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.

Protagonist Therapeutics Inc (PTGX) 2025 Conference June 04, 2025 01:25 PM ET Speaker0 All right. Welcome everyone to twenty twenty five Jefferies Global Healthcare Conference. My name is Roger Song, one of the senior analysts covering SMICHA Biotech in The US. It's my pleasure to have the first set chat with our next printing company, Protagonist Therapeutics. I welcome Dinesh Patel. Speaker1 Thank you. It has always been a pleasure. Awesome. We have even stopped counting the number of years we have been a ...

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]

Post-ASCO Update: Phase 3 VERIFY Study Results Protagonist Therapeutics, Inc. Newark, CA June 2, 2025 Forward-looking Statements This presentation and the accompanying oral presentation contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business stra ...

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]

Peptide Therapeutics Development - The company is focused on peptide therapeutics, with two novel peptides, icotrokinra and rusfertide, in advanced Phase 3 clinical development, with potential NDA submissions to the FDA in 2025 [91]. - Icotrokinra has shown significant clinical improvement in treating moderate-to-severe plaque psoriasis, with a PASI-90 response rate of 74% at Week 24 compared to 8% in the placebo group (P<0.001) in the ICONIC-LEAD trial [101]. - The Phase 2b Anthem-UC trial of icotrokinra met its primary endpoint of clinical response at Week 12, with a response rate of 63.5% for the highest dose compared to 27.0% for placebo (p<0.001) [102]. - The ICONIC-ASCEND trial will be initiated to demonstrate the superiority of icotrokinra compared to ustekinumab, an injectable biologic [98]. - Rusfertide is in Phase 3 development for the treatment of Polycythemia Vera (PV) with 293 patients enrolled in the VERIFY trial, which has shown a 77% clinical response rate compared to 33% for placebo [109][112]. - The primary endpoint of the VERIFY trial was met with statistical significance (p<0.0001), showing a mean of 0.5 phlebotomies per patient in the rusfertide arm versus 1.8 in the placebo arm [112]. - The company plans additional clinical studies of icotrokinra in ulcerative colitis and Crohn's disease [103]. - PN-881, a potential best-in-class oral peptide IL-17 antagonist, has been selected for development, with a Phase 1 study expected to initiate in Q4 2025 [107]. Financial Performance and Revenue - The company earned a total of $337.5 million in non-refundable payments from JNJ from inception in 2017 through March 31, 2025, and is eligible for up to $630.0 million in future milestone payments [105]. - License and collaboration revenue for the three months ended March 31, 2025, was $28.3 million, a decrease of 89% compared to $255 million in the same period in 2024 [134]. - License and collaboration revenue for Q1 2025 was $28.3 million, including $22.8 million from a milestone related to the Phase 3 VERIFY trial of rusfertide [136]. - For Q1 2024, license and collaboration revenue was $255.0 million, primarily from a $300.0 million upfront payment for the rusfertide license to Takeda [137]. - Cumulative net losses from inception through March 31, 2025, amount to $352.2 million, primarily due to research and development costs [120]. - The company expects revenue in 2025 to decrease significantly compared to 2024, primarily due to lower milestone achievements [140]. Research and Development Expenses - Research and development expenses for the three months ended March 31, 2025, were $35.9 million, an increase of 6% from $33.7 million in 2024 [134]. - Research and development expenses increased by $2.2 million, or 6%, from $33.7 million in Q1 2024 to $35.9 million in Q1 2025, driven by a $5.3 million increase in pre-clinical and drug discovery research expenses [141]. - The company anticipates continued significant research and development expenses as it prepares for regulatory filings and commercialization of rusfertide [130]. Cash and Financing Activities - Cash provided by operating activities for Q1 2025 was $125.4 million, significantly up from a cash used of $27.4 million in Q1 2024, primarily due to a $165.0 million milestone payment received [161]. - As of March 31, 2025, the company had $697.9 million in cash, cash equivalents, and marketable securities, up from $559.2 million at the end of 2024 [147]. - Cash provided by financing activities for Q1 2025 was $11.4 million, a $4.2 million increase compared to Q1 2024, primarily due to a $4.1 million increase in proceeds from stock issuance [163]. - The company had $697.9 million in cash, cash equivalents, and marketable securities as of March 31, 2025, up from $559.2 million at December 31, 2024 [166]. Collaborations and Agreements - Icotrokinra is co-developed with JNJ and Takeda, with the company primarily responsible for clinical development activities [92]. - The JNJ License and Collaboration Agreement was amended to increase milestone payments and eliminate certain previous milestone payments [108]. - The company received a one-time, non-refundable upfront payment of $300 million from Takeda under a collaboration agreement for rusfertide, with potential milestone payments of up to $305 million [111][114]. - Upcoming milestones under the Takeda agreement include tiered royalties of 10% to 17% on ex-U.S. net sales of rusfertide [114][115]. - Upcoming potential milestones under the Takeda Collaboration Agreement include a $50.0 million increase for a Phase 3 clinical trial milestone and various NDA approval milestones for rusfertide and icotrokinra [150][151][152]. Interest Income and Market Risks - Interest income increased by 73% to $7.6 million for the three months ended March 31, 2025, compared to $4.4 million in 2024 [134]. - Interest income rose by $3.2 million, or 73%, from $4.4 million in Q1 2024 to $7.6 million in Q1 2025, attributed to higher invested balances [145]. - An immediate 100 basis point increase in interest rates would increase annual interest income by approximately $3.4 million, while a decrease would have the same negative impact [166]. - The company is exposed to market risks, including interest rate sensitivities and inflation risk affecting labor and clinical trial costs [165]. Operational Insights - Inflation has not had a material adverse effect on the company's operations during Q1 2025 [168]. - There were no material changes to the company's cash requirements or commitments for capital expenditures during Q1 2025 [164]. - The company has not implemented a formal hedging program for foreign currency but may consider it if exposure increases significantly [167]. - The majority of expenses related to Australian operations are denominated in Australian dollars, while other expenses are generally in U.S. dollars [167]. - Approximately $1.3 million of the cash balance was located in Australia as of March 31, 2025, compared to $0.6 million at December 31, 2024 [167].

Financial Performance - License and collaboration revenue for the first quarter of 2025 was $28.3 million, compared to $255.0 million for the same period in 2024[12] - Net loss for the first quarter of 2025 was $11.7 million, or $0.19 per share, compared to net income of $207.3 million, or $3.41 per share, for the first quarter of 2024[15] - Total stockholders' equity as of March 31, 2025, was $689.1 million, compared to $675.3 million as of December 31, 2024[23] Cash Position - Cash, cash equivalents, and marketable securities as of March 31, 2025, were $697.9 million, up from $559.2 million as of December 31, 2024[9] - The company anticipates cash runway through at least the end of 2028 based on its current cash position[2] Research and Development - Research and development expenses increased to $35.9 million in Q1 2025 from $33.7 million in Q1 2024[12] - The Phase 3 VERIFY trial of rusfertide met its primary endpoint with a significantly higher proportion of clinical responders compared to placebo (p<0.0001) during weeks 20-32[7] - Positive topline results from the Phase 2b ANTHEM trial of icotrokinra in ulcerative colitis were announced, laying the foundation for further studies[2] - The full dataset from the Phase 3 ICONIC-LEAD trial with icotrokinra was presented at the 2025 AAD Meeting in March[1] - The company is focusing on advancing pre-clinical candidates, including the oral IL-17 antagonist PN-881, in 2025[2]

Core Viewpoint - Protagonist Therapeutics (PTGX) has shown a significant price increase of 45.9% over the past four weeks, with analysts suggesting further upside potential based on price targets and earnings estimates [1][11]. Price Targets - The mean price target for PTGX is $66.90, indicating a potential upside of 27.4% from the current price of $52.53 [1]. - The mean estimate consists of 10 short-term price targets with a standard deviation of $11.56, suggesting variability in analyst predictions [2]. - The lowest estimate is $38, indicating a potential decline of 27.7%, while the highest estimate is $80, suggesting a potential increase of 52.3% [2]. Analyst Consensus and Earnings Estimates - There is strong agreement among analysts regarding PTGX's ability to report better earnings than previously predicted, which supports the view of potential upside [4][11]. - The Zacks Consensus Estimate for the current year has increased by 6.9% over the past month, with three estimates going higher and one going lower [12]. - PTGX holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13]. Limitations of Price Targets - Analysts' price targets can often mislead investors, as empirical research indicates that they rarely accurately predict stock price movements [7][10]. - Analysts may set overly optimistic price targets due to business incentives, which can inflate expectations [8]. - A low standard deviation in price targets indicates a high degree of agreement among analysts, but it does not guarantee that the stock will reach the average target [9].

Core Viewpoint - Protagonist Therapeutics (PTGX) has received a Zacks Rank 2 (Buy) upgrade, indicating a positive trend in earnings estimates which is a significant factor influencing stock prices [1][3]. Earnings Estimates and Stock Price Impact - The Zacks rating system is based on changes in earnings estimates, which are closely correlated with near-term stock price movements [4][6]. - Rising earnings estimates for Protagonist Therapeutics suggest an improvement in the company's underlying business, likely leading to an increase in stock price [5][10]. Zacks Rating System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a strong historical performance, particularly Zacks Rank 1 stocks averaging a +25% annual return since 1988 [7][9]. - Protagonist Therapeutics' upgrade to Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, indicating a strong potential for market-beating returns in the near term [10]. Earnings Estimate Revisions - Protagonist Therapeutics is projected to earn -$1.23 per share for the fiscal year ending December 2025, reflecting a year-over-year change of -129.1% [8]. - Over the past three months, the Zacks Consensus Estimate for Protagonist Therapeutics has increased by 11.2%, indicating a positive revision trend [8].