PTG-200 PTG-300 PN-943 COMPANY OVERVIEW Dinesh V. Patel, PhD President & CEO 1 June 2020 Forward Looking Statements This presentation contains forward-looking statements of Protagonist Therapeutics, Inc. (Protagonist) that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, our capital resources, business strategy, prospective products, pot ...

Protagonist Therapeutics, Inc. (NASDAQ:PTGX) Q1 2020 Results Conference Call May 7, 2020 5:00 PM ET Company Participants Don Kalkofen - Chief Financial Officer Dinesh Patel - President and Chief Executive Officer Samuel Saks - Chief Medical Officer Ronald Hoffman - M.D., Director of the Myeloproliferative Diseases Program Conference Call Participants Chris Marai - Nomura Gobind Singh - BMO Joe Schwartz - Leerink Chris Bialas - HCW Operator Good day, and welcome to the Protagonist Therapeutics PTG-300 Devel ...

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, 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) (State or other jurisdiction of ...

Financial Data and Key Metrics Changes - Protagonist reported a net loss of $77.2 million for the full year of 2019, compared to a net loss of $38.9 million for 2018, and a net loss of $17.5 million for Q4 2019, compared to a net loss of $13.9 million for Q4 2018 [32] - License and collaboration revenue for the full year of 2019 was $0.2 million, significantly down from $30.9 million in 2018, primarily due to a one-time cumulative adjustment related to revenue recognition principles [33] - Research and development expenses were $65 million for the full year of 2019, up from $59.5 million in 2018, while general and administrative expenses increased to $15.7 million from $13.7 million in the previous year [34][35] - Protagonist ended 2019 with $133 million in cash, cash equivalents, and marketable securities, with access to a debt facility of $10 million, sufficient to fund operations through the end of 2021 [36] Business Line Data and Key Metrics Changes - The company has three clinical assets in development: PTG-300 for blood disorders, and PTG-200 and PN-943 for inflammatory bowel diseases (IBD) [11] - PTG-300 is being pursued in four different indications, with ongoing studies expected to yield data-driven decisions in 2020 [13][20] - PTG-200 has progressed into a Phase II clinical proof-of-concept study in Crohn's disease, with results expected in the first half of 2021 [22] - PN-943 is set to initiate a Phase II study in ulcerative colitis in Q2 2020, with topline efficacy results anticipated in the second half of 2021 [25] Market Data and Key Metrics Changes - The company has expanded its collaboration with Janssen, resulting in milestone payments and the nomination of a second-generation development candidate [22][23] - The competitive landscape for ulcerative colitis trials is noted, with Protagonist confident in the advantages of its drug offerings [54] Company Strategy and Development Direction - The company aims to evaluate PTG-300 in multiple indications and select the first indication for a pivotal study in 2021 [28] - Continued collaboration with Janssen for the development of PTG-200 and exploration of second-generation oral IL-23 receptor antagonists is a priority [28] - Advancing PN-943 in a Phase II study is also a key focus, with the potential for significant impact in the IBD treatment paradigm [26][28] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing studies and the potential impact of the coronavirus outbreak on operations, stating that guidance on objectives and timelines remains unchanged [30] - The company is encouraged by progress made in 2019 and looks forward to multiple data-driven decisions in 2020 [87] Other Important Information - The company has strengthened its team and extended its cash runway through the end of 2021, allowing for continued clinical development [9][27] Q&A Session Summary Question: Update on PTG-300 and exploration in non-transfusion-dependent patients - Management confirmed that both transfusion-dependent and non-transfusion-dependent populations are being pursued, though enrollment in the latter is slow [39] Question: Potential for multiple indications for PTG-300 - The focus is currently on selecting the first indication for a pivotal study, with the possibility of pursuing multiple indications in the future [42] Question: Timing for TRANSCEND data announcement - Management indicated that definitive data, including clinical responders, would be shared in 2020 as conclusions are reached [49] Question: Improvement of PN-943 over PTG-100 - PN-943 was found to be roughly threefold more effective than PTG-100 based on preclinical and Phase I studies [50] Question: Competition for ulcerative colitis trials - Management acknowledged competition but expressed confidence in the advantages of their drug, including proven targets and a GI-restricted approach [54] Question: Dosing strategy for PTG-300 - Management stated that while the current focus is on 40 mg twice-weekly dosing, there is flexibility to explore higher doses if necessary [58][61] Question: Lessons learned from PTG-100 study for PN-943 - Management highlighted the importance of addressing high placebo effects and maintaining close communication with key opinion leaders in the IBD community [64] Question: Future Phase II study design for PN-943 - The upcoming Phase II study will be designed to gather sufficient information for potential pivotal study preparation [68]

Drug Development and Clinical Trials - PTG-200 is an orally delivered gut-restricted IL-23R antagonist for IBD, with a $25 million milestone payment received from Janssen in May 2019 for expanded collaboration[20] - PN-943, a backup compound to PTG-100, completed Phase 1 studies in 2019, with a U.S. IND submitted in December 2019, and a Phase 2 study anticipated to start in Q2 2020[21] - PTG-300, an injectable hepcidin mimetic, is being developed for disorders like beta-thalassemia, with orphan drug designation and Fast Track designation from the FDA[32] - The TRANSCEND Phase 2 study for PTG-300 in beta-thalassemia began in Q1 2019, focusing on safety and efficacy, with primary endpoints including changes in hemoglobin and transfusion burden[33] - Preliminary results from the Phase 2 study of PTG-300 showed significant reductions in transfusion burden and serum iron levels at doses of 40 mg and 80 mg[34] - The Phase 2 study of PTG-300 in polycythemia vera (PV) is expected to enroll approximately 30 patients, evaluating safety and efficacy over a 16-week period[38] - An open-label study of PTG-300 in hereditary hemochromatosis (HH) was initiated in January 2020, targeting reductions in TSAT and phlebotomy requirements[39] - The company plans to initiate an investigator-sponsored trial of PTG-300 in myelodysplastic syndromes (MDS) in the first half of 2020[40] - A Phase 2 clinical study called PRISM is evaluating PTG-200 in 90 patients with moderate-to-severe CD, with results expected in 2021[57] - PN-943, an orally delivered α4β7 integrin antagonist, is being developed for moderate-to-severe UC, targeting the same pathway as the FDA-approved drug Entyvio[58][61] - The Phase 1 clinical trial for PN-943 was completed in 2019, involving dose escalation from 100 mg to 1,400 mg for the single ascending dose (SAD) portion[63] - The company filed an Investigational New Drug (IND) application for PN-943 in January 2020, with plans to initiate a Phase 2 proof-of-concept study in ulcerative colitis (UC) in Q2 2020[66] Market Opportunities - The global market opportunity for beta-thalassemia is estimated between $1.4 billion to $2.5 billion, with approximately 300,000 patients globally[28] - The market opportunity for polycythemia vera is estimated between $1.0 billion to $2.0 billion, with over 150,000 diagnosed patients in key markets[29] - There are over 1.6 million IBD patients in the United States, with an increase of approximately 200,000 patients since 2011[42] - The UC market is estimated at $5.3 billion and is expected to grow at a CAGR of approximately 2.5% to $6.8 billion by 2026[42] - The CD market reached approximately $9.6 billion and is projected to grow at approximately 3.7% per year to $13.8 billion by 2026[42] - Johnson & Johnson's Stelara sales exceeded $5.0 billion in 2018, while Takeda Pharmaceuticals' Entyvio sales reached approximately $3.0 billion in 2019[43] - Current treatments for moderate-to-severe IBD show clinical remission rates of only 15% to 31%, indicating a significant unmet medical need[43] Regulatory and Compliance - The FDA's review process for new drug applications (NDAs) typically takes about 12 months from submission, with a goal of 10 months for standard NDAs[95] - The company must comply with substantial regulatory requirements imposed by the FDA and other authorities throughout the drug development process[87] - The FDA may grant fast track designation for drugs intended to treat serious conditions, allowing for expedited development and review[103] - Orphan designation can provide financial incentives and exclusivity for drugs treating rare diseases affecting fewer than 200,000 individuals in the U.S.[105] - The company is subject to extensive FDA regulations post-approval, including requirements for recordkeeping, periodic reporting, and product sampling[106] - The FDA may require post-marketing testing and surveillance to monitor product safety and effectiveness after commercialization[107] - The company must maintain compliance with cGMP requirements to avoid regulatory penalties and ensure product quality[108] - The company must ensure compliance with GCPs during clinical trials, as failure could lead to unreliable data and regulatory rejection[179] Financial Condition and Funding - The company has incurred significant operating losses, with a net loss of $77.2 million for the year ended December 31, 2019, and an accumulated deficit of $217.7 million as of the same date[156] - The company does not anticipate generating revenue from product sales for the foreseeable future and has no product candidates in registration or pivotal clinical trials[158] - The company expects to continue incurring significant research and development expenses related to ongoing operations and product development, including clinical activities under the Janssen License and Collaboration Agreement[156] - As of December 31, 2019, the company had cash, cash equivalents, and marketable securities of $133.0 million, which is expected to fund operations for at least the next 12 months[161] - The company may require substantial additional funding to complete clinical development and commercialize product candidates, which may not be available on acceptable terms[160] - The company faces challenges with third-party payors regarding coverage and reimbursement, which may limit product sales if deemed not cost-effective[111] Collaboration and Partnerships - The Janssen License and Collaboration Agreement, effective July 2017, included a non-refundable upfront cash payment of $50 million and a subsequent payment of $25 million in Q2 2019[71] - The collaboration with Janssen triggered a $25.0 million milestone payment for expanding efforts towards second-generation IL-23R antagonists[56] - The company currently has no active collaborations for its product candidates, relying solely on the Janssen License and Collaboration Agreement[175] - Future collaborations may not be successful, with risks including reduced payments and conflicts over development plans[177] - The Co-Detailing Option with Janssen allows the company to provide up to 30% of the PTG-200 selling effort in the U.S. if approved, but a separate agreement specifying detailed responsibilities is still needed[198] Manufacturing and Supply Chain - All product candidates are manufactured by third-party contract manufacturing organizations (CMOs), with no plans to establish owned manufacturing facilities[85] - The company engages CMOs on a "fee for services" basis and plans to enter into longer-term contracts as product candidates progress to Phase 3 clinical trials[86] - The company has not assessed the capabilities of third-party manufacturers beyond the supply of clinical materials to date[86] - Manufacturing risks exist as the company relies on third parties for drug production, lacking internal capabilities for clinical or commercial scale[183] - The company faces potential delays in clinical trials due to reliance on contract manufacturers for raw materials[184] - Critical active pharmaceutical ingredients sourced from suppliers in China may disrupt the supply chain due to port closures and country lockdowns[216] Challenges and Risks - The company is an early clinical-stage biopharmaceutical firm with no approved products and no historical product revenue, making it difficult to assess future prospects[135] - The company expects significant fluctuations in financial condition and operating results due to factors such as clinical outcomes, funding, competition, and regulatory approvals[136] - The company has no product candidates in registrational or pivotal clinical trials, and the success of its business heavily depends on the success of its early-stage clinical candidates[138] - If clinical trials reveal unacceptable safety or efficacy results, it could lead to delays or halts in development, adversely affecting the company's business[169] - The company may face disagreements with Janssen regarding the development and commercialization of PTG-200, which could impact financial condition and operational plans[172] - The company faces challenges in recruiting and retaining patients for clinical trials, which may lead to delays and increased costs[147] - The company may face scrutiny over pricing practices, with potential legislative measures aimed at reducing drug prices and increasing transparency[119] - The company anticipates that future healthcare reforms could limit government payments for therapies, potentially reducing demand for its products[207] - The company may face adverse effects on operations due to health epidemics like COVID-19, particularly in regions with significant manufacturing and distribution facilities[213] - The full impact of the COVID-19 outbreak on the company's operations and supply chain remains uncertain, with potential material effects[218] - The company is closely monitoring the COVID-19 situation and implementing risk mitigation strategies as needed[218]

PTG-200 PTG-300 PN-943 COMPANY OVERVIEW Dinesh V. Patel, PhD President & CEO 1 February 2020 Forward Looking Statements This presentation contains forward-looking statements of Protagonist Therapeutics, Inc. (Protagonist) that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, our capital resources, business strategy, prospective products, ...

PTG-200 PTG-300 PN-943 COMPANY OVERVIEW Dinesh V. Patel, PhD President & CEO 1 January 2020 Forward Looking Statements This presentation contains forward-looking statements of Protagonist Therapeutics, Inc. (Protagonist) that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, our capital resources, business strategy, prospective products, ...

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 September 30, 2019 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 o ...

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, 2019 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Table of Contents Commission File No. 001‑37852 PROTAGONIST THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of i ...

Financial Performance - The net loss for the three months ended March 31, 2019, was $14.1 million, compared to $7.7 million for the same period in 2018, resulting in an accumulated deficit of $154.6 million as of March 31, 2019[123]. - The company has incurred net losses since inception and does not anticipate achieving sustained profitability in the near term[123]. - License and collaboration revenue decreased by $9.2 million, or 86%, from $10.8 million in Q1 2018 to $1.6 million in Q1 2019, primarily due to nearing the end of revenue recognition from a $50 million upfront payment received from Janssen[142]. - Total research and development expenses decreased by $2.9 million, or 19%, from $15.4 million in Q1 2018 to $12.4 million in Q1 2019, mainly due to a reduction in PTG-100 clinical trial expenses[144]. - General and administrative expenses increased by $0.1 million, or 3%, from $3.6 million in Q1 2018 to $3.8 million in Q1 2019, driven by higher personnel costs[146]. - Interest income increased by $0.2 million, or 28%, from $0.6 million in Q1 2018 to $0.7 million in Q1 2019, attributed to a rising interest rate environment[147]. - Cash used in operating activities for Q1 2019 was $16.7 million, compared to $15.1 million in Q1 2018, reflecting an increase in net loss and changes in operating assets[159][160]. - The company reported a net loss of $14.1 million for Q1 2019, which included non-cash charges of $2.7 million[159]. - The company had $112.5 million in cash, cash equivalents, and available-for-sale securities as of March 31, 2019, down from $128.9 million at the end of 2018[169]. - The effective income tax rate for Q1 2019 was (1.3%), primarily due to foreign income tax, with no income tax expense recorded in Q1 2018[148]. - The company has no outstanding debt as of March 31, 2019, which limits financial risk[169]. Research and Development - PTG-300, the most advanced clinical product candidate, is under development for beta-thalassemia and has received orphan drug designation and Fast Track designation from the FDA[115]. - A global Phase 2 study of PTG-300 began in Q1 2019, with top-line results expected in the second half of 2019[115]. - PTG-200, an oral gut-restricted IL-23R antagonist, is being co-developed with Janssen, with an IND filing anticipated in Q2 2019[117][118]. - PN-943, a backup compound to PTG-100, is currently in a Phase 1 clinical trial, with top-line results expected in Q2 2019[119][120]. - The company replaced PTG-100 with PN-943 based on preclinical data suggesting greater potency[119][133]. - The proprietary discovery platform enables the engineering of novel peptides for various therapeutic applications[121]. - The company expects research and development expenses to increase as product candidates progress, particularly under the Janssen License and Collaboration Agreement[135]. - The company anticipates needing to raise additional capital to advance product candidates through clinical development and to fund operations in the foreseeable future[154]. Collaboration and Agreements - The Janssen License and Collaboration Agreement includes a $50 million upfront payment and a potential $25 million payment upon IND filing for PTG-200[124][125]. - The transaction price of the Janssen License and Collaboration Agreement was $60.6 million as of March 31, 2019, a slight decrease from $60.7 million at the end of 2018[143]. Cash and Investments - As of March 31, 2019, the company had $112.5 million in cash, cash equivalents, and available-for-sale securities, with an accumulated deficit of $154.6 million[149]. - Approximately $1.7 million of the cash balance was located in Australia, with expenses primarily denominated in U.S. dollars[170]. - Cash provided by investing activities for Q1 2019 was $4.1 million, primarily from maturities of available-for-sale securities totaling $26.0 million, offset by purchases of $21.7 million[162]. - Cash provided by financing activities for Q1 2019 was $0.4 million, similar to $0.5 million in Q1 2018, from stock option exercises and employee stock purchases[164][165]. - The company has $107.3 million of common stock remaining available for sale under a registration statement, with $48.8 million available under an at-the-market financing facility[150]. Other Information - There were no material changes to contractual obligations and commitments during Q1 2019[166]. - The company has not entered into any off-balance sheet arrangements as defined under SEC rules[167]. - A 10% change in current exchange rates would not have a material effect on the company's results of operations[170].