Shares”) of Common Stock, subject to adjustment pursuant to the terms of the Certificate of Designation. Deerfield Private
Design Fund IV utilized working capital to purchase such Preferred Shares.

Item 4.         Purpose of Transaction.

Item
4 of the Schedule 13D is hereby amended by adding the following:

On August 1, 2017, the Company filed the
Certificate of Designation with the Delaware Secretary of State, a copy of which was filed by the Company as Exhibit 3.1 to the
Company’s Form 8-K filed with the Securities and Exchange Commission on August 3, 2017.

On August 2, 2017, the Company closed the
Transaction, pursuant to which Deerfield Private Design Fund IV acquired 16,000 Preferred Shares. Deerfield Private Design Fund
IV acquired the Preferred Shares reported herein for investment purposes.

Item 5.          Interests in Securities of the
Issuer

Items 5(a), (b) and (c) of the Schedule
13D are hereby amended and restated as follows:

(a) Throughout this report, the percentage
of outstanding Common Stock beneficially owned by the Reporting Persons has been determined based on 17,619,418 shares of Common
Stock outstanding as of August 2, 2017, based on information set forth in the Company’s Registration Statement on Form S-3,
filed with the Securities and Exchange Commission on August 3, 2017.

(1) Deerfield Management

Number of shares: 17,306,917

Percentage of shares: 9.985%

(2) Deerfield Mgmt

Number of shares: 347,100

Percentage of shares: 1.97%

Page 13 of 21

(3) Deerfield Mgmt III

Number of
Shares: 877,799

Percentage
of Shares: 4.98%

(4) Deerfield Partners

Number of shares: 86,867

Percentage of shares: 0.49%

(5) Deerfield Special Situations
Fund

Number of shares: 149,676

Percentage of shares: 0.85%

(6) Deerfield International Master
Fund

Number of
Shares: 110,557

Percentage
of Shares: 0.63%

(7) Deerfield Private Design
Fund III

Number of
Shares: 877,799

Percentage
of Shares: 4.98%

(8) Deerfield Private Design
Fund IV

Number of
Shares: 16,082,018

Percentage
of Shares: 9.985%

(9) Deerfield Mgmt IV

Number of
Shares: 16,082,018

Percentage
of Shares: 9.985%

(10) Flynn

Number of shares: 17,306,917

Percentage of shares: 9.985%

(b)

(1) Deerfield Management

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 17,306,917

Sole power to dispose or to direct
the disposition: 0

Shared power to dispose or direct
the disposition: 17,306,917

Page 14 of 21

(2) Deerfield Mgmt

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 347,100

Sole power to dispose or to direct
the disposition: 0

Shared power to dispose or direct
the disposition: 347,100

(4) Deerfield Mgmt III

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 877,799

Sole power to dispose or to direct
the disposition: 0

Shared power to dispose or direct
the disposition: 877,799

(4) Deerfield Partners

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 86,867

Sole power to dispose or to direct
the disposition: 0

Shared power to dispose or direct
the disposition: 86,867

(5) Deerfield Special Situations
Fund

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 149,676

Sole power to dispose or to direct
the disposition: 0

Shared power to dispose or direct
the disposition: 149,676

(6) Deerfield International Master
Fund

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 110,557

Sole power to dispose or to direct
the disposition: 0

Shared power to dispose or direct
the disposition: 110,557

(7) Deerfield Private Design
Fund III

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 877,799

Sole power to dispose or to direct
the disposition: 0

Shared power
to dispose or direct the disposition: 877,799

(8) Deerfield Private Design
Fund IV

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 16,082,018

Sole power to dispose or to direct
the disposition: 0

Shared power
to dispose or direct the disposition: 16,082,018

Page 15 of 21

(9) Deerfield Mgmt IV

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 16,082,018

Sole power to dispose or to direct
the disposition: 0

Shared power to dispose or direct
the disposition: 16,082,018

(10) Flynn

Sole power to vote or direct the
vote: 0

Shared power to vote or direct
the vote: 17,306,917

Sole power to dispose or to direct
the disposition: 0

Shared power to dispose or direct
the disposition: 17,306,917

Flynn is the sole member of the general partner of each of Deerfield
Mgmt, Deerfield Mgmt III, Deerfield Mgmt IV and Deerfield Management.  Deerfield Mgmt is the general partner of Deerfield
Special Situations Fund, Deerfield Partners and Deerfield International Master Fund. Deerfield Mgmt III is the general partner
of Deerfield Private Design Fund III. Deerfield Mgmt IV is the general partner of Deerfield Private Design Fund IV. Deerfield Management
is the investment manager of each of Deerfield Special Situations Fund, Deerfield Private Design Fund III and Deerfield Private
Design Fund IV.

(c) Except as set forth in Items 3, 4 and 6 of the Schedule
13D, no Reporting Person has effected any transactions in the Common Stock during the past 60 days.

Item 6 of the Schedule 13D is hereby amended by adding the
following:

Series A Director

In connection with the closing of the Transaction,
Jonathan Leff, a partner at Deerfield Management, was named to the board of directors of the Company, to serve as the Series A
Director, and the Company granted Mr. Leff an option to purchase 13,333 shares of Common Stock, at an exercise price of $1.30 per
share, for his service on the board, subject to the terms and conditions of the Company’s stock plan. The option is scheduled
to vest with respect to one-third of the underlying shares of Common Stock on each of August 2, 2018, August 2, 2019 and August
2, 2020. Mr. Leff does not have any pecuniary interest, and disclaims beneficial ownership of, such option and holds the option
for, and at the direction of, Deerfield Management.

Registration Rights Agreement

On August 2, 2017, at the closing of the
Transaction, the Company entered into the Registration Rights Agreement. Pursuant to the Registration Rights Agreement, the Investors
are entitled to certain shelf and “piggyback” registration rights with respect to Series A Conversion Shares, subject
to the limitations set forth in the Registration Rights Agreement.

Page 16 of 21

The foregoing description of the Registration
Rights Agreement, is not, and does not purport to be, complete and is qualified in its entirety by reference to the full text thereof,
which has been filed by the Company as Exhibit 4.1 to the Company’s Form 8-K filed with the Securities and Exchange Commission
on August 3, 2017 and is incorporated by reference as Exhibit 99.8 hereto.

Item 7. Material to be Filed as Exhibits.

Item
7 of the Schedule 13D is hereby amended by adding the following as Exhibits 99.

_______________

* Filed herewith.

Page 17 of 21

SIGNATURE

After reasonable inquiry
and to the best of their knowledge and belief, the undersigned certify that the information set forth in this statement is true,
complete and correct.

Dated: August 4, 2017

Page 18 of 21

Page 19 of 21

Schedule A

Schedule A to the 13D is hereby amended by adding the following:

General Partner of Deerfield Mgmt IV,
L.P.

The general partner of Deerfield Mgmt IV is J.E. Flynn Capital
IV, LLC.  The address of the principal business and/or principal office of each of Deerfield Mgmt IV and J.E. Flynn Capital
IV, LLC is 780 Third Avenue, 37th Floor, New York, New York 10017.

General Partner of Deerfield Private
Design Fund IV, L.P.

The general partner of Deerfield Private Design Fund IV is Deerfield
Mgmt IV. The address of the principal business and/or principal office of Deerfield Mgmt IV and Deerfield Private Design Fund IV
is 780 Third Avenue, 37^th Floor, New York, New York 10017.