Use these links to rapidly review the document

TABLE OF CONTENTS
TABLE OF CONTENTS

Table of Contents

As filed with the Securities and Exchange Commission on September 1, 2017August 5, 2022

Registration No. 333-      


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



FORM S-3

REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933



PROTAGONIST THERAPEUTICS, INC.

Protagonist Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

Delaware

(State or other jurisdiction of

incorporation or organization)
001-37852
(Commission File Number)
98-0505495

(I.R.S. Employer

Identification Number)



7707 Gateway Boulevard, Suite 140
Newark, CaliforniaCA 94560-1160
(510) 474-0170


(Address, including zip code, and telephone number, including

area code, of registrant'sregistrant’s principal executive offices)



Dinesh V. Patel, Ph.D.
President and Chief Executive Officer
Protagonist Therapeutics, Inc.
7707 Gateway Boulevard, Suite 140
Newark, CaliforniaCA 94560-1160
(510) 474-0170
(Name, address, including zip code, and telephone number, including
area code, of agent for service)



CopiesWith copies to:

Ryan A. Murr
Branden C. Berns
Gibson, Dunn & Crutcher LLP
555 Mission Street
San Francisco, CA 94105-0921
(415) 393-8373
Matthew Gosling
Executive Vice President, General Counsel
Protagonist Therapeutics, Inc.
7707 Gateway Boulevard, Suite 140
Newark, CA 94560-1160
(510) 474-0170
Kenneth L. Guernsey
Michael E. Tenta
Cooley LLP
3175 Hanover Street
Palo Alto, CA 94304
(650) 843-5000



Approximate date of commencement of proposed sale to the public:
From time to time after this Registration Statementregistration statement becomes effective.

If the only securities being registered on this Form are being offered pursuant to dividend or interest reinvestment plans, please check the following box. o

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, as amended, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box.    ý

box: ☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. o

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. o

If this Form is a registration statement pursuant to General Instruction I.D. or a post-effective amendment thereto that shall become effective upon filing with the Commission pursuant to Rule 462(e) under the Securities Act, check the following box. o

If this Form is a post-effective amendment to a registration statement filed pursuant to General Instruction I.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box. o

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of "large“large accelerated filer," "accelerated” “accelerated filer," "smaller” “smaller reporting company," and "emerging“emerging growth company"company” in Rule 12b-2 of the Exchange Act.

(Check one):
Large accelerated filero
Accelerated filero
Non-accelerated filerý
(Do not check if a
smaller reporting company)
Smaller reporting companyo


Emerging growth companyý


If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ý

CALCULATION OF REGISTRATION FEE

        
 
Title of Each Class of Securities
to be Registered

 Amount to be
Registered(1)

 Proposed Maximum
Offering Price Per
Unit

 Proposed Maximum
Aggregate Offering
Price

 Amount of
Registration Fee(2)

 

Common Stock, par value $0.00001 per share

 (3) (4) (4) 
 

Preferred Stock, par value $0.00001 per share

 (3) (4) (4) 
 

Debt Securities

 (3) (4) (4) 
 

Total

 (3)   $200,000,000 $23,180

 

(1)
Pursuant to Rule 416 under the Securities Act, the shares being registered hereunder include such indeterminate number of shares of common stock and preferred stock as may be issuable with respect to the shares being registered hereunder as a result of stock splits, stock dividends or similar transactions.

(2)
Calculated pursuant to Rule 457(o) under the Securities Act of 1933, as amended, or the Securities Act.

(3)
There are being registered hereunder such indeterminate number of shares of common stock and preferred stock, and such indeterminate principal amount of debt securities as may be sold by the Registrant from time to time, which together shall have an aggregate initial offering price not to exceed $200,000,000. If any debt securities are issued at an original issue discount, then the offering price of such debt securities shall be in such greater principal amount as shall result in an aggregate offering price not to exceed $200,000,000, less the aggregate dollar amount of all securities previously issued hereunder. Any securities registered hereunder may be sold separately or in combination with other securities registered hereunder. The proposed maximum offering price of the securities will be determined, from time to time, by the Registrant in connection with the issuance by the Registrant of the securities registered hereunder. The securities registered hereunder also include such indeterminate number of shares of common stock and preferred stock and amount of debt securities as may be issued upon conversion of or exchange for preferred stock or debt securities that provide for conversion or exchange, or pursuant to the antidilution provisions of any of such securities.

(4)
The proposed maximum aggregate offering price per class of security will be determined from time to time by the Registrant in connection with the issuance by the Registrant of the securities registered hereunder and is not specified as to each class of security pursuant to General Instruction II.D. of Form S-3 under the Securities Act.

The Registrantregistrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrantregistrant shall file a further amendment thatwhich specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, as amended, or until this registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.



Table of Contents


EXPLANATORY NOTE

This registration statement contains:

    contains the following documents:

a base prospectus which covers the offering, issuance and sales by us of up to $200,000,000 in the aggregate of the securities identified above from time to time in one or more offerings; and

a sales agreement prospectus covering the offering, issuance and salessale by us of up to a maximum aggregate offering price of $50,000,000$300,000,000 of common stock, preferred stock, debt securities, warrants and/or units from time to time in one or more offerings; and

a sales agreement prospectus supplement covering the offering, issuance and sale by us of up to a maximum aggregate offering price of $100,000,000 of our common stock that may be offered, issued and sold from time to time under a sales agreementan Open Market Sale AgreementSM, dated August 5, 2022, with Cantor Fitzgerald & Co.Jefferies LLC (“Jefferies”) (the "Sales Agreement"“Sales Agreement”).

The base prospectus immediately follows this explanatory note. The specific terms of any securities to be offered pursuant to the base prospectus other than the shares under the Sales Agreement will be specified in a prospectus supplement to the base prospectus. The specific terms of the securities to be issued and sold under the Sales Agreement are specified in the sales agreement prospectus supplement that immediately follows the base prospectus. The $50,000,000$100,000,000 of shares of common stock that may be offered, issued and sold under the sales agreement prospectus supplement is included in the $200,000,000$300,000,000 of securities that may be offered, issued and sold by usthe registrant under the base prospectus. Upon termination of the Sales Agreement, any portion of the $50,000,000$100,000,000 included in the sales agreement prospectus supplement that is not sold pursuant to the Sales Agreement will be available for sale in other offerings pursuant to the base prospectus, and if no shares of common stock are sold under the Sales Agreement, the full $50,000,000$300,000,000 of securities may be sold in other offerings pursuant to the base prospectus.

prospectus and a corresponding prospectus supplement.


The information contained in this prospectus is not complete and may be changed. We may not sell these securities or accept an offer to buy these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and it is not soliciting offers to buy these securities in any statejurisdiction where such offer or sale is not permitted.


SUBJECT TO COMPLETION, DATED SEPTEMBER 1, 2017Subject to Completion, Dated August 5, 2022

PROSPECTUS

[MISSING IMAGE: lg_protagonist-pn.jpg]
LOGOCOMMON STOCK


$200,000,000PREFERRED STOCK


Common StockDEBT SECURITIES


Preferred StockWARRANTS


Debt SecuritiesUNITS

        We may, from

From time to time, offer and sellwe may issue, in one or more series or classes, up to $200,000,000an aggregate of any combination$300,000,000 of our common stock, preferred stock, or debt securities, described in this prospectus, either individually warrants and/or in combination,units, at prices and on terms described in one or more supplements to this prospectus. We may also offer common stock or preferred stock upon conversionthat we will determine at the time of debt securities, or common stock upon conversion of preferred stock.

the offering.

This prospectus describes someprovides you with a general description of the general terms thatsecurities we may apply to an offering of our securities. Weoffer. Each time we offer securities, we will provide the specific terms of these offerings andthe securities offered in one or more supplementsa supplement to this prospectus. We may also authorize one or more free writing prospectuses to be provided to you in connection with these offerings. The prospectus supplement and any related free writing prospectus may also add, update or change information contained in this prospectus. We may not sell any securities under this prospectus without delivery of the applicable prospectus supplement. If information in any prospectus supplement is inconsistent with the information in this prospectus, then the information in that prospectus supplement will apply and will supersede the information in this prospectus.
You should carefully read this prospectus, the applicable prospectus supplement and any related free writing prospectus carefully, as well as theany documents incorporated by reference, before buyingyou invest in any of the securities being offered.

        This prospectus may not be used to consummate a sale

Our shares of securities unless accompanied by a prospectus supplement.

        Securities may be sold by us to or through underwriters or dealers, directly to purchasers or through agents designated from time to time. For additional information on the methods of sale, you should refer to the section entitled "Plan of Distribution" in this prospectus and in the applicable prospectus supplement. If any underwriters are involved in the sale of any securities with respect to which this prospectus is being delivered, the names of such underwriters and any applicable discounts or commissions and over-allotment options will be set forth in a prospectus supplement. The price to the public of such securities and the net proceeds we expect to receive from such sale will also be set forth in a prospectus supplement.

        Our common stock isare listed on the NASDAQThe Nasdaq Global Market under the symbol "PTGX." On August 31, 2017, the“PTGX.” The last reported sale price of our common stock on the NASDAQThe Nasdaq Global Market on August 2, 2022 was $16.33$10.63 per share.

We recommend that you obtain current market quotations for our common stock prior to making an investment decision.

Investing in our securities involves a high degree of risk. You should review carefully the risks and uncertainties described under the heading "Risk Factors"“Risk Factors” contained in thethis prospectus beginning on page 4 and any applicable prospectus supplement, and in any free writing prospectuses we have authorized for use in connection with a specific offering, and under similar headings in the other documents that are incorporated by reference into this prospectus.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The date of this

Prospectus dated            , 2022


TABLE OF CONTENTS
1
2
3
4
5
6
7
11
22
23
26
28
28
29
30



ABOUT THIS PROSPECTUS
This prospectus is , 2017.


Table of Contents


TABLE OF CONTENTS


Page

About this Prospectus

i

Summary

1

The Securities We May Offer

4

Risk Factors

7

Forward-Looking Statements

7

Financial Ratios

9

Use of Proceeds

9

Description of Capital Stock

10

Description of Debt Securities

16

Legal Ownership of Securities

23

Plan of Distribution

27

Legal Matters

30

Experts

30

Where You Can Find More Information

30

Incorporation of Certain Information by Reference

31



        You should rely only on the information contained in, or incorporated by reference into, this prospectus and the applicable prospectus supplement, along with the information contained in any free writing prospectuses we have authorized for use in connection with a specific offering. We have not authorized anyone to provide you with different information. We are not making an offer to sell or seeking an offer to buy securities under this prospectus or the applicable prospectus supplement and any related free writing prospectus in any jurisdiction where the offer or sale is not permitted. The information contained in this prospectus, the applicable prospectus supplement or any related free writing prospectus, and the documents incorporated by reference herein and therein, are accurate only as of their respective dates, regardless of the time of delivery of this prospectus, the applicable prospectus supplement or any related free writing prospectus, or any sale of a security.




ABOUT THIS PROSPECTUS

        This prospectus is part of a registration statement on Form S-3 that we filed with the Securities and Exchange Commission (the “SEC” or SEC, usingthe “Commission”) utilizing a "shelf"“shelf” registration process. Under this shelf registration statement,process, we may sell from time to timeany combination of the securities described in this prospectus in one or more offerings up to a total dollar amount of $200,000,000$300,000,000. This prospectus provides you with a general description of common stock and preferred stock, and various series of debt securities. the securities we may offer.

Each time we sell any type or series of securities under this prospectus, we will provide a prospectus supplement that will contain more specific information about the terms of that offering. We may also authorize one or more free writing prospectuses to be provided to you that may contain material information relating to these offerings. We may also add, update or change in a prospectus supplement or free writing prospectus any of the information contained in this prospectus or in the documents we have incorporated by reference into this prospectus. This prospectus, together with the applicable prospectus supplement, any related free writing prospectus and the documents incorporated by reference into this prospectus and the applicable prospectus supplement, will include all material information relating to the applicable offering. You should carefully read both this prospectus and the applicable prospectus supplement and any related free writing prospectus, together with the additional information described under "Where You Can Find More Information," before buying any of the securities being offered.

i


Table of Contents

        This prospectus may not be used to consummate a sale of securities unless accompanied by a prospectus supplement.

        This prospectus contains and incorporates by reference market data and industry statistics and forecasts that are based on independent industry publications and other publicly available information. Although we believe that these sources are reliable, we do not guarantee the accuracy or completeness of this information and we have not independently verified this information. Although we are not aware of any misstatements regarding the market and industry data presented in this prospectus and the documents incorporated herein by reference, these estimates involve risks and uncertainties and are subject to change based on various factors, including those discussed under the heading "Risk Factors" contained in the applicable prospectus supplement and any related free writing prospectus, and under similar headings in the other documents that are incorporated by reference into this prospectus. Accordingly, investors should not place undue reliance on this information.

        This prospectus contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed, will be filed or will be incorporated by reference as exhibits to the registration statement of which this prospectus is a part, and you may obtain copies of those documents as described below under the section entitled "Where You Can Find More Information."

        Except as otherwise indicated herein or as the context otherwise requires, references in this prospectus to "Protagonist," "the company," "we," "us," "our" and similar references refer to Protagonist Therapeutics, Inc., a corporation under the laws of the State of Delaware.

        This prospectus and the information incorporated herein by reference include trademarks, service marks and trade names owned by us or other companies. All trademarks, service marks and trade names included or incorporated by reference into this prospectus, any applicable prospectus supplement or any related free writing prospectus are the property of their respective owners.

ii


Table of Contents



SUMMARY

This summary highlights selected information contained elsewhere in this prospectus or incorporated by reference herein and does not contain all of the information that you need to consider in making your investment decision. You should carefully read the entire prospectus, the applicable prospectus supplement and any related free writing prospectus, including the risks of investing in our securities discussed under the heading "Risk Factors" contained in the applicable prospectus supplement and any related free writing prospectus, and under similar headings in the other documents that are incorporated by reference into this prospectus. You should also carefully read the information incorporated by reference into this prospectus, including our financial statements and related notes, and the exhibits to the registration statement of which this prospectus is a part, before making your investment decision.


Protagonist Therapeutics, Inc.

Overview

        We are a clinical-stage biopharmaceutical company with a proprietary technology platform which is utilized to discover and develop novel peptide-based drugs to address significant unmet medical needs. Our primary focus is on developing potential first-in-class oral targeted therapy-based peptide drugs that work by blocking biological pathways that are currently targeted by marketed injectable antibody drugs. Our initial lead peptide product candidates, PTG-100 and PTG-200, are based on this approach, and we believe these candidates have the potential to transform the existing treatment paradigm for inflammatory bowel disease ("IBD"), chronic gastrointestinal diseases consisting primarily of ulcerative colitis ("UC") and Crohn's disease ("CD").

        PTG-100, a potential first-in-class oral, alpha-4-beta-7 ("a4b7") integrin antagonist, is currently in a global Phase 2B clinical trial for the treatment of moderate-to-severe UC that is anticipated to randomize approximately 240 patients at approximately 100 clinical sites. We anticipate completing this trial in the second half of 2018. PTG-200, a potential first-in-class oral Interleukin-23 receptor ("IL-23R") antagonist for the potential treatment of CD, is currently in pre-clinical development and is expected to enter Phase 1 clinical studies in the second half of 2017. We have a worldwide collaboration agreement with Janssen Biotech, Inc. to co-develop and commercialize PTG-200 for all indications, including IBD, as described below in the section titled "Janssen Collaboration Agreement." In addition to PTG-100 and PTG-200, we are also developing an injectable hepcidin mimetic, PTG-300, for the treatment of rare diseases such as beta-thalassemia. PTG-300 is currently being studied in a Phase 1 clinical trial.

        We have not generated any revenue from product sales and we do not currently have any products approved for commercialization. We have never been profitable and have incurred net losses in each year since inception and we do not anticipate that we will achieve profitability in the near term. Our net losses were $15.0 million and $29.1 million for the three and six months ended June 30, 2017, respectively, and $7.1 million and $18.8 million for the three and six months ended June 30, 2016, respectively. As of June 30, 2017, we had an accumulated deficit of $93.7 million. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect to continue to incur significant research, development and other expenses related to our ongoing operations and product development, including clinical development activities under the Janssen Collaboration Agreement, and as a result, we expect to continue to incur losses for the foreseeable future. We also expect these losses to increase as we continue our development of, and seek regulatory approval for, our product candidates.


Table of Contents

Janssen Collaboration Agreement

        On May 26, 2017, we and Janssen Biotech, Inc., ("Janssen") entered into an exclusive license and collaboration agreement (the "Janssen Collaboration Agreement") for the development, manufacture and commercialization of PTG-200 worldwide for the treatment of CD and UC. The Janssen Collaboration Agreement became effective on July 13, 2017. Upon the effectiveness of the agreement, we became eligible for a non-refundable, upfront cash payment of $50.0 million from Janssen, which we received during the third quarter of 2017.

        Under the Janssen Collaboration Agreement, we granted Janssen an exclusive worldwide license to develop, manufacture and commercialize PTG-200 and related IL-23R compounds for all indications, including CD and UC. We are responsible, at our own expense, for the conduct of the Phase 1 clinical trial for PTG-200, and Janssen will be responsible for the conduct of a potential Phase 2 clinical trial for PTG-200 in CD. All such clinical trials would be conducted in accordance with a mutually agreed upon clinical development plan and budget. Development costs for the Phase 2 clinical trial would be shared between the parties on an 80%/20% basis, with Janssen assuming the larger share. Should Janssen elect to retain its license following completion of the Phase 2 clinical trial, it would be responsible, at its own expense, for the manufacture, continued development of, seeking regulatory approval for, and commercialization of PTG-200 worldwide. The parties' development activities under the Janssen Collaboration Agreement through the Phase 2 clinical trial will be overseen by a joint governance structure which will have equal representation by both parties.

        Following the conclusion of the planned Phase 2A portion of the Phase 2 clinical trial, if Janssen elects to maintain its license rights and continue the development of PTG-200 in the Phase 2B portion of such clinical trial (the "First Opt-in Election"), we would be eligible to receive a $125 million payment. Following the conclusion of the planned Phase 2B portion of the Phase 2 clinical trial, if Janssen elects again to maintain its license rights (the "Second Opt-in Election"), we would be eligible to receive a $200 million payment. In addition to the opt-in fees, we are eligible to receive potential development, regulatory and sales milestone payments of up to an aggregate of $615 million and tiered royalties paid as a percentage of Janssen's worldwide net sales at rates ranging from ten to the mid-teens, with certain customary reductions in certain circumstances. If Janssen does not make either the First Opt-in Election or the Second Opt-in Election, the Janssen Collaboration Agreement would terminate. If Janssen does not make the Second Opt-in Election, or if at any time after the Second Opt-in Election, Janssen terminates the Janssen Collaboration Agreement, we would be obligated to pay Janssen a royalty on worldwide net sales of PTG-200. We would also have an option to provide up to 30% of the required U.S. details for PTG-200 to prescribers, using our own sales force personnel, upon commercial launch in the United States. If such right is exercised, our detailing costs would be reimbursed by Janssen.

        The Janssen Collaboration Agreement contains customary representations, warranties and covenants by us and Janssen and includes an obligation by us not to develop or commercialize other compounds which also target IL-23R outside of the Janssen Collaboration Agreement until completion of the Phase 2B portion of the Phase 2 clinical trial. We and Janssen are required to indemnify the other party against all losses and expenses related to breaches of its representations, warranties and covenants under the Janssen Collaboration Agreement.

        The Janssen Collaboration Agreement remains in effect until the royalty obligations cease following patent and regulatory expiry, unless terminated earlier. Either we or Janssen may terminate the Janssen Collaboration Agreement for uncured material breach. Janssen retains the right to terminate the Janssen Collaboration Agreement for convenience and without cause on written notice of a certain period to us. Upon a termination of the Janssen Collaboration Agreement, all rights revert back to us, and in certain circumstances, if such termination occurs during ongoing clinical trials,


Table of Contents

Janssen would, if requested, provide certain financial and operational support to us for the completion of such trials.

Company Information

        Protagonist Pty Limited (Protagonist Australia) was incorporated in Australia in September 2001. We were incorporated under the laws of the State of Delaware in 2006, under the name Protagonist Therapeutics, Inc., and became the parent of Protagonist Australia pursuant to a transaction in which all of the issued and outstanding capital stock of Protagonist Australia was exchanged for shares of our common stock and Series A preferred stock. Our principal executive offices are located at 7707 Gateway Boulevard, Suite 140, Newark, California 94560. Our telephone number is (510) 474-0170. Our website address is www.protagonist-inc.com. The information contained in, or accessible through, our website does not constitute part of this prospectus, should not be relied on in determining whether to make an investment decision, and the inclusion of our website address in this prospectus is an inactive textual reference only.

        The Protagonist logo and other trademarks or service marks of Protagonist Therapeutics, Inc. appearing in this prospectus are the property of Protagonist Therapeutics, Inc. Other trademarks, service marks or trade names appearing in this prospectus are the property of their respective owners. We do not intend our use or display of other companies' trade names, trademarks or service marks to imply a relationship with, or endorsement or sponsorship of us by, these other companies.

Risks Associated with our Business

        Our business is subject to numerous risks, as described under the heading "Risk Factors" contained in the applicable prospectus supplement and in any free writing prospectuses we have authorized for use in connection with a specific offering, and under similar headings in the documents that are incorporated by reference into this prospectus.


Table of Contents


THE SECURITIES WE MAY OFFER

        We may offer shares of our common stock and preferred stock, and various series of debt securities, either individually or in combination, with a total dollar amount up to $200,000,000 from time to time under this prospectus, together with the applicable prospectus supplement and any related free writing prospectus, at prices and on terms to be determined at the time of any offering. This prospectus provides you with a general description of the securities we may offer. Each time we offer a type or series of securities under this prospectus, we will provide a prospectus supplement that will describe the specific amounts, prices and other important terms of the securities, including, to the extent applicable:

    designation or classification;

    aggregate principal amount or aggregate offering price;

    maturity;

    original issue discount;

    rates and times of payment of interest or dividends;

    redemption, conversion, exercise, exchange or sinking fund terms;

    ranking;

    restrictive covenants;

    voting or other rights;

    conversion or exchange prices or rates and, if applicable, any provisions for changes to or adjustments in the conversion or exchange prices or rates and in the securities or other property receivable upon conversion or exchange; and

    a discussion of material United States federal income tax considerations, if any.

        The applicable prospectus supplement and any related free writing prospectus that we may authorize to be provided to you may also add, update or change information contained in this prospectus or in any documents that we have incorporated by reference. However, noreference into this prospectus. You should carefully read both this prospectus and any prospectus supplement together with additional information under the headings “Where You Can Find More Information” and “Incorporation of Certain Information by Reference.”

We have not authorized anyone to provide you with any information other than that contained or free writing prospectus will offer a security that is not registered and describedincorporated by reference in this prospectus at the time of the effectiveness of the registration statement of which this prospectus is a part.

        This prospectus may not be used to consummate a sale of securities unless it is accompanied by a prospectus supplement.

        We may sell the securities directly to investors or to or through agents, underwriters or dealers. We, and our agents, underwriters or dealers reserve the right to accept or reject all or part of any proposed purchase of securities. If we do offer securities to or through agents, underwriters or dealers, we will include in the applicable prospectus supplement:

    the names of those agents, underwriters or dealers;

    applicable fees, discounts and commissions to be paid to them;

    details regarding over-allotment options, if any; and

    the net proceeds to us.

Common Stock.

        We may issue shares of our common stock from time to time. Each holder of our common stock is entitled to one vote for each share on all matters submitted to a vote of the stockholders, including the


Table of Contents

election of directors. Under our amended and restated certificate of incorporation, or certificate of incorporation, and amended and restated bylaws, or bylaws, our stockholders do not have cumulative voting rights. Because of this, the holders of a majority of the shares of common stock entitled to vote in any election of directors can elect all of the directors standing for election, if they should so choose. Subject to preferences that may be applicable to any then-outstanding preferred stock, holders of common stock are entitled to receive ratably those dividends, if any, as may be declared from time to time by our board of directors out of legally available funds. In the event of our liquidation, dissolution or winding up, holders of common stock are entitled to share ratably in the net assets legally available for distribution to stockholders after the payment of all of our debts and other liabilities and the satisfaction of any liquidation preference granted to the holders of any then-outstanding shares of preferred stock. Holders of common stock have no preemptive, conversion or subscription rights and there are no redemption or sinking fund provisions applicable to the common stock. The rights, preferences and privileges of the holders of common stock are subject to, and may be adversely affected by, the rights of the holders of shares of any series of preferred stock that we may designate in the future. In this prospectus, we have summarized certain general features of the common stock under "Description of Capital Stock—Common Stock." We urge you, however, to read the applicable prospectus supplement (and any related free writing prospectus that we may authorize to be provided to you) related to any common stock being offered.

Preferred Stock.

        We may issue shares of our preferred stock from time to time, in one or more series. Our board of directors will determine the designations, voting powers, preferences and rights of the preferred stock, as well as the qualifications, limitations or restrictions thereof, including dividend rights, conversion rights, preemptive rights, terms of redemption or repurchase, liquidation preferences, sinking fund terms and the number of shares constituting any series or the designation of any series. Convertible preferred stock will be convertible into our common stock or exchangeable for other securities. Conversion may be mandatory or at your option and would be at prescribed conversion rates.

        If we sell any series of preferred stock under this prospectus, we will fix the designations, voting powers, preferences and rights of such series of preferred stock, as well as the qualifications, limitations or restrictions thereof, in the certificate of designation relating to that series. We will file as an exhibit to the registration statement of which this prospectus is a part, or will incorporate by reference from reports that we file with the SEC, the form of any certificate of designation that describes the terms of the series of preferred stock that we are offering before the issuance of the related series of preferred stock. In this prospectus, we have summarized certain general features of the preferred stock under "Description of Capital Stock—Preferred Stock." We urge you to read the applicable prospectus supplement (and any free writing prospectus that we may authorize to be provided to you) related to the series of preferred stock being offered, as well as the complete certificate of designation that contains the terms of the applicable series of preferred stock.

Debt Securities.

        We may issue debt securities from time to time, in one or more series, as either senior or subordinated debt or as senior or subordinated convertible debt. The senior debt securities will rank equally with any other unsecured and unsubordinated debt. The subordinated debt securities will be subordinate and junior in right of payment, to the extent and in the manner described in the instrument governing the debt, to all of our senior indebtedness. Convertible debt securities will be convertible into or exchangeable for our common stock or other securities. Conversion may be mandatory or at your option and would be at prescribed conversion rates.

        Any debt securities issued under this prospectus will be issued under one or more documents called indentures, which are contracts between us and a national banking association or other eligible


Table of Contents

party, as trustee. In this prospectus, we have summarized certain general features of the debt securities under "Description of Debt Securities." We urge you, however, to read the applicable prospectus supplement (and any free writing prospectus that we may authorize to be provided to you) related to the series of debt securities being offered, as well as the complete indentures that contain the terms of the debt securities. A form of indenture has been filed as an exhibit to the registration statement of which this prospectus is a part, and supplemental indentures and forms of debt securities containing the terms of the debt securities being offered will be filed as exhibits to the registration statement of which this prospectus is a part or will be incorporated by reference from reports that we file with the SEC.

Use of Proceeds

        Except as described in any applicable prospectus supplement, oralong with the information contained in any free writing prospectusprospectuses we have authorized for use in connection with a specific offering, we currently intendoffering. We take no responsibility for, and can provide no assurance as to use the net proceeds fromreliability of, any other information that others may give you. This prospectus is an offer to sell only the sale of the shares of our securities offered by us hereunder, ifhereby, but only under circumstances and in jurisdictions where it is lawful to do so. This prospectus, any for working capital, capital expenditures and other general corporate purposes. See "Use of Proceeds" inapplicable supplement to this prospectus.

NASDAQ Global Market Listing

        Our common stock is listed on the NASDAQ Global Market under the symbol "PTGX." The applicable prospectus supplement will contain information, where applicable, as to other listings, if any, on the NASDAQ Global Market or other securities exchange of the shares of our common stock covered by the applicable prospectus supplement.


Table of Contents


RISK FACTORS

        Investing in our securities involves a high degree of risk. Before deciding whether to invest in our securities, you should consider carefully the risks and uncertainties described under the heading "Risk Factors" contained in the applicable prospectus supplement and any related free writing prospectus and discussed underdo not constitute an offer to sell or the section entitled "Risk Factors" contained in our most recent Annual Report on Form 10-K and in our most recent Quarterly Report on Form 10-Q, as well assolicitation of an offer to buy any amendments thereto reflected in subsequent filings withsecurities other than the SEC,registered securities to which are incorporated by reference intothey relate, nor do this prospectus, in their entirety, together with other information inany applicable supplement to this prospectus the documents incorporated by reference andor any related free writing prospectus that we may authorize for useconstitute an offer to sell or the solicitation of an offer to buy securities in connection with this offering. The risks describedany jurisdiction to any person to whom it is unlawful to make such offer or solicitation in these documents are not the only ones we face, but those that we consider to be material. There may be other unknown or unpredictable economic, business, competitive, regulatory or other factors that could have material adverse effects on our future results. Past financial performance may not be a reliable indicator of future performance, and historical trendssuch jurisdiction.

You should not be used to anticipate results or trendsassume that the information contained in future periods. If any of these risks actually occurs, our business, financial condition, results of operations or cash flow could be seriously harmed. This could cause the trading price of our common stock to decline, resulting in a loss of all or part of your investment. Please also read carefully the section below entitled "Forward-Looking Statements."


FORWARD-LOOKING STATEMENTS

        Thisthis prospectus, including the documents that we incorporate by reference herein, contains, and any applicable prospectus supplement or any related free writing prospectus includingis accurate on any date subsequent to the date set forth on the front of the document or that any information we have incorporated by reference is correct on any date subsequent to the date of the document incorporated by reference, even though this prospectus, any applicable prospectus supplement or any related free writing prospectus is delivered, or securities are sold, on a later date.

Unless the context otherwise requires, we use the terms “Protagonist,” the “company,” “we,” “us,” and “our” in this prospectus to refer to Protagonist Therapeutics, Inc. and, where appropriate, our subsidiaries.

1


CAUTIONARY STATEMENT CONCERNING FORWARD-LOOKING STATEMENTS
This prospectus and the documents that we incorporatehave filed with the SEC that are incorporated by reference therein mayherein contain forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, and amended, or the Exchange Act, including statements regarding our future financial condition, business strategy and plans and objectives of management for future operations. Forward-looking statements include all statements that are not historical facts. In some cases, you can identify forward-looking statements by terminology such as "believe," "will," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "might," "approximately," "expect," "predict," "could," "potentially"“believe,” “will,” “may,” “estimate,” “continue,” “anticipate,” “intend,” “should,” “plan,” “might,” “approximately,” “expect,” “predict,” “could,” “potentially” or the negative of these terms or other similar expressions. Forward-looking statements appear in a number of places throughout this prospectus, the documents incorporated by reference and any free writing prospectus that we have authorized for use in connection with this offering and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the potential for our programs, the timing of our clinical trials, the potential for eventual regulatory approval and commercialization of our product candidates and our potential receipt of milestone payments and royalties under our collaboration agreement with Janssen,agreements; future operating results or the ability to generate sales, income or cash flow, and the impact of the ongoing COVID-19 pandemic, are forward-looking statements.

Discussions containing these forward-looking statements may be found, among other places, in the Sectionssection of this prospectus under the heading “Risk Factors” and in the sections entitled "Business," "Risk Factors"“Business” and "Management's“Management’s Discussion and Analysis of Financial Condition and Results of Operations"Operations” incorporated by reference from our most recent Annual Report on Form 10-K and in ourany subsequent Quarterly Reports on Form 10-Q, as well as any amendments thereto, filed with the SEC.U.S. Securities and Exchange Commission (the “SEC”). These statements relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that could cause our actual results, levels of activity, performance or achievement to differ materially from those expressed or implied by these forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these risks and uncertainties, you should not place undue reliance on these forward-looking statements. We discuss in greater detail and incorporate by reference into this prospectus in their entirety, many of these risks and uncertainties under the heading "Risk Factors" contained“Risk Factors” and elsewhere in the applicablethis prospectus supplement, in any free writing prospectus we may authorize for use in connection with a specific offering, and in our most recent Annual Report on Form 10-K and in our most recentany subsequent Quarterly ReportReports on Form 10-Q, as well as any amendments thereto reflected in subsequent filings with the SEC. SEC and in the other documents incorporated by reference herein. Also, these forward-looking statements represent our estimates and assumptions only as of the date of the document containing the applicable statement and, except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
In addition, statements that "we believe"such as “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information


Table of Contents

available to us as of the date of this prospectus, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.


2


We are a biopharmaceutical company with peptide-based new chemical entities rusfertide, PN-943 and PN-235 in different stages of Contentsdevelopment, all derived from the Company’s proprietary discovery technology platform. Our clinical programs fall into two broad categories of diseases; (i) hematology and blood disorders, and (ii) inflammatory and immunomodulatory diseases.
Corporate Information


FINANCIAL RATIOS

        The following table sets forth, for each

Our principal executive offices are located at 7707 Gateway Boulevard, Suite 140, Newark, California 94560. Our telephone number is (510) 474-0170. Our website address is www.protagonist-inc.com. References to our website address do not constitute incorporation by reference of the periods presented,information contained on the website, and the information contained on the website is not part of this document. We have included our deficiency of earnings to cover fixed charges. Amounts shown arewebsite in thousands.

this prospectus solely as an inactive textual reference.
 
 Year Ended December 31,  
 
 
 Six Months
Ended
June 30, 2017
 
 
 2014 2015 2016 

Ratio of earnings to fixed charges(1)

  N/A  N/A  N/A  N/A 

Deficiency of earnings available to cover fixed charges

 $(11,072)$(14,858)$(37,177)$(14,979)

3

(1)
For

RISK FACTORS
Investing in our securities involves risks. You should carefully consider the six months ended June 30, 2017risks, uncertainties and years ended December 31, 2016, 2015other factors described in our most recent Annual Report on Form 10-K, as supplemented and 2014, earnings were not sufficient to cover fixed charges. Earnings consistupdated by subsequent Quarterly Reports on Form 10-Q and Current Reports on Form 8-K that we have filed or will file with the SEC, and in other documents which are incorporated by reference into this prospectus, as well as the risk factors and other information contained in or incorporated by reference into any accompanying prospectus supplement before investing in any of loss from continuingour securities. Our business, financial condition, results of operations, before income taxes, extraordinary items, cumulative effect of accounting changes, equity in net losses of affiliatescash flows or prospects could be materially and fixed charges, adjusted for capitalized interest. Fixed charges consist of interest expensed and capitalized and amortized premiums, discounts and capitalized expenses related to indebtedness. Becauseadversely affected by any of these deficiencies,risks. The risks and uncertainties described in the ratiodocuments incorporated by reference herein are not the only risks and uncertainties that you may face.
For more information is not applicable for those periods.
about our SEC filings, please see “Where You Can Find More Information” and “Incorporation of Certain Information by Reference.”


4


USE OF PROCEEDS

Except as described in any applicable prospectus supplement or in any free writing prospectuses we have authorized for use in connection with a specific offering, we currently intend to use the net proceeds from this offeringthe sale of the securities offered by us hereunder for working capital and general corporate purposes, which may include, among other things, funding research and development, clinical trials, vendor payables, potential regulatory submissions, hiring additional personnel and capital expenditures.

Our expected use of proceeds from the sale of the securities offered hereby represents our current intentions based on our present plans and business condition. As of the date of this prospectus, we cannot predict with certainty all of the particular uses for the proceeds to be received from the sale of the securities offered hereby or the amounts that we will actually spend on the uses set forth above.
Pending the use of the net proceeds, we may invest the proceeds in interest-bearing, investment-grade securities, certificates of deposit or government securities. When we offer and sell the securities to which this prospectus relates, the prospectus supplement related to such offering will set forth our intended use of the proceeds, if any, received from the sale of such securities.

5


This prospectus contains summary descriptions of Contentsthe securities we may offer from time to time. These summary descriptions are not meant to be complete descriptions of each security. The particular terms of any security will be described in the applicable prospectus supplement.

6




DESCRIPTION OF CAPITAL STOCK

The description below of our capital stock and provisions of our amended and restated certificate of incorporation (our “certificate of incorporation”) and amended and restated bylaws (our “bylaws”) are summaries and are qualified by reference to our certificate of incorporation and our bylaws which are filed as exhibits to the registration statement of which this prospectus is part, and by the applicable provisions of Delaware law. For more information on how you can obtain our certificate of incorporation and our bylaws, see the heading “Where You Can Find More Information.”
As of the date of this prospectus, our certificate of incorporation, authorizes us to issue up to 90,000,000 shares of common stock, $0.00001 par value per share, and 10,000,000 shares of preferred stock, $0.00001 par value per share. As of July 31, 2017, 16,902,761June 30, 2022, 48,683,931 shares of common stock were outstanding and no shares of preferred stock were outstanding.

        The following summary describes the material terms of our capital stock. The description of capital stock is qualified by reference to our certificate of incorporation and our bylaws.

Common Stock

Voting Rights

Holders of our common stock are entitled to one vote for each share held on all matters submitted to a vote of stockholders, including the election of directors, and do not have cumulative voting rights. Accordingly, the holders of a majority of the outstanding shares of common stock entitled to vote in any election of directors can elect all of the directors standing for election, if they so choose, other than any directors that holders of any preferred stock we may issue may be entitled to elect.

Dividend Rights

Subject to preferences that may be applicable to any then outstanding preferred stock, holders of common stock are entitled to receive ratably those dividends, if any, as may be declared by the board of directors out of legally available funds.

Liquidation

In the event of our liquidation, dissolution or winding up, the holders of common stock will be entitled to share ratably in the assets legally available for distribution to stockholders after the payment of or provision for all of our debts and other liabilities, subject to the prior rights of any preferred stock then outstanding.

Rights and Preferences

Holders of common stock have no preemptive or conversion rights or other subscription rights and there are no redemption or sinking funds provisions applicable to the common stock. The rights, preferences and privileges of holders of common stock are subject to and may be adversely affected by the rights of the holders of shares of any series of preferred stock that we may designate and issue in the future.

Anti-Takeover Effects of Delaware Law and our Certificate of Incorporation and Bylaws
Some provisions of Delaware law, our certificate of incorporation and our bylaws contain provisions that could make the following transactions more difficult: an acquisition of us by means of a tender offer; an acquisition of us by means of a proxy contest or otherwise; or the removal of our incumbent officers and directors. It is possible that these provisions could make it more difficult to accomplish or could deter transactions that stockholders may otherwise consider to be in their best interest or in our best interests, including transactions which provide for payment of a premium over the market price for our shares.
These provisions, summarized below, are intended to discourage coercive takeover practices and inadequate takeover bids. These provisions are also designed to encourage persons seeking to acquire control of us to first negotiate with our board of directors. We believe that the benefits of the increased protection of our potential ability to negotiate with the proponent of an unfriendly or unsolicited proposal to acquire or restructure us outweigh the disadvantages of discouraging these proposals because negotiation of these proposals could result in an improvement of their terms.

7


Undesignated Preferred Stock — The ability to authorize undesignated preferred stock makes it possible for our board of directors to issue preferred stock with voting or other rights or preferences that could impede the success of any attempt to change control of us. These and other provisions may have the effect of deterring hostile takeovers or delaying changes in control or management of our company.
Stockholder Meetings — Our bylaws provide that a special meeting of stockholders may be called only by our chairman of the board, chief executive officer or president, or by a resolution adopted by a majority of our board of directors.
Requirements for Advance Notification of Stockholder Nominations and Proposals — Our bylaws establish advance notice procedures with respect to stockholder proposals to be brought before a stockholder meeting and the nomination of candidates for election as directors, other than nominations made by or at the direction of the board of directors or a committee of the board of directors.
Elimination of Stockholder Action by Written Consent — Our certificate of incorporation and our bylaws eliminate the right of stockholders to act by written consent without a meeting.
Staggered Board — Our board of directors is divided into three classes. The directors in each class will serve for a three-year term, one class being elected each year by our stockholders. This system of electing and removing directors may tend to discourage a third-party from making a tender offer or otherwise attempting to obtain control of us, because it generally makes it more difficult for stockholders to replace a majority of the directors.
Removal of Directors — Our certificate of incorporation provides that no member of our board of directors may be removed from office by our stockholders except for cause and, in addition to any other vote required by law, upon the approval of not less than two thirds of the total voting power of all of our outstanding voting stock then entitled to vote in the election of directors.
Stockholders Not Entitled to Cumulative Voting — Our certificate of incorporation does not permit stockholders to cumulate their votes in the election of directors. Accordingly, the holders of a majority of the outstanding shares of our common stock entitled to vote in any election of directors can elect all of the directors standing for election, if they choose, other than any directors that holders of our preferred stock may be entitled to elect.
Delaware Anti-Takeover Statute — We are subject to Section 203 of the Delaware General Corporation Law, which prohibits persons deemed to be “interested stockholders” from engaging in a “business combination” with a publicly held Delaware corporation for three years following the date these persons become interested stockholders unless the business combination is, or the transaction in which the person became an interested stockholder was, approved in a prescribed manner or another prescribed exception applies. Generally, an “interested stockholder” is a person who, together with affiliates and associates, owns, or within three years prior to the determination of interested stockholder status did own, 15% or more of a corporation’s voting stock. Generally, a “business combination” includes a merger, asset or stock sale, or other transaction resulting in a financial benefit to the interested stockholder. The existence of this provision may have an anti-takeover effect with respect to transactions not approved in advance by the board of directors.
Choice of Forum — Our certificate of incorporation provides that, unless we consent in writing to the selection of an alternative form, the Court of Chancery of the State of Delaware is the exclusive forum for the following types of actions or proceedings under Delaware statutory or common law: (1) any derivative action or proceeding brought on our behalf; (2) any action asserting a claim of breach of a fiduciary duty or other wrongdoing by any of our directors, officers, employees or agents to us or our stockholders; (3) any action asserting a claim against us arising pursuant to any provision of the General Corporation Law of the State of Delaware or our certificate of incorporation or bylaws; (4) any action to interpret, apply, enforce or determine the validity of our certificate of incorporation or bylaws; or (5) any action asserting a claim governed by the internal affairs doctrine. This provision does not apply to suits brought to enforce a duty or liability created by the Exchange Act or any other claim for which the U.S. federal courts have exclusive jurisdiction. Our certificate of incorporation also provides that any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock will be deemed to have notice of and to have consented

8


to this choice of forum provision. It is possible that a court of law could rule that the choice of forum provision contained in our certificate of incorporation is inapplicable or unenforceable if it is challenged in a proceeding or otherwise.
Amendment of Charter Provisions — The amendment of any of the above provisions, except for the provision making it possible for our board of directors to issue preferred stock, would require approval by holders of at least two thirds of the total voting power of all of our outstanding voting stock.
The provisions of Delaware law, our certificate of incorporation and our bylaws could have the effect of discouraging others from attempting hostile takeovers and, as a consequence, they may also inhibit temporary fluctuations in the market price of our common stock that often result from actual or rumored hostile takeover attempts. These provisions may also have the effect of preventing changes in the composition of our board and management. It is possible that these provisions could make it more difficult to accomplish transactions that stockholders may otherwise deem to be in their best interests.
Transfer Agent and Registrar
The transfer agent and registrar for our common stock is American Stock Transfer & Trust Company, LLC. The transfer agent’s address is 6201 15th Avenue, Brooklyn, New York 11219. The transfer agent for any series of preferred stock that we may offer under this prospectus will be named and described in the prospectus supplement for that series.
Listing
Our common stock is listed on The Nasdaq Global Market under the symbol “PTGX.” The applicable prospectus supplement will contain information, where applicable, as to any other listing, if any, on the Nasdaq Global Market or any securities market or other exchange of the preferred stock covered by such prospectus supplement.
Preferred Stock

Our board of directors may, without further action by our stockholders, fix the rights, preferences, privileges and restrictions of up to an aggregate of 10,000,000 shares of preferred stock in one or more series and authorize their issuance. These rights, preferences and privileges could include dividend rights, conversion rights, voting rights, terms of redemption, liquidation preferences, sinking fund terms and the number of shares constituting any series or the designation of such series, any or all of which may be greater than the rights of our common stock. The issuance of our preferred stock could adversely affect the voting power of holders of our common stock and the likelihood that such holders will receive dividend payments and payments upon liquidation. In addition, the issuance of preferred stock could have the effect of delaying, deferring or preventing a change of control or other corporate action.


Table of Contents

The following summary of terms of our preferred stock is not complete. You should refer to the provisions of our certificate of incorporation and bylaws and the resolutions containing the terms of each class or series of the preferred stock which have been or will be filed with the SEC at or prior to the time of issuance of such class or series of preferred stock and described in the applicable prospectus supplement. The applicable prospectus supplement may also state that any of the terms set forth herein are inapplicable to such series of preferred stock, provided that the information set forth in such prospectus supplement does not constitute material changes to the information herein such that it alters the nature of the offering or the securities offered.

We will fix the designations, voting powers, preferences and rights of the preferred stock of each series we issue under this prospectus, as well as the qualifications, limitations or restrictions thereof, in the certificate of designation relating to that series. We will file as an exhibit to the registration statement of which this prospectus is a part, or will incorporate by reference from reports that we file with the SEC, the form of any certificate of designation that describes the terms of the series of preferred stock we are offering. We will describe in the applicable prospectus supplement the terms of the series of preferred stock being offered, including, to the extent applicable:


9



the title and stated value;


the number of shares we are offering;


the liquidation preference per share;


the purchase price;


the dividend rate, period and payment date and method of calculation for dividends;


whether dividends will be cumulative or non-cumulative and, if cumulative, the date from which dividends will accumulate;


the procedures for any auction and remarketing;


the provisions for a sinking fund;


the provisions for redemption or repurchase, if applicable, and any restrictions on our ability to exercise those redemption and repurchase rights;


any listing of the preferred stock on any securities exchange or market;


whether the preferred stock will be convertible into our common stock, and, if applicable, the conversion price, or how it will be calculated, and the conversion period;


whether the preferred stock will be exchangeable into debt securities, and, if applicable, the exchange price, or how it will be calculated, and the exchange period;


voting rights of the preferred stock;


preemptive rights;


restrictions on transfer, sale or other assignment;


whether interests in the preferred stock will be represented by depositary shares;


a discussion of material United States federal income tax considerations applicable to the preferred stock;


the relative ranking and preferences of the preferred stock as to dividend rights and rights if we liquidate, dissolve or wind up our affairs;

Table of Contents

    any limitations on the issuance of any class or series of preferred stock ranking senior to or on a parity with the series of preferred stock as to dividend rights and rights if we liquidate, dissolve or wind up our affairs; and


any other specific terms, preferences, rights or limitations of, or restrictions on, the preferred stock.

If we issue shares of preferred stock under this prospectus, the shares will be fully paid and non-assessable.

The issuance of preferred stock could adversely affect the voting power of holders of common stock and reduce the likelihood that common stockholders will receive dividend payments and payments upon liquidation. The issuance could have the effect of decreasing the market price of the common stock. The issuance of preferred stock also could have the effect of delaying, deterring or preventing a change in control of us.

Options

        As of July 31, 2017, (i) options to purchase an aggregate of 2,509,759 shares of common stock were outstanding and (ii) an additional 562,490 shares were reserved for future issuance under our 2016 Equity Incentive Plan.

Stockholder Registration Rights

Registration Rights

        We are party to an amended and restated investors rights agreement that provides that holders of our capital stock, including certain holders of 5% of our capital stock and entities affiliated with certain of our directors, have certain registration rights, as set forth below. The registration of shares of our common stock pursuant to the exercise of registration rights described below would enable the holders to sell these shares without restriction under the Securities Act when the applicable registration statement is declared effective. These shares are referred to as registrable securities. We will pay the registration expenses, other than the underwriting discounts and commissions, of the shares registered pursuant to the demand, piggyback and Form S-3 registrations described below.

        Generally, in an underwritten offering, the managing underwriter, if any, has the right, subject to specified conditions, to limit the number of shares such holders may include. The demand, piggyback and Form S-3 registration rights described below will expire upon the earlier of August 10, 2019, or when all investors, considered with their affiliates, can sell all of their shares in a 90-day period under Rule 144.

Demand registration rights

        The holders of certain shares of our registerable securities are entitled to certain demand registration rights. The holders of a majority of these shares may, on not more than two occasions, request that we register all or a portion of their shares, subject to certain specified exceptions.

Piggyback registration rights

        In connection with this offering, the holders of certain shares of our registrable securities, were entitled to, and the necessary percentage of holders waived, their rights to notice of this offering and to include their shares of registrable securities in this offering. In the event that we propose to register any of our securities under the Securities Act in another offering, either for our own account or for the account of other security holders, the holders of these shares will be entitled to certain "piggyback" registration rights allowing them to include their shares in such registration, subject to certain


Table of Contents10

marketing and other limitations. As a result, whenever we propose to file a registration statement under the Securities Act, including a registration statement on Form S-3 as discussed below, other than with respect to a demand registration or a registration statement on Forms S-4 or S-8 or related to stock issued upon conversion of debt securities, the holders of these shares are entitled to notice of the registration and have the right, subject to limitations that the underwriters may impose on the number of shares included in the registration, to include their shares in the registration. However, in no event shall the aggregate value of securities of the selling stockholders included in the offering be reduced below twenty-five percent of the total value of all of securities included in such offering.

Form S-3 registration rights

        The holders of certain shares of our registrable securities are entitled to certain Form S-3 registration rights, provided that we have not already effected two such registrations within the twelve-month period preceding the date of such request. Such holders may make a request that we register their shares on Form S-3 if we are qualified to file a registration statement on Form S-3. Such request for registration on Form S-3 must cover securities the aggregate offering price of which, before payment of underwriting discounts and commissions, is at least $2.5 million.

Anti-Takeover Effects of Delaware Law and our Certificate of Incorporation and Bylaws

        Some provisions of Delaware law, our certificate of incorporation and our bylaws contain provisions that could make the following transactions more difficult: an acquisition of us by means of a tender offer; an acquisition of us by means of a proxy contest or otherwise; or the removal of our incumbent officers and directors. It is possible that these provisions could make it more difficult to accomplish or could deter transactions that stockholders may otherwise consider to be in their best interest or in our best interests, including transactions which provide for payment of a premium over the market price for our shares.

        These provisions, summarized below, are intended to discourage coercive takeover practices and inadequate takeover bids. These provisions are also designed to encourage persons seeking to acquire control of us to first negotiate with our board of directors. We believe that the benefits of the increased protection of our potential ability to negotiate with the proponent of an unfriendly or unsolicited proposal to acquire or restructure us outweigh the disadvantages of discouraging these proposals because negotiation of these proposals could result in an improvement of their terms.

        Undesignated Preferred Stock—The ability to authorize undesignated preferred stock makes it possible for our board of directors to issue preferred stock with voting or other rights or preferences that could impede the success of any attempt to change control of us. These and other provisions may have the effect of deterring hostile takeovers or delaying changes in control or management of our company.

        Stockholder Meetings—Our bylaws provide that a special meeting of stockholders may be called only by our chairman of the board, chief executive officer or president, or by a resolution adopted by a majority of our board of directors.

        Requirements for Advance Notification of Stockholder Nominations and Proposals—Our bylaws establish advance notice procedures with respect to stockholder proposals to be brought before a stockholder meeting and the nomination of candidates for election as directors, other than nominations made by or at the direction of the board of directors or a committee of the board of directors.

        Elimination of Stockholder Action by Written Consent—Our certificate of incorporation and bylaws eliminate the right of stockholders to act by written consent without a meeting.



TABLE OF CONTENTS

Table of Contents

        Staggered Board—Our board of directors is divided into three classes. The directors in each class will serve for a three-year term, one class being elected each year by our stockholders. This system of electing and removing directors may tend to discourage a third-party from making a tender offer or otherwise attempting to obtain control of us, because it generally makes it more difficult for stockholders to replace a majority of the directors.

        Removal of Directors—Our certificate of incorporation provides that no member of our board of directors may be removed from office by our stockholders except for cause and, in addition to any other vote required by law, upon the approval of not less than two thirds of the total voting power of all of our outstanding voting stock then entitled to vote in the election of directors.

        Stockholders Not Entitled to Cumulative Voting—Our certificate of incorporation does not permit stockholders to cumulate their votes in the election of directors. Accordingly, the holders of a majority of the outstanding shares of our common stock entitled to vote in any election of directors can elect all of the directors standing for election, if they choose, other than any directors that holders of our preferred stock may be entitled to elect.

        Delaware Anti-Takeover Statute—We are subject to Section 203 of the Delaware General Corporation Law, which prohibits persons deemed to be "interested stockholders" from engaging in a "business combination" with a publicly held Delaware corporation for three years following the date these persons become interested stockholders unless the business combination is, or the transaction in which the person became an interested stockholder was, approved in a prescribed manner or another prescribed exception applies. Generally, an "interested stockholder" is a person who, together with affiliates and associates, owns, or within three years prior to the determination of interested stockholder status did own, 15% or more of a corporation's voting stock. Generally, a "business combination" includes a merger, asset or stock sale, or other transaction resulting in a financial benefit to the interested stockholder. The existence of this provision may have an anti-takeover effect with respect to transactions not approved in advance by the board of directors.

        Choice of Forum—Our certificate of incorporation provides that, unless we consent in writing to the selection of an alternative form, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for: (1) any derivative action or proceeding brought on our behalf; (2) any action asserting a claim of breach of a fiduciary duty or other wrongdoing by any of our directors, officers, employees or agents to us or our stockholders; (3) any action asserting a claim against us arising pursuant to any provision of the General Corporation Law of the State of Delaware or our certificate of incorporation or bylaws; (4) any action to interpret, apply, enforce or determine the validity of our certificate of incorporation or bylaws; or (5) any action asserting a claim governed by the internal affairs doctrine. Our certificate of incorporation also provides that any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock will be deemed to have notice of and to have consented to this choice of forum provision. It is possible that a court of law could rule that the choice of forum provision contained in our certificate of incorporation is inapplicable or unenforceable if it is challenged in a proceeding or otherwise.

        Amendment of Charter Provisions—The amendment of any of the above provisions, except for the provision making it possible for our board of directors to issue preferred stock, would require approval by holders of at least two thirds of the total voting power of all of our outstanding voting stock.

        The provisions of Delaware law, our certificate of incorporation and our bylaws could have the effect of discouraging others from attempting hostile takeovers and, as a consequence, they may also inhibit temporary fluctuations in the market price of our common stock that often result from actual or rumored hostile takeover attempts. These provisions may also have the effect of preventing changes in the composition of our board and management. It is possible that these provisions could make it more difficult to accomplish transactions that stockholders may otherwise deem to be in their best interests.


Table of Contents

Transfer Agent and Registrar

        The transfer agent and registrar for our common stock is American Stock Transfer & Trust Company, LLC. The transfer agent's address is 6201 15th Avenue, Brooklyn, New York 11219. The transfer agent for any series of preferred stock that we may offer under this prospectus will be named and described in the prospectus supplement for that series.

Listing on the NASDAQ Global Market

        Our common stock is listed on the NASDAQ Global Market under the symbol "PTGX." The applicable prospectus supplement will contain information, where applicable, as to any other listing, if any, on the NASDAQ Capital Market or any securities market or other exchange of the preferred stock covered by such prospectus supplement.


Table of Contents


DESCRIPTION OF DEBT SECURITIES

        We may issue

The paragraphs below describe the general terms and provisions of the debt securities from time to time, in one or more series, as either senior or subordinated debt or as senior or subordinated convertible debt. While the terms we have summarized below will apply generally to any debt securities that we may issue. When we offer under this prospectus, we will describe the particular terms of any debt securities that we may offer in more detail in the applicable prospectus supplement. The terms of any debt securities offered under a prospectus supplement may differ from the terms described below. Unless the context requires otherwise, whenever we refer to the indenture, we also are referring to any supplemental indentures that specify the terms ofsell a particular series of debt securities, we will describe the specific terms of the securities in a supplement to this prospectus, including any additional covenants or changes to existing covenants relating to such series. The prospectus supplement also will indicate whether the general terms and provisions described in this prospectus apply to a particular series of debt securities.

You should read the actual indenture if you do not fully understand a term or the way we use it in this prospectus.

We may offer senior or subordinated debt securities. Each series of debt securities may have different terms. The senior debt securities will be issued under one or more senior indentures, dated as of a date prior to such issuance, between us and the trustee identified in the applicable prospectus supplement, as amended or supplemented from time to time. We will issuerefer to any such indenture throughout this prospectus as the “senior indenture.” Any subordinated debt securities will be issued under one or more separate indentures, dated as of a date prior to such issuance, between us and the trustee identified in the applicable prospectus supplement, as amended or supplemented from time to time. We will refer to any such indenture throughout this prospectus as the “subordinated indenture” and to the trustee under the senior or subordinated indenture that we will enter into withas the trustee named“trustee.” The senior indenture and the subordinated indenture are sometimes collectively referred to in this prospectus as the indenture.“indentures.” The indentureindentures will be qualified undersubject to and governed by the Trust Indenture Act of 1939, as amended or(the “Trust Indenture Act”). We included copies of the Trust Indenture Act. forms of the indentures as exhibits to our registration statement and they are incorporated into this prospectus by reference.
If we issue debt securities at a discount from their principal amount, then, for purposes of calculating the aggregate initial offering price of the offered securities issued under this prospectus, we will include only the initial offering price of the debt securities and not the principal amount of the debt securities.
We have filedsummarized below the formmaterial provisions of indenture as an exhibitthe indentures and the debt securities, or indicated which material provisions will be described in the related prospectus supplement. The prospectus supplement relating to any particular securities offered will describe the specific terms of the securities, which may be in addition to or different from the general terms summarized in this prospectus. Because the summary in this prospectus and in any prospectus supplement does not contain all of the information that you may find useful, you should read the documents relating to the registration statement of whichsecurities that are described in this prospectus isor in any applicable prospectus supplement. Please read “Where You Can Find More Information” to find out how you can obtain a part, and supplemental indentures and formscopy of debt securities containingthose documents. Except as otherwise indicated, the terms of the indentures are identical. As used under this caption, the term “debt securities” includes the debt securities being offered will be filed as exhibits to the registration statement of whichby this prospectus is a part or will be incorporated by reference from reports that we file with the SEC.

        The following summary of material provisions of theand all other debt securities andissued by us under the indenture is subject to, and qualified in its entirety by reference to, all of the provisions of the indenture applicable to a particular series of debt securities. We urge you to read the applicable prospectus supplements and any related free writing prospectus related to the debt securities that we may offer under this prospectus, as well as the complete indenture that contains the terms of the debt securities.

indentures.

General

The indenture doesindentures:

do not limit the amount of debt securities that we may issue. It provides that we mayissue;

allow us to issue debt securities up to the principal amount that we may authorize and may be in any currencyone or currency unit that we may designate. Except for the limitations on consolidation, merger and sale of all or substantially all of our assets contained in the indenture, the terms of the indenture more series;

do not contain any covenants or other provisions designedrequire us to give holdersissue all of any debt securities protection against changes in our operations, financial condition or transactions involving us.

        We may issue the debt securities issued underof a series at the indenture as "discount securities," which means they may be sold atsame time; and


allow us to reopen a discount below their stated principal amount. Theseseries to issue additional debt securities as well as other debt securities that are not issued at a discount, may be issued with "original issue discount," or OID, for U.S. federal income tax purposes becausewithout the consent of interest payment and other characteristics or termsthe holders of the debt securities. Material U.S. federal income tax considerations applicable to debt securities issued with OID will be described in more detail in any applicable prospectus supplement.

        We will describeof such series.

Unless we give you different information in the applicable prospectus supplement, the termssenior debt securities will be unsubordinated obligations and will rank equally with all of our other senior unsecured and unsubordinated indebtedness. Payments on the subordinated debt securities will be subordinated to the prior payment in full of all of our senior indebtedness, as described under “Description of Debt Securities — Subordination” and in the applicable prospectus supplement.
Each indenture provides that we may, but need not, designate more than one trustee under an indenture. Any trustee under an indenture may resign or be removed and a successor trustee may be appointed to act with respect to the series of debt securities being offered, including:

    administered by the resigning or removed trustee. If two or more persons are acting as trustee with respect to different series of debt securities, each trustee shall be a

11


trustee of a trust under the applicable indenture separate and apart from the trust administered by any other trustee. Except as otherwise indicated in this prospectus, any action described in this prospectus to be taken by each trustee may be taken by each trustee with respect to, and only with respect to, the one or more series of debt securities for which it is trustee under the applicable indenture.
The prospectus supplement for each offering will provide the following terms, where applicable:

the title of the series of debt securities;securities and whether they are senior or subordinated;


any limit upon
the aggregate principal amount that may be issued;

the maturity date or dates;

the form of the debt securities being offered, the aggregate principal amount of the series;

debt securities outstanding as of the applicabilitymost recent practicable date and any limit on their aggregate principal amount, including the aggregate principal amount of any guarantees;debt securities authorized;


whether or not
the price at which the debt securities will be secured or unsecured, and the terms of any secured debt;

Table of Contents

    whether the debt securities rank as senior debt, senior subordinated debt, subordinated debt or any combination thereof, and the terms of any subordination;

    if the price (expressedissued, expressed as a percentage of the aggregate principal amount thereof) at which such debt securities will be issued is a priceand, if other than the principal amount thereof, the portion of the principal amount thereof payable upon declaration of acceleration of the maturity thereof or, if applicable, the portion of the principal amount of such debt securities that is convertible into another securitycommon stock or other securities of ours or the method by which any such portion shall be determined;


if convertible, the interestterms on which such debt securities are convertible, including the initial conversion price or rate and the conversion period and any applicable limitations on the ownership or rates, which may be fixedtransferability of common stock or variable,other securities of ours received on conversion;

the date or dates, or the method for determining the date or dates, on which the principal of the debt securities will be payable;

the fixed or variable interest rate and or rates of the debt securities, or the method by which the interest rate or rates is determined;

the date or dates, or the method for determining the date or dates, from which interest will begin to accrue, accrue;

the dates on which interest will be payable and payable;

the regular record dates for interest payment dates, or the method by which such dates will be determined;

the persons to whom interest will be payable;

the basis upon which interest will be calculated if other than that of a 360-day year of twelve 30-day months;

any make-whole amount, which is the amount in addition to principal and interest that is required to be paid to the holder of a debt security as a result of any optional redemption or accelerated payment of such debt security, or the method for determining such dates;the make-whole amount;


our right, if
the place or places where the principal of, and any premium or make-whole amount, and interest on, the debt securities will be payable;

where the debt securities may be surrendered for registration of transfer or conversion or exchange;

where notices or demands to defer paymentor upon us in respect of interestthe debt securities and the maximum length of any such deferral period;

if applicable indenture may be served;

the date or dates after which, or the period or periods during which,times, prices and the price or prices atother terms and conditions upon which we may at our option, redeem the series ofdebt securities;

any obligation we have to redeem, repay or purchase the debt securities pursuant to any optionalsinking fund or provisional redemption provisionsanalogous provision or at the option of holders of the debt securities, and the terms of those redemption provisions;

the date or dates, if any, on which,times and the price or prices at which we are obligated, pursuant to any mandatory sinking fundmust redeem, repay or analogous fund provisions or otherwise, to redeem, or at the holder's option to purchase the series of debt securities and as a result of such obligation;

the currency or currency unitcurrencies in which the debt securities are payable;

the denominations in which we will issue the series of debt securities,denominated and payable if other than denominations of $1,000 and any integral multiple thereof;

any and all terms, if applicable, relating to any auction or remarketing of the debt securities of that series and any security for our obligations with respect to such debt securities and any other termsUnited States dollars, which may be advisablea foreign currency or units of two or more foreign currencies or a composite currency or currencies and the terms and conditions relating thereto, and the manner of determining the equivalent of such foreign currency in connection withUnited States dollars;

whether the marketingprincipal of, debt securities of that series;

whetherand any premium or make-whole amount, or interest on, the debt securities of the series shallare to be issued in wholepayable, at our election or in part inat the formelection of a global securityholder, in a currency or securities;currencies other than that in which the debt securities are denominated or stated to be payable, and other related terms and conditions, ifconditions;

12



whether the amount of payments of principal of, and any upon which such global securitypremium or make-whole amount, or interest on, the debt securities may be determined according to an index, formula or other method and how such amounts will be determined;

whether the debt securities will be in registered form, bearer form, or both, and (i) if in registered form, the person to whom any interest shall be payable, if other than the person in whose name the security is registered at the close of business on the regular record date for such interest, or (ii) if in bearer form, the manner in which, or the person to whom, any interest on the security shall be payable if otherwise than upon presentation and surrender upon maturity;

any restrictions applicable to the offer, sale or delivery of securities in bearer form and the terms upon which securities in bearer form of the series may be exchanged for securities in wholeregistered form of the series and vice versa, if permitted by applicable laws and regulations;

whether any debt securities of the series are to be issuable initially in temporary global form and whether any debt securities of the series are to be issuable in permanent global form with or without coupons and, if so, whether beneficial owners of interests in partany such permanent global security may, or shall be required to, exchange their interests for other individual securities; and the depositary for such global security or securities;

if applicable, the provisions relating to conversion or exchange of any debt securities of the series, and the terms and conditions uponmanner in which interest shall be paid;

the identity of the depositary for securities in registered form, if such series are to be issuable as a global security;

the date as of which any debt securities willin bearer form or in temporary global form shall be so convertible or exchangeable, including the conversion or exchange price, as applicable, or how it will be calculated and may be adjusted, any mandatory or optional (at our option or the holders' option) conversion or exchange features, the applicable conversion or exchange period and the manner of settlement for any conversion or exchange;

dated if other than the full principal amount thereof, the portionoriginal issuance date of the principal amountfirst security of the series to be issued;

the applicability, if any, of the defeasance and covenant defeasance provisions described in this prospectus or in the applicable indenture;

whether and under what circumstances we will pay any additional amounts on the debt securities in respect of any tax, assessment or governmental charge and, if so, whether we will have the option to redeem the debt securities in lieu of making such a payment;

whether and under what circumstances the debt securities being offered are convertible into common stock or other securities of ours, as the case may be, including the conversion price or rate and the manner or calculation thereof;

the circumstances, if any, specified in the applicable prospectus supplement, under which beneficial owners of interests in the global security may obtain definitive debt securities and the manner in which payments on a permanent global debt security will be made if any debt securities are issuable in temporary or permanent global form;

any provisions granting special rights to holders of securities upon the occurrence of such events as specified in the applicable prospectus supplement;

if the debt securities of such series are to be issuable in definitive form only upon receipt of certain certificates or other documents or satisfaction of other conditions, then the form and/or terms of such certificates, documents or conditions;

the name of the applicable trustee and the nature of any material relationship with us or any of our affiliates, and the percentage of debt securities of the series which shallclass necessary to require the trustee to take action;

any deletions from, modifications of or additions to our events of default or covenants with regard to such debt securities and any change in the right of any trustee or any of the holders to declare the principal amount of any of such debt securities due and payable;

applicable CUSIP numbers; and

any other terms of such debt securities not inconsistent with the provisions of the applicable indenture.
We may issue debt securities that provide for less than the entire principal amount thereof to be payable upon declaration of acceleration of the maturity thereof;

additionsof the debt securities. We refer to or changesany such debt

13


securities throughout this prospectus as “original issue discount securities.” The applicable prospectus supplement will describe the United States federal income tax consequences and other relevant considerations applicable to original issue discount securities, including the portion of the principal amount thereof to be payable upon declaration of acceleration of the maturity of the debt securities.
Except as described in the covenants applicableindentures under “Compliance with Consolidation Provisions” and “Successor Entity” or as may be set forth in any prospectus supplement, the debt securities will not contain any provisions that (i) would limit our ability to incur indebtedness or (ii) would afford holders of debt securities protection in the event of (a) a highly leveraged or similar transaction involving us, or (b) a change of control or reorganization, restructuring, merger or similar transaction involving us that may adversely affect the holders of the debt securities. In the future, we may enter into transactions, such as the sale of all or substantially all of our assets or a merger or consolidation, that may have an adverse effect on our ability to service our indebtedness, including the debt securities, by, among other things, substantially reducing or eliminating our assets.
Our governing instruments do not define the term “substantially all” as it relates to the sale of assets. Additionally, Delaware cases interpreting the term “substantially all” rely upon the facts and circumstances of each particular case. Consequently, to determine whether a sale of “substantially all” of our assets has occurred, a holder of debt securities being issued, including, among others,must review the consolidation, mergerfinancial and other information that we have disclosed to the public.
We will provide you with more information in the applicable prospectus supplement regarding any deletions, modifications, or sale covenant;

additions to or changes in the events of default with respect toor covenants that are described below, including any addition of a covenant or other provision providing event risk or similar protection.
Payment
Unless we give you different information in the securitiesapplicable prospectus supplement, the principal of, and any change inpremium or make-whole amount, and interest on, any series of the rightdebt securities will be payable at the corporate trust office of the trustee. We will provide you with the address of the trustee in the applicable prospectus supplement. We may also pay interest by mailing a check to the address of the person entitled to it as it appears in the applicable register for the debt securities or by wire transfer of funds to that person at an account maintained within the holdersUnited States.
All monies that we pay to declarea paying agent or a trustee for the payment of the principal of, and any premium or make-whole amount, or interest on, any debt security will be repaid to us if any, and interest, if any, with respect to such securities to beunclaimed at the end of two years after the obligation underlying payment becomes due and payable;

additionspayable. After funds have been returned to or changes in or deletionsus, the holder of the provisions relatingdebt security may look only to covenant defeasanceus for payment, without payment of interest for the period which we hold the funds.
Denomination, Interest, Registration and legal defeasance;Transfer

Table of Contents

    additions to or changesUnless otherwise described in the provisions relatingapplicable prospectus supplement, the debt securities of any series will be issuable in denominations of $1,000 and integral multiples of $1,000.
Subject to satisfaction and discharge of the indenture;

additions to or changeslimitations imposed upon debt securities that are evidenced by a computerized entry in the provisions relating to the modificationrecords of the indenture both with and without the consenta depository company rather than by physical delivery of holdersa note, a holder of debt securities issued under the indenture;

the currency of paymentany series may:

exchange them for any authorized denomination of other debt securities if other than U.S. dollarsof the same series and the manner of determining the equivalenta like aggregate principal amount in U.S. dollars;

whether interest will be payable in cash or additionaland kind upon surrender of such debt securities at ourthe corporate trust office of the applicable trustee or at the office of any transfer agent that we designate for such purpose; and

surrender them for registration of transfer or exchange at the corporate trust office of the applicable trustee or at the office of any transfer agent that we designate for such purpose.
Every debt security surrendered for registration of transfer or exchange must be duly endorsed or accompanied by a written instrument of transfer satisfactory to the applicable trustee or transfer agent. Payment of a service charge will not be required for any registration of transfer or exchange of any debt

14

TABLE OF CONTENTS

securities, but we or the holders' option and the terms and conditions upon which the electiontrustee may be made;

the terms and conditions, ifrequire payment of a sum sufficient to cover any upon which we will pay amountstax or other governmental charge payable in connection therewith. If in addition to the stated interest, premium, ifapplicable trustee, the applicable prospectus supplement refers to any and principal amountstransfer agent initially designated by us for any series of debt securities, we may at any time rescind the designation of any such transfer agent or approve a change in the location through which any such transfer agent acts, except that we will be required to maintain a transfer agent in each place of payment for such series. We may at any time designate additional transfer agents for any series of debt securities.
Neither we, nor any trustee, will be required to:

issue, register the transfer of or exchange debt securities of any series during a period beginning at the opening of business 15 days before the day that a notice of redemption of less than all the outstanding debt securities of the same series to any holder that is not a "United States person" for federal tax purposes;

any restrictionsmailed and ending at the close of business on transfer, sale or assignmentthe day of such mailing;

register the debt securities of the series; and

any other specific terms, preferences, rights or limitationstransfer of or restrictions on,exchange any debt security, or portion thereof, so selected for redemption, in whole or in part, except the unredeemed portion of any debt securities, any other additions or changessecurity being redeemed in part; and

issue, register the provisionstransfer of the indenture, and any terms that may be required by us or advisable under applicable laws or regulations.

Conversion or Exchange Rights

        We will set forth in the prospectus supplement the terms on which a series of debt securities may be convertible into or exchangeable for our common stock or our other securities. We will include provisions as to settlement upon conversion or exchange and whether conversion or exchange is mandatory,any debt security that has been surrendered for repayment at the option of the holder, except the portion, if any, of such debt security not to be so repaid.

Merger, Consolidation or atSale of Assets
The indentures provide that we may, without the consent of the holders of any outstanding debt securities, (i) consolidate with, (ii) sell, lease or convey all or substantially all of our option. We may include provisions pursuantassets to, or (iii) merge with or into, any other entity provided that:

either we are the continuing entity, or the successor entity, if other than us, assumes the obligations (a) to pay the principal of, and any premium or make-whole amount, and interest on, all of the debt securities and (b) to duly perform and observe all of the covenants and conditions contained in each indenture;

the holders of any outstanding debt securities shall be entitled to receive upon conversion or exchange of such debt securities the number of securities or property to which a holder of the number of shares of our common stock or our other securities that the holders of the Company deliverable upon conversion or exchange of such debt securities would have been entitled had such conversion or exchange occurred immediately prior to the transaction; and

an officers’ certificate and legal opinion covering such conditions are delivered to each applicable trustee.
Covenants
Existence.   Except as described therein under “Company May Consolidate, Etc.,” the indentures require us to do or cause to be done all things necessary to preserve and keep in full force and effect our existence, rights and franchises. However, the indentures do not require us to preserve any right or franchise if we determine that any right or franchise is no longer desirable in the conduct of our business.
Provision of financial information.   The indentures require us to (i) within 30 days of each of the respective dates by which we are required to file our annual reports, quarterly reports and other documents with the SEC, file with the trustee copies of the annual report, quarterly report and other documents that we file with the SEC under Section 13 or 15(d) of the Exchange Act and (ii) file with the trustee and the SEC any additional information, documents and reports regarding compliance by us with the conditions and covenants of the indentures, as required.
Additional covenants.   The applicable prospectus supplement will set forth any of our additional covenants relating to any series of debt securities receive would be subject to adjustment.

securities.


Consolidation, Merger or Sale15

        Unless we provide otherwise in the prospectus supplement applicable to a particular series of debt securities, the indenture will not contain any covenant that restricts our ability to merge or consolidate, or sell, convey, transfer or otherwise dispose of our assets as an entirety or substantially as an entirety. However, any successor to or acquirer of such assets (other than a subsidiary of ours) must assume all of our obligations under the indenture or the debt securities, as appropriate.



TABLE OF CONTENTS

Events of Default, underNotice and Waiver
Unless the Indenture

        Unlessapplicable prospectus supplement states otherwise, when we provide otherwiserefer to “events of default” as defined in the prospectus supplement applicable to a particular series of debt securities, the following are events of default under the indentureindentures with respect to any series of debt securities, that we may issue:

    mean:
if we fail to pay
default in the payment of any installment of interest on any debt security of such series of debt securities, as and when the same shall become due and payable, and such default continuescontinuing for a period of 90 days; provided, however, that a valid extension of an interest payment period by us in accordance with the terms of any indenture supplemental thereto shall not constitute a

default in the payment of interest for this purpose;

if we fail to pay the principal of, or any premium if any,or make-whole amount on, any seriesdebt security of debt securitiessuch series as and when the same shall become due and payable, whether at maturity, upon redemption, by declaration or otherwise, orotherwise;

default in any payment required bymaking any sinking or analogous fund established with respect to such series; provided, however, that a valid extension of the maturitypayment as required for any debt security of such debt securities in accordance with the terms of any indenture supplemental thereto shall not constitute a series as and when due and payable;

default in the paymentperformance or breach of principal or premium, if any;

Table of Contents

    if we fail to observe or perform any other covenant or agreement containedwarranty in the debt securities or in the indenture other thanby us continuing for 90 days after written notice as provided in the applicable indenture, but not of a covenant specifically relatingadded to anotherthe indenture solely for the benefit of a series of debt securities and our failure continues for 90 days after we receive written notice ofissued thereunder other than such failure, requiring the same to be remedied and stating that such is a notice of default thereunder, from the trustee or holders of at least 25% in aggregate principal amount of the outstanding debt securities of the applicable series; and


if specified events of
bankruptcy, insolvency or reorganization, occur.

        If anor court appointment of a receiver, liquidator or trustee of us; and


any other event of default provided with respect to a particular series of debt securitiessecurities.
Notice of any series occurs and is continuing, other than an event ofsuch default specified in the last bullet point above,shall be given to us by the trustee, or to us and the trustee by the holders of at least 25% in aggregate principal amount of the outstanding debt securities of that series, byseries. The written notice shall specify such default and require us to us in writing,cause such indebtedness to be discharged or cause such acceleration to be rescinded or annulled and to the trustee ifshall state that such notice is given bya “Notice of Default” under such holders, may declare the unpaid principal of, premium, if any, and accrued interest, if any, due and payable immediately. indenture.
If an event of default specified in the last bullet point above occurs and is continuing with respect to us,debt securities of any series outstanding, then the applicable trustee or the holders of 25% or more in principal amount of the debt securities of that series will have the right to declare the principal amount of all the debt securities of that series to be due and accrued interest, ifpayable. However, at any time after such a declaration of each issueacceleration has been made, but before a judgment or decree for payment of the money due has been obtained by the applicable trustee, the holders of at least a majority in principal amount of outstanding debt securities of such series or of all debt securities then outstanding under the applicable indenture may rescind and annul such declaration and its consequences if:

we have deposited with the applicable trustee all matured installments of interest upon and the principal of (and premium, if any, on) all the outstanding debt securities of such series that shall be duehave become other than by acceleration (with interest upon such principal and payable withoutpremium, if any, notice or other action on the partand upon overdue installments of interest), plus applicable fees, expenses, disbursements and advances of the applicable trustee; and

all events of default, other than the non-payment of accelerated principal (and premium, if any) and accrued and unpaid interest on debt securities of such series, have been cured or waived.
The indentures require each trustee to give notice to the holders of debt securities within the later of 90 days after of a default occurs and 30 days after it is actually known to a trustee or any holder.

        Thewritten notice of it is received by the trustee, unless such default has been cured or waived. However, the trustee may withhold notice if specified persons of such trustee consider such withholding to be in the interest of the holders of debt securities. The trustee may not withhold notice of a majoritydefault in the payment of principal, any premium or interest on any debt security of such series or in the payment of any sinking fund installment in respect of any debt security of such series.

The indentures provide that holders of debt securities of any series may not institute any proceedings, judicial or otherwise, with respect to such indenture or for any remedy under the indenture, unless the trustee fails to act for a period of 90 days after the trustee has received a written request to institute proceedings in respect of an event of default from the holders of 25% or more in principal amount of the outstanding debt securities of such series, as well as an affected series may waive any default or eventoffer of default with respectindemnity reasonably satisfactory to the series and its consequences, except defaults or eventstrustee. However, this provision will not prevent any holder of default regarding debt securities from instituting suit for the enforcement of

16

TABLE OF CONTENTS

payment of the principal of, and any premium if any, or make-whole amount, and interest unless we have curedon, such debt securities at the respective due dates thereof.
The indentures provide that, subject to provisions in each indenture relating to its duties in the case of a default, or event of default in accordance with the indenture. Any waiver shall cure the default or event of default.

        Subject to the terms of the indenture, if an event of default under an indenture shall occur and be continuing, thea trustee will be underhas no obligation to exercise any of its rights or powers under such indenture at the request or direction of any of the holders of the applicableany series of debt securities then outstanding under the indenture, unless suchthe holders have offered to the trustee reasonable security or indemnity. The holders of at least a majority in principal amount of the outstanding debt securities of any series willor of all debt securities then outstanding under an indenture shall have the right to direct the time, method and place of conducting any proceeding for any remedy available to the applicable trustee, or of exercising any trust or power conferred on theupon such trustee. However, a trustee with respectmay refuse to the debt securities of that series, provided that:

    thefollow any direction so given by the holder which:

is not in conflict with any law or the applicable indenture; and


subject to its duties under the Trust Indenture Act,
may involve the trustee need not take any action that might involve it in personal liabilityliability; or might

may be unduly prejudicial to the holders of debt securities of the series not involvedjoining the proceeding.
Within 120 days after the close of each fiscal year, we will be required to deliver to each trustee a certificate, signed by one of our several specified officers, stating whether or not that officer has knowledge of any default under the applicable indenture. If the officer has knowledge of any default, the notice must specify the nature and status of the default.
Modification of the Indentures
The indentures provide that no modifications or amendments may, without the consent of each affected holder, impair the right of any holder of any debt security to (i) receive payment of the principal of (and premium, if any) and interest on the debt securities, as provided in the proceeding.

        A holderdebt securities or indentures, on or after the respective due dates expressed in the debt securities or the indentures (or in the case of redemption, on the redemption date) or (ii) institute suit for the enforcement of any such payment on or after such respective dates or redemption date. Furthermore, no modification or amendment may, without the consent of the holders of all of the debt securities affected by the modification or amendment:


change the stated maturity of the principal of, or any premium or make-whole amount on, or any installment of principal of or interest on, any such debt security, or reduce the amount of interest payable thereon or principal thereof; or

reduce the percentage in principal amount of any series will haveoutstanding debt securities necessary to modify or amend the right to institute a proceeding under theapplicable indenture or to appoint a receiver or trustee, or to seek other remedies only if:

    the holder has given written notice to the trustee of a continuing event of default with respect to that series;

    the holders of at least 25% in aggregate principal amount of the outstandingsuch debt securities of that series have made written request;

    such holders have offered to the trustee indemnity satisfactory to it against the costs, expenses and liabilities to be incurred by the trustee in compliance with the request; and

    the trustee does not institute the proceeding, and does not receive from thesecurities.
The holders of a majority in aggregate principal amount of the outstanding debt securities of thateach affected series other conflicting directions within 90 days after the notice, request and offer.

Tablemay, on behalf of Contents

        These limitations do not apply to a suit instituted by a holderall holders of debt securities if we default in the payment of the principal, premium, if any, or interest on, the debt securities.

        We will periodically file statements with the trustee regardingthat series, waive, insofar as that series is concerned, our compliance with specifiedmaterial restrictive covenants inof the applicable indenture.

Modification of Indenture; Waiver

We and theour respective trustee may changemake modifications and amendments of an indenture without the consent of any holders with respect to specific matters:

    to cure any ambiguity, defect or inconsistency in the indenture or in theholder of debt securities, including for any of any series;the following purposes:


to complyevidence the succession of another person to us as obligor under such indenture in compliance with the provisions described above under "Description of Debt Securities—Consolidation, Merger or Sale;"Trust Indenture Act;


to provide for uncertificated debt securities in addition to or in place of certificated debt securities;

to add to our covenants restrictions, conditions or provisions such new covenants, restrictions, conditions or provisions for the benefit of the holders of all or any series of debt securities to make the occurrence, or the occurrence and the continuance, of a default in any such additional covenants, restrictions, conditions or provisions an event of default or to surrender any right or power conferred upon us in thesuch indenture;


to add events of default for the benefit of the holders of all or any series of debt securities;

to delete fromadd or revise the conditions, limitations, andchange any provisions of an indenture (i) to change or eliminate restrictions on the authorizedpayment of principal of, or premium or make-whole amount, terms, or purposes of issue, authentication and deliveryinterest on, debt securities in bearer form, (ii) to permit or facilitate the issuance of debt securities as set forth in the indenture;

to make any changeuncertificated form, or (iii) that otherwise does not adversely affect the interests of any holderthe holders of the debt securities of any series in any material respect;

to establish the form or terms of debt securities of any series;

17

TABLE OF CONTENTS


to provide for the issuanceacceptance of appointment by a successor trustee or facilitate the administration of the trusts under an indenture by more than one trustee; and

to cure any ambiguity, defect or inconsistency in an indenture.
Subordination
Unless otherwise provided in the applicable prospectus supplement, subordinated debt securities will be subject to the following subordination provisions.
Upon any distribution to our creditors in a liquidation, dissolution or reorganization, the payment of the principal of and establishinterest on any subordinated debt securities will be subordinated to the form and terms and conditionsextent provided in the applicable indenture in right of payment to the prior payment in full of all senior debt. However, our obligation to make payments of the principal of and interest on such subordinated debt securities otherwise will not be affected. No payment of any series as provided above under "Description of Debt Securities—General" to establish the form of any certifications requiredprincipal or interest will be permitted to be furnished pursuantmade on subordinated debt securities at any time if a default on senior debt exists that permits the holders of such senior debt to accelerate its maturity and the termsdefault is the subject of judicial proceedings or we receive notice of the indenture or any series ofdefault. After all senior debt is paid in full and until the subordinated debt securities or to addare paid in full, holders of subordinated debt securities will be subrogated to the rights of holders of senior debt to the extent that distributions otherwise payable to holders of subordinated debt securities have been applied to the payment of senior debt. The subordinated indenture will not restrict the amount of senior debt or other indebtedness of ours. As a result of these subordination provisions, in the event of a distribution of assets upon insolvency, holders of subordinated debt securities may recover less, ratably, than our general creditors.
The term “senior debt” will be defined in the applicable indenture as the principal of and interest on, or substantially similar payments to be made by us in respect of, other outstanding indebtedness, whether outstanding at the date of execution of the applicable indenture or subsequently incurred, created or assumed. The prospectus supplement may include a description of additional terms implementing the subordination feature.
No restrictions will be included in any indenture relating to subordinated debt securities upon the creation of additional senior debt.
If this prospectus is being delivered in connection with the offering of a series of subordinated debt securities, the accompanying prospectus supplement or the information incorporated in this prospectus by reference will set forth the approximate amount of senior debt outstanding as of the end of our most recent fiscal quarter.
Discharge, Defeasance and Covenant Defeasance
Unless otherwise indicated in the applicable prospectus supplement, the indentures allow us to discharge our obligations to holders of any series of debt securities;

to evidence and provide for the acceptance of appointmentsecurities issued under any indenture by a successor trustee;when:

either (i) all securities of such series have already been delivered to the applicable trustee for cancellation; or

(ii) all securities of such series have not already been delivered to comply with any requirements of the SEC in connectionapplicable trustee for cancellation but (a) have become due and payable, (b) will become due and payable within one year, or (c) if redeemable at our option, are to be redeemed within one year, and we have irrevocably deposited with the qualification of any indenture under the Trust Indenture Act.

        In addition, under the indenture, the rights of holders of a series ofapplicable trustee, in trust, funds in such currency or currencies, currency unit or units or composite currency or currencies in which such debt securities mayare payable, an amount sufficient to pay the entire indebtedness on such debt securities in respect of principal and any premium or make-whole amount, and interest to the date of such deposit if such debt securities have become due and payable or, if they have not, to the stated maturity or redemption date;


we have paid or caused to be changed by uspaid all other sums payable; and

an officers’ certificate and an opinion of counsel stating the trusteeconditions to discharging the debt securities have been satisfied has been delivered to the trustee.
Unless otherwise indicated in the applicable prospectus supplement, the indentures provide that, upon our irrevocable deposit with the written consentapplicable trustee, in trust, of the holders of at least a majorityan amount, in aggregate principal amount of the outstandingsuch currency or currencies,

18

TABLE OF CONTENTS

currency unit or units or composite currency or currencies in which such debt securities of each series that is affected. However, unless we provide otherwise in the prospectus supplementare payable at stated maturity, or government obligations, or both, applicable to a particular series ofsuch debt securities, wewhich through the scheduled payment of principal and interest in accordance with their terms will provide money in an amount sufficient to pay the trustee may make the following changes only with the consentprincipal of, each holder ofand any outstandingpremium or make-whole amount, and interest on, such debt securities, affected:

    extendingand any mandatory sinking fund or analogous payments thereon, on the fixed maturity ofscheduled due dates therefor, the we may elect either:

to defease and be discharged from any debt securities of any series;

reducing the principal amount, reducing the rate of or extending the time of payment of interest, or reducing any premium payable upon the redemption of any series of anyand all obligations with respect to such debt securities; or

Table of Contents

    reducing the percentage of debt securities, the holders of which are required to consent to any amendment, supplement, modification or waiver.

Discharge

        Each indenture provides that we can elect

to be dischargedreleased from our obligations with respect to one or more series ofsuch debt securities except for specifiedunder the applicable indenture or, if provided in the applicable prospectus supplement, our obligations includingwith respect to any other covenant, and any omission to comply with such obligations to:

    provide for payment;

    registershall not constitute an event of default with respect to such debt securities.
When we use the transferterm “government obligations,” we mean securities that are:

direct obligations of the United States or exchange ofthe government that issued the foreign currency in which the debt securities of a particular series are payable, for the series;payment of which its full faith and credit is pledged; or


replace stolen, lost
obligations of a person controlled or mutilatedsupervised by and acting as an agency or instrumentality of the United States or other government that issued the foreign currency in which the debt securities of such series are payable, the series;

paypayment of which is unconditionally guaranteed as a full faith and credit obligation by the United States or such other government, which are not callable or redeemable at the option of the issuer thereof and shall also include a depository receipt issued by a bank or trust company as custodian with respect to any such government obligation or a specific payment of interest on or principal of any such government obligation held by such custodian for the account of the holder of a depository receipt. However, except as required by law, such custodian is not authorized to make any deduction from the amount payable to the holder of such depository receipt from any amount received by the custodian in respect of the government obligation or the specific payment of interest on or principal of the government obligation evidenced by such depository receipt.
Unless otherwise provided in the applicable prospectus supplement, if after we have deposited funds and/or government obligations to effect defeasance or covenant defeasance with respect to debt securities of any series, (i) the holder of a debt security of such series is entitled to, and does, elect under the terms of the applicable indenture or the terms of such debt security to receive payment in a currency, currency unit or composite currency other than that in which such deposit has been made in respect of such debt security, or (ii) a conversion event occurs in respect of the currency, currency unit or composite currency in which such deposit has been made, the indebtedness represented by such debt security will be deemed to have been, and will be, fully discharged and satisfied through the payment of the principal of, and premium or make-whole amount, and interest on, such debt security as they become due out of the proceeds yielded by converting the amount so deposited in respect of such debt security into the currency, currency unit or composite currency in which such debt security becomes payable as a result of such election or such cessation of usage based on the applicable market exchange rate.
When we use the term “conversion event,” we mean the cessation of use of:

a currency, currency unit or composite currency both by the government of the country that issued such currency and for the settlement of transactions by a central bank or other public institutions of or within the international banking community;

the European Currency Unit both within the European Monetary System and for the settlement of transactions by public institutions of or within the European Communities; or

any currency unit or composite currency other than the European Currency Unit for the purposes for which it was established.
Unless otherwise provided in the applicable prospectus supplement, all payments of principal of, and any premium or make-whole amount, and interest on, any debt securities of the series;

maintain paying agencies;

hold monies for paymentsecurity that is payable in trust;

recover excess money held by the trustee;

compensate and indemnify the trustee; and

appoint any successor trustee.

        In order to exercise our rightsa foreign currency that ceases to be discharged, we must deposit withused by its government of issuance shall be made in United States dollars.


19

TABLE OF CONTENTS

The applicable prospectus supplement may further describe the trustee money or government obligations sufficient to pay all the principal of, any premium,provisions, if any, and interest on,permitting such defeasance or covenant defeasance, including any modifications to the provisions described above, with respect to the debt securities of the series on the dates payments are due.

or within a particular series.

Form, ExchangeConversion Rights
The terms and Transfer

        We will issueconditions, if any, upon which the debt securities are convertible into common stock or other securities of each series only in fully registered form without coupons and, unless we provide otherwiseours will be set forth in the applicable prospectus supplement,supplement. The terms will include whether the debt securities are convertible into shares of common stock or other securities of ours, the conversion price, or manner of calculation thereof, the conversion period, provisions as to whether conversion will be at the issuing company’s option or the option of the holders, the events requiring an adjustment of the conversion price and provisions affecting conversion in denominationsthe event of $1,000the redemption of the debt securities and any integral multiple thereof. restrictions on conversion.

Global Securities
The indenture provides that we may issue debt securities of a series may be issued in temporarywhole or permanentin part in the form of one or more global form and as book-entry securities that will be deposited with, or on behalf of, The Depository Trust Company, or DTC, or another depositary named by us anda depository identified in a prospectus supplement with respect to that series. To the extent the debt securities of a series are issued in global form and as book-entry, a description of terms relating such securities will be set forth in the applicable prospectus supplement.

        At the option of the holder, subject to the terms of the indenture and the limitations applicable to global securities described in the applicable prospectus supplement relating to such series. Global securities, if any, issued in the United States are expected to be deposited with The Depository Trust Company (“DTC”), as depository. We may issue global securities in either registered or bearer form and in either temporary or permanent form. We will describe the specific terms of the depository arrangement with respect to a series of debt securities in the applicable prospectus supplement relating to such series. We expect that unless the applicable prospectus supplement provides otherwise, the following provisions will apply to depository arrangements.

Once a global security is issued, the depository for such global security or its nominee will credit on its book-entry registration and transfer system the respective principal amounts of the individual debt securities represented by such global security to the accounts of participants that have accounts with such depository. Such accounts shall be designated by the underwriters, dealers or agents with respect to such debt securities or by us if we offer such debt securities directly. Ownership of beneficial interests in such global security will be limited to participants with the depository or persons that may hold interests through those participants.
We expect that, under procedures established by DTC, ownership of beneficial interests in any global security for which DTC is the depository will be shown on, and the transfer of that ownership will be effected only through, records maintained by DTC or its nominee, with respect to beneficial interests of participants with the depository, and records of participants, with respect to beneficial interests of persons who hold through participants with the depository. Neither we nor the trustee will have any responsibility or liability for any aspect of the records of DTC or for maintaining, supervising or reviewing any records of DTC or any of its participants relating to beneficial ownership interests in the debt securities. The laws of some states require that certain purchasers of securities take physical delivery of such securities in definitive form. Such limits and laws may impair the ability to own, pledge or transfer beneficial interest in a global security.
So long as the depository for a global security or its nominee is the registered owner of such global security, such depository or such nominee, as the case may be, will be considered the sole owner or holder of the debt securities represented by the global security for all purposes under the applicable indenture. Except as described below or in the applicable prospectus supplement, owners of beneficial interest in a global security will not be entitled to have any of the individual debt securities represented by such global security registered in their names, will not receive or be entitled to receive physical delivery of any such debt securities in definitive form and will not be considered the owners or holders thereof under the applicable indenture. Beneficial owners of debt securities evidenced by a global security will not be considered the owners or holders thereof under the applicable indenture for any purpose, including with respect to the giving of any direction, instructions or approvals to the trustee under the indenture. Accordingly, each person owning a beneficial interest in a global security with respect to which DTC is the depository must rely on the procedures of DTC and, if such person is not a participant with the depository, on the procedures of the participant through which such person owns its interests, to exercise any rights of a holder under the applicable indenture. We understand that, under existing industry practice, if DTC requests any action of holders or if an owner of a beneficial interest in a global security desires to give or take any action which a holder is entitled to give or take under the applicable indenture, DTC would authorize the participants holding the

20

TABLE OF CONTENTS

relevant beneficial interest to give or take such action, and such participants would authorize beneficial owners through such participants to give or take such actions or would otherwise act upon the instructions of beneficial owners holding through them.
Payments of principal of, and any premium or make-whole amount, and interest on, individual debt securities represented by a global security registered in the name of a depository or its nominee will be made to or at the direction of the depository or its nominee, as the case may be, as the registered owner of the global security under the applicable indenture. Under the terms of the applicable indenture, we and the trustee may treat the persons in whose name debt securities, including a global security, are registered as the owners thereof for the purpose of receiving such payments. Consequently, neither we nor the trustee have or will have any responsibility or liability for the payment of such amounts to beneficial owners of debt securities including principal, any premium or make-whole amount, or interest. We believe, however, that it is currently the policy of DTC to immediately credit the accounts of relevant participants with such payments, in amounts proportionate to their respective holdings of beneficial interests in the relevant global security as shown on the records of DTC or its nominee. We also expect that payments by participants to owners of beneficial interests in such global security held through such participants will be governed by standing instructions and customary practices, as is the case with securities held for the account of customers in bearer form or registered in street name, and will be the responsibility of such participants. Redemption notices with respect to any debt securities represented by a global security will be sent to the depository or its nominee. If less than all of the debt securities of any series can exchangeare to be redeemed, we expect the depository to determine the amount of the interest of each participant in such debt securities to be redeemed to be determined by lot. Neither we, the trustee, any paying agent nor the security registrar for othersuch debt securities will have any responsibility or liability for any aspect of the same series,records relating to or payments made on account of beneficial ownership interests in the global security for such debt securities or for maintaining any authorized denominationrecords with respect thereto.
Neither we nor the trustee will be liable for any delay by the holders of a global security or the depository in identifying the beneficial owners of debt securities, and of like tenor and aggregate principal amount.

        Subject to the terms of the indenturewe and the limitationstrustee may conclusively rely on, and will be protected in relying on, instructions from the holder of a global security or the depository for all purposes. The rules applicable to DTC and its participants are on file with the SEC.

If a depository for any debt securities is at any time unwilling, unable or ineligible to continue as depository and we do not appoint a successor depository within 90 days, we will issue individual debt securities in exchange for the global securities set forthsecurity representing such debt securities. In addition, we may at any time and at our sole discretion, subject to any limitations described in the applicable prospectus supplement holders of therelating to such debt securities, may present thedetermine not to have any of such debt securities for exchangerepresented by one or for registration of transfer, duly endorsed or with the form of transfer endorsed thereon duly executed if so required by us or the security registrar, at the office of the security registrar or at the office of any transfer agent designated by us for this purpose. Unless otherwise providedmore global securities and in thesuch event will issue individual debt securities thatin exchange for the holder presents for transferglobal security or exchange, we will impose no service charge for any registration of transfer or exchange, but we may require payment of any taxes or other governmental charges.

        We will name in the applicable prospectus supplement the security registrar, and any transfer agent in addition to the security registrar, that we initially designate for anysecurities representing such debt securities. We may at any time designate additional transfer agents or rescind the designation of any transfer agent or approve a


Table of Contents

change in the office through which any transfer agent acts, except that weIndividual debt securities so issued will be required to maintain a transfer agentissued in each placedenominations of payment for the$1,000 and integral multiples of $1,000.

The debt securities of each series.

        If we elect to redeem the debt securities of anya series we will notmay also be required to:

    issue, register the transfer of, or exchange any debt securities of that series during a period beginning at the opening of business 15 days before the day of mailing of a notice of redemption of any debt securities that may be selected for redemption and ending at the close of business on the day of the mailing; or

    register the transfer of or exchange any debt securities so selected for redemption,issued in whole or in part except the unredeemed portion of any debt securities we are redeeming in part.

Information Concerning the Trustee

        The trustee, other than during the occurrence and continuance of an event of default under an indenture, undertakes to perform only those duties as are specifically set forth in the applicable indenture. Upon an event of default under an indenture, the trustee must use the same degree of care as a prudent person would exercise or use in the conduct of his or her own affairs. Subject to this provision, the trustee is under no obligation to exercise any of the powers given it by the indenture at the request of any holder of debt securities unless it is offered reasonable security and indemnity against the costs, expenses and liabilities that it might incur.

Payment and Paying Agents

        Unless we otherwise indicate in the applicable prospectus supplement, we will make payment of the interest on any debt securities on any interest payment date to the person in whose name the debt securities, or one or more predecessor securities, are registered at the close of business on the regular record date for the interest.

        We will pay principal of and any premium and interest on the debt securities of a particular series at the office of the paying agents designated by us, except that unless we otherwise indicate in the applicable prospectus supplement, we will make interest payments by check that we will mail to the holder or by wire transfer to certain holders. Unless we otherwise indicate in the applicable prospectus supplement, we will designate the corporate trust office of the trustee as our sole paying agent for payments with respect to debt securities of each series. We will name in the applicable prospectus supplement any other paying agents that we initially designate for the debt securities of a particular series. We will maintain a paying agent in each place of payment for the debt securities of a particular series.

        All money we pay to a paying agent or the trustee for the payment of the principal of or any premium or interest on any debt securities that remains unclaimed at the end of two years after such principal, premium or interest has become due and payable will be repaid to us, and the holder of the debt security thereafter may look only to us for payment thereof.

Governing Law

        The indenture and the debt securities will be governed by and construed in accordance with the internal laws of the State of New York, except to the extent that the Trust Indenture Act of 1939 is applicable.


Table of Contents


LEGAL OWNERSHIP OF SECURITIES

        We can issue securities in registered form or in the form of one or more global securities. We describebearer global securities in greater detail below. We refer to those persons who have securities registered in their own names on the books that we or any applicable trustee, depositary or warrant agent maintain for this purpose as the "holders" of those securities. These persons are the legal holders of the securities. We refer to those persons who, indirectly through others, own beneficial interests in securities that are not registered in their own names, as "indirect holders" of those securities. As we discuss below, indirect holders are not legal holders, and investors in securities issued in book-entry form or in street name will be indirect holders.

Book-Entry Holders

        We may issue securities in book-entry form only, as we will specifydeposited with a depository, or with a nominee for such depository, identified in the applicable prospectus supplement. This meansAny such bearer global securities may be issued in temporary or permanent form. The specific terms and procedures, including the specific terms of the depositary arrangement, with respect to any portion of a series of debt securities to be represented by one or more bearer global securities registeredwill be described in the applicable prospectus supplement.

No Recourse
There is no recourse under any obligation, covenant or agreement in the applicable indenture or with respect to any security against any of our or our successor’s past, present or future shareholders, employees, officers or directors.

21

TABLE OF CONTENTS

DESCRIPTION OF WARRANTS
The following description, together with the additional information we may include in any applicable prospectus supplements, summarizes the material terms and provisions of the warrants that we may offer under this prospectus and the related warrant agreements and warrant certificates. While the terms summarized below will apply generally to any warrants that we may offer, we will describe the particular terms of any series of warrants in more detail in the applicable prospectus supplement. If we indicate in the prospectus supplement, the terms of any warrants offered under that prospectus supplement may differ from the terms described below. Specific warrant agreements will contain additional important terms and provisions and will be incorporated by reference as an exhibit to the registration statement, which includes this prospectus.
General
We may issue warrants for the purchase of common stock, preferred stock and/or debt securities in one or more series. We may issue warrants independently or together with common stock, preferred stock and/or debt securities, and the warrants may be attached to or separate from these securities.
We will evidence each series of warrants by warrant certificates that we will issue under a separate warrant agreement. We will enter into the warrant agreement with a warrant agent. We will indicate the name and address of the warrant agent in the applicable prospectus supplement relating to a particular series of warrants.
We will describe in the applicable prospectus supplement the terms of the series of warrants, including:

the offering price and aggregate number of warrants offered;

the currency for which the warrants may be purchased;

if applicable, the designation and terms of the securities with which the warrants are issued and the number of warrants issued with each such security or each principal amount of such security;

if applicable, the date on and after which the warrants and the related securities will be separately transferable;

in the case of warrants to purchase debt securities, the principal amount of debt securities purchasable upon exercise of one warrant and the price at, and currency in which, this principal amount of debt securities may be purchased upon such exercise;

in the case of warrants to purchase common stock or preferred stock, the number of shares of common stock or preferred stock, as the case may be, purchasable upon the exercise of one warrant and the price at which these shares may be purchased upon such exercise;

the effect of any merger, consolidation, sale or other disposition of our business on the warrant agreement and the warrants;

the terms of any rights to redeem or call the warrants;

any provisions for changes to or adjustments in the exercise price or number of securities issuable upon exercise of the warrants;

the periods during which, and places at which, the warrants are exercisable;

the manner of exercise;

the dates on which the right to exercise the warrants will commence and expire;

the manner in which the warrant agreement and warrants may be modified;

federal income tax consequences of holding or exercising the warrants;

the terms of the securities issuable upon exercise of the warrants; and

any other specific terms, preferences, rights or limitations of or restrictions on the warrants.

22

TABLE OF CONTENTS

DESCRIPTION OF UNITS
We may issue units comprised of shares of common stock, shares of preferred stock, debt securities and warrants in any combination. We may issue units in such amounts and in as many distinct series as we wish. This section outlines certain provisions of the units that we may issue. If we issue units, they will be issued under one or more unit agreements to be entered into between us and a bank or other financial institution, that holds them as depositary on behalfunit agent. The information described in this section may not be complete in all respects and is qualified entirely by reference to the unit agreement with respect to the units of other financial institutions that participateany particular series. The specific terms of any series of units offered will be described in the depositary's book-entry system. These participating institutions, which are referredapplicable prospectus supplement. If so described in a particular supplement, the specific terms of any series of units may differ from the general description of terms presented below. We urge you to read any prospectus supplement related to any series of units we may offer, as participants, in turn, hold beneficial interests in the securities on behalf of themselves or their customers.

        Only the person in whose name a security is registered is recognizedwell as the holdercomplete unit agreement and unit certificate that contain the terms of that security. Securities issued in global formthe units. If we issue units, forms of unit agreements and unit certificates relating to such units will be registered inincorporated by reference as exhibits to the name of the depositary or its participants. Consequently, for securitiesregistration statement, which includes this prospectus.

Each unit that we may issue will be issued in global form, we will recognize only the depositary asso that the holder of the securities,unit is also the holder of each security included in the unit. Thus, the holder of a unit will have the rights and we will make all payments onobligations of a holder of each included security. The unit agreement under which a unit is issued may provide that the securities toincluded in the depositary.unit may not be held or transferred separately, at any time or at any time before a specified date. The depositary passes along applicable prospectus supplement may describe:

the payments it receives to its participants, which in turn pass the payments along to their customers who are the beneficial owners. The depositarydesignation and its participants do so under agreements they have made with one another or with their customers; they are not obligated to do so under the terms of the securities.

        Asunits and of the securities comprising the units, including whether and under what circumstances those securities may be held or transferred separately;


any provisions of the governing unit agreement;

the price or prices at which such units will be issued;

the applicable United States federal income tax considerations relating to the units;

any provisions for the issuance, payment, settlement, transfer or exchange of the units or of the securities comprising the units; and

any other terms of the units and of the securities comprising the units.
The provisions described in this section, as well as those described under “Description of Capital Stock,” “Description of Debt Securities” and “Description of Warrants” will apply to the securities included in each unit, to the extent relevant and as may be updated in any prospectus supplements.
Issuance in Series
We may issue units in such amounts and in as many distinct series as we wish. This section summarizes terms of the units that apply generally to all series. Most of the financial and other specific terms of your series will be described in the applicable prospectus supplement.
Unit Agreements
We will issue the units under one or more unit agreements to be entered into between us and a result, investors in a global security will not own securities directly. Instead, they will own beneficial interests in a global security, through a bank broker or other financial institution, as unit agent. We may add, replace or terminate unit agents from time to time. We will identify the unit agreement under which each series of units will be issued and the unit agent under that participatesagreement in the depositary's book-entry systemapplicable prospectus supplement.
The following provisions will generally apply to all unit agreements unless otherwise stated in the applicable prospectus supplement:
Modification without Consent
We and the applicable unit agent may amend any unit or holds an interest through a participant. As long asunit agreement without the securities are issued in global form, investors will be indirect holders, and not legal holders,consent of any holder:

to cure any ambiguity, including modifying any provisions of the securities.

governing unit agreement that differ from those described below;


Street Name Holders23

        We may terminate a global security


TABLE OF CONTENTS


to correct or issue securities in non-global form. In these cases, investors may choose supplement any defective or inconsistent provision; or

to hold their securities in their own namesmake any other change that we believe is necessary or in "street name." Securities held by an investor in street name would be registered indesirable and will not adversely affect the name of a bank, broker or other financial institution that the investor chooses, and the investor would hold only a beneficial interest in those securities through an account he or she maintains at that institution.

        For securities held in street name, we or any applicable trustee or depositary will recognize only the intermediary banks, brokers and other financial institutions in whose names the securities are registered as the holders of those securities, and we or any applicable trustee or depositary will make all payments on those securities to them. These institutions pass along the payments they receive to their customers who are the beneficial owners, but only because they agree to do so in their customer agreements or because they are legally required to do so. Investors who hold securities in street name will be indirect holders, not holders, of those securities.


Table of Contents

Legal Holders

        Our obligations, as well as the obligations of any applicable trustee and of any third parties employed by us or a trustee, run only to the legal holdersinterests of the securities. affected holders in any material respect.

We do not have obligationsneed any approval to investors who hold beneficial interests in global securities, in street name or by any other indirect means. This will be the case whether an investor choosesmake changes that affect only units to be an indirect holder ofissued after the changes take effect. We may also make changes that do not adversely affect a security or has no choice because we are issuing the securities onlyparticular unit in global form.

        For example, once we make a payment or give a notice to the legal holder, we have no further responsibility for the payment or noticeany material respect, even if that legal holder is required, under agreements with its participants or customers or by law, to pass it along to the indirect holders but doesthey adversely affect other units in a material respect. In those cases, we do not do so. Similarly, we may wantneed to obtain the approval of the legal holders to amend an indenture, to relieve usholder of the consequences of a default or of our obligation to comply with a particular provision of the indenture or for other purposes. In such an event,unaffected unit; we would seek approvalneed only obtain any required approvals from the holders of the affected units.

Modification with Consent
We may not amend any particular unit or a unit agreement with respect to any particular unit unless we obtain the consent of the holder of that unit, if the amendment would:

impair any right of the holder to exercise or enforce any right under a security included in the unit if the terms of that security require the consent of the holder to any changes that would impair the exercise or enforcement of that right; or

reduce the percentage of outstanding units or any series or class the consent of whose holders is required to amend that series or class, or the applicable unit agreement with respect to that series or class, as described below.
Any other change to a particular unit agreement and not the indirectunits issued under that agreement would require the following approval:

if the change affects only the units of a particular series issued under that agreement, the change must be approved by the holders of a majority of the securities. Whetheroutstanding units of that series; or

if the change affects the units of more than one series issued under that agreement, it must be approved by the holders of a majority of all outstanding units of all series affected by the change, with the units of all the affected series voting together as one class for this purpose.
These provisions regarding changes with majority approval also apply to changes affecting any securities issued under a unit agreement, as the governing document.
In each case, the required approval must be given by written consent.
Unit Agreements Will Not Be Qualified under Trust Indenture Act
No unit agreement will be qualified as an indenture, and howno unit agent will be required to qualify as a trustee, under the legalTrust Indenture Act. Therefore, holders contactof units issued under unit agreements will not have the indirect holders is upprotections of the Trust Indenture Act with respect to the legal holders.

their units.

Special Considerations for Indirect HoldersMergers and Similar Transactions Permitted; No Restrictive Covenants or Events of Default

        If you hold securities through a bank, broker

The unit agreements will not restrict our ability to merge or consolidate with, or sell our assets to, another corporation or other financial institution, eitherentity or to engage in book-entry form becauseany other transactions. If at any time we merge or consolidate with, or sell our assets substantially as an entirety to, another corporation or other entity, the securities are represented by one or more global securities or in street name, you should check with your own institutionsuccessor entity will succeed to find out:

    how it handles securities payments and notices;

    whether it imposes fees or charges;

    how it would handle a request for the holders' consent, if ever required;

    whether and how you can instruct it to send you securities registered in your own name so you can be a holder, if that is permitted in the future;

    how it would exercise rightsassume our obligations under the securities if there were aunit agreements. We will then be relieved of any further obligation under these agreements.
The unit agreements will not include any restrictions on our ability to put liens on our assets, nor will they restrict our ability to sell our assets. The unit agreements also will not provide for any events of default or other event triggeringremedies upon the need for holders to act to protect their interests;occurrence of any events of default.
Governing Law
The unit agreements and

if the securities areunits will be governed by Delaware law.

24

TABLE OF CONTENTS

Form, Exchange and Transfer
Unless the accompanying prospectus supplement states otherwise, we will issue each unit in global — i.e., book-entry — form how the depositary's rules and procedures will affect these matters.

Global Securities

        A global security is a security that represents one or any other number of individual securities held by a depositary. Generally, all securities represented by the same global securities will have the same terms.

        Each security issuedonly. Units in book-entry form will be represented by a global security that we issue to, deposit with and registerregistered in the name of a financial institution ordepositary, which will be the holder of all the units represented by the global security. Those who own beneficial interests in a unit will do so through participants in the depositary’s system, and the rights of these indirect owners will be governed solely by the applicable procedures of the depositary and its nominee that we select. The financial institution that we select for this purpose is calledparticipants. We will describe book-entry securities, and other terms regarding the depositary. Unless we specify otherwiseissuance and registration of the units in the applicable prospectus supplement.

Unless the accompanying prospectus supplement DTCstates otherwise, each unit and all securities comprising the unit will be issued in the same form.
If we issue any units in registered, non-global form, the following will apply to them.
The units will be issued in the denominations stated in the applicable prospectus supplement. Holders may exchange their units for units of smaller denominations or combined into fewer units of larger denominations, as long as the total amount is not changed.

Holders may exchange or transfer their units at the office of the unit agent. Holders may also replace lost, stolen, destroyed or mutilated units at that office. We may appoint another entity to perform these functions or perform them ourselves.

Holders will not be required to pay a service charge to transfer or exchange their units, but they may be required to pay for any tax or other governmental charge associated with the transfer or exchange. The transfer or exchange, and any replacement, will be made only if our transfer agent is satisfied with the holder’s proof of legal ownership. The transfer agent may also require an indemnity before replacing any units.

If we have the right to redeem, accelerate or settle any units before their maturity, and we exercise our right as to less than all those units or other securities, we may block the exchange or transfer of those units during the period beginning 15 days before the day we mail the notice of exercise and ending on the day of that mailing, in order to freeze the list of holders to prepare the mailing. We may also refuse to register transfers of or exchange any unit selected for early settlement, except that we will continue to permit transfers and exchanges of the unsettled portion of any unit being partially settled. We may also block the transfer or exchange of any unit in this manner if the unit includes securities that are or may be selected for early settlement.
Only the depositary for all securities issuedwill be entitled to transfer or exchange a unit in book-entry form.

        A global security may not be transferred to or registered in the name of anyone other than the depositary, its nominee or a successor depositary, unless special termination situations arise. We describe those situations below under "Special Situations When a Global Security Will Be Terminated." As a result of these arrangements, the depositary, or its nominee,form, since it will be the sole registered owner and legal holder of all securities represented by a global security, and investors will be permitted to own only beneficial interests in a global security. Beneficial interests must be held by means of an account with a broker, bank or other financial institution that in turn has an account with the depositary or with


Table of Contents

another institution that does. Thus, an investor whose security is represented by a global security will not be a legal holder of the security, but only an indirect holder of a beneficial interestunit.

Payments and Notices
In making payments and giving notices with respect to our units, we will follow the procedures as described in the global security.

        Ifapplicable prospectus supplement.


25

TABLE OF CONTENTS

PLAN OF DISTRIBUTION
We may sell the prospectus supplement for a particular security indicates that the security will be issued in global form only, then the security will be represented by a global security at all times unless and until the global security is terminated. If termination occurs, we may issue the securities through another book-entry clearing system or decide that the securities may no longer be held through any book-entry clearing system.

Special Considerations for Global Securities

        The rights of an indirect holder relating to a global security will be governed by the account rules of the investor's financial institution and of the depositary, as well as general laws relating to securities transfers. We do not recognize an indirect holder as a holder of securities and instead deal only with the depositary that holds the global security.

        If securities are issued only in the form of a global security, an investor should be aware of the following:

    an investor cannot cause the securities to be registered in his or her name, and cannot obtain non-global certificates for his or her interest in the securities, except in the special situations we describe below;

    an investor will be an indirect holder and must look to his or her own bank, broker or other financial institution for payments on the securities and protection of his or her legal rights relating to the securities, as we describe above;

    an investor may not be able to sell interests in the securities to some insurance companies and to other institutions that are required by law to own their securities in non-book-entry form;

    an investor may not be able to pledge his or her interest in a global security in circumstances where certificates representing the securities must be delivered to the lender or other beneficiary of the pledge in order for the pledge to be effective;

    the depositary's policies, which may change from time to time will govern payments, transfers, exchanges and other matters relatingpursuant to an investor's interest inunderwritten public offerings, negotiated transactions, block trades or a global security;

    we and any applicable trustee have no responsibility for any aspectcombination of the depositary's actions or for its records of ownership interests in a global security, nor do we or any applicable trustee supervise the depositary in any way;

    the depositary may, and we understand that DTC will, require that those who purchase and sell interests in a global security within its book-entry system use immediately available funds, and your bank, broker or other financial institution may require you to do so as well; and

    financial institutions that participate in the depositary's book-entry system, and through which an investor holds its interest in a global security, may also have their own policies affecting payments, notices and other matters relating to the securities.

        There may be more than one financial intermediary in the chain of ownership for an investor. We do not monitor and are not responsible for the actions of any of those intermediaries.

Special Situations When a Global Security Will Be Terminated

        In a few special situations described below, the global security will terminate and interests in it will be exchanged for physical certificates representing those interests. After that exchange, the choice of


Table of Contents

whether to hold securities directly or in street name will be up to the investor. Investors must consult their own banks, brokers or other financial institutions to find out how to have their interests in securities transferred to their own name, so that they will be direct holders. We have described the rights of holders and street name investors above.

        Unless we provide otherwise in the applicable prospectus supplement, the global security will terminate when the following special situations occur:

    if the depositary notifies us that it is unwilling, unable or no longer qualified to continue as depositary for that global security and we do not appoint another institution to act as depositary within 90 days;

    if we notify any applicable trustee that we wish to terminate that global security; or

    if an event of default has occurred with regard to securities represented by that global security and has not been cured or waived.

        The prospectus supplement may also list additional situations for terminating a global security that would apply only to the particular series of securities covered by the applicable prospectus supplement. When a global security terminates, the depositary, and not we or any applicable trustee, is responsible for deciding the names of the institutions that will be the initial direct holders.


Table of Contents

PLAN OF DISTRIBUTION

these methods. We may sell ourthe securities covered by this prospectus in any of three ways (or in any combination):

    to or through underwriters or dealers;

    dealers, through agents, or directly to one or more purchasers; or

    through agents.

purchasers. We may distribute the securities:

    securities from time to time in one or more transactions transactions:

at a fixed price or prices, which may be changed from time to time;changed;


at market prices prevailing at the time of sale;


at prices related to thesuch prevailing market prices; or


at negotiated prices.

        Each time we offer and

We may also sell equity securities covered by this prospectus, we will provideregistration statement in an “at the market offering” as defined in Rule 415 under the Securities Act. Such offering may be made into an existing trading market for such securities in transactions at other than a fixed price, either:

on or through the facilities of The Nasdaq Global Market or any other securities exchange or quotation or trading service on which such securities may be listed, quoted or traded at the time of sale; and/or

to or through a market maker otherwise than on The Nasdaq Global Market or such other securities exchanges or quotation or trading services.
Such at the market offerings, if any, may be conducted by underwriters acting as principal or agent.
A prospectus supplement or supplements (and any related free writing prospectus that we may authorize to be provided to you) will describe the method of distribution and set forth the terms of the offering including:

    of the securities, including, to the extent applicable:

the name or names of any underwriters, dealers or agents;agents, if any;


the amounts of securities underwritten or purchased by each of them;

the purchase price of the securities and the proceeds we will receive from the sale;


any over-allotment options under which underwriters may purchase additional securities from us;


any agency fees or underwriting discounts or commissions or agency fees and other items constituting underwriters'agents’ or agents'underwriters’ compensation;


the
any public offering price of the securities;price;


any discounts commissions or concessions allowed or reallowedre-allowed or paid to dealers; and


any securities exchange or market on which the securities may be listed.

        Any public offering price and any discounts or concessions allowed or reallowed or paid to dealers may be changed from time to time. We may determine

Only underwriters named in the price or other termsprospectus supplement are underwriters of the securities offered under thisby the prospectus by use of an electronic auction. We will describe how any auction will determine the price or any other terms, how potential investors may participatesupplement.
If underwriters are used in the auctionsale, they will acquire the securities for their own account and the nature of the obligations of the underwriter, dealer or agent in the applicable prospectus supplement.

        Underwriters or dealers may offer and sellresell the offered securities from time to time in one or more transactions, including negotiated transactions at a fixed public offering price or at varying prices determined at the time of sale. IfThe obligations of the underwriters or dealers are used in the sale of any securities,to purchase the securities will be acquired bysubject to the underwriters or dealers for their own account andconditions set forth in the applicable underwriting agreement. We may be resold from time to time in one or more transactions described above. Theoffer the securities may be either offered to the public through underwriting syndicates represented by managing underwriters or directly by underwriters or dealers. Generally, the underwriters' or dealers' obligations to purchase the securities will be subjectwithout a syndicate. Subject to certain conditions, precedent. Thethe underwriters or dealers will be obligated to purchase all of the securities if they purchase any of the securities, unless otherwise specified inoffered by the prospectus supplement. Any public offering price and any discounts or concessions allowed or re-allowed or paid to dealers may change from time to time. We may use underwriters with whom we have a material relationship. We will describe the nature of any such relationship in the prospectus supplement, naming the underwriter.


Tableunderwriter, the nature of Contents

any such relationship.

We may sell the securities directly or through agents we designate from time to time. The prospectus supplementWe will name any agent involved in the offer oroffering and sale of the securities, and we will describe any commissions we will pay to them. Generally, anythe agent in the prospectus supplement. Unless the prospectus supplement states otherwise, our agent will be actingact on a best effortsbest-efforts basis for the period of its appointment.

26

TABLE OF CONTENTS

We may authorize underwriters, dealersagents or agentsunderwriters to solicit offers by certain purchaserstypes of institutional investors to purchase the securities from us at the public offering price set forth in the prospectus supplement pursuant to delayed delivery contracts providing for payment and delivery on a specified date in the future. TheWe will describe the conditions to these contracts will be subject only to those conditions set forth in the prospectus supplement, and the prospectus supplement will set forth any commissions we must pay for solicitation of these contracts.

        Agents, dealerscontracts in the prospectus supplement.

We may provide agents and underwriters may be entitledwith indemnification against civil liabilities related to indemnification by us against certain civil liabilities,offerings pursuant to this prospectus, including liabilities under the Securities Act, or to contribution with respect to payments whichthat the agents dealers or underwriters may be requiredmake with respect to make in respect thereof.these liabilities. Agents dealers and underwriters may be customers of, engage in transactions with, or perform services for, us in the ordinary course of business.

All securities we may offer, other than our shares of common stock, will be new issues of securities with no established trading market. Any underwriters may make a market in these securities, but will not be obligated to do so and may discontinue any market making at any time without notice. We cannot guarantee the liquidity of the trading markets for any securities.

Any underwriter may engage in overallotment, stabilizing transactions, short covering transactions and penalty bids in accordance with Regulation M under the Securities Exchange Act of 1934, as amended.Act. Overallotment involves sales in excess of the offering size, which create a short position. This short sales position may involve either "covered" short sales or "naked" short sales. Covered short sales are short sales made in an amount not greater than the underwriters' over-allotment option to purchase additional securities in this offering described above. The underwriters may close out any covered short position either by exercising their over-allotment option or by purchasing securities in the open market. To determine how they will close the covered short position, the underwriters will consider, among other things, the price of securities available for purchase in the open market, as compared to the price at which they may purchase securities through the over-allotment option. Naked short sales are short sales in excess of the over-allotment option. The underwriters must close out any naked short position by purchasing securities in the open market. A naked short position is more likely to be created if the underwriters are concerned that, in the open market after pricing, there may be downward pressure on the price of the securities that could adversely affect investors who purchase securities in this offering. Stabilizing transactions permit bids to purchase the underlying security for the purpose of fixing the price of the security so long as the stabilizing bids do not exceed a specified maximum. Short covering transactions involve purchases of the securities in the open market after the distribution is completed to cover short positions. Penalty bids permit the underwriters to reclaim a selling concession from a dealer when the securities originally sold by the dealer are purchased in a stabilizing or covering transaction to cover short positions.

Those activities may cause the price of the securities to be higher than it would otherwise be. If commenced, the underwriters may discontinue any of the activities at any time. These transactions may be effected on any exchange or over-the-counter market or otherwise.

Any underwriters who are qualified market makers on the NASDAQThe Nasdaq Global Market may engage in passive market making transactions in our common stock, preferred stock and debtthe securities as applicable, on the NASDAQThe Nasdaq Global Market in accordance with Rule 103 of Regulation M, during the business day prior to the pricing of the offering, before the commencement of offers or sales of the securities. Passive market makers must comply with applicable volume and price limitations and must be identified as passive market makers. In general, a passive market maker must display its bid at a price not in excess of the highest independent bid for such security; if all independent bids are lowered below the passive market maker'smaker’s bid, however, the passive market maker'smaker’s bid must then be lowered when certain purchase limits are exceeded.


Table of Contents

        Similar to other purchase transactions, an underwriter's purchase to cover the syndicate short sales or to Passive market making may stabilize the market price of ourthe securities may have the effect of raising or maintaining the market price of our securities or preventing or mitigatingat a decline in the market price of our securities. As a result, the price of our securities may be higher than the pricelevel above that which might otherwise existprevail in the open market. The imposition of a penalty bid might also have an effect onmarket and, if commenced, may be discontinued at any time.


27

TABLE OF CONTENTS

LEGAL MATTERS
Certain legal matters, including the pricelegality of the securities if it discourages resales of the securities.

        Neither we nor the underwriters make any representation or prediction as to the effect that the transactions described above may have on the price of the securities. If such transactions are commenced, they may be discontinued without notice at any time.


Table of Contents

LEGAL MATTERS

        Unless otherwise indicated in the applicable prospectus supplement, the validity of the securities offered, by this prospectus, and any supplement thereto, will be passed upon for us by Cooley LLP.

Gibson, Dunn & Crutcher LLP, San Francisco, California. Additional legal matters may be passed upon for us or any underwriters, dealers or agents, by counsel that we will name in the applicable prospectus supplement.

EXPERTS

Ernst & Young LLP, independent registered public accounting firm, has audited our consolidated financial statements as of December 31, 2021 and 2020 and for each of the years then ended, included in our Annual Report on Form 10-K for the year ended December 31, 2021, and the effectiveness of our internal control over financial reporting as of December 31, 2021, as set forth in their reports, which are incorporated by reference in this prospectus and elsewhere in the registration statement. Our financial statements are incorporated by reference in reliance on Ernst & Young LLP’s report, given on their authority as experts in accounting and auditing.
The financial statements for the year ended December 31, 2019 incorporated in this prospectus by reference to the Annual Report on Form 10-K for the year ended December 31, 20162021 have been so incorporated in reliance on the report of PricewaterhouseCoopers LLP, an independent registered public accounting firm, given on the authority of said firm as experts in auditing and accounting.


28

TABLE OF CONTENTS


WHERE YOU CAN FIND MORE INFORMATION

We file annual, quarterly and other reports, proxy statements and other information with the SEC. Our SEC filings are available to the public over the Internet at the SEC’s website at www.sec.gov. Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, including any amendments to those reports, and other information that we file with or furnish to the SEC pursuant to Section 13(a) or 15(d) of the Exchange Act can also be accessed free of charge through the Internet. These filings will be available as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.
This prospectus is part of a registration statement that we filed with the SEC. This prospectus does not contain all of theomits some information set forthcontained in the registration statement in accordance with SEC rules and regulations. You should review the information and exhibits toin the registration statement. Forstatement for further information with respect toabout us and our subsidiaries and the securities we are offering underoffering. Statements in this prospectus concerning any document we refer youfiled as an exhibit to the registration statement or that we otherwise filed with the SEC are not intended to be comprehensive and are qualified by reference to these filings. You should review the exhibitscomplete document to evaluate these statements.

29

TABLE OF CONTENTS

INCORPORATION OF CERTAIN INFORMATION BY REFERENCE
The SEC allows us to incorporate by reference the information and schedulesreports we file with it, which means that we can disclose important information to you by referring you to these documents. The information incorporated by reference is an important part of this prospectus, and information that we file after the date hereof with the SEC will automatically update and supersede the information already incorporated by reference. We are incorporating by reference the documents listed below:


our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2022, filed with the SEC on May 5, 2022, and June 30, 2022, filed with the SEC on August 4, 2022;

our Current Reports on Form 8-K filed with the SEC on February 22, 2022, March 23, 2022, March 31, 2022 and June 2, 2022; and

the description of our common stock set forth in our registration statement on Form 8-A, filed with the SEC on August 9, 2016, including any amendments thereto or reports filed for the purposes of updating this description, including Exhibit 4.7 to our Annual Report on Form 10-K for the fiscal year ended December 31, 2021, filed with the SEC on February 28, 2022.
All documents we file with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act shall be deemed incorporated by reference in this prospectus and to be a part of this prospectus from the date of filing of those documents, with the exception of any portion of any report or document that is not deemed “filed” under such provisions on or after the date of this prospectus, until the earlier of the date on which: (1) all of the securities registered hereunder have been sold; or (2) the registration statement. Neitherstatement of which this prospectus is a part has been withdrawn.
Under no circumstances will any information filed under Items 2.02 or 7.01 of Current Report on Form 8-K be deemed incorporated herein by reference unless such Form 8-K expressly provides to the contrary.
Upon written or oral request, we nor any agent, underwriterwill provide without charge to each person to whom a copy of the prospectus is delivered a copy of the documents incorporated by reference herein (other than exhibits to such documents unless such exhibits are specifically incorporated by reference herein). You may request a copy of these filings, at no cost, by writing, calling or dealer hasemailing us at the contact information set forth below. We have authorized any personno one to provide you with different information. We are not making an offer of these securitiesany information that differs from that contained in this prospectus. Accordingly, we take no responsibility for any state where the offer is not permitted.other information that others may give you. You should not assume that the information in this prospectus is accurate as of any date other than the date onof the front pagecover of this prospectus, regardless of the time of delivery of this prospectus or any sale of the securities offered by this prospectus.

        We file annual, quarterly and current reports, proxy statements and other information with the SEC. You may read and copy any document we file with the SEC at the SEC's public reference room at 100 F Street, N.E., Washington, D.C., 20549. Please call the SEC at 1.800.SEC.0330 for further information on the operation of the public reference room. Our SEC filings are also available to the public at the SEC's website at http://www.sec.gov.


Table of Contents

INCORPORATION OF CERTAIN INFORMATION BY REFERENCE

        The SEC allows us to "incorporate by reference" the information we file with it, which means that we can disclose important information to you by referring you to those documents instead of having to repeat the information in this prospectus. The information incorporated by reference is considered to be part of this prospectus, and later information that we file with the SEC will automatically update and supersede this information. We incorporate by reference the documents listed below and any future filings (including those made after the date of the initial filing of the registration statement of which this prospectus is a part and prior to the effectiveness of such registration statement) we will make with the SEC under Sections 13(a), 13(c), 14, or 15(d) of the Exchange Act until the termination of the offering of the shares covered by this prospectus (other than information furnished under Item 2.02 or Item 7.01 of Form 8-K):

    our annual report on Form 10-K for the year ended December 31, 2016, filed with the SEC on March 7, 2017, including the information specifically incorporated by reference therein from our definitive proxy statement on Schedule 14A, filed on April 24, 2017;

    our Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, filed with the SEC on May 10, 2017;

    our Quarterly Report on Form 10-Q for the quarter ended June 30, 2017, filed with the SEC on August 8, 2017;

    our current reports on Form 8-K, filed with the SEC on February 9, 2017, May 23, 2017, May 25, 2017, May 30, 2017 and June 8, 2017;

    our current report on Form 8-K/A, filed with the SEC on July 31, 2017; and

    the description of our common stock set forth in our registration statement on Form 8-A, filed with the SEC on August 9, 2016, including any amendments thereto or reports filed for the purposes of updating this description.

        You can request a copy of these filings, at no cost, by writing or telephoning us at the following address or telephone number:

Protagonist Therapeutics, Inc.
7707 Gateway Boulevard, Suite 140
Newark, California 94560CA 94560-1160
(510) 474-0170


Attn: Chief Financial Officer

        This prospectus is part of a registration statement we filed with the SEC. That registration statement and the exhibits filed along with the registration statement contain more

30

TABLE OF CONTENTS
Protagonist Therapeutics, Inc.
[MISSING IMAGE: lg_protagonist-pn.jpg]
COMMON STOCK
PREFERRED STOCK
DEBT SECURITIES
WARRANTS
UNITS
PROSPECTUS
           , 2022

TABLE OF CONTENTS
The information about us and the shares in this offering. Because information about documents referred to in this prospectus is not always complete, you should read the full documents which are filed as exhibits to the registration statement. You may read and copy the full registration statement and its exhibits at the SEC's public reference rooms or its website.


Table of Contents

The information contained in this prospectussupplement is not complete and may be changed. We may not sell these securities or accept an offer to buy these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus supplement is not an offer to sell these securities and it is not soliciting offersan offer to buy these securities in any state where suchthe offer or sale is not permitted.


SUBJECT TO COMPLETION, DATED SEPTEMBER 1, 2017AUGUST 5, 2022

PROSPECTUS SUPPLEMENT


LOGO(To prospectus dated            , 2022)

[MISSING IMAGE: lg_protagonist-pn.jpg]
Up to $50,000,000$100,000,000 of Shares

Common Stock



We have entered into a Controlled Equity Offeringan Open Market Sale AgreementSM sales agreement (the “sales agreement”) with Cantor Fitzgerald & Co.,Jefferies LLC (“Jefferies”) relating to the sale of shares of our common stock offered by this prospectus supplement and the accompanying prospectus. In accordance with the terms of the sales agreement, we may offer and sell shares of our common stock, $0.00001 par value per share, from time to time having an aggregate offering price of up to $50,000,000 from time to time$100.0 million through Cantor Fitzgerald & Co.,Jefferies, acting as our sales agent.

Our common stock is listedtraded on the NASDAQThe Nasdaq Global Market under the symbol "PTGX."“PTGX.” On August 31, 2017,2, 2022, the last reported sale price of our common stock on the NASQAQ Global Market was $16.33$10.63 per share.

Sales of our common stock,shares, if any, under this prospectus supplement and the accompanying prospectus may be made in sales deemed to be "at-the-market" equity offeringsan “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (the “Securities Act”). Jefferies is not required to sell any specific number or the Securities Act. Cantor Fitzgerald & Co.dollar amount of securities, but will act as a sales agent on a best efforts basis and useusing commercially reasonable efforts to sell on our behalf all of the shares of common stock requested to be sold by us, consistent with its normal trading and sales practices, on mutually agreed terms between Cantor Fitzgerald & Co.Jefferies and us. There is no arrangement for funds to be received in any escrow, trust or similar arrangement.

        Cantor Fitzgerald & Co.

Jefferies will be entitled to compensation for salesunder the terms of common stock sold pursuant to the sales agreement at an amounta fixed commission rate of up to 3.0%3% of the gross proceeds of any shares of common stocksales price per share sold under the sales agreement. See “Plan of Distribution” beginning on page S-11 for additional information regarding Jefferies’ compensation. In connection with the sale of our common stock on our behalf, Cantor Fitzgerald & Co.Jefferies will be deemed to be an "underwriter"“underwriter” within the meaning of the Securities Act and the compensation of Cantor Fitzgerald & Co.Jefferies will be deemed to be underwriting commissions or discounts. We have also agreed to provide indemnification and contribution to Cantor Fitzgerald with respect toJefferies against certain liabilities, including liabilities under the Securities Act or the Securities Exchange Act of 1934, as amended or the Exchange Act.(the “Exchange Act”). See section titled "Plan“Plan of Distribution"Distribution” on page 14S-11 of this prospectus.

prospectus supplement.

Investing in our securities involves a high degree of risk. You should review carefully the risks and uncertainties described under the heading "Risk Factors"See “Risk Factors” beginning on page 5S-6 of this prospectus supplement and under similar headings in the other documents that are incorporated by reference into this prospectus.prospectus supplement.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities, or determined if this prospectus issupplement or the accompanying prospectus are truthful or complete. Any representation to the contrary is a criminal offense.

LOGOJefferies

The date of this prospectus is

           , 2017.

2022

Table of Contents


TABLE OF CONTENTS


TABLE OF CONTENTS

Page

About this Prospectus

S-2i

Prospectus Summary

1S-3

The Offering

4S-4

Risk Factors

5S-6

Forward-Looking Statements

6S-8

Use of Proceeds

7S-9

Dilution

8S-11

Description of Capital Stock

10S-13

Plan of Distribution

14S-13

Legal Matters

15S-14

Experts

15

Where You Can Find More Information

S-1515

Incorporation of Certain Information by Reference

15


S-1



        You should rely only on the information contained in, or incorporated by reference into, this prospectus and in any free writing prospectus that we may authorize for use in connection with this offering. We have not, and Cantor Fitzgerald & Co., or Cantor Fitzgerald, has not, authorized any other person to provide you with different information. We are not, and Cantor Fitzgerald is not, making an offer to sell or seeking an offer to buy common stock under this prospectus in any jurisdiction where the offer or sale is not permitted. You should assume that the information appearing in this prospectus, the documents incorporated by reference into this prospectus, and in any free writing prospectus that we may authorize for use in connection with this offering, is accurate only as of the date of those respective documents. Our business, financial condition, results of operations and prospects may have changed since those dates.



ABOUT THIS PROSPECTUS SUPPLEMENT

This prospectus supplement relates to the offering of shares of our common stock. Before buying any of the shares of common stock that we are offering, we urge you to carefully read this prospectus supplement, together with the information incorporated by reference as described under the headings "Where“Where You Can Find More Information"Information” and "Incorporation“Incorporation of Certain Information by Reference" in thisReference”, the accompanying prospectus and any free writing prospectus or prospectus supplement that we have authorized for use in connection with this offering. These documents contain important information that you should consider when making your investment decision.

In general, when we refer only to the prospectus, we are referring to both the prospectus supplement and the accompanying prospectus combined.

This prospectus describes the terms of this offering of shares of common stock and also adds to and updates information contained in the documents incorporated by reference into this prospectus. To the extent there is a conflict between the information contained in this prospectus, on the one hand, and the information contained in any document incorporated by reference into this prospectus that was filed with the Securities and Exchange Commission or SEC,(“SEC”) before the date of this prospectus, on the other hand, you should rely on the information in this prospectus. If any statement in one of these documents is inconsistent with a statement in another document having a later date—date — for example, a document incorporated by reference into this prospectus—prospectus — the statement in the document having the later date modifies or supersedes the earlier statement.

We have not, and the sales agentJefferies has not, authorized anyoneany other person to provide you with information that is in addition to or different thanfrom that contained or incorporated by reference in this prospectus, andalong with the information contained in any permitted free writing

i


Table of Contents

prospectus or prospectus supplement that prospectuses we have authorized for use in connection with this offering. WeNeither we nor Jefferies take noany responsibility for, andor can provide noany assurance as to the reliability of, any information other than the information that others may give you.contained or incorporated by reference in this prospectus or any permitted free writing prospectuses we have authorized for use in connection with this offering. You should assume that the information appearing in this prospectus the documents incorporated by reference herein, and in any free writing prospectus or prospectus supplement that we have authorized for use in connection with this offering is accurate only as of the date on the front cover of those respective documents. this prospectus.

Our business, financial condition, results of operations and prospects may have changed since those dates. You should readthat date. Information contained on, or accessible through, our website is not part of this prospectus. We and Jefferies are offering to sell, and seeking offers to buy, shares of common stock only in jurisdictions where offers and sales are permitted. The distribution of this prospectus and the documents incorporatedoffering of the common stock in certain jurisdictions may be restricted by reference herein,law. Persons outside the United States who come into possession of this prospectus must inform themselves about, and observe any free writingrestrictions relating to, the offering of the common stock and the distribution of this prospectus oroutside the United States. This prospectus supplement that we have authorized for usedoes not constitute, and may not be used in connection with, an offer to sell, or a solicitation of an offer to buy, any securities offered by this offeringprospectus by any person in their entirety before makingany jurisdiction in which it is unlawful for such person to make such an investment decision.

        Except as otherwise indicated hereinoffer or assolicitation.

Unless the context otherwise requires, referenceswe use the terms “Protagonist,” the “company,” “we,” “us,” and “our” in this prospectus to "Protagonist," "the company," "we," "us," "our" and similar references refer to Protagonist Therapeutics, Inc., a corporation under the laws and, where appropriate, our subsidiaries.

S-2


PROSPECTUS SUPPLEMENT SUMMARY
The following summary of our business highlights certain of the State of Delaware.

        This prospectus and the information incorporated herein by reference include trademarks, service marks and trade names owned by us or other companies. All trademarks, service marks and trade names includedcontained elsewhere in, or incorporated by reference into, this prospectus any applicable prospectus supplement or any related free writing prospectus areand the property of their respective owners.

ii


Table of Contents



PROSPECTUS SUMMARY

accompanying prospectus. This summary highlights selected information contained elsewhere in this prospectus or incorporated by reference hereinis not complete and does not contain all of the information that you needshould consider before deciding whether to considerinvest in making your investment decision.shares of our common stock. You should carefully read thethis entire prospectus supplement and the accompanying prospectus, including any applicableinformation incorporated by reference, which are described under the headings “Where You Can Find Additional Information” and “Incorporation of Certain Information by Reference” herein and therein. In particular, you should carefully consider the risks and uncertainties described under the heading “Risk Factors” in this prospectus supplement orand in the accompanying prospectus, as well as those contained in the other documents incorporated by reference herein and any related free writing prospectus including the risks of investing in our securities discussed under the heading "Risk Factors" contained in this prospectus and any applicable prospectus supplement or related free writing prospectus, and under similar headings in the other documents that are incorporated by reference into this prospectus. You should also carefully read the information incorporated by reference into this prospectus, including our financial statements and related notes, and the exhibits to the registration statement of which this prospectus is a part, before making your investment decision.


Protagonist Therapeutics, Inc.
.

Company Overview

We are a clinical-stage biopharmaceutical company with apeptide-based new chemical entities rusfertide, PN-943 and PN-235 in different stages of development, all derived from the Company’s proprietary discovery technology platform which is utilized to discoverplatform. Our clinical programs fall into two broad categories of diseases; (i) hematology and develop novel peptide-based drugs to address significant unmet medical needs. Our primary focus is on developing potential first-in-class oral targeted therapy-based peptide drugs that work by blocking biological pathways that are currently targeted by marketed injectable antibody drugs. Our initial lead peptide product candidates, PTG-100blood disorders, and PTG-200, are based on this approach,(ii) inflammatory and we believe these candidates have the potential to transform the existing treatment paradigm for inflammatory bowel disease ("IBD"), chronic gastrointestinal diseases consisting primarily of ulcerative colitis ("UC") and Crohn's disease ("CD").

        PTG-100, a potential first-in-class oral, alpha-4-beta-7 ("a4b7") integrin antagonist, is currently in a global Phase 2B clinical trial for the treatment of moderate-to-severe UC that is anticipated to randomize approximately 240 patients at approximately 100 clinical sites. We anticipate completing this trial in the second half of 2018. PTG-200, a potential first-in-class oral Interleukin-23 receptor ("IL-23R") antagonist for the potential treatment of CD, is currently in pre-clinical development and is expected to enter Phase 1 clinical studies in the second half of 2017. We have a worldwide collaboration agreement with Janssen Biotech, Inc. to co-develop and commercialize PTG-200 for all indications, including IBD, as described below in the section titled "Janssen Collaboration Agreement." In addition to PTG-100 and PTG-200, we are also developing an injectable hepcidin mimetic, PTG-300, for the treatment of rare diseases such as beta-thalassemia. PTG-300 is currently being studied in a Phase 1 clinical trial.

        We have not generated any revenue from product sales and we do not currently have any products approved for commercialization. We have never been profitable and have incurred net losses in each year since inception and we do not anticipate that we will achieve profitability in the near term. Our net losses were $15.0 million and $29.1 million for the three and six months ended June 30, 2017, respectively, and $7.1 million and $18.8 million for the three and six months ended June 30, 2016, respectively. As of June 30, 2017, we had an accumulated deficit of $93.7 million. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect to continue to incur significant research, development and other expenses related to our ongoing operations and product development, including clinical development activities under the Janssen Collaboration Agreement, and as a result, we expect to continue to incur losses for the foreseeable future. We also expect these losses to increase as we continue our development of, and seek regulatory approval for, our product candidates.

immunomodulatory diseases.

Table of ContentsCorporate Information

Janssen Collaboration Agreement

        On May 26, 2017, we and Janssen Biotech, Inc., ("Janssen") entered into an exclusive license and collaboration agreement (the "Janssen Collaboration Agreement") for the development, manufacture and commercialization of PTG-200 worldwide for the treatment of CD and UC. The Janssen Collaboration Agreement became effective on July 13, 2017. Upon the effectiveness of the agreement, we became eligible for a non-refundable, upfront cash payment of $50.0 million from Janssen, which we received during the third quarter of 2017.

        Under the Janssen Collaboration Agreement, we granted Janssen an exclusive worldwide license to develop, manufacture and commercialize PTG-200 and related IL-23R compounds for all indications, including CD and UC. We are responsible, at our own expense, for the conduct of the Phase 1 clinical trial for PTG-200, and Janssen will be responsible for the conduct of a potential Phase 2 clinical trial for PTG-200 in CD. All such clinical trials would be conducted in accordance with a mutually agreed upon clinical development plan and budget. Development costs for the Phase 2 clinical trial would be shared between the parties on an 80%/20% basis, with Janssen assuming the larger share. Should Janssen elect to retain its license following completion of the Phase 2 clinical trial, it would be responsible, at its own expense, for the manufacture, continued development of, seeking regulatory approval for, and commercialization of PTG-200 worldwide. The parties' development activities under the Janssen Collaboration Agreement through the Phase 2 clinical trial will be overseen by a joint governance structure which will have equal representation by both parties.

        Following the conclusion of the planned Phase 2A portion of the Phase 2 clinical trial, if Janssen elects to maintain its license rights and continue the development of PTG-200 in the Phase 2B portion of such clinical trial (the "First Opt-in Election"), we would be eligible to receive a $125 million payment. Following the conclusion of the planned Phase 2B portion of the Phase 2 clinical trial, if Janssen elects again to maintain its license rights (the "Second Opt-in Election"), we would be eligible to receive a $200 million payment. In addition to the opt-in fees, we are eligible to receive potential development, regulatory and sales milestone payments of up to an aggregate of $615 million and tiered royalties paid as a percentage of Janssen's worldwide net sales at rates ranging from ten to the mid-teens, with certain customary reductions in certain circumstances. If Janssen does not make either the First Opt-in Election or the Second Opt-in Election, the Janssen Collaboration Agreement would terminate. If Janssen does not make the Second Opt-in Election, or if at any time after the Second Opt-in Election, Janssen terminates the Janssen Collaboration Agreement, we would be obligated to pay Janssen a royalty on worldwide net sales of PTG-200. We would also have an option to provide up to 30% of the required U.S. details for PTG-200 to prescribers, using our own sales force personnel, upon commercial launch in the United States. If such right is exercised, our detailing costs would be reimbursed by Janssen.

        The Janssen Collaboration Agreement contains customary representations, warranties and covenants by us and Janssen and includes an obligation by us not to develop or commercialize other compounds which also target IL-23R outside of the Janssen Collaboration Agreement until completion of the Phase 2B portion of the Phase 2 clinical trial. We and Janssen are required to indemnify the other party against all losses and expenses related to breaches of its representations, warranties and covenants under the Janssen Collaboration Agreement.

        The Janssen Collaboration Agreement remains in effect until the royalty obligations cease following patent and regulatory expiry, unless terminated earlier. Either we or Janssen may terminate the Janssen Collaboration Agreement for uncured material breach. Janssen retains the right to terminate the Janssen Collaboration Agreement for convenience and without cause on written notice of a certain period to us. Upon a termination of the Janssen Collaboration Agreement, all rights revert back to us, and in certain circumstances, if such termination occurs during ongoing clinical trials,


Table of Contents

Janssen would, if requested, provide certain financial and operational support to us for the completion of such trials.

Company Information

        Protagonist Pty Limited (Protagonist Australia) was incorporated in Australia in September 2001. We were incorporated under the laws of the State of Delaware in 2006, under the name Protagonist Therapeutics, Inc., and became the parent of Protagonist Australia pursuant to a transaction in which all of the issued and outstanding capital stock of Protagonist Australia was exchanged for shares of our common stock and Series A preferred stock. Our principal executive offices are located at 7707 Gateway Boulevard, Suite 140, Newark, California 94560. Our telephone number is (510) 474-0170. Our website address is www.protagonist-inc.com. Thewww.protagonist‑inc.com. References to our website address do not constitute incorporation by reference of the information contained in, or accessible through, ouron the website, doesand the information contained on the website is not constitute part of this prospectus, should not be relied on in determining whether to make an investment decision, and the inclusion ofdocument. We have included our website address in this prospectus issupplement solely as an inactive textual reference only.

reference.

Table of Contents



THE OFFERING

Common Stock Offered By UsShares of our common stock having an aggregate offering price of up to $50.0 million.

Manner of Offering


"At the market offering" that may be made from time to time through our sales agent, Cantor Fitzgerald. See "Plan of Distribution" on page 14.

Use of Proceeds


We currently intend to use the net proceeds from the sale of the securities offered by us hereunder primarily for research, development and manufacturing of product candidates, and for other general corporate purposes. See "Use of Proceeds" on page 7 of this prospectus.

Risk Factors


Investing in our common stock involves significant risks. Please read the information contained in and incorporated by reference under the heading "Risk Factors" on page 5 of this prospectus and under similar headings in the other documents that are filed after the date hereof and incorporated by reference into this prospectus, together with the other information included in or incorporated by reference into this prospectus, before deciding whether to invest in our common stock.

NASDAQ Global Market Symbol


PTGX
S-3



THE OFFERING

Table

Shares of Contentsour common stock having an aggregate offering price of up to $100.0 million.
Common stock to be outstanding immediately after this



offering
RISK FACTORS

Up to 58,091,268 shares of our common stock, assuming sales of 9,407,337 shares of our common stock in this offering at a public offering price of $10.63 per share, which was the last reported sale price per share of our common stock on the Nasdaq Global Market on August 2, 2022. The actual number of shares of our common stock issued will vary depending on the sales price under this offering.
Plan of distribution
“At the market offering” that may be made from time to time through our sales agent, Jefferies. See “Plan of Distribution” on page S-11 of this prospectus supplement.
Use of proceeds
We currently intend to use the net proceeds from this offering for working capital, capital expenditures and general corporate purposes, which may include, among other things, funding research and development, clinical trials, vendor payables, potential regulatory submissions, hiring additional personnel and capital expenditures. See “Use of Proceeds” on page S-8 of this prospectus supplement.
Risk factors
Investing in our common stock involves a high degree of risk. Before deciding whether to investsignificant risks. Please read the information contained in our common stock, you should consider carefully the risks and uncertainties described below andincorporated by reference under the heading "Risk Factors" contained in our Quarterly Report“Risk Factors” on Form 10-Q for the period ended June 30, 2017, which are incorporated by reference intopage S-6 of this prospectus in their entirety, as updated or superseded bysupplement and page 4 of the risksaccompanying prospectus and uncertainties described under similar headings in the other documents that are filed after the date hereof and incorporated by reference into this prospectus supplement, together with the other information included in or incorporated by reference into this prospectus supplement and the accompanying prospectus, before deciding whether to invest in our common stock.
Nasdaq Global Market
symbol
“PTGX”
The number of shares of common stock to be outstanding after this offering is based on 48,683,931 shares of our common stock outstanding as of June 30, 2022 and excludes:

5,564,352 shares of common stock issuable upon the exercise of stock options issued and outstanding under our 2016 Equity Incentive Plan (the “2016 Plan”), as of June 30, 2022, having a weighted average exercise price of $19.96 per share;

737,340 shares of common stock issuable upon the vesting of outstanding restricted stock units, under the 2016 Plan, as of June 30, 2022;

219,000 shares of common stock issuable upon the vesting of outstanding performance stock units, under the 2016 Plan, as of June 30, 2022;

an aggregate of 817,303 shares of common stock, subject to increase on an annual basis, reserved for future issuance under the 2016 Plan, as of June 30, 2022;

944,197 shares of common stock issuable upon the exercise of stock options issued and outstanding under our Amended and Restated 2018 Inducement Plan, as amended (the “Inducement Plan”), as of June 30, 2022, having a weighted average exercise price of $22.38 per share;

S-4



28,750 shares of common stock issuable upon the vesting of outstanding restricted stock units, under the Inducement Plan, as of June 30, 2022;

an aggregate of 601,042 shares of common stock reserved for future issuance under the Inducement Plan, as of June 30, 2022;

316,572 shares of common stock issuable upon the exercise of stock options issued and outstanding under our 2007 Equity Incentive Plan, as of June 30, 2022, having a weighted average exercise price of $3.38 per share;

1,285,068 shares of our common stock reserved for future issuance under our 2016 Employee Stock Purchase Plan, as of June 30, 2022;

2,750,000 shares of common stock issuable upon the exercise of warrants outstanding as of June 30, 2022, at a weighted average exercise price of $12.50 per share; and

400,000 shares of common stock issuable upon the exercise of warrants outstanding as of June 30, 2022, at a weighted average exercise price of $0.00001 per share.
Unless otherwise indicated, all information in this prospectus supplement assumes no exercise of outstanding stock options or warrants or vesting of restricted stock units or performance stock units as of June 30, 2022.

S-5


RISK FACTORS
Investing in our securities involves risks. You should carefully consider the risks, uncertainties and other factors described in our most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and Current Reports on Form 8-K that we have filed or will file with the SEC, and in other documents which are incorporated by reference into this prospectus supplement, including the risk factors and any free writingother information contained in or incorporated by reference into this prospectus that we may authorize for usesupplement before investing in connection with this offering. The risks described in these documents are not the only ones we face, but those that we consider to be material. There may be other unknown or unpredictable economic, business, competitive, regulatory or other factors that could have material adverse effects on our future results. Past financial performance may not be a reliable indicator of future performance, and historical trends should not be used to anticipate results or trends in future periods. If any of these risks actually occurs, our securities. Our business, financial condition, results of operations, cash flows or cash flowprospectus supplement could be seriously harmed. This could causematerially adversely affected by any of these risks. The risks and uncertainties described in the trading price of our common stockdocuments incorporated by reference herein are not the only risks and uncertainties that you may face.
Risks Relating to decline, resulting in a loss of all or part of your investment. Please also read carefully the section below titled "Forward-Looking Statements."

Additional Risks Related to Thisthis Offering

Management willWe have broad discretion as to the use of the proceeds from this offering and may not use the proceeds effectively.

        Because we have

Our management will retain broad discretion as to the allocation of the proceeds and may spend these proceeds in ways in which you may not designatedagree. We intend to use the amount of net proceeds, if any, from this offering to be used for any particular purpose, ourworking capital, capital expenditures and general corporate purposes, which may include, among other things, funding research and development, clinical trials, vendor payables, potential regulatory submissions, hiring additional personnel and capital expenditures. Our management will have broadconsiderable discretion as toin the application of the net proceeds, from this offering and you will not have the opportunity, as part of your investment decision, to assess whether the proceeds are being used appropriately. The failure of our management to apply these funds effectively could use them for purposes other than those contemplated atresult in unfavorable returns and uncertainty about our prospects, each of which could cause the timeprice of the offering. Our management may use the net proceeds for corporate purposes that may not improve our financial condition or market value.

common stock to decline.

You may experience immediate and substantial dilution.dilution in the net tangible book value per share of the common stock you purchase.

The offering price per share in this offeringof common stock being offered may exceedbe higher than the net tangible book value per share of our outstanding common stock outstanding prior to this offering. Assuming that an aggregate of 3,061,8499,407,337 shares of our common stock are sold at a price of $16.33$10.63 per share, the last reported sale price of shares of our common stock on the NASDAQThe Nasdaq Global Market on August 31, 2017,2, 2022, for aggregate gross proceeds of $50.0approximately $100 million, and after deducting commissions and estimated offering expenses payable by us, you will experiencenew investors in this offering would incur immediate dilution of $5.50$4.34 per share. In addition, you may also experience additional dilution after this offering on any future equity issuances, including the issuance of common stock in connection with the 2016 Plan or the Inducement Plan. To the extent we raise additional capital by issuing equity securities, our stockholders will experience substantial additional dilution. See “Dilution” for additional information.
You may experience future dilution as a result of future equity offerings.
In order to raise additional capital, we expect to in the future offer additional shares of our common stock or other securities convertible into or exchangeable for our common stock. We cannot assure you that we will be able to sell shares or other securities in any other offering at a price per share representingthat is equal to or greater than the difference between our as adjusted net tangible book valueprice per share as of June 30, 2017 after giving effect topaid by investors in this offering, and investors purchasing shares or other securities in the assumed offering price.future could have rights superior to existing stockholders. The exerciseprice per share at which we sell additional shares of outstandingour common stock optionsor other securities convertible into or exchangeable for our common stock in future transactions may be higher or lower than the price per share in this offering.
The actual number of shares of common stock we will resultissue under the sales agreement, at any one time or in further dilution of your investment. Seetotal, is uncertain.
Subject to certain limitations in the section titled "Dilution" below forsales agreement and compliance with applicable law, we have the discretion to deliver a more detailed illustrationplacement notice to Jefferies at any time throughout the term of the dilution you would incur if you participatesales agreement. The number of shares of common stock that are sold by Jefferies after delivering a placement notice will fluctuate based on the market price of the shares of common stock during the sales period and limits we set with Jefferies. Because the price per share of each share sold will fluctuate based on the market price of

S-6


shares of our common stock during the sales period, it is not possible at this stage to predict the number of shares of common stock that will be ultimately issued.
The shares of common stock offered hereby will be sold in “at the market offerings,” and investors who buy common stock at different times will likely pay different prices.
Investors who purchase shares in this offering.


Table of Contents


FORWARD-LOOKING STATEMENTS

        This prospectus, including the documents that we incorporate by reference herein, contains,offering at different times will likely pay different prices, and any applicable prospectus supplement or free writing prospectus including the documents we incorporate by reference thereinso may contain, forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, and amended, or the Exchange Act, including statements regarding our future financial condition, business strategy and plans and objectives of management for future operations. Forward-looking statements include all statements that are not historical facts. In some cases, you can identify forward-looking statements by terminology such as "believe," "will," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "might," "approximately," "expect," "predict," "could," "potentially" or the negative of these terms or other similar expressions. Forward-looking statements appearexperience different outcomes in a number of places throughout this prospectus and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the potential for our programs,their investment results. We will have discretion, subject to market demand, to vary the timing, prices, and numbers of shares sold, and there is no maximum sales price. Pursuant to the parameters set by our board of directors, there will be a minimum sales price for shares of our clinical trials,common stock sold in this offering, which will limit our ability to make sales if the potential for eventual regulatory approval and commercializationpublic trading price of our product candidates andcommon stock drops below that minimum sales price. Such minimum sales price may be below the price paid by investors in this offering. Further, our potential receiptboard of milestone payments and royalties under our collaboration agreement with Janssen, future operating results ordirectors will retain the ability to generateincrease or decrease such minimum sales income or cash flow are forward-looking statements.

        Discussions containing these forward-looking statements may be found, among other places,price in the Sections entitled "Business," "Risk Factors" and "Management's Discussion and Analysisfuture. Investors may experience a decline in the value of Financial Condition and Resultstheir shares as a result of Operations" incorporated by reference from our most recent Annual Report on Form 10-K and in our Quarterly Reports on Form 10-Q, as well as any amendments thereto, filed withshare sales made at prices lower than the SEC. These statements relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that could cause our actual results, levels of activity, performance or achievement to differ materially from those expressed or implied by these forward-looking statements. prices they paid.


S-7


USE OF PROCEEDS
We discuss in greater detail, and incorporate by reference into this prospectus in their entirety, many of these risks and uncertainties underwill retain broad discretion over the heading "Risk Factors" contained in any prospectus supplement or free writing prospectus we may authorize for use in connection with a specific offering, and in our most recent Annual Report on Form 10-K and in our most recent Quarterly Report on Form 10-Q, as well as any amendments thereto reflected in subsequent filings with the SEC. In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the datenet proceeds, if any, from the sale of this prospectus, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.


Table of Contents


USE OF PROCEEDS

the securities offered hereby. We may issue and sell shares of our common stock having aggregate sales proceeds of up to $50 million$100,000,000 from time to time. Because there is no minimum offering amount required as a condition to close this offering, the actual total public offering amount, commissions and proceeds to us, if any, are not determinable at this time.

We currently intend to use the net proceeds from the sale by us of the securities to which this offering primarilyprospectus supplement relates for research, developmentworking capital, capital expenditures and manufacturing of product candidates, and for other general corporate purposes. purposes, which may include, among other things, funding research and development, clinical trials, vendor payables, potential regulatory submissions, hiring additional personnel and capital expenditures.
Pending these uses, we expect to investthe use of the net proceeds, we may invest the proceeds in short-term, interest-bearing, investment-grade securities, certificates of deposit or government securities.


S-8


DILUTIONDILUTION

        Our net tangible book value as of June 30, 2017 was approximately $61.0 million, or $3.61 per share. Net tangible book value per share is determined by dividing our total tangible assets, less total liabilities, by the number of shares of our common stock outstanding as of June 30, 2017.

Dilution with respect to net tangible book value per share represents the difference between the amount per share of common stock paid by purchasers of shares of common stock in this offering and the as-adjusted net tangible book value per share of our common stock immediately after this offering.

The data in this section are derived from our balance sheet as of June 30, 2022. Net tangible book value per share of common stock is equal to our total tangible assets less the amount of our total liabilities, divided by the sum of the number of shares of common stock outstanding as of June 30, 2022, excluding shares of common stock underlying outstanding options. Our net tangible book value as of June 30, 2022 was $268.0 million, or $5.50 per share of common stock.

After giving effect to the assumed sale of 3,061,849 shares of our common stock in this offeringthe aggregate amount of $100,000,000 at an assumed offering price of $16.33$10.63 per share, which was the last reported sale price per share of our common stock on The Nasdaq Global Market on August 2, 2022, and after deducting commissions and estimated offering expenses payable by us, our as-adjusted net tangible book value as of June 30, 2022 would have been $365.4 million, or $6.29 per share of common stock. This would represent an immediate increase in net tangible book value to existing stockholders of $0.79 per share of common stock and immediate dilution in pro forma to purchasers of shares of common stock in this offering of $4.34 per share of common stock. The following table illustrates this dilution per share of common stock:
Assumed public offering price per share of common stock$10.63
Net tangible book value per share of common stock as of June 30, 2022$5.50
Increase in net tangible book value per share of common stock attributable to new investors$0.79
As-adjusted net tangible book value per share of common stock immediately after this
offering
$6.29
Dilution per share of common stock to new investors$4.34
The table above assumes, for illustrative purposes, that an aggregate of 9,407,337 shares of our common stock are sold at a price of $10.63 per share, the last reported sale price of our common stock on the NASDAQNasdaq Global Market on August 31, 2017, and after deducting estimated offering commissions and estimated offering expenses payable by us, our as adjusted net tangible book value as of June 30, 2017 would have been approximately $109.78 million, or $5.50 per share. This represents an immediate increase in net tangible book value of $1.89 per share to existing stockholders and immediate dilution of $10.83 per share to investors purchasing our common stock in this offering at the public offering price. The following table illustrates this dilution on a per share basis:

Assumed public offering price per share

    $16.33 

Net tangible book value per share of as June 30, 2017

 $3.61    

Increase in net tangible book value per share attributable to this offering

 $1.89    

As adjusted net tangible book value per share as of June 30, 2017, after giving effect to this offering

    $5.50 

Dilution per share to new investors purchasing our common stock in this offering

    $10.83 

        The table above assumes for illustrative purposes that an aggregate of 3,061,849 shares of our common stock are sold during the term of the sales agreement with Cantor Fitzgerald at a price of $16.33 per share, the last reported sale price of our common stock on The NASDAQ Global Market on August 31, 2017,2, 2022, for aggregate gross proceeds of $50$100 million. The shares subject to the sales agreement with Cantor Fitzgerald maysold in this offering, if any, will be sold from time to time at various prices. An increase of $0.50$1.00 per share in the price at which the shares are sold from the assumed offering price of $16.83$10.63 per share shown in the table above, assuming all of our common stock in the aggregate amount of $50$100 million during the term of the sales agreement with Cantor FitzgeraldJefferies is sold at that price, would result in an increase our adjusted net tangible book value per share after the offering to $5.52 per share and would increasein the dilution in net tangible book value per share to new investors in this offering to $11.31$4.25 per share, after deducting commissions and estimated aggregate offering expenses payable by us. A decrease of $0.50$1.00 per share in the price at which the shares are sold from the assumed offering price of $15.83$10.63 per share shown in the table above, assuming all of our common stock in the aggregate amount of $50$100 million during the term of the sales agreement with Cantor FitzgeraldJefferies is sold at that price, would result in a decrease our adjusted net tangible book value per share after the offering to $5.47 per share and would decreasein the dilution in net tangible book value per share to new investors in this offering to $10.36$4.44 per share, after deducting commissions and estimated aggregate offering expenses payable by us. This information is supplied for illustrative purposes only and may differ based on the actual offering price and the actual number of shares offered.

The above discussion and table are based on 16,899,26148,683,931 shares of our common stock outstanding as of June 30, 2017,2022 and exclude as of that date:

    exclude:
2,453,259
5,564,352 shares of common stock issuable upon the exercise of outstanding stock options issued and outstanding under the 2016 Plan, as of June 30, 2017,2022, having a weighted average exercise price of $10.80$19.96 per share;

737,340 shares of common stock issuable upon the vesting of outstanding restricted stock units, under the 2016 Plan, as of June 30, 2022;

219,000 shares of common stock issuable upon the vesting of outstanding performance stock units, under the 2016 Plan, as of June 30, 2022;

an aggregate of 622,490817,303 shares of common stock, subject to increase on an annual basis, reserved for future issuance under the 2016 Plan, as of June 30, 2022;

S-9



944,197 shares of common stock issuable upon the exercise of stock options issued and outstanding under the Inducement Plan, as of June 30, 2022, having a weighted average exercise price of $22.38 per share;

28,750 shares of common stock issuable upon the vesting of outstanding restricted stock units under the Inducement Plan, as of June 30, 2022;

an aggregate of 601,042 shares of common stock reserved for future issuance under the Inducement Plan, as of June 30, 2022;

316,572 shares of common stock issuable upon the exercise of stock options issued and outstanding under our 20162007 Equity Incentive Plan, as of June 30, 2017; and2022, having a weighted average exercise price of $3.38 per share;

Table of Contents

    291,540
    1,285,068 shares of our common stock reserved for future issuance under our 2016 Employee Stock Purchase Plan, as of June 30, 2017.

2022;


2,750,000 shares of common stock issuable upon the exercise of warrants outstanding as of June 30, 2022, at a weighted average exercise price of $12.50 per share; and

400,000 shares of common stock issuable upon the exercise of warrants outstanding as of June 30, 2022, at a weighted average exercise price of $0.00001 per share.
To the extent that options or warrants outstanding as of June 30, 20172022 have been or may be exercised, restricted stock units or performance units outstanding as of June 30, 2022 continue to vest, or other shares are issued, investors purchasing our common stock in this offering may experience further dilution. In addition, we may choose to raise additional capital due to market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. To the extent that additional capital is raised through the sale of equity or convertible debt securities, the issuance of these securities could result in further dilution to our stockholders.


S-10

Table of Contents

TABLE OF CONTENTS
DESCRIPTION OF CAPITAL STOCK

        As of the date of this prospectus, our amended and restated certificate of incorporation, or certificate of incorporation, authorizes us to issue up to 90,000,000 shares of common stock, $0.00001 par value per share, and 10,000,000 shares of preferred stock, $0.00001 par value per share. As of July 31, 2017, 16,902,761 shares of common stock were outstanding and no shares of preferred stock were outstanding.

        The following summary describes the material terms of our capital stock. The description of capital stock is qualified by reference to our certificate of incorporation and our amended and restated bylaws, or bylaws.

Common Stock

Voting Rights

        Holders of our common stock are entitled to one vote for each share held on all matters submitted to a vote of stockholders, including the election of directors, and do not have cumulative voting rights. Accordingly, the holders of a majority of the outstanding shares of common stock entitled to vote in any election of directors can elect all of the directors standing for election, if they so choose, other than any directors that holders of any preferred stock we may issue may be entitled to elect.

Dividend Rights

        Subject to preferences that may be applicable to any then outstanding preferred stock, holders of common stock are entitled to receive ratably those dividends, if any, as may be declared by the board of directors out of legally available funds.

Liquidation

        In the event of our liquidation, dissolution or winding up, the holders of common stock will be entitled to share ratably in the assets legally available for distribution to stockholders after the payment of or provision for all of our debts and other liabilities, subject to the prior rights of any preferred stock then outstanding.

Rights and Preferences

        Holders of common stock have no preemptive or conversion rights or other subscription rights and there are no redemption or sinking funds provisions applicable to the common stock. The rights, preferences and privileges of holders of common stock are subject to and may be adversely affected by the rights of the holders of shares of any series of preferred stock that we may designate and issue in the future.

Preferred Stock

        Our board of directors may, without further action by our stockholders, fix the rights, preferences, privileges and restrictions of up to an aggregate of 10,000,000 shares of preferred stock in one or more series and authorize their issuance. These rights, preferences and privileges could include dividend rights, conversion rights, voting rights, terms of redemption, liquidation preferences, sinking fund terms and the number of shares constituting any series or the designation of such series, any or all of which may be greater than the rights of our common stock. The issuance of our preferred stock could adversely affect the voting power of holders of our common stock and the likelihood that such holders will receive dividend payments and payments upon liquidation. In addition, the issuance of preferred stock could have the effect of delaying, deferring or preventing a change of control or other corporate action.


Table of Contents

Options

        As of July 31, 2017, (i) options to purchase an aggregate of 2,509,759 shares of common stock were outstanding and (ii) an additional 562,490 shares were reserved for future issuance under our 2016 Equity Incentive Plan.

Stockholder Registration Rights

Registration Rights

        We are party to an amended and restated investors' rights agreement that provides that holders of our capital stock, including certain holders of 5% of our capital stock and entities affiliated with certain of our directors, have certain registration rights, as set forth below. The registration of shares of our common stock pursuant to the exercise of registration rights described below would enable the holders to sell these shares without restriction under the Securities Act when the applicable registration statement is declared effective. These shares are referred to as registrable securities. We will pay the registration expenses, other than the underwriting discounts and commissions, of the shares registered pursuant to the demand, piggyback and Form S-3 registrations described below.

        Generally, in an underwritten offering, the managing underwriter, if any, has the right, subject to specified conditions, to limit the number of shares such holders may include. The demand, piggyback and Form S-3 registration rights described below will expire upon the earlier of August 10, 2019, or when all investors, considered with their affiliates, can sell all of their shares in a 90-day period under Rule 144.

Demand registration rights

        The holders of certain shares of our registerable securities are entitled to certain demand registration rights. The holders of a majority of these shares may, on not more than two occasions, request that we register all or a portion of their shares, subject to certain specified exceptions.

Piggyback registration rights

        In connection with this offering, the holders of certain shares of our registrable securities, were entitled to, and the necessary percentage of holders waived, their rights to notice of this offering and to include their shares of registrable securities in this offering. In the event that we propose to register any of our securities under the Securities Act in another offering, either for our own account or for the account of other security holders, the holders of these shares will be entitled to certain "piggyback" registration rights allowing them to include their shares in such registration, subject to certain marketing and other limitations. As a result, whenever we propose to file a registration statement under the Securities Act, including a registration statement on Form S-3 as discussed below, other than with respect to a demand registration or a registration statement on Forms S-4 or S-8 or related to stock issued upon conversion of debt securities, the holders of these shares are entitled to notice of the registration and have the right, subject to limitations that the underwriters may impose on the number of shares included in the registration, to include their shares in the registration. However, in no event shall the aggregate value of securities of the selling stockholders included in the offering be reduced below twenty-five percent of the total value of all of securities included in such offering.

Form S-3 registration rights

        The holders of certain shares of our registrable securities are entitled to certain Form S-3 registration rights, provided that we have not already effected two such registrations within the twelve-month period preceding the date of such request. Such holders may make a request that we register their shares on Form S-3 if we are qualified to file a registration statement on Form S-3. Such request


Table of Contents

for registration on Form S-3 must cover securities the aggregate offering price of which, before payment of underwriting discounts and commissions, is at least $2.5 million.

Anti-Takeover Effects of Our Charter Documents and Some Provisions of Delaware Law

        Some provisions of Delaware law, our certificate of incorporation and our bylaws contain provisions that could make the following transactions more difficult: an acquisition of us by means of a tender offer; an acquisition of us by means of a proxy contest or otherwise; or the removal of our incumbent officers and directors. It is possible that these provisions could make it more difficult to accomplish or could deter transactions that stockholders may otherwise consider to be in their best interest or in our best interests, including transactions which provide for payment of a premium over the market price for our shares.

        These provisions, summarized below, are intended to discourage coercive takeover practices and inadequate takeover bids. These provisions are also designed to encourage persons seeking to acquire control of us to first negotiate with our board of directors. We believe that the benefits of the increased protection of our potential ability to negotiate with the proponent of an unfriendly or unsolicited proposal to acquire or restructure us outweigh the disadvantages of discouraging these proposals because negotiation of these proposals could result in an improvement of their terms.

        Undesignated Preferred Stock—The ability to authorize undesignated preferred stock makes it possible for our board of directors to issue preferred stock with voting or other rights or preferences that could impede the success of any attempt to change control of us. These and other provisions may have the effect of deterring hostile takeovers or delaying changes in control or management of our company.

        Stockholder Meetings—Our bylaws provide that a special meeting of stockholders may be called only by our chairman of the board, chief executive officer or president, or by a resolution adopted by a majority of our board of directors.

        Requirements for Advance Notification of Stockholder Nominations and Proposals—Our bylaws establish advance notice procedures with respect to stockholder proposals to be brought before a stockholder meeting and the nomination of candidates for election as directors, other than nominations made by or at the direction of the board of directors or a committee of the board of directors.

        Elimination of Stockholder Action by Written Consent—Our certificate of incorporation and bylaws eliminate the right of stockholders to act by written consent without a meeting.

        Staggered Board—Our board of directors is divided into three classes. The directors in each class will serve for a three-year term, one class being elected each year by our stockholders. This system of electing and removing directors may tend to discourage a third-party from making a tender offer or otherwise attempting to obtain control of us, because it generally makes it more difficult for stockholders to replace a majority of the directors.

        Removal of Directors—Our certificate of incorporation provides that no member of our board of directors may be removed from office by our stockholders except for cause and, in addition to any other vote required by law, upon the approval of not less than two thirds of the total voting power of all of our outstanding voting stock then entitled to vote in the election of directors.

        Stockholders Not Entitled to Cumulative Voting—Our certificate of incorporation does not permit stockholders to cumulate their votes in the election of directors. Accordingly, the holders of a majority of the outstanding shares of our common stock entitled to vote in any election of directors can elect all of the directors standing for election, if they choose, other than any directors that holders of our preferred stock may be entitled to elect.


Table of Contents

        Delaware Anti-Takeover Statute—We are subject to Section 203 of the Delaware General Corporation Law, which prohibits persons deemed to be "interested stockholders" from engaging in a "business combination" with a publicly held Delaware corporation for three years following the date these persons become interested stockholders unless the business combination is, or the transaction in which the person became an interested stockholder was, approved in a prescribed manner or another prescribed exception applies. Generally, an "interested stockholder" is a person who, together with affiliates and associates, owns, or within three years prior to the determination of interested stockholder status did own, 15% or more of a corporation's voting stock. Generally, a "business combination" includes a merger, asset or stock sale, or other transaction resulting in a financial benefit to the interested stockholder. The existence of this provision may have an anti-takeover effect with respect to transactions not approved in advance by the board of directors.

        Choice of Forum—Our certificate of incorporation provides that, unless we consent in writing to the selection of an alternative form, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for: (1) any derivative action or proceeding brought on our behalf; (2) any action asserting a claim of breach of a fiduciary duty or other wrongdoing by any of our directors, officers, employees or agents to us or our stockholders; (3) any action asserting a claim against us arising pursuant to any provision of the General Corporation Law of the State of Delaware or our certificate of incorporation or bylaws; (4) any action to interpret, apply, enforce or determine the validity of our certificate of incorporation or bylaws; or (5) any action asserting a claim governed by the internal affairs doctrine. Our certificate of incorporation also provides that any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock will be deemed to have notice of and to have consented to this choice of forum provision. It is possible that a court of law could rule that the choice of forum provision contained in our certificate of incorporation is inapplicable or unenforceable if it is challenged in a proceeding or otherwise.

        Amendment of Charter Provisions—The amendment of any of the above provisions, except for the provision making it possible for our board of directors to issue preferred stock, would require approval by holders of at least two thirds of the total voting power of all of our outstanding voting stock.

        The provisions of Delaware law, our certificate of incorporation and our bylaws could have the effect of discouraging others from attempting hostile takeovers and, as a consequence, they may also inhibit temporary fluctuations in the market price of our common stock that often result from actual or rumored hostile takeover attempts. These provisions may also have the effect of preventing changes in the composition of our board and management. It is possible that these provisions could make it more difficult to accomplish transactions that stockholders may otherwise deem to be in their best interests.

Transfer Agent and Registrar

        The transfer agent and registrar for our common stock is American Stock Transfer & Trust Company, LLC. The transfer agent's address is 6201 15th Avenue, Brooklyn, New York 11219.

Listing on the NASDAQ Global Market

        Our common stock is listed on the NASDAQ Global Market under the symbol "PTGX."


Table of Contents


PLAN OF DISTRIBUTION

We have entered into a Controlled Equity OfferingSM Sales Agreement, or the Sales Agreement,sales agreement with Cantor Fitzgerald & Co., or Cantor Fitzgerald,Jefferies, under which we may offer and sell up to $100,000,000 of our shares of our common stock having an aggregate gross sales price of up to $50,000,000 from time to time through Cantor FitzgeraldJefferies acting as agent. The Sales Agreement has been filed as an exhibit toof our registration statement on Form S-3shares of whichcommon stock, if any, under this prospectus forms a part.

        Upon delivery of a placement noticesupplement and subject to the terms and conditions of the Sales Agreement, Cantor Fitzgerald may offer and sell shares of our common stockaccompanying prospectus will be made by any method permitted by lawthat is deemed to be an "at“at the market offering"offering” as defined in Rule 415(a)(4) promulgated under the Securities Act. We may instruct Cantor Fitzgerald not

Each time we wish to issue and sell common stock if the sales cannot be effected at or above the price designated by us from time to time. We or Cantor Fitzgerald may suspend the offeringour shares of common stock uponunder the sales agreement, we will notify Jefferies of the number of shares to be issued, the dates on which such sales are anticipated to be made, any limitation on the number of shares to be sold in any one day and any minimum price below which sales may not be made. Once we have so instructed Jefferies, unless Jefferies declines to accept the terms of such notice, Jefferies has agreed to use its commercially reasonable efforts consistent with its normal trading and sales practices to sell such shares up to the amount specified on such terms. The obligations of Jefferies under the sales agreement to sell our shares of common stock are subject to a number of conditions that we must meet.
The settlement of sales of shares between us and Jefferies is generally anticipated to occur on the second trading day following the date on which the sale was made. Sales of our shares of common stock as contemplated in this prospectus supplement will be settled through the facilities of The Depository Trust Company or by such other conditions.

means as we and Jefferies may agree upon. There is no arrangement for funds to be received in an escrow, trust or similar arrangement.

We will pay Cantor Fitzgerald commissions, in cash, for its services in acting as agent inJefferies a commission of up to 3% of the aggregate gross proceeds we receive from each sale of our shares of common stock. Cantor Fitzgerald is entitled to compensation at a commission rate of up to 3.0% of the gross sales price per share sold under the Sales Agreement. Because there is no minimum offering amount required as a condition to close this offering, the actual total public offering amount, commissions and proceeds to us, if any, are not determinable at this time. WeIn addition, we have also agreed to reimburse Cantor FitzgeraldJefferies for certain specified expenses, including the reasonable and documented fees and disbursements of its legal counsel, payable upon execution of the sales agreement, in an amount not to exceed $50,000.$75,000, in addition to certain ongoing disbursements of its legal counsel. We estimate that the total expenses for the offering, under this prospectus, excluding compensation and reimbursementsany commissions or expense reimbursement payable to Cantor FitzgeraldJefferies under the terms of the Sales Agreement,sales agreement, will be approximately $273,000.

        Settlement for sales$300,000. The remaining sale proceeds, after deducting any other transaction fees, will equal our net proceeds from the sale of such shares.

Jefferies will provide written confirmation to us before the open on The Nasdaq Global Market on the day following each day on which our shares of common stock are sold under the sales agreement. Each confirmation will occurinclude the number of shares sold on that day, the third business day following the date on which any sales are made (or the second business day following the date on which anyaggregate gross proceeds of such sales are made, if such sales are made on or after September 5, 2017), or on some other date that is agreed upon by us and Cantor Fitzgerald in connection with a particular transaction, in return for payment of the net proceeds to us. Sales of our common stock as contemplated in this prospectus will be settled through the facilities of The Depository Trust Company or by such other means as we and Cantor Fitzgerald may agree upon. There is no arrangement for funds to be received in an escrow, trust or similar arrangement.

        Cantor Fitzgerald will use its commercially reasonable efforts, consistent with its sales and trading practices, to solicit offers to purchase the shares of common stock under the terms and subject to the conditions set forth in the Sales Agreement.

In connection with the sale of theour shares of common stock on our behalf, Cantor FitzgeraldJefferies will be deemed to be an "underwriter"“underwriter” within the meaning of the Securities Act, and the compensation of Cantor FitzgeraldJefferies will be deemed to be underwriting commissions or discounts. We have agreed to provide indemnification and contribution to Cantor Fitzgeraldindemnify Jefferies against certain civil liabilities, including liabilities under the Securities Act.

We have also agreed to contribute to payments Jefferies may be required to make in respect of such liabilities.

The offering of our shares of our common stock pursuant to the Sales Agreementsales agreement will terminate upon the earlier of (i) the sale of all shares of common stock subject to the sales agreement and (ii) the termination of the Sales Agreementsales agreement as permitted therein. We and Cantor FitzgeraldJefferies may each terminate the Sales Agreementsales agreement at any time upon ten days'trading days’ prior notice.

        Cantor Fitzgerald

This summary of the material provisions of the sales agreement does not purport to be a complete statement of its terms and conditions. The sales agreement has been filed as an exhibit to our Registration Statement on Form S-3 of which this prospectus supplement forms a part.
Jefferies and its affiliates may in the future provide various investment banking, commercial banking, financial advisory and other financial services for us and our affiliates, for which services they may in the future receive customary fees. ToIn the extent required by Regulation M, Cantor Fitzgerald will not engagecourse of its business, Jefferies may actively trade our securities for its own account or for the accounts of customers, and, accordingly, Jefferies may at any time hold long or short positions in any market making activities involving our common stock whilesuch securities.

S-11


A prospectus supplement and the offering is ongoing under this prospectus.

        Thisaccompanying prospectus in electronic format may be made available on a website maintained by Cantor FitzgeraldJefferies, and Cantor FitzgeraldJefferies may distribute thisthe prospectus supplement and the accompanying prospectus electronically.


S-12


LEGAL MATTERS

        Cooley

Gibson, Dunn & Crutcher LLP, has passedSan Francisco, California will pass upon the validity of the shares of common stock offered by this prospectus.hereby. Latham & Watkins LLP is counsel for Cantor FitzgeraldJefferies in connection with this offering.

EXPERTS
Ernst & Young LLP, independent registered public accounting firm, has audited our consolidated financial statements as of December 31, 2021 and 2020 and for each of the years then ended, included in our Annual Report on Form 10-K for the year ended December 31, 2021
, and the effectiveness of our internal control over financial reporting as of December 31, 2021, as set forth in their reports, which are incorporated by reference in this prospectus and elsewhere in the registration statement. Our financial statements are incorporated by reference in reliance on Ernst & Young LLP’s report, given on their authority as experts in accounting and auditing.
EXPERTS

The financial statements for the year ended December 31, 2019 incorporated in this prospectus supplement by reference to the Annual Report on Form 10-K for the year ended December 31, 20162021 have been so incorporated in reliance on the report of PricewaterhouseCoopers LLP, an independent registered public accounting firm, given on the authority of said firm as experts in auditing and accounting.


S-13


WHERE YOU CAN FIND MORE INFORMATION

        This prospectus is part of

We file annual, quarterly and special reports, proxy statements and other information with the SEC, and we have filed with the SEC a registration statement we filedon Form S-3 under the Securities Act of 1933, as amended (the “Securities Act”) with respect to the SEC.securities offered by this prospectus. This prospectus, which forms part of the registration statement, does not contain all of the information set forthincluded in the registration statement, including its exhibits and the exhibits to the registration statement.schedules. For further information with respect toabout us and the securities we are offering underdescribed in this prospectus, weyou should refer you to the registration statement, and theits exhibits and schedules and our reports, proxies, information statements and other information filed aswith the SEC.
Our filings are available to the public on the Internet, through a database maintained by the SEC at
http://www.sec.gov. We also maintain a website at www.protagonist-inc.com. We have included our website address for the information of prospective investors and do not intend it to be an active link to our website. Information contained on our website does not constitute a part of this prospectus (or any document incorporated by reference herein).

S-14


INCORPORATION OF CERTAIN INFORMATION BY REFERENCE
The SEC allows us to incorporate by reference the information and reports we file with it, which means that we can disclose important information to you by referring you to these documents. The information incorporated by reference is an important part of this prospectus, and information that we file after the date hereof with the SEC will automatically update and supersede the information already incorporated by reference. We are incorporating by reference the documents listed below:


our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2022, filed with the SEC on May 5, 2022, and June 30, 2022, filed with the SEC on August 4, 2022;

our Current Reports on Form 8-K filed with the SEC on February 22, 2022, March 23, 2022, March 31, 2022 and June 2, 2022; and

the description of our common stock set forth in our registration statement on Form 8-A, filed with the SEC on August 9, 2016, including any amendments thereto or reports filed for the purposes of updating this description, including Exhibit 4.7 to our Annual Report on Form 10-K for the fiscal year ended December 31, 2021, filed with the SEC on February 28, 2022.
All documents we file with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act shall be deemed incorporated by reference in this prospectus and to be a part of this prospectus from the date of filing of those documents, with the exception of any portion of any report or document that is not deemed “filed” under such provisions on or after the date of this prospectus, until the earlier of the date on which: (1) all of the securities registered hereunder have been sold; or (2) the registration statement. Neitherstatement of which this prospectus is a part has been withdrawn.
Under no circumstances will any information filed under Items 2.02 or 7.01 of Current Report on Form 8-K be deemed incorporated herein by reference unless such Form 8-K expressly provides to the contrary.
Upon written or oral request, we nor any agent, underwriterwill provide without charge to each person to whom a copy of the prospectus is delivered a copy of the documents incorporated by reference herein (other than exhibits to such documents unless such exhibits are specifically incorporated by reference herein). You may request a copy of these filings, at no cost, by writing, calling or dealer hasemailing us at the contact information set forth below. We have authorized any personno one to provide you with different information. We are not making an offer of these securitiesany information that differs from that contained in this prospectus. Accordingly, we take no responsibility for any state where the offer is not permitted.other information that others may give you. You should not assume that the information in this prospectus is accurate as of any date other than the date onof the front pagecover of this prospectus, regardless of the time of delivery of this prospectus or any sale of the securities offered by this prospectus.

        We file annual, quarterly and current reports, proxy statements and other information with the SEC. You may read and copy any document we file with the SEC at the SEC's public reference room at 100 F Street, N.E., Washington, D.C., 20549. Please call the SEC at 1.800.SEC.0330 for further information on the operation of the public reference room. Our SEC filings are also available to the public at the SEC's website at http://www.sec.gov.


INCORPORATION OF CERTAIN INFORMATION BY REFERENCE

        The SEC allows us to "incorporate by reference" the information we file with it, which means that we can disclose important information to you by referring you to those documents instead of having to repeat the information in this prospectus. The information incorporated by reference is considered to be part of this prospectus, and later information that we file with the SEC will automatically update and supersede this information. We incorporate by reference the documents listed below and any future filings (including those made after the date of the initial filing of the registration statement of which this prospectus is a part and prior to the effectiveness of such registration statement) we will make with the SEC under Sections 13(a), 13(c), 14, or 15(d) of the Exchange Act until the termination of the offering of the shares covered by this prospectus (other than information furnished under Item 2.02 or Item 7.01 of Form 8-K):

    our annual report on Form 10-K for the year ended December 31, 2016, filed with the SEC on March 7, 2017, including the information specifically incorporated by reference therein from our definitive proxy statement on Schedule 14A, filed on April 24, 2017;

    our Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, filed with the SEC on May 10, 2017;

    our Quarterly Report on Form 10-Q for the quarter ended June 30, 2017, filed with the SEC on August 8, 2017;

    our current reports on Form 8-K, filed with the SEC on February 9, 2017, May 23, 2017, May 25, 2017, May 30, 2017 and June 8, 2017;

Table of Contents

    our current report on Form 8-K/A, filed with the SEC on July 31, 2017; and

    the description of our common stock set forth in our registration statement on Form 8-A, filed with the SEC on August 9, 2016, including any amendments thereto or reports filed for the purposes of updating this description.

        You can request a copy of these filings, at no cost, by writing or telephoning us at the following address or telephone number:

Protagonist Therapeutics, Inc.
7707 Gateway Boulevard, Suite 140
Newark, California 94560CA 94560-1160
(510) 474-0170
Attn: Chief Financial Officer

        This prospectus is part of a registration statement we filed with the SEC. That registration statement and the exhibits filed along with the registration statement contain more information about us and the shares in this offering. Because information about documents referred to in this prospectus is not always complete, you should read the full documents which are filed as exhibits to the registration statement. You may read and copy the full registration statement and its exhibits at the SEC's public reference rooms or its website.


Table of Contents



LOGOS-15



UP TO $100,000,000
[MISSING IMAGE: lg_protagonist-pn.jpg]
Up to $50,000,000$100,000,000 of Shares

Common Stock



PROSPECTUS SUPPLEMENT

ProspectusJefferies



LOGO

      , 2017

2022



INFORMATION NOT REQUIRED IN THE PROSPECTUS

Item 14.   Other Expenses of Issuance and Distribution.
Distribution

The following sets forth the estimated costs and expenses all of which shall be bornepayable by the Registrant,us in connection with the offeringissuance and distribution of the securities pursuant to this Registration Statement:

being registered hereunder on Form S-3 (other than underwriting discounts and commissions, if any) are set forth below. Each item listed is estimated, except for the SEC registration fee.
Amount
To Be Paid
Securities and Exchange Commission registration fee$27,810
Printing fees and expenses*
Legal fees and expenses*
Accounting fees and expenses*
Transfer agent and registrar fees*
Miscellaneous fees and expenses*
Total$*

SEC Registration Fee

 $23,180 

Legal Fees and Expenses

 $100,000*

Listing Fees

 $35,000*

Accounting Fees

 $150,000*

Printing and Miscellaneous Fees

 $14,820*

Total

 $323,000*

*
*
Estimated.
Estimated expenses not presently known. Each prospectus supplement will reflect estimated expenses based on the amount of the related offering.

Item 15.   Indemnification of Directors and Officers.
Officers

Section 145 of the Delaware General Corporation Law authorizes a court to award, or a corporation'scorporation’s board of directors to grant, indemnity to directors and officers in terms sufficiently broad to permit such indemnification under certain circumstances for liabilities, including reimbursement for expenses incurred, arising under the Securities Act.

Act of 1933, as amended. Our amended and restated certificate of incorporation provides for indemnification of our directors, officers, employees and other agents to the maximum extent permitted by the Delaware General Corporation Law, and our amended and restated bylaws provide for indemnification of our directors, officers, employees and other agents to the maximum extent permitted by the Delaware General Corporation Law.

We have entered into indemnification agreements with our directors and officers whereby we have agreed to indemnify our directors and officers to the fullest extent permitted by law, including indemnification against expenses and liabilities incurred in legal proceedings to which the director or officer was, or is threatened to be made, a party by reason of the fact that such director or officer is or was a director, officer, employee or agent of Protagonist, provided that such director or officer acted in good faith and in a manner that the director or officer reasonably believed to be in, or not opposed to, the best interest of Protagonist. At present, there is no pending litigation or proceeding involving a director or officer of Protagonist regarding which indemnification is sought, nor is the registrant aware of any threatened litigation that may result in claims for indemnification.

We maintain insurance policies that indemnify our directors and officers against various liabilities arising under the Securities Act of 1933, as amended, and the Securities Exchange Act of 1934, as amended, that might be incurred by any director or officer in his capacity as such.

The underwriting agreement(s) that the Registrant may enter into may provide for indemnification by any underwriters of the Registrant, its directors, its officers who sign the registration statement and the Registrant'sRegistrant’s controlling persons for some liabilities, including liabilities arising under the Securities Act.

II-1


Table




Item 16.   Exhibits
A list of exhibits filed with this registration statement on Form S-3 is set forth on the Exhibit Index and Financial Statement Schedules

is incorporated herein by reference.
Exhibit
Number
Description of Exhibit
1.1*Form of Underwriting Agreement.
1.2***Open Market Sale AgreementSM, dated August 5, 2022, by and between Protagonist Therapeutics, Inc. and Jefferies LLC.
3.1Amended and Restated Certificate of Incorporation of the Registrant (incorporated by reference from Exhibit 3.1 to the Registrant’s Current Report on Form 8-K filed on August 16, 2016 (Commission File No. 001-37852)).
3.2Bylaws of the Registrant (incorporated by reference from Exhibit 3.2 to the Registrant’s Registration Statement on Form S-1, as amended, filed on August 1, 2016 (Commission File No. 333-212476)).
4.1Specimen stock certificate evidencing the shares of common stock (incorporated by reference from Exhibit 4.1 to the Registrant’s Registration Statement on Form S-1, as amended, filed on August 1, 2016 (Commission File No. 333-212476)).
4.2***
4.3***
4.4*Form of Warrant Agreement and Warrant Certificate.
4.5*Form of Unit Agreement and Unit Certificate.
5.1***
5.2***
23.1***
23.2***
23.3***
24.1***
25.1**Form T-1 Statement of Eligibility of Trustee for Senior Indenture under the Trust Indenture Act of 1939.
 25.2**Form T-1 Statement of Eligibility of Trustee for Subordinated Indenture under the Trust Indenture Act of 1939.
107***
Exhibit
Number
 Description
 1.1*Form of Underwriting Agreement.
     
 1.2 Sales Agreement, dated September 1, 2017, by and between Protagonist Therapeutics, Inc. and Cantor Fitzgerald & Co.
     
 3.1(1)Amended and Restated Certificate of Incorporation of the Registrant, as amended.
     
 3.2(2)Amended and Restated Bylaws of the Registrant.
     
 4.1 Reference is made to Exhibits 3.1 and 3.2.
     
 4.2(2)Specimen Common Stock Certificate.
     
 4.3(2)Third Amended and Restated Investor Rights Agreement, by and among Protagonist Therapeutics, Inc. and the stockholders named therein, dated July 31, 2016.
     
 4.4*Specimen Preferred Stock Certificate and Form of Certificate of Designation of Preferred Stock.
     
 4.5 Form of Indenture.
     
 4.6*Form of Debt Securities.
     
 5.1 Opinion of Cooley LLP.
     
 12.1 Statement Regarding Computation of Ratio of Earnings to Fixed Charges.
     
 23.1 Consent of PricewaterhouseCoopers LLP, Independent Registered Public Accounting Firm.
     
 23.2 Consent of Cooley LLP is contained in Exhibit 5.1 to this Registration Statement.
     
 24.1 Power of Attorney is contained on the signature pages.
     
 25.1**Statement of Eligibility of Trustee under the Indenture.

*
*
To be filed, if necessary, by amendment or as an exhibit to a document to be incorporated or deemed to be incorporated by reference in this registration statement, including a Current Report on Form 8-K and incorporated herein by reference, if applicable.

8-K.
**

To be filed separately under electronic form type 305B2, if applicable.

(1)
Previously filed as an exhibit to the Registrant's Current Report on Form 8-K (File No. 001-37852) filedin accordance with the Securities and Exchange Commission on August 16, 2016 and incorporated herein by reference.

requirements of Section 305(b)(2)
Previously filed as an exhibit to of the Registrant's Registration Statement on Form S-1,Trust Indenture Act of 1939, as amended, (File No. 333-212476), filed withand the Securities and Exchange Commission on August 1, 2016 and incorporated herein by reference.
applicable rules thereunder.

***
Filed herewith.

II-2




Table of Contents

Item 17.   Undertakings

The undersigned registrantsregistrant hereby undertakes:

(a)(1)   To file, during any period in which offers or sales are being made, a post-effective amendment to this registration statement:

(i)   toTo include any prospectus required by Section 10(a)(3) of the Securities Act of 1933;

1933, as amended (“Securities Act”);

(ii)   toTo reflect in the prospectus any facts or events arising after the effective date of the registration statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the registration statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the Securities and Exchange Commission pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than 20%a 20 percent change in the maximum aggregate offering price set forth in the "Calculation“Calculation of Registration Fee"Fee” table in the effective registration statement; and

(iii)   toTo include any material information with respect to the plan of distribution not previously disclosed in the registration statement or any material change to such information in the registration statement;

provided, however,, that the undertakings set forth in paragraphs (a)(1)(i), (a)(1)(ii) and (a)(1)(iii) of this section do not apply if the registration statement is on Form S-3, Form SF-3 or Form F-3 and the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Securities and Exchange Commission by the registrant pursuant to Section 13 or Section 15(d) of the Securities Exchange Act of 1934, as amended (“Exchange Act”), that are incorporated by reference in the registration statement, or is contained in a form of prospectus filed pursuant to Rule 424(b) that is part of the registration statement.

        (b)statement;

(2)   That, for the purpose of determining any liability under the Securities Act, of 1933, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

        (c)thereof;

(3)   To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.

        (d)offering;

(4)   That, for the purpose of determining liability under the Securities Act of 1933 to any purchaser:

(i)   Each prospectus filed by the registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of the date the filed prospectus was deemed part of and included in the registration statement; and

(ii)   Each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5), or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule 415(a)(1)(i), (vii), or (x) for the purpose of providing the information required by Section 10(a) of the Securities Act of 1933 shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the offering described in the prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration

II-3


Table of Contents

      statement to which that prospectus relates, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.Provided,thereof; provided, however, that no statement made in a registration statement or prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was part of the registration statement or made in any such document immediately prior to such effective date.date;


II-3

        (e)



(5)   That, for the purpose of determining liability of the registrant under the Securities Act of 1933 to any purchaser in the initial distribution of the securities, the undersigned registrant undertakes that in a primary offering of securities of the undersigned registrant pursuant to this registration statement, regardless of the underwriting method used to sell the securities to the purchaser, if the securities are offered or sold to such purchaser by means of any of the following communications, the undersigned registrant will be a seller to the purchaser and will be considered to offer or sell such securities to such purchaser:

(i)   Any preliminary prospectus or prospectus of the undersigned registrant relating to the offering required to be filed pursuant to Rule 424;

(ii)   Any free writing prospectus relating to the offering prepared by or on behalf of the undersigned registrant or used or referred to by the undersigned registrant;

(iii)   The portion of any other free writing prospectus relating to the offering containing material information about the undersigned registrant or its securities provided by or on behalf of the undersigned registrant; and

(iv)   Any other communication that is an offer in the offering made by the undersigned registrant to the purchaser.

        (f)purchaser;

(6)   That, for purposes of determining any liability under the Securities Act, of 1933, each filing of the registrant'sregistrant’s annual report pursuant to Section 13(a) or Section 15(d) of the Securities Exchange Act of 1934 (and, where applicable, each filing of an employee benefit plan'splan’s annual report pursuant to Section 15(d) of the Securities Exchange Act of 1934)Act) that is incorporated by reference in the registration statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

        (g)   That, for purposes of determining any liability under the Securities Act, (i) the information omitted from the form of prospectus filed as part of the registration statement in reliance upon Rule 430A and contained in the form of prospectus filed by the registrant pursuant to Rule 424(b)(l) or (4) or 497(h) under the Securities Act shall be deemed to be a part of the registration statement as of the time it was declared effective; and (ii) each post-effective amendment that contains a form of prospectus shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

        (h)   To file an application for the purpose of determining the eligibility of the trustee to act under subsection (a) of Section 310 of the Trust Indenture Act in accordance with the rules and regulations prescribed by the Commission under Section 305(b)(2) of the Trust Indenture Act.

        (i)thereof;

(7)   Insofar as indemnification for liabilities arising under the Securities Act of 1933 may be permitted to directors, officers and controlling persons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant has been advised that in the opinion of the Securities and Exchange Commission such indemnification is against public policy as expressed in the Securities Act and is,

II-4


Table of Contents

    therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrant of expenses incurred or paid by a director, officer or controlling person of the registrant in the successful defense of any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

II-5


Tableissue;

(8)   That, for purposes of Contents


EXHIBIT INDEX

Exhibit
Number
 Description
 1.1*Form of Underwriting Agreement.
     
 1.2 Sales Agreement, dated September 1, 2017, by and between Protagonist Therapeutics, Inc. and Cantor Fitzgerald & Co.
     
 3.1(1)Amended and Restated Certificate of Incorporation of the Registrant, as amended.
     
 3.2(2)Amended and Restated Bylaws of the Registrant.
     
 4.1 Reference is made to Exhibits 3.1 and 3.2.
     
 4.2(2)Specimen Common Stock Certificate.
     
 4.3(2)Third Amended and Restated Investor Rights Agreement, by and among Protagonist Therapeutics, Inc. and the stockholders named therein, dated July 31, 2016.
     
 4.4*Specimen Preferred Stock Certificate and Form of Certificate of Designation of Preferred Stock.
     
 4.5 Form of Indenture.
     
 4.6*Form of Debt Securities.
     
 5.1 Opinion of Cooley LLP.
     
 12.1 Statement Regarding Computation of Ratio of Earnings to Fixed Charges.
     
 23.1 Consent of PricewaterhouseCoopers LLP, Independent Registered Public Accounting Firm.
     
 23.2 Consent of Cooley LLP is contained in Exhibit 5.1 to this Registration Statement.
     
 24.1 Power of Attorney is contained on the signature pages.
     
 25.1**Statement of Eligibility of Trustee under the Indenture.

*
To bedetermining any liability under the Securities Act of 1933, the information omitted from the form of prospectus filed as part of this registration statement in reliance upon Rule 430A and contained in a form of prospectus filed by the registrant pursuant to Rule 424(b)(1) or (4) or 497(h) under the Securities Act of 1933 shall be deemed to be part of this registration statement as of the time it was declared effective;
(9)   That, for the purpose of determining any liability under the Securities Act of 1933, each post-effective amendment or as an exhibitthat contains a form of prospectus shall be deemed to be a Current Report on Form 8-K and incorporated herein by reference, if applicable.

**
To be filed separately under electronic form type 305B2, if applicable.

(1)
Previously filed as an exhibitnew registration statement relating to the Registrant's Current Report on Form 8-K (File No. 001-37852) filedsecurities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof; and
(10)   To file an application for the purpose of determining the eligibility of the trustee to act under subsection (a) of Section 310 of the Trust Indenture Act of 1939 in accordance with the rules and regulations prescribed by the Securities and Exchange Commission on August 16, 2016 and incorporated herein by reference.

under Section 305(b)(2)
Previously filed as an exhibit to of the Registrant's Registration Statement on Form S-1, as amended (File No. 333-212476), filed with the Securities and Exchange Commission on August 1, 2016 and incorporated herein by reference.

II-6


TableTrust Indenture Act of Contents1939.


II-4




SIGNATURESSIGNATURES

Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Newark, State of California, on September 1, 2017.

August 5, 2022.
PROTAGONIST THERAPEUTICS, INC.
By:
/s/ Dinesh V. Patel, Ph.D.
PROTAGONIST THERAPEUTICS, INC.



By:


/s/ DINESH V. PATEL, PH.D.

Dinesh V. Patel, Ph.D.
President, Chief Executive Officer and Director

President, Chief Executive Officer and Director (Principal Executive Officer)
POWER OF ATTORNEY

        KNOW ALL PERSONS BY THESE PRESENTS, that each

Each person whose individual signature appears below constituteshereby authorizes and appoints Dinesh V. Patel and Thomas P. O'Neil, his or her trueAsif Ali and lawful agent, proxy and attorney-in-fact, each acting alone,of them, with full power of substitution and resubstitution for himand full power to act without the other, as his or her true and lawful attorney in fact and agent to act in his or her name, place and stead and to execute in anythe name and all capacities,on behalf of each person, individually and in each capacity stated below, and to (i) act on, sign, and file with the SEC any and all amendments (including post-effective amendments) to this Registration Statement, including any and all post effective amendments and amendments thereto, and any registration statement together with all schedules and exhibits thereto, (ii) act on, sign and file such certificates, instruments, agreements and other documentsrelating to the same offering as maythis Registration Statement that is to be necessary or appropriate in connection therewith, (iii) act on and file any supplement to any prospectus included in this registration statement or any such amendment or any subsequent registration statement filedeffective upon filing pursuant to Rule 462(b) under the Securities Act of 1933, as amended, and (iv) take anyto file the same, with all exhibits thereto, and all actions which may be necessary or appropriateother documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys in fact and agents, and each of them, full power and authority to be done, as fully for all intentsdo and purposes as he or she might or could do in person, hereby approving,perform each and every act and thing, ratifying and confirming all that such agent, proxysaid attorneys in fact and attorney-in-factagents or any of them or their or his substitute or substitutes may lawfully do or cause to be done by virtue thereof.

Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration Statement and Power of Attorney has been signed by the following personsperson in the capacities and on the dates indicated:

date indicated.
Signature
Signatures
Title
Date




Date

/s/ DINESH V. PATEL, PH.D.

Dinesh V. Patel, Ph.D.
Dinesh V. Patel, Ph.D.
President, Chief Executive Officer and Director (Principal(Principal Executive Officer)Officer)September 1, 2017August 5, 2022

/s/ THOMAS P. O'NEIL

Thomas P. O'NeilAsif Ali
Asif Ali


Chief Financial Officer (Principal(Principal Financial andAnd Accounting Officer)Officer)

September 1, 2017
August 5, 2022

/s/ HAROLD E. SELICK, PH.D.

Harold E. Selick, Ph.D.
Harold E. Selick, Ph.D.


Director

Chairman of the Board of Directors

September 1, 2017
August 5, 2022

/s/ CHAITAN KHOSLA, PH.D.

Chaitan Khosla,Bryan Giraudo
Bryan Giraudo
DirectorAugust 5, 2022
/s/ Sarah Noonberg, M.D., Ph.D.
Sarah Noonberg, M.D., Ph.D.


Director

Director

September 1, 2017
August 5, 2022
/s/ Sarah O’Dowd
Sarah O’Dowd
DirectorAugust 5, 2022

II-7


Table of Contents


II-5


SignatureTitleDate
/s/ JULIE PAPANEK GRANT

Julie Papanek GrantWilliam D. Waddill
William D. Waddill
DirectorSeptember 1, 2017August 5, 2022

/s/ ARMEN SHANAFELT, PH.D.

Armen Shanafelt, Ph.D.


Director


September 1, 2017

/s/ WILLIAM D. WADDILL

William D. Waddill


Director


September 1, 2017

/s/  LEWIS T. "RUSTY" WILLIAMS, M.D., PH.D.

Lewis T. "Rusty" Williams, M.D., Ph.D.
Lewis T. Williams, M.D., Ph.D.


Director

Director

September 1, 2017
August 5, 2022

II-8


II-6