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]

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].