1 COMPANY OVERVIEW Dinesh V. Patel, PhD | President & CEO January 2022 Forward-looking Statements This presentation and the accompanying oral presentation contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, product candidates, capit ...

8 Protagonist 1 COMPANY OVERVIEW December 2021 Dinesh V. Patel, PhD President & CEO Forward-looking Statements This presentation and the accompanying oral presentation contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, product cand ...

PART I FINANCIAL INFORMATION [Item 1. Condensed Consolidated Financial Statements (unaudited)](index=3&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(unaudited)) The unaudited statements present the company's financial position, results of operations, and cash flows for the periods ended September 30, 2021 [Condensed Consolidated Balance Sheets](index=3&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets grew to $373.2 million, driven by financing activities, while stockholders' equity increased to $329.7 million Condensed Consolidated Balance Sheets (in thousands) | | September 30, 2021 | December 31, 2020 | | :--- | :--- | :--- | | **Total current assets** | $327,687 | $315,606 | | **Total assets** | **$373,175** | **$324,468** | | **Total current liabilities** | $39,156 | $40,241 | | **Total liabilities** | **$43,515** | **$44,862** | | **Total stockholders' equity** | **$329,660** | **$279,606** | | **Total liabilities and stockholders' equity** | **$373,175** | **$324,468** | [Condensed Consolidated Statements of Operations](index=4&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) The company reported a net loss of $88.6 million for the nine months ended September 30, 2021, widened by increased R&D expenses Condensed Consolidated Statements of Operations (in thousands, except per share data) | | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | | :--- | :--- | :--- | | License and collaboration revenue | $18,740 | $22,978 | | Research and development | $87,633 | $55,020 | | General and administrative | $19,936 | $13,644 | | **Loss from operations** | **$(88,829)** | **$(45,686)** | | **Net loss** | **$(88,644)** | **$(47,264)** | | **Net loss per share, basic and diluted** | **$(1.94)** | **$(1.45)** | [Condensed Consolidated Statements of Cash Flows](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operations was $80.9 million, while financing activities provided $127.8 million, primarily from a stock offering Net Cash Flow Summary (in thousands) | Cash Flow Activity | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | | :--- | :--- | :--- | | Net cash used in operating activities | $(80,926) | $(53,617) | | Net cash used in investing activities | $(43,727) | $(16,563) | | Net cash provided by financing activities | $127,750 | $120,645 | | **Net increase in cash, cash equivalents and restricted cash** | **$2,949** | **$50,619** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) The notes detail significant accounting policies, the Janssen collaboration amendment, an arbitration resolution, and capital raised from stock offerings - The company is a biopharmaceutical firm with **$352.5 million in cash, cash equivalents, and marketable securities**, and an accumulated deficit of **$372.5 million**[21](index=21&type=chunk)[22](index=22&type=chunk) - In July 2021, the company entered into a Restated Agreement with Janssen, modifying development milestones and expense obligations, which resulted in a cumulative catch-up adjustment that **increased revenue by $8.0 million** in Q3 2021[59](index=59&type=chunk)[74](index=74&type=chunk) - An arbitration with Zealand Pharma was resolved in August 2021, requiring payments that were recorded as **$4.0 million in R&D expense** for the three and nine months ended September 30, 2021[96](index=96&type=chunk)[114](index=114&type=chunk) - In June 2021, the company completed an underwritten public offering, raising **net proceeds of $123.8 million**[121](index=121&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=49&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses increased R&D expenses, strong liquidity, and the recent clinical hold and subsequent removal for its rusfertide studies [Overview](index=50&type=section&id=Overview) The company focuses on peptide-based drugs, with its lead asset rusfertide facing a temporary clinical hold that has since been lifted - The FDA placed a clinical hold on rusfertide studies on September 16, 2021, following findings in a mouse carcinogenicity study, but **the hold was lifted on October 8, 2021**[149](index=149&type=chunk)[151](index=151&type=chunk) - A **global Phase 3 clinical trial** of rusfertide in polycythemia vera (PV) is expected to begin in the first quarter of 2022[152](index=152&type=chunk) - In the Janssen collaboration, development of the first-generation IL-23R antagonist PTG-200 was stopped in favor of advancing **second-generation candidates PN-235 and PN-232**[156](index=156&type=chunk) - The company became eligible for a **$7.5 million milestone payment** from Janssen in October 2021 for the completion of data collection for PN-235 Phase 1 activities[158](index=158&type=chunk) [Results of Operations](index=63&type=section&id=Results%20of%20Operations) For the first nine months of 2021, revenue decreased 18% while R&D expenses rose 59%, widening the net loss to $88.6 million Comparison of Three Months Ended September 30, 2021 and 2020 (in thousands) | | 2021 | 2020 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | License and collaboration revenue | $10,286 | $13,114 | $(2,828) | (22)% | | Research and development | $36,956 | $15,995 | $20,961 | 131% | | General and administrative | $7,256 | $4,891 | $2,365 | 48% | | **Net loss** | **$(33,804)** | **$(7,763)** | **$(26,041)** | **335%** | Comparison of Nine Months Ended September 30, 2021 and 2020 (in thousands) | | 2021 | 2020 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | License and collaboration revenue | $18,740 | $22,978 | $(4,238) | (18)% | | Research and development | $87,633 | $55,020 | $32,613 | 59% | | General and administrative | $19,936 | $13,644 | $6,292 | 46% | | **Net loss** | **$(88,644)** | **$(47,264)** | **$(41,380)** | **88%** | [Liquidity and Capital Resources](index=71&type=section&id=Liquidity%20and%20Capital%20Resources) The company holds $352.5 million in cash and marketable securities, which is deemed sufficient to fund operations for at least 12 months - The company had **$352.5 million in cash, cash equivalents, and marketable securities** as of September 30, 2021[223](index=223&type=chunk) - In June 2021, the company raised **$123.8 million in net proceeds** from an underwritten public offering of common stock[219](index=219&type=chunk) - Management believes existing capital is **sufficient to meet operating requirements for at least the next 12 months**[223](index=223&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=79&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risks include interest rate sensitivity on its investments and foreign currency exposure from Australian operations - The company's primary market risks are interest rate sensitivity on its **$352.5 million of cash, cash equivalents, and marketable securities**, and foreign exchange risk from its Australian operations[242](index=242&type=chunk)[243](index=243&type=chunk) - A 10% change in foreign exchange rates for its Australian operations **would not have a material effect** on results[244](index=244&type=chunk) [Item 4. Controls and Procedures](index=79&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of September 30, 2021, with no material changes in internal control - The CEO and CFO concluded that the company's disclosure controls and procedures were **effective at a reasonable assurance level** as of the end of the period[246](index=246&type=chunk) - **No changes in internal control over financial reporting** occurred during the quarter that materially affected, or are reasonably likely to materially affect, internal controls[247](index=247&type=chunk) PART II OTHER INFORMATION [Item 1. Legal Proceedings](index=81&type=section&id=Item%201.%20Legal%20Proceedings) The company is not party to any material legal proceedings, having resolved its arbitration with Zealand Pharma in Q3 2021 - The company reports **no material legal proceedings** but notes the resolution of an arbitration with Zealand Pharma during Q3 2021[249](index=249&type=chunk) [Item 1A. Risk Factors](index=81&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks related to clinical development, financial dependency, third-party collaborations, and regulatory challenges [Risks Related to Clinical Development](index=87&type=section&id=Risks%20Related%20to%20Clinical%20Development) The company's success depends on its clinical-stage candidates, which face uncertain development processes and regulatory risks like clinical holds - The company is **heavily dependent on the success of its clinical product candidates**, which face uncertain outcomes in a lengthy and expensive development process[272](index=272&type=chunk)[274](index=274&type=chunk) - The FDA placed a **full clinical hold on rusfertide studies** on September 16, 2021, due to non-clinical findings, which was lifted on October 8, 2021, underscoring the risk of trial delays[278](index=278&type=chunk)[286](index=286&type=chunk) [Risks Related to Financial Position and Capital Requirements](index=93&type=section&id=Risks%20Related%20to%20Financial%20Position%20and%20Capital%20Requirements) The company has a history of significant losses and will require substantial additional funding for future operations and development - The company has incurred significant losses since inception, with an **accumulated deficit of $372.5 million** as of September 30, 2021, and anticipates continued losses[288](index=288&type=chunk) - **Substantial additional funding will be required** to complete clinical development and commercialize product candidates, which may cause dilution to existing stockholders[291](index=291&type=chunk)[293](index=293&type=chunk) [Risks Related to Our Reliance on Third Parties](index=95&type=section&id=Risks%20Related%20to%20Our%20Reliance%20on%20Third%20Parties) The business model relies heavily on third parties, including collaborators like Janssen and various contract research and manufacturing organizations - The company relies on Janssen to continue development under their collaboration agreement, which **Janssen can terminate for convenience**[294](index=294&type=chunk) - The company **depends on third-party CROs** to conduct clinical trials and on contract manufacturers for drug supply, exposing it to risks of performance failure[298](index=298&type=chunk)[300](index=300&type=chunk) [Other Items (Items 2, 3, 4, 5, 6)](index=132&type=section&id=Other%20Items%20(Items%202,%203,%204,%205,%206)) The company reports no unregistered sales of equity securities, defaults, or other material information for the period under these items - The company reported **no unregistered sales of equity securities**, use of proceeds, or repurchases of equity securities for the period[398](index=398&type=chunk)[399](index=399&type=chunk) - There were **no defaults upon senior securities**, and no mine safety disclosures were applicable[400](index=400&type=chunk)[401](index=401&type=chunk)

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File No. 001-37852 PROTAGONIST THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Indicate by check mark whether th ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File No. 001-37852 PROTAGONIST THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of ...

8 Protagonist 1 PN-943 PTG-200 PN-235 PN-232 rusfertide (PTG-300) PTG-100 March 2021 COMPANY OVERVIEW Dinesh V. Patel, PhD President & CEO Forward-looking Statements This presentation and the accompanying oral presentation contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations ...

Protagonist Therapeutics, Inc. (NASDAQ:PTGX) Q4 2020 Earnings Conference Call March 10, 2021 4:30 PM ET Company Participants Dinesh Patel - President and Chief Executive Officer Don Kalkofen - Chief Financial Officer Samuel Saks - Chief Medical Officer David Liu - Chief Scientific Officer Suneel Gupta - Chief Development Officer Conference Call Participants Chris Howerton - Jefferies Anupam Rama - JPMorgan Douglas Tsao - H.C. Wainwright Operator Good afternoon and welcome to Protagonist Therapeutics Fourth ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2020 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File No. 001-37852 PROTAGONIST THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware 98-0505495 (State or other j ...

Table of Contents Commission File No. 001-37852 PROTAGONIST THERAPEUTICS, INC. UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2020 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to (Exact name of registrant as specified in its charter) (State or other jurisdiction ...

Financial Performance - The net loss for the three and six months ended June 30, 2020, was $19.4 million and $39.5 million, respectively, compared to $29.2 million and $43.3 million for the same periods in 2019[137][138]. - The net loss for the six months ended June 30, 2020, was $39.5 million, a decrease of $3.8 million, or 9%, from a net loss of $43.3 million in 2019[186]. - Net loss decreased by $9.8 million, or 33%, from $29.2 million in Q2 2019 to $19.4 million in Q2 2020[161]. - The company does not anticipate achieving sustained profitability in the foreseeable future, continuing to incur significant losses related to ongoing operations and product development[139]. Cash and Capital - As of June 30, 2020, the company had $208.7 million in cash, cash equivalents, and marketable securities, with an accumulated deficit of $257.2 million[186]. - Cash used in operating activities for the six months ended June 30, 2020 was $37.3 million, compared to $13.0 million for the same period in 2019[201][202]. - Cash provided by financing activities for the six months ended June 30, 2020 was $113.0 million, primarily from a public offering of common stock totaling $105.7 million[207]. - The company anticipates needing to raise substantial additional capital to advance product candidates and fund operations[196]. - The company completed a public offering of 7,000,000 shares at $14.00 per share in May 2020, generating net proceeds of $105.3 million[192]. Research and Development - PTG-300, the most advanced clinical asset, is in Phase 2 studies for polycythemia vera and hereditary hemochromatosis, with preliminary results showing the ability to control hematocrit levels below 45%[128]. - PTG-200 is in a global Phase 2 clinical study for moderate-to-severe Crohn's disease, with a milestone payment of $5.0 million received for the nomination of a second-generation development candidate[130][132]. - PN-943, an orally delivered integrin antagonist, completed Phase 1 studies and is expected to initiate a Phase 2 proof of concept study in ulcerative colitis, pending conditions for safe patient accrual[133]. - Research and development expenses increased by $0.9 million, or 5%, from $19.4 million in Q2 2019 to $20.3 million in Q2 2020[165]. - Research and development expenses rose by $7.2 million, or 23%, from $31.8 million in 2019 to $39.0 million in 2020, driven by increased pre-clinical and clinical trial costs[178]. - The proprietary technology platform enables the development of novel peptide-based drugs, addressing significant unmet medical needs in various therapeutic areas[126][134]. - The company is discontinuing the development of PTG-300 for beta-thalassemia and myelodysplastic syndromes, focusing efforts on polycythemia vera and hereditary hemochromatosis[128]. Revenue and Expenses - License and collaboration revenue increased by $14.4 million, or 176%, from a loss of $8.2 million in Q2 2019 to $6.2 million in Q2 2020[163]. - License and collaboration revenue increased by $16.5 million, or 249%, from a loss of $6.6 million in 2019 to $9.9 million in 2020[176]. - Total operating expenses rose by $1.2 million, or 5%, from $23.2 million in Q2 2019 to $24.4 million in Q2 2020[161]. - General and administrative expenses increased by $0.3 million, or 8%, from $3.9 million in Q2 2019 to $4.2 million in Q2 2020[166]. - General and administrative expenses increased by $1.1 million, or 15%, from $7.6 million in 2019 to $8.8 million in 2020, primarily due to higher insurance and salary costs[179]. - Interest income decreased by $0.4 million, or 68%, from $0.6 million in Q2 2019 to $0.2 million in Q2 2020[167]. - Interest income decreased by $0.6 million, or 47%, from $1.4 million in 2019 to $0.7 million in 2020, attributed to a declining interest rate environment[180]. - Income tax expense increased by $2.8 million, or 169%, from a tax benefit of $1.6 million in Q2 2019 to an expense of $1.1 million in Q2 2020[172]. - Income tax expense increased by $2.8 million, or 190%, from a benefit of $1.4 million in 2019 to an expense of $1.3 million in 2020[185]. Impact of COVID-19 - The impact of the COVID-19 pandemic has introduced significant uncertainties, potentially affecting clinical trials, patient recruitment, and overall business operations[135][136]. Collaboration and Agreements - The company has received a total of $75.0 million in non-refundable cash payments from Janssen under the collaboration agreement, including $50.0 million upfront and $25.0 million upon the execution of the First Amendment[140]. - The transaction price of the initial performance obligation under the Janssen License and Collaboration Agreement was $113.9 million as of June 30, 2020, an increase of $0.3 million from March 31, 2020[164]. - The transaction price of the initial performance obligation under the Janssen License and Collaboration Agreement was $113.9 million as of June 30, 2020, an increase of $1.0 million from December 31, 2019[177]. - The company had a decrease of $7.5 million in deferred revenue related to the Janssen License and Collaboration Agreement during the first half of 2020[201]. Debt and Financial Obligations - Loss on early repayment of debt was $0.6 million for Q2 2020, reflecting fees related to the repayment of a term loan[170]. - The company prepaid a $10.0 million term loan in June 2020, incurring a loss of $0.6 million on early repayment[184]. Off-Balance Sheet Arrangements - The company has not entered into any off-balance sheet arrangements as defined under SEC rules[210].