Summary of Protagonist Therapeutics FY Conference Call Company Overview - **Company**: Protagonist Therapeutics (NasdaqGM:PTGX) - **Key Focus**: Development of innovative therapeutics, particularly in the areas of polycythemia vera (PV) and inflammatory bowel disease (IBD) Key Points and Arguments Drug Development and Breakthrough Designation - Protagonist Therapeutics is on the verge of obtaining approval for its first two drugs, with resveratide for polycythemia vera recently receiving breakthrough designation, indicating the FDA's confidence in its efficacy and safety [2][8][9] - The company achieved significant phase three results, meeting primary and secondary endpoints, including patient-reported outcomes, which are critical in the treatment of PV [6][7] - The breakthrough designation allows for expedited review, with an expected NDA filing by the end of the year and potential approval within a year, contingent on priority review [11][12] Market Opportunity in Polycythemia Vera - The prevalence of PV in the US is over 150,000 patients, with approximately 70% receiving treatment; however, two-thirds of these patients struggle to maintain hematocrit levels below 45% [13][14] - Protagonist estimates a market opportunity of $1 to $2 billion for resveratide, with a target population of around 50,000 patients who could benefit from the drug [15] Opt-In/Opt-Out Decision - The company is evaluating whether to opt in or out of a partnership with Takeda, with a potential opt-out fee of $400 million and higher milestone payments if they choose to opt out [19][20] - The decision will be made by mid-next year, with the NDA filing influencing the timeline [19] Oral Hepcidin Development - Protagonist is also developing an oral hepcidin, which is distinct from resveratide but related mechanistically; the company aims to explore its utility beyond PV [29][30] ICO and IBD Market - ICO, another key asset, has filed for NDA for psoriasis, with expectations for approval in July next year; it is the only oral IL-23 blocker, presenting a significant opportunity in both dermatology and IBD [31][32] - The phase two data for ICO in ulcerative colitis (UC) shows a 30% clinical remission rate, indicating strong potential in the IBD market [36][37] Differentiation in Obesity and Other Areas - Protagonist acknowledges the crowded obesity market but emphasizes differentiation through their unique oral GLP-1/GIP/GCG platform [41][42] - The company is developing both oral and subcutaneous formulations to cater to different patient preferences [45] Future Directions - Protagonist is committed to investing in internal R&D and exploring external innovations to strengthen its platform and pipeline [22][23] - The company is optimistic about the potential of its assets in both the PV and IBD markets, with ongoing clinical studies and strategic partnerships [50] Additional Important Insights - The company is focused on maintaining a strong cash position while exploring various avenues for growth, including potential buybacks and investments in new technologies [25][26] - Protagonist's approach to drug development emphasizes the importance of clinical data and market feedback, which shapes their strategic decisions [9][15]

Core Insights - The company is focused exclusively on peptide therapeutics, emphasizing the versatility of its platform which is agnostic to disease areas or targets [2][3] - The company aims to avoid scenarios where scientific success does not translate into practical utility for drugs, highlighting the importance of both scientific and commercial viability [2] Group 1 - The peptide platform is viewed as a renewable resource, with potential for greater value in the future [1] - The company seeks strong differentiation in its approach to peptide therapeutics, ensuring that scientific achievements align with market needs [3]

Summary of Protagonist Therapeutics Conference Call Company Overview - **Company**: Protagonist Therapeutics (PTGX) - **Event**: Citi Biopharma Back to School Summit - **Date**: September 03, 2025 Key Points Peptide Platform and Strategy - Protagonist focuses exclusively on peptide therapeutics, which are versatile and agnostic to disease areas or targets [2][3] - The company aims to differentiate its products from existing drugs by targeting biologically validated pathways, particularly those successful in injectable antibody drugs [5] - The strategy has evolved from gut-restricted peptides to orally bioavailable peptides, broadening the scope of potential opportunities [8] Rasvirtide Development - Rasvirtide has shown outstanding phase three data, leading to a breakthrough designation from regulatory agencies [12][13] - The drug addresses an unmet need in polycythemia vera, with positive interactions with regulatory agencies [13] - Protagonist and its partner Takeda are focused on increasing awareness and establishing relationships with key opinion leaders (KOLs) and physicians to drive market penetration [20][21] Partnership with Takeda - The partnership with Takeda is characterized by a collaborative spirit, leveraging Protagonist's historical knowledge of Rasvirtide and Takeda's resources [15][17] - Protagonist retains the option to opt-out of the partnership, which includes a significant financial incentive of $425 million, allowing flexibility in future decisions [22][24][30] ICO and Market Potential - ICO, an oral IL-23 blocker, is positioned to capture a significant market share due to its oral administration and efficacy in treating inflammatory bowel diseases [46][47] - The drug is expected to appeal to patients currently not seeking treatment due to dissatisfaction with existing options [46] - Protagonist's royalty structure with J&J ranges from 6% to 10%, with optimistic sales projections for ICO [45][46] Obesity Drug Development - Protagonist is entering the obesity market with a focus on developing both oral and injectable formulations, aiming to differentiate its product through unique mechanisms [58][60] - The company is conducting preclinical studies to ensure efficacy and tolerability, with plans to initiate phase one studies in the near future [69] Future Outlook - Protagonist is committed to maintaining flexibility in its partnerships and product development strategies, aiming to maximize shareholder value while leveraging the expertise of larger pharmaceutical partners [53][51] - The company is optimistic about the potential of its pipeline, particularly in the areas of rare diseases and obesity, with ongoing studies expected to yield valuable insights [69][70] Additional Insights - The company emphasizes the importance of partnerships for validation and resource access, while also planning to retain more control over its assets in future collaborations [50][52] - Protagonist's approach to drug development focuses on validated targets, reducing biological risk and enhancing the predictability of clinical outcomes [68]

Core Insights - Protagonist Therapeutics reported Q2 2025 results, highlighting advancements in its late-stage clinical pipeline despite GAAP revenue falling short of estimates [1][8] - The company achieved a narrower GAAP earnings per share loss of $0.55, better than the anticipated loss of $0.58, while GAAP revenue was $5.5 million, significantly below the estimate of $7.51 million [1][2] Financial Performance - GAAP EPS for Q2 2025 was $(0.55), a 10% decrease year-over-year from $(0.50) in Q2 2024 [2] - GAAP revenue was $5.5 million, a 31% increase from $4.2 million in Q2 2024, but below the estimate of $7.51 million [2] - Research and Development expenses rose to $37.0 million, a 10.4% increase from $33.5 million in Q2 2024 [2] - Cash, cash equivalents, and marketable securities totaled $673.0 million, a 20.3% increase from $559.2 million in the previous year [2] Business Overview - Protagonist Therapeutics focuses on developing peptide-based drugs for hematological and inflammatory diseases, with key programs targeting polycythemia vera and plaque psoriasis [3][4] - The company relies on clinical milestones and strategic partnerships for funding, with significant collaborations with Takeda Pharmaceuticals and Johnson & Johnson [4] Drug Development Progress - The lead drug candidate, rusfertide, showed positive phase 3 data for polycythemia vera, with a New Drug Application expected to be filed by Takeda later in 2025 [5] - Icotrokinra, targeting moderate to severe plaque psoriasis, submitted its first U.S. drug application in July 2025, with positive early data from the ANTHEM study for ulcerative colitis [6] - Preclinical assets like PN-881 and PN-477 are advancing, with promising results in autoimmune diseases and metabolic disorders, respectively [7] Strategic Focus and Future Outlook - The company is transitioning from large upfront payments to a model dependent on product launches, with all operating income coming from license and collaboration revenue [8] - Rising R&D expenses are driven by new preclinical programs, while general and administrative expenses are increasing as the company approaches potential commercialization [9] - Management indicated that cash reserves are expected to fund operations through at least the end of 2028, with upcoming regulatory filings and pipeline readouts being key catalysts for growth [10][11]

Company Performance - Protagonist Therapeutics reported a quarterly loss of $0.55 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.53, and compared to a loss of $0.50 per share a year ago, indicating a decline in performance [1] - The company posted revenues of $5.55 million for the quarter ended June 2025, missing the Zacks Consensus Estimate by 46.67%, while year-ago revenues were $4.17 million [2] - Over the last four quarters, Protagonist Therapeutics has surpassed consensus EPS estimates three times, but the recent earnings surprise was -3.77% [1][2] Stock Movement and Outlook - Protagonist Therapeutics shares have increased by approximately 39.6% since the beginning of the year, significantly outperforming the S&P 500's gain of 7.1% [3] - The company's earnings outlook is crucial for future stock performance, with current consensus EPS estimates for the coming quarter at -$0.60 on revenues of $10.67 million, and for the current fiscal year at -$1.05 on revenues of $116.15 million [7] Industry Context - The Medical - Biomedical and Genetics industry, to which Protagonist Therapeutics belongs, is currently ranked in the bottom 42% of over 250 Zacks industries, which may negatively impact stock performance [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, suggesting that investors should monitor these revisions closely [5]

PART I FINANCIAL INFORMATION [Item 1. Condensed Consolidated Financial Statements (Unaudited)](index=4&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20%28unaudited%29) The company reported a **$46.4 million** net loss for H1 2025, a shift from **$176.7 million** net income in H1 2024, driven by lower collaboration revenue and increased R&D expenses [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Balance Sheet Items (in thousands) | Balance Sheet Items (in thousands) | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $168,543 | $97,249 | | Marketable securities | $504,415 | $461,916 | | Total current assets | $602,526 | $591,641 | | Total assets | $718,006 | $744,725 | | **Liabilities & Equity** | | | | Total current liabilities | $35,507 | $47,398 | | Total liabilities | $49,988 | $69,430 | | Total stockholders' equity | $668,018 | $675,295 | - Cash, cash equivalents, and marketable securities increased to **$673.0 million** as of June 30, 2025, from **$559.2 million** as of December 31, 2024[10](index=10&type=chunk)[168](index=168&type=chunk) [Condensed Consolidated Statements of Operations](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) Statement of Operations (in thousands) | Statement of Operations (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | License and collaboration revenue | $33,867 | $259,120 | | Research and development | $72,929 | $67,254 | | General and administrative | $22,289 | $24,350 | | Total operating expenses | $95,218 | $91,604 | | (Loss) income from operations | ($61,351) | $167,516 | | Net (loss) income | ($46,426) | $176,724 | Per Share Data | Per Share Data | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net (loss) income per share, basic | ($0.73) | $2.89 | | Net (loss) income per share, diluted | ($0.73) | $2.77 | - The significant decrease in revenue and shift from net income to net loss in the first six months of 2025 compared to 2024 is primarily due to the one-time recognition of **$254.1 million** from the Takeda collaboration upfront payment in March 2024[12](index=12&type=chunk)[62](index=62&type=chunk)[160](index=160&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Cash Flow Data (in thousands) | Cash Flow Data (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash provided by operating activities | $96,583 | $241,193 | | Net cash used in investing activities | ($39,592) | ($82,048) | | Net cash provided by financing activities | $14,368 | $9,771 | | Net increase in cash, cash equivalents and restricted cash | $71,359 | $168,916 | - Cash from operations decreased primarily due to the receipt of a **$300.0 million** upfront payment from Takeda in 2024, partially offset by a **$165.0 million** milestone payment from JNJ received in 2025[21](index=21&type=chunk)[182](index=182&type=chunk) [Notes to Unaudited Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) - The company's clinical programs focus on inflammatory/immunomodulatory diseases and hematology/blood disorders, with two key assets in Phase 3: icotrokinra (licensed to JNJ) and rusfertide (co-developed with Takeda)[22](index=22&type=chunk) - Under the Takeda collaboration for rusfertide, Protagonist received a **$300.0 million** upfront payment in April 2024, and in March 2025, a **$25.0 million** milestone was deemed probable following positive Phase 3 VERIFY trial results[49](index=49&type=chunk)[60](index=60&type=chunk) - For the six months ended June 30, 2025, the company recognized **$33.9 million** in revenue from the Takeda agreement, primarily related to a **$25.0 million** milestone and ongoing development services[61](index=61&type=chunk) - Under the JNJ agreement for icotrokinra, the company earned a **$165.0 million** milestone payment in Q4 2024 (received in January 2025) and has earned a total of **$337.5 million** from JNJ since 2017[45](index=45&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=31&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management highlights significant clinical progress and pipeline expansion, noting a sharp revenue decrease due to a prior year upfront payment, while maintaining strong liquidity [Overview and Pipeline Developments](index=33&type=section&id=Overview%20and%20Pipeline%20Developments) - **Icotrokinra (IL-23R):** JNJ submitted an NDA to the FDA in July 2025 for moderate-to-severe plaque psoriasis based on positive data from the Phase 3 ICONIC program, and the drug also met its primary endpoint in a Phase 2b trial for ulcerative colitis[92](index=92&type=chunk)[97](index=97&type=chunk)[101](index=101&type=chunk) - **Rusfertide (Hepcidin Mimetic):** The Phase 3 VERIFY trial for polycythemia vera (PV) met its primary endpoint, with **76.9%** of patients achieving a clinical response versus **32.9%** for placebo, and an NDA filing is expected in Q4 2025[93](index=93&type=chunk)[113](index=113&type=chunk)[114](index=114&type=chunk) - **Pipeline Expansion:** The company has advanced new candidates, including PN-881 (oral IL-17 antagonist) for immune-mediated skin diseases and PN-477 (oral/subcutaneous triple agonist) for obesity[94](index=94&type=chunk)[110](index=110&type=chunk)[124](index=124&type=chunk) [Results of Operations](index=48&type=section&id=Results%20of%20Operations) Financial Comparison (in thousands) | Financial Comparison (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | License and collaboration revenue | $33,867 | $259,120 | | Research and development expenses | $72,929 | $67,254 | | General and administrative expenses | $22,289 | $24,350 | | Net (loss) income | ($46,426) | $176,724 | - The **87%** decrease in revenue for the six months ended June 30, 2025, compared to the prior year, was due to the 2024 period including **$254.1 million** from the upfront payment for the Takeda collaboration[159](index=159&type=chunk)[160](index=160&type=chunk) - R&D expenses increased by **$5.7 million (8%)** year-over-year, driven by a **$9.8 million** increase in pre-clinical and drug discovery costs for new candidates PN-881 and PN-477, partially offset by a **$4.1 million** decrease in rusfertide Phase 3 trial expenses[162](index=162&type=chunk) - G&A expenses decreased by **$2.1 million (8%)** year-over-year, primarily because the 2024 period included **$4.6 million** in one-time advisory and legal fees related to the Takeda agreement[164](index=164&type=chunk) [Liquidity and Capital Resources](index=53&type=section&id=Liquidity%20and%20Capital%20Resources) - As of June 30, 2025, the company had **$673.0 million** in cash, cash equivalents, and marketable securities[168](index=168&type=chunk) - The company received a **$165.0 million** milestone payment from JNJ in January 2025 and expects a **$25.0 million** milestone payment from Takeda upon completion of the VERIFY clinical study report[169](index=169&type=chunk)[170](index=170&type=chunk) - Management believes that existing cash, cash equivalents, and marketable securities will be sufficient to fund operations for at least the next twelve months[175](index=175&type=chunk) Cash Flow Summary (in thousands) | Cash Flow Summary (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Cash provided by operating activities | $96,583 | $241,193 | | Cash used in investing activities | ($39,592) | ($82,048) | | Cash provided by financing activities | $14,368 | $9,771 | [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=59&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is primarily exposed to interest rate risk on its **$673.0 million** portfolio of cash, cash equivalents, and marketable securities, where a 100 basis point change would impact annual interest income by approximately **$3.7 million** - The company's primary market risk is interest rate sensitivity on its investment portfolio, where an immediate 100 basis point change in interest rates would affect annual interest income by approximately **$3.7 million**[187](index=187&type=chunk) - Foreign currency risk from Australian operations and inflation risk are not considered material at this time[188](index=188&type=chunk)[189](index=189&type=chunk) [Item 4. Controls and Procedures](index=59&type=section&id=Item%204.%20Controls%20and%20Procedures) Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were effective as of June 30, 2025, with no material changes to internal control over financial reporting during the quarter - The CEO and CFO concluded that as of the end of the quarter, the company's disclosure controls and procedures were effective[192](index=192&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that have materially affected, or are reasonably likely to materially affect, internal controls[194](index=194&type=chunk) PART II OTHER INFORMATION [Item 1. Legal Proceedings](index=61&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings and is not aware of any pending or threatened legal actions that could have a material adverse effect on its business - The company is not currently involved in any material legal proceedings[195](index=195&type=chunk) [Item 1A. Risk Factors](index=61&type=section&id=Item%201A.%20Risk%20Factors) There have been no material changes to the risk factors previously disclosed in the company's Annual Report on Form 10-K for the year ended December 31, 2024 - No material changes have been made to the risk factors identified in the company's 2024 Annual Report on Form 10-K[196](index=196&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=61&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales of equity securities and no repurchases of its equity securities during the period - There were no unregistered sales of equity securities or company repurchases of its stock during the quarter[197](index=197&type=chunk)[198](index=198&type=chunk) [Item 5. Other Information](index=62&type=section&id=Item%205.%20Other%20Information) During the fiscal quarter ended June 30, 2025, no director or Section 16 officer adopted or terminated any Rule 10b5-1 trading arrangement or other non-Rule 10b5-1 trading plan - No directors or Section 16 officers adopted or terminated any Rule 10b5-1 or similar trading plans during the quarter[201](index=201&type=chunk)

[Corporate Update and Q2 2025 Highlights](index=1&type=section&id=Protagonist%20Reports%20Second%20Quarter%202025%20Financial%20Results%20and%20Provides%20Corporate%20Update) [Corporate Update and Q2 2025 Highlights](index=1&type=section&id=Corporate%20Update%20and%20Q2%202025%20Highlights) Protagonist Therapeutics reported significant progress in Q2 2025, highlighted by an NDA submission for icotrokinra and a strong cash position of $673.0 million - Submitted a New Drug Application (NDA) to the U.S. FDA for icotrokinra for the treatment of moderate to severe plaque psoriasis in adults and adolescents[1](index=1&type=chunk) - The U.S. NDA filing for rusfertide in polycythemia vera (PV) is **on track for the fourth quarter of 2025**[1](index=1&type=chunk)[3](index=3&type=chunk) - Announced a new oral and injectable triple agonist anti-obesity peptide development candidate in June[2](index=2&type=chunk) Cash Position and Runway | Metric | Value | | :--- | :--- | | Cash, cash equivalents and marketable securities (as of June 30, 2025) | $673.0 million | | Anticipated cash runway | Through at least end of 2028 | [Pipeline Developments](index=1&type=section&id=Second%20Quarter%202025%20Recent%20Developments%20and%20Upcoming%20Milestones) [Rusfertide (Hepcidin Mimetic for PV)](index=1&type=section&id=Rusfertide%3A%20Subcutaneous%20Injectable%20Hepcidin%20Mimetic%20for%20Polycythemia%20Vera%20(PV)%20and%20Other%20Blood%20Disorders) Positive Phase 3 VERIFY trial data for rusfertide was presented at ASCO, with a U.S. NDA filing on track for the fourth quarter of 2025 by partner Takeda - The complete data from the positive Phase 3 VERIFY trial was presented during the plenary session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting[3](index=3&type=chunk) - The U.S. NDA filing for rusfertide for the treatment of patients with PV is **expected in Q4 2025**, to be submitted by partner Takeda Pharmaceuticals[6](index=6&type=chunk) [Icotrokinra (Oral IL-23 Receptor Antagonist)](index=2&type=section&id=Icotrokinra%20(JNJ-2113)%3A%20Oral%20IL-23%20Receptor%20Antagonist) An NDA for icotrokinra in psoriasis was submitted based on four Phase 3 studies, and positive Phase 2b data in ulcerative colitis will be presented in October - The first icotrokinra NDA was filed in July for treating adults and adolescents with moderate to severe plaque psoriasis (PsO), based on data from four pivotal Phase 3 studies (ICONIC program)[6](index=6&type=chunk) - Positive top-line results from the Phase 2b ANTHEM trial in moderately to severely active ulcerative colitis (UC) were announced, with a full data presentation scheduled for UEGW on October 7[1](index=1&type=chunk)[6](index=6&type=chunk) [Early-Stage Development Pipeline (PN-881 & PN-477)](index=2&type=section&id=Development%20Pipeline%3A%20First-in-Class%20Oral%20IL-17%20Peptide%20Antagonist%20(PN-881)%20%26%20GLP-1%2C%20GIP%2C%20%26%20GCG%20Triple%20Agonist%20(PN-477)) The company advanced its early-stage pipeline by selecting PN-477 for obesity and presenting positive preclinical data for the oral IL-17 antagonist PN-881 - Selected PN-477, a GLP-1, GIP, GCG receptor triple agonist peptide, as a development candidate for obesity treatment, with potential for both oral and subcutaneous administration[5](index=5&type=chunk)[6](index=6&type=chunk) - Preclinical data on the oral IL-17 peptide antagonist PN-881 showed it **potently and selectively binds IL-17A and -17F**, with in vitro potency comparable to bimekizumab[6](index=6&type=chunk)[11](index=11&type=chunk) - PN-881 demonstrated metabolic stability for oral delivery and **dose-dependent efficacy** in a rat IL-23 induced skin inflammation model[11](index=11&type=chunk) [Second Quarter 2025 Financial Results](index=3&type=section&id=Second%20Quarter%202025%20Financial%20Results) [Financial Summary](index=3&type=section&id=Financial%20Summary) The company reported a Q2 2025 net loss of $34.8 million, wider than Q2 2024, and a six-month net loss of $46.4 million compared to a significant net income in H1 2024 Q2 & H1 2025 Financial Performance (in thousands, except per share data) | Metric | Q2 2025 | Q2 2024 | H1 2025 | H1 2024 | | :--- | :--- | :--- | :--- | :--- | | License and collaboration revenue | $5,546 | $4,167 | $33,867 | $259,120 | | Research and development expense | $37,036 | $33,520 | $72,929 | $67,254 | | General and administrative expense | $10,551 | $9,440 | $22,289 | $24,350 | | Net (Loss) Income | $(34,771) | $(30,616) | $(46,426) | $176,724 | | Diluted (Loss) Earnings Per Share | $(0.55) | $(0.50) | $(0.73) | $2.77 | - The significant decrease in net income for the six-month period year-over-year was primarily due to the recognition of **$259.1 million in revenue in H1 2024** related to the upfront payment from the Takeda collaboration[10](index=10&type=chunk)[13](index=13&type=chunk) [Revenue Analysis](index=3&type=section&id=Revenue%20Analysis) Q2 2025 revenue rose to $5.5 million from development services, while H1 2025 revenue of $33.9 million included a $25 million milestone from Takeda - Q2 2025 revenue of **$5.5 million** was comprised of development services provided under the Takeda collaboration agreement, an increase from $4.2 million in Q2 2024[9](index=9&type=chunk) - Revenue for the six months ended June 30, 2025, was **$33.9 million**, which included proportional recognition of a $25 million milestone from Takeda earned in Q1 2025[10](index=10&type=chunk) [Expense Analysis](index=3&type=section&id=Expense%20Analysis) Operating expenses increased in Q2 2025, driven by higher R&D costs for new candidates and increased G&A expenses from stock-based compensation - The increase in R&D expenses was primarily due to costs related to new product candidates, IL-17 oral peptide antagonist PN-881 and obesity triple agonist peptide PN-477[12](index=12&type=chunk) - The increase in G&A expense for Q2 2025 was mainly due to higher stock-based compensation and other personnel-related expenses[12](index=12&type=chunk) Stock-based Compensation Expense (in thousands) | Category | Q2 2025 | Q2 2024 | H1 2025 | H1 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $6,291 | $5,097 | $14,282 | $10,385 | | General and administrative | $4,621 | $3,847 | $10,432 | $7,911 | | **Total** | **$10,912** | **$8,944** | **$24,714** | **$18,296** | [Financial Position](index=3&type=section&id=Financial%20Position) The company ended Q2 2025 with a robust cash position of $673.0 million and total stockholders' equity of $668.0 million Selected Balance Sheet Data (in thousands) | Metric | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash, cash equivalents and marketable securities | $672,958 | $559,165 | | Working capital | $567,019 | $544,243 | | Total assets | $718,006 | $744,725 | | Total stockholders' equity | $668,018 | $675,295 | [Corporate Information](index=4&type=section&id=About%20Protagonist) [About Protagonist Therapeutics](index=4&type=section&id=About%20Protagonist) Protagonist is a late-stage biopharmaceutical company with a proprietary peptide platform and an advanced pipeline including two assets with pending NDAs - A discovery through late-stage development biopharmaceutical company with a proprietary peptide discovery platform[14](index=14&type=chunk) - Key assets include **icotrokinra** (licensed to J&J, NDA submitted) and **rusfertide** (co-developed with Takeda, NDA expected by end of 2025)[14](index=14&type=chunk) - Maintains pre-clinical programs including IL-17 oral peptide antagonist **PN-881** and obesity triple agonist peptide **PN-477**[14](index=14&type=chunk) [Cautionary Note on Forward-Looking Statements](index=5&type=section&id=Cautionary%20Note%20on%20Forward-Looking%20Statements) This release contains forward-looking statements subject to risks and uncertainties, and readers are directed to SEC filings for a full discussion of risk factors - The press release contains forward-looking statements regarding the potential benefits and timing of clinical trials and regulatory submissions for icotrokinra and rusfertide[16](index=16&type=chunk) - These statements are subject to risks and uncertainties that could cause actual results to differ materially from those anticipated[16](index=16&type=chunk) - Investors are advised to review the 'Risk Factors' section in the company's most recent Form 10-K and 10-Q filings with the SEC for more information[16](index=16&type=chunk)

Icotrokinra (JNJ-2113) - Oral IL-23 Receptor Antagonist - Icotrokinra has the potential for NDA filings in 2025 for psoriasis[5, 8] - JNJ collaboration includes $3375 million upfront and milestones achieved to date, with $630 million in future potential milestones and royalties ranging from 6% to 10%, reaching 10% at ≥ $4 billion net sales[13] - Phase 3 ICONIC-LEAD study showed that 65% of patients achieved an IGA score of 0/1 (clear or almost clear skin) and 50% achieved a PASI 90 response at Week 16[121] - In adolescents receiving Icotrokinra, skin response rates increased through Week 24, with 86% achieving IGA 0/1 and 89% achieving PASI 90[76] - In the ICONIC-TOTAL study, Icotrokinra demonstrated significantly higher rates of IGA 0/1 vs placebo at Week 16[95] - Clinical response rates of up to 635% and clinical remission rates up to 302% at week 12 were observed in the phase 2b ANTHEM-UC study for ulcerative colitis[58, 149] Rusfertide - SC Hepcidin Mimetic - Rusfertide also has the potential for NDA filing in Q4 2025 for Polycythemia Vera (PV)[6, 8] - Takeda partnership includes $300 million upfront received in January 2024[16] - In the VERIFY Phase 3 study, 769% of patients on rusfertide achieved clinical response compared to 329% on placebo (p<00001)[178] - The VERIFY study also met all four key secondary endpoints, including phlebotomy rate (p<00001), hematocrit control, and patient-reported outcomes[185] - Rusfertide may provide consistent hematocrit control and reduce treatment burden to achieve peak revenue potential of $1-2 billion[191, 192] PN-881 - Oral IL-17 Antagonist - Phase 1 study initiation for oral IL-17 antagonist PN-881 is expected in Q4 2025[8, 26] - IL-17 inhibitors are expected to capture 31% of the psoriasis (PsO) market by 2031, generating $93 billion[26]

Protagonist Therapeutics (PTGX) Conference Call Summary Company Overview - **Company**: Protagonist Therapeutics (PTGX) - **Date of Call**: June 30, 2025 - **Key Speakers**: - Dr. Dinesh Patel, President and CEO - Dr. Newman Yielding, Chief Scientific Officer - Asif Ali, CFO - Dr. Sam Sachs, Clinical Development Advisor - Dr. Kirk Waze, Clinical Advisor on obesity program Core Industry and Product Focus - **Industry**: Biotechnology, specifically focusing on obesity treatment - **Product**: PN-477, a novel triple receptor agonist for obesity treatment targeting GLP, GIP, and GCG receptors Key Points and Arguments 1. **Product Development**: PN-477 is a triple agonist with high potency against GLP, GIP, and GCG receptors, designed for both oral and subcutaneous administration [6][10][29] 2. **Obesity Epidemic**: Nearly 75% of the U.S. population is overweight or obese, with 40% qualifying as obese (BMI ≥ 30). Current injectable treatments only reach about 2% of eligible patients, indicating significant unmet needs [7][8] 3. **Market Opportunity**: The current market is dominated by injectable drugs (semaglutide and tirzepatide), which have limitations in accessibility and patient compliance. An oral option is highly desirable [8][9] 4. **Clinical Development Strategy**: Protagonist plans to develop both oral and subcutaneous formulations of PN-477 to maximize treatment options for patients and healthcare providers [11][32] 5. **Preclinical Data**: PN-477 demonstrated up to 50% weight loss in diet-induced obesity (DIO) mouse models, showing superior efficacy compared to existing treatments [18][30] 6. **Pharmacokinetics**: Oral dosing in monkeys resulted in sustained weight loss of up to 11% even after treatment cessation, indicating potential for long-term efficacy [24][25] 7. **Safety Profile**: The design of PN-477 aims to minimize gastrointestinal tolerability issues, which are common with current obesity treatments [10][68] 8. **Market Positioning**: PN-477 is positioned as a best-in-class agent with the flexibility of both oral and injectable forms, catering to diverse patient preferences [32][79] Additional Important Insights 1. **Long Half-Life**: Anticipated longer half-lives in humans based on preclinical data suggest potential for less frequent dosing, which could improve patient adherence [35][38] 2. **Bioavailability**: The focus is on achieving effective bioavailability for chronic therapy, with confidence in the oral formulation based on preclinical results [40][41] 3. **Regulatory Pathway**: Protagonist is preparing for IND enabling studies and aims to initiate clinical trials in the following year [31][32] 4. **Market Competition**: PN-477 is expected to compete with existing therapies like tirzepatide and retatrutide, with a focus on providing a more convenient and effective treatment option [75][78] Conclusion Protagonist Therapeutics is advancing its obesity treatment candidate PN-477, which offers a promising alternative to current injectable therapies. The dual formulation strategy, combined with strong preclinical data and a focus on patient compliance, positions the company well in the growing obesity treatment market. The upcoming clinical trials will be crucial in validating the efficacy and safety of PN-477.

Summary of Protagonist Therapeutics Inc (PTGX) Conference Call Company Overview - **Company**: Protagonist Therapeutics Inc (PTGX) - **Event**: 2025 Jefferies Global Healthcare Conference - **Date**: June 04, 2025 Key Highlights from ASCO - Protagonist Therapeutics presented at the ASCO conference, where their drug Rasvotide was featured in a plenary session, selected from over 7,500 abstracts submitted [4][5] - The drug demonstrated significant efficacy in phase two studies, with p-values less than 0.0001, and showed consistent results across various subgroups [5][6] - Rasvotide is noted for improving the quality of life for patients with polycythemia vera (PV), marking it as a disease experience modifying drug [5][6] - The safety profile of Rasvotide was discussed, indicating it is well tolerated with no extraordinary safety concerns observed [7][9] Market Potential and Treatment Paradigm - The drug is positioned to address a significant unmet need in the treatment of PV, which affects patients over a long duration, averaging twenty years [6][11] - Current treatment paradigms often fail to maintain hematocrit levels below 45%, with over 75% of patients not achieving this goal [10][11] - Rasvotide is described as the first erythrocytosis-specific agent, differentiating it from existing treatments that indiscriminately lower red blood cells [11] Partnership and Regulatory Strategy - Protagonist is collaborating with Takeda, who will take over regulatory responsibilities for the NDA filing with the FDA [16][17] - The partnership includes an opt-out scenario for commercialization rights, with significant financial incentives for opting out, including a $400 million fee and higher milestone payments [18][19][20] - The peak market potential for Rasvotide is estimated between $1 billion to $2 billion, with Protagonist believing it can achieve the higher end of this range [19] Pipeline Developments - Protagonist is advancing its second lead program, ICO, which is in pivotal stages for psoriasis and ulcerative colitis [24][35] - The company is also developing an oral IL-17 agent, which is expected to enter phase one studies in Q4 of this year, and an oral hepcidin mimetic [43][47] - The obesity franchise is being developed with a focus on oral candidates, aiming to differentiate from existing injectable treatments [46] Financial Strategy - Protagonist is considering cash allocation strategies due to an anticipated influx of cash from upcoming milestones and potential approvals [57][59] - The company is exploring share buybacks as a tax-efficient method to return value to shareholders [59] Conclusion - Protagonist Therapeutics is positioned for significant growth with its innovative drug Rasvotide, a strong partnership with Takeda, and a promising pipeline of oral therapies. The company is strategically planning for future financial stability and shareholder value enhancement.