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.

Summary of Protagonist Therapeutics Inc (PTGX) Conference Call - June 02, 2025 Company Overview - **Company**: Protagonist Therapeutics Inc (PTGX) - **Focus**: Discovery and development of peptide therapeutics - **Key Products**: Ruspatercept (Respotec) and Iotrokinra, both nearing NDA filing Industry Context - **Industry**: Biotechnology, specifically focused on treatments for polycythemia vera (PV) - **Collaboration**: Partnership with Takeda Pharmaceuticals for co-development and commercialization of ruspatercept Key Findings from the VERIFI Study - **Study Design**: Phase 3 randomized double-blind placebo-controlled study of ruspatercept in patients with phlebotomy-dependent PV - **Primary Endpoint**: 77% of ruspatercept patients achieved clinical response compared to 33% in the placebo group, with a p-value of <0.0001 [14] - **Secondary Endpoints**: - Mean number of phlebotomies: 0.5 for ruspatercept vs. 1.8 for placebo, p-value <0.0001 [18] - 73% of ruspatercept patients had zero phlebotomies during the treatment period [19] - Hematocrit control: Ruspatercept maintained hematocrit below 45% significantly better than placebo [20] - **Patient-Reported Outcomes (PROs)**: - Significant improvement in fatigue (PROMIS Fatigue Questionnaire) with a p-value of 0.03 [22] - Improvement in symptoms measured by MFSAF with a p-value of 0.24 [24] Safety Profile - **Adverse Events**: Generally well tolerated, with most adverse events being mild to moderate [26] - **Cancer Incidence**: No new safety signals; cancer rates were similar between treatment and placebo groups [28] Market Potential - **Revenue Potential**: Takeda estimates $1 to $2 billion market potential for ruspatercept in PV [32] - **Adoption Strategy**: Ruspatercept is positioned to potentially become a new standard of care in PV treatment [31] Regulatory and Commercial Strategy - **NDA Filing**: Planned for Q4 2025 [39] - **Commercial Readiness**: Takeda is preparing for the launch and marketing of ruspatercept [38] Additional Insights - **Patient Demographics**: The study included a diverse patient population, with a notable percentage having high-risk disease characteristics [11] - **Future Studies**: Ongoing analysis of long-term effects and potential combination therapies with ruspatercept [46][51] - **Payer Considerations**: The unique mechanism of action and patient experience improvements are expected to resonate well with payers [82] Conclusion - **Overall Assessment**: The VERIFI study results are seen as practice-changing, with ruspatercept showing significant efficacy, safety, and potential to improve patient quality of life in the treatment of PV [29][30]

VERIFY Study Results - The Phase 3 VERIFY study met its primary endpoint, with 76.9% of patients in the rusfertide plus current standard-of-care (CSC) group achieving a clinical response compared to 32.9% in the placebo plus CSC group (p<0.0001)[14] - Rusfertide significantly reduced the mean number of phlebotomies (PHL) from weeks 0-32, with the rusfertide group averaging 0.5 PHL compared to 1.8 PHL in the placebo group (p<0.0001)[21] - 72.8% of patients in the rusfertide group experienced freedom from phlebotomy during weeks 0-32, compared to only 21.9% in the placebo group[23] - 62.6% of patients in the rusfertide group maintained a hematocrit (Hct) level below 45% from baseline through week 32, compared to 14.4% in the placebo group (p<0.0001)[26] Symptom Improvement - Rusfertide demonstrated a statistically significant improvement in fatigue symptoms as measured by the PROMIS Fatigue SF-8a, with a LS means difference of -1.95 between the rusfertide and placebo groups at week 32 (p=0.0268)[33] - Rusfertide also showed a statistically significant improvement in the MFSAF TSS7, with a LS means difference of -1.87 between the rusfertide and placebo groups at week 32 (p=0.0239)[39] Safety and Tolerability - The most common treatment-emergent adverse events (TEAEs) in the rusfertide group were injection site reactions (55.9%) and anemia (15.9%)[46] - Discontinuation rates due to TEAEs were 5.5% in the rusfertide group and 2.7% in the placebo group[47] Commercial Potential and Partnership - Rusfertide has a peak revenue potential of $1-2 billion[53] - Protagonist Therapeutics has a partnership with Takeda for the commercialization of rusfertide, with potential milestones up to $975 million and royalty rates of 14-29% worldwide if Takeda opts out of a 50:50 US profit/loss share[59]

Group 1 - Protagonist Therapeutics reported a quarterly loss of $0.19 per share, significantly better than the Zacks Consensus Estimate of a loss of $0.50, representing an earnings surprise of 62% [1] - The company posted revenues of $28.32 million for the quarter ended March 2025, exceeding the Zacks Consensus Estimate by 149.90%, compared to year-ago revenues of $254.95 million [2] - Protagonist Therapeutics shares have increased by approximately 14.7% since the beginning of the year, contrasting with the S&P 500's decline of -3.9% [3] Group 2 - The current consensus EPS estimate for the upcoming quarter is -$0.56 on revenues of $11.33 million, and for the current fiscal year, it is -$1.23 on revenues of $97.8 million [7] - The Medical - Biomedical and Genetics industry, to which Protagonist Therapeutics belongs, is currently ranked in the top 31% of over 250 Zacks industries, indicating a favorable outlook [8]