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].

Financial Data and Key Metrics Changes - Protagonist ended 2018 with $128.9 million in cash and cash equivalents and investments, sufficient to fund operations through the end of 2020 [36] - The company reported a net loss of $13.9 million or a negative $0.57 per share for Q4 2018, compared to a net loss of $3.1 million or a negative $0.15 per share for the same period in 2017 [37] - License and collaboration revenue decreased to $2.4 million for Q4 2018 from $11.3 million in Q4 2017, primarily due to nearing the end of revenue recognition from a previous agreement [38][39] - R&D expenses increased to $14.2 million for Q4 2018 from $11.7 million in Q4 2017, driven by costs related to contract manufacturing and clinical trials [40] Business Line Data and Key Metrics Changes - The company has three distinct therapeutic candidates in development: PTG-300, PTG-200, and PN-943, all utilizing its proprietary peptide technology platform [7][11] - PTG-300 is the most advanced asset, targeting multiple blood disorders, with a global Phase 2 study initiated in beta-thalassemia patients [24] - PTG-200 is ready for a Phase 2 study in Crohn's patients, expected to be initiated by Janssen in the first half of 2019 [16] - PN-943 is currently in Phase 1 studies in healthy volunteers, with initial clinical safety and pharmacodynamic results expected in the first half of 2019 [33] Market Data and Key Metrics Changes - The company is focused on addressing unmet medical needs in rare diseases and inflammatory bowel diseases (IBD) through its peptide therapeutics [10][18] - There is a noted shift towards oral targeted therapies in IBD, with Protagonist's oral gut-restricted candidates positioned to meet this demand [18] Company Strategy and Development Direction - Protagonist is exclusively focused on peptide therapeutics, leveraging its proprietary technology to develop unique drug candidates that address specific medical challenges [9][10] - The company anticipates six key milestones for 2019, including results from the TRANSCEND study for PTG-300 and IND filings for PTG-200 and PN-943 [34][35] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's financial resources to support clinical development through 2020 and highlighted the potential for PTG-300 in multiple indications [20][36] - The management team emphasized the unique mechanisms of action of their drug candidates and the barriers to entry for competitors [11][19] Other Important Information - PTG-300 has received orphan drug designation and fast-track designation from the FDA, enhancing its development prospects [24] - The company has a strong partnership with Janssen for PTG-200, which is expected to enhance the Stelara franchise [16][28] Q&A Session Summary Question: Details on PTG-300 study and its efficacy in different patient types - Management provided insights into the trial design for PTG-300, focusing on safety and preliminary efficacy in both transfusion-dependent and non-transfusion-dependent beta-thalassemia patients [44][45] Question: Regulatory pathway for PTG-300 - Management indicated that once adequate safety data is obtained, they plan to propose a pivotal study to the FDA, with primary endpoints focused on anemia and transfusion burden [60][61] Question: Updates on PN-943 and its Phase 1 data - Management confirmed that the Phase 1 data will inform the design of the Phase 2 study for PN-943, with a focus on pharmacodynamic markers [65][72] Question: IND submission for PTG-200 - Management clarified that Janssen is responsible for filing the U.S. IND for PTG-200, with both teams collaborating closely on the clinical development [74][76] Question: Operating expense targets for 2019 - Management did not provide specific targets but indicated that they have sufficient cash to support operations through 2020 [85]

Drug Development and Clinical Trials - PTG-200 is a potential first-in-class oral IL-23R antagonist for IBD, with a worldwide collaboration agreement with Janssen for co-development[21]. - The Phase 1 clinical study of PTG-200 was completed in 2018, and Janssen is expected to file an IND for PTG-200 in Crohn's disease in the first half of 2019[21]. - PN-943, a more potent oral α4β7 antagonist, is currently in a Phase 1 clinical trial, with top-line results anticipated in the first half of 2019[22][23]. - A global Phase 2 study of PTG-300 in beta-thalassemia patients was initiated in the first quarter of 2019, focusing on safety, tolerability, and preliminary efficacy[29]. - The Phase 1 study of PTG-300 demonstrated dose-dependent reductions in serum iron, persisting beyond 72 hours at higher doses[27]. - The company plans to initiate an additional Phase 2 study for PTG-300 in a second indication in the second half of 2019[30]. - The development of PN-943 is informed by extensive preclinical studies and pharmacodynamic biomarker assays, leveraging insights from previous studies with PTG-100[35]. - PTG-100 was discontinued in a Phase 2 trial due to an unusually high placebo effect, but subsequent analyses indicated potential clinical efficacy[34]. - PTG-300's Phase 2 study aims to evaluate safety, tolerability, and preliminary efficacy in patients with both non-transfusion dependent and transfusion dependent beta-thalassemia[52]. - The company expects Janssen to file an IND for PTG-200 to support a Phase 2 clinical study in Crohn's disease in the first half of 2019[72]. - Phase 1 clinical trial of PN-943 includes dose escalation from 100 mg to 1,400 mg to assess safety, tolerability, and pharmacodynamics[92]. - The company plans to conduct at least two large-scale, well-controlled clinical trials for each product candidate to demonstrate safety and efficacy[179]. Market Potential and Competition - The ulcerative colitis (UC) market was estimated at approximately $5.4 billion in 2017, projected to reach $6.9 billion by 2025, while the Crohn's disease (CD) market is expected to grow from $9.0 billion to $13.8 billion in the same period[55]. - Greater than 84% of UC product sales are derived from injectable biologic products, highlighting a significant market trend towards biologics[55]. - The company’s PTG-200 is positioned as the only oral IL-23 receptor antagonist, competing against injectable agents expected to be approved by 2028[109]. - The company faces competition in chronic iron overload disorders from products like luspatercept and LJPC-401, both in advanced clinical stages[108]. - The company faces competition from existing therapies and investigational drugs for inflammatory bowel disease (IBD), which may complicate patient recruitment for clinical trials[184]. Financial Overview and Funding - The company has incurred significant operating losses, with a net loss of $38.9 million for the year ended December 31, 2018, and an accumulated deficit of $140.5 million[193]. - 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[194]. - The company will require substantial additional funding to complete clinical development and commercialize its product candidates, with funding requirements subject to change based on various factors[200]. - If the Janssen License and Collaboration Agreement is terminated, the company may not receive any development fees or milestone payments, significantly impacting its financial condition[197]. - The company has never generated any revenue from product sales and may never be profitable, which could adversely affect the market price of its common stock[194]. - The company had cash, cash equivalents, and available-for-sale securities of $128.9 million as of December 31, 2018, which is expected to fund operations for at least the next 12 months[198]. Regulatory Environment - The FDA regulatory process requires substantial time and financial resources, with potential sanctions for non-compliance during product development and approval[120]. - The FDA aims to review and act on a standard NDA for a new molecular entity within ten months from the filing date, although the typical review period is twelve months[124]. - The FDA may require a risk evaluation and mitigation strategy (REMS) plan to ensure that the benefits of the drug outweigh its risks, which could include various safety measures[126]. - The FDA conducts a preliminary review of all NDAs within the first 60 days after submission to determine completeness before substantive review[127]. - Orphan designation can provide financial incentives such as grant funding, tax advantages, and user-fee waivers for drugs intended to treat rare diseases affecting fewer than 200,000 individuals in the U.S.[133]. - Post-approval, the FDA may impose requirements such as Phase 4 clinical trials to further assess the product's safety and effectiveness[135]. - The FDA strictly regulates marketing and promotion of drugs, allowing promotion only for approved indications[138]. Intellectual Property and Collaboration - The company holds eleven issued patents and numerous patent applications related to its clinical-stage product candidates, with expiration dates ranging from October 2033 to February 2039[111]. - The company is focused on expanding its portfolio of patents and applications to protect its product candidates and related technologies[112]. - The proprietary peptide technology platform has led to several pre-clinical and clinical-stage candidates, optimizing potency, selectivity, and oral stability[93]. - The company relies on contract manufacturing organizations (CMOs) for all product candidates, with plans to establish longer-term contracts as products advance to Phase 3 trials[118]. - The company relies on third-party collaborations, such as the Janssen agreement, which may not be successful and could adversely affect its business prospects[209]. - The company may need to relinquish rights to its product candidates or technologies if it seeks additional funding through collaborations or licensing arrangements[201]. - The company is subject to risks related to disagreements with Janssen, which could delay or preclude the development and commercialization of its product candidates[207]. Operational Challenges - The company is subject to a variety of health care regulations, including HIPAA and anti-kickback statutes, which could impact operations and compliance efforts[150]. - The company is classified as an "emerging growth company," allowing it to benefit from reduced reporting requirements until certain financial thresholds are met[165]. - The company has not yet demonstrated an ability to generate product revenue or overcome risks associated with biopharmaceutical development[169]. - The company must obtain requisite approvals from regulatory authorities in foreign countries before commencing clinical studies or marketing products[155]. - Clinical development is lengthy and expensive, with the potential for failure at any stage, which could adversely affect the company's business and stock price[179]. - The company has experienced a significant setback with the premature discontinuation of the global Phase 2 clinical trial of PTG-100, which negatively impacted its stock price[178]. Safety and Efficacy Concerns - Undesirable side effects from product candidates could delay or prevent regulatory approval, limit commercial opportunities, or result in product liability claims[188]. - The company expects that clinical trials for PTG-200 and PN-943 will need to demonstrate a competitive risk/benefit profile compared to existing injectable antibody drugs to obtain regulatory approval[189]. - All toxicology studies for PN-943 have shown no safety issues, with good tolerability at all dose levels tested[89]. - The company is responsible for ensuring compliance with Good Clinical Practices (GCPs) in clinical trials, and failure to do so may result in unreliable clinical data[217]. - Significant portions of clinical studies for peptide-based product candidates are expected to be conducted outside the U.S., complicating monitoring and compliance efforts[217].