Company Overview - Verrica Pharmaceuticals Inc. (NASDAQ:VRCA) is focused on developing and commercializing treatments for skin diseases, with its lead product candidate, VP-102, targeting molluscum contagiosum [1] Financial Performance - VRCA has a Return on Invested Capital (ROIC) of -166.93%, significantly lower than its Weighted Average Cost of Capital (WACC) of 17.69%, indicating inefficiencies in capital utilization [2][6] - The ROIC to WACC ratio for VRCA is -9.44, further emphasizing the challenge in generating sufficient returns to cover its cost of capital [2] Comparative Analysis - Y-mAbs Therapeutics (YMAB) has a ROIC of -27.64% and a WACC of 6.11%, resulting in a ROIC to WACC ratio of -4.53, making it the least inefficient among its peers [3][5] - Scholar Rock Holding Corporation (SRRK) shows a ROIC of -109.48% against a WACC of 5.32%, leading to a ROIC to WACC ratio of -20.57, indicating similar inefficiencies as VRCA [4] - Crinetics Pharmaceuticals (CRNX) and Kezar Life Sciences (KZR) also exhibit negative ROIC to WACC ratios of -6.99 and -10.94, respectively, highlighting broader challenges within the sector [4][5] Sector Insights - All companies analyzed, including VRCA, are currently operating at a loss relative to their cost of capital, with Y-mAbs Therapeutics managing its capital more effectively than its peers [5][6]

Core Viewpoint - Kezar Life Sciences, Inc. (KZR) has received an upgrade to a Zacks Rank 2 (Buy), indicating a positive trend in earnings estimates which is a significant factor influencing stock prices [1][3]. Earnings Estimates and Stock Performance - The Zacks rating system tracks the Zacks Consensus Estimate, which reflects EPS estimates from sell-side analysts for the current and following years, highlighting the importance of earnings revisions in stock valuation [1][4]. - A strong correlation exists between changes in earnings estimates and near-term stock price movements, primarily due to institutional investors adjusting their valuations based on these estimates [4][6]. Recent Developments for Kezar Life Sciences - For the fiscal year ending December 2025, Kezar Life Sciences is expected to earn -$7.22 per share, which remains unchanged from the previous year, but analysts have raised their estimates by 3.4% over the past three months [8]. - The upgrade to Zacks Rank 2 places Kezar Life Sciences in the top 20% of Zacks-covered stocks, suggesting potential for higher stock prices in the near term [10]. Zacks Rating System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a proven track record of Zacks Rank 1 stocks generating an average annual return of +25% since 1988 [7][9]. - The system maintains a balanced distribution of "buy" and "sell" ratings, ensuring that only the top 5% of stocks receive a "Strong Buy" rating, indicating superior earnings estimate revisions [9][10].

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q _______________________________________________________________________________________________ (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ______________ to ______________ Commission Fil ...

[Kezar Life Sciences Reports Second Quarter 2025 Financial Results and Provides Business Update](index=1&type=section&id=Kezar%20Life%20Sciences%20Reports%20Second%20Quarter%202025%20Financial%20Results%20and%20Provides%20Business%20Update) Kezar Life Sciences announced its Q2 2025 financial results and provided updates on clinical development and regulatory progress for zetomipzomib [Company Announcement & CEO Statement](index=1&type=section&id=Company%20Announcement%20%26%20CEO%20Statement) Kezar Life Sciences reported Q2 2025 financial results and business updates, with CEO Chris Kirk highlighting zetomipzomib's clinical development and regulatory submission progress for autoimmune hepatitis - Kezar Life Sciences, a clinical-stage biotechnology company, reported financial results for the second quarter ended June 30, 2025, and provided a business update on August 13, 2025[1](index=1&type=chunk)[2](index=2&type=chunk) - CEO Chris Kirk stated the company is on track with clinical development and regulatory submission for zetomipzomib in autoimmune hepatitis, proposing a registration-enabling study and anticipating a Type C meeting with the FDA[3](index=3&type=chunk) [Business Update](index=1&type=section&id=Business%20Update) This section details the clinical and regulatory advancements for zetomipzomib, corporate personnel changes, and upcoming medical conference presentations [Zetomipzomib Clinical & Regulatory Progress](index=1&type=section&id=Zetomipzomib%20Clinical%20%26%20Regulatory%20Progress) Kezar achieved significant milestones for zetomipzomib, including FDA's removal of a partial clinical hold on the PORTOLA Phase 2a trial for autoimmune hepatitis (AIH) and the submission of a Type C meeting request to discuss the AIH development plan - FDA removed partial clinical hold on PORTOLA Phase 2a trial evaluating zetomipzomib for autoimmune hepatitis (AIH) in July[5](index=5&type=chunk)[6](index=6&type=chunk) - Submitted Type C meeting request to the FDA to meet during Q4 2025 to discuss the AIH development plan for zetomipzomib[5](index=5&type=chunk)[6](index=6&type=chunk) - Submitted a complete response to the FDA Division of Rheumatology and Transplant Medicine with a request to remove the clinical hold on zetomipzomib in lupus nephritis[7](index=7&type=chunk) - PORTOLA Phase 2a trial results in relapsed or refractory AIH patients showed **36% (5 of 14) achieved a complete biochemical response (CR)** and clinically significant steroid taper to 5 mg/day or less by 6 months, compared to 0 of 7 placebo patients[6](index=6&type=chunk) - The median duration of response in zetomipzomib patients achieving CR was **27.6 weeks**, with no disease flares reported during the study[6](index=6&type=chunk) - A favorable safety profile was observed during the 6-month blinded treatment period[6](index=6&type=chunk) [Corporate & Personnel Updates](index=2&type=section&id=Corporate%20%26%20Personnel%20Updates) Zung To was promoted to Chief Development Officer in June 2025, bringing 35 years of industry experience and leading Kezar's development strategy - Zung To was promoted to Chief Development Officer in June 2025, bringing **35 years of industry experience**, including over 20 years in senior leadership roles in clinical development[8](index=8&type=chunk) [Medical Conference Presentations](index=2&type=section&id=Medical%20Conference%20Presentations) PORTOLA Phase 2a data and biomarker data have been selected for oral and poster presentations, respectively, at The Liver Meeting® 2025 in November - An abstract featuring PORTOLA Phase 2a data has been selected for an oral presentation at The Liver Meeting® 2025 (November 7-11, Washington, DC)[5](index=5&type=chunk)[10](index=10&type=chunk) - An abstract featuring PORTOLA biomarker data has been selected for poster presentation at The Liver Meeting® 2025[10](index=10&type=chunk) [Financial Results](index=2&type=section&id=Financial%20Results) This section presents Kezar's second quarter 2025 financial performance, including key income statement and balance sheet data [Summary of Q2 2025 Financial Performance](index=2&type=section&id=Summary%20of%20Q2%202025%20Financial%20Performance) Kezar reported a net loss of $13.7 million for Q2 2025, an improvement from $21.5 million in Q2 2024, driven by decreased R&D, G&A, and restructuring expenses Key Financial Highlights (Q2 2025 vs Q2 2024) | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (Millions) | | :-------------------------------- | :----------------- | :----------------- | :---------------- | | Cash, Cash Equivalents & Marketable Securities (as of period end) | $100.8 | $132.2 (Dec 31, 2024) | $(31.4) | | Research & Development (R&D) Expenses | $9.6 | $16.3 | $(6.7) | | General & Administrative (G&A) Expenses | $5.0 | $5.6 | $(0.6) | | Restructuring & Impairment Charges | $0.0 | $1.5 | $(1.5) | | Net Loss | $(13.7) | $(21.5) | $7.8 | | Net Loss per Share (Basic & Diluted) | $(1.87) | $(2.96) | $1.09 | - The decrease in R&D expenses was primarily due to reduced clinical activities from trial completion and closeout, lower personnel costs (including non-cash stock-based compensation), and decreased facility-related expenses[11](index=11&type=chunk) - The decrease in G&A expenses was mainly attributable to lower non-cash stock-based compensation and personnel-related expenses[11](index=11&type=chunk) - Restructuring and impairment charges decreased due to an impairment charge in 2024 related to a vacated floor in the company's leased office facility[11](index=11&type=chunk) [Selected Balance Sheets Data](index=3&type=section&id=Selected%20Balance%20Sheets%20Data) As of June 30, 2025, Kezar's cash, cash equivalents, and marketable securities totaled $100.8 million, a decrease from December 31, 2024, with all major balance sheet items also decreasing Selected Balance Sheets Data (as of June 30, 2025 vs. December 31, 2024) | Metric (in thousands) | June 30, 2025 | December 31, 2024 | Change | | :----------------------------------- | :------------ | :---------------- | :----- | | Cash, cash equivalents and marketable securities | $100,849 | $132,245 | $(31,396) | | Total assets | $109,123 | $144,682 | $(35,559) | | Total current liabilities | $14,365 | $20,329 | $(5,964) | | Total noncurrent liabilities | $2,972 | $7,437 | $(4,465) | | Total stockholders' equity | $91,786 | $116,916 | $(25,130) | [Summary of Operations Data](index=3&type=section&id=Summary%20of%20Operations%20Data) For Q2 2025, total operating expenses decreased significantly to $14.6 million, resulting in a reduced net loss of $13.7 million, with similar trends observed for the six-month period Summary of Operations Data (Three Months Ended June 30) | Metric (in thousands) | Q2 2025 | Q2 2024 | Change | | :------------------------------------------ | :------ | :------ | :----- | | Research and development | $9,583 | $16,298 | $(6,715) | | General and administrative | $5,016 | $5,603 | $(587) | | Restructuring and impairment charges | $0 | $1,482 | $(1,482) | | Total operating expenses | $14,599 | $23,383 | $(8,784) | | Loss from operations | $(14,599) | $(23,383) | $8,784 | | Interest income | $1,197 | $2,237 | $(1,040) | | Interest expense | $(302) | $(401) | $99 | | Net loss | $(13,704) | $(21,547) | $7,843 | | Net loss per common share, basic and diluted | $(1.87) | $(2.96) | $1.09 | | Weighted-average shares used to compute net loss per common share, basic and diluted | 7,311,032 | 7,284,587 | 26,445 | Summary of Operations Data (Six Months Ended June 30) | Metric (in thousands) | H1 2025 | H1 2024 | Change | | :------------------------------------------ | :------ | :------ | :----- | | Research and development | $21,763 | $33,470 | $(11,707) | | General and administrative | $10,465 | $12,142 | $(1,677) | | Restructuring and impairment charges | $0 | $1,482 | $(1,482) | | Total operating expenses | $32,228 | $47,094 | $(14,866) | | Loss from operations | $(32,228) | $(47,094) | $14,866 | | Interest income | $2,617 | $4,690 | $(2,073) | | Interest expense | $(649) | $(801) | $152 | | Net loss | $(30,260) | $(43,205) | $12,945 | | Net loss per common share, basic and diluted | $(4.14) | $(5.93) | $1.79 | | Weighted-average shares used to compute net loss per common share, basic and diluted | 7,308,360 | 7,282,289 | 26,071 | [About Kezar Life Sciences](index=3&type=section&id=About%20Kezar%20Life%20Sciences) This section provides an overview of Kezar Life Sciences as a clinical-stage biopharmaceutical company and its lead product candidate, zetomipzomib [Company Overview](index=3&type=section&id=Company%20Overview) Kezar Life Sciences is a clinical-stage biopharmaceutical company developing novel small molecule therapeutics for immune-mediated diseases, with zetomipzomib as its lead product candidate for autoimmune hepatitis - Kezar Life Sciences is a clinical-stage biopharmaceutical company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases[12](index=12&type=chunk) - Zetomipzomib, a selective immunoproteasome inhibitor, is currently being evaluated for autoimmune hepatitis and has the potential to address multiple chronic immune-mediated diseases[12](index=12&type=chunk) [Cautionary Note on Forward-looking Statements](index=3&type=section&id=Cautionary%20Note%20on%20Forward-looking%20Statements) This section provides a disclaimer regarding forward-looking statements, outlining inherent risks and uncertainties that may affect actual results [Forward-looking Statements Disclaimer](index=3&type=section&id=Forward-looking%20Statements%20Disclaimer) This section serves as a disclaimer, indicating that the press release contains forward-looking statements subject to risks and uncertainties that could cause actual results to differ materially - The press release contains forward-looking statements regarding clinical development programs, regulatory submission plans for zetomipzomib in AIH, and the likelihood of obtaining regulatory approval[13](index=13&type=chunk) - These statements involve risks and uncertainties, such as unexpected safety or efficacy data, difficulties in clinical trials, changes in competition or the regulatory environment, and the timing of the regulatory approval process, which could cause actual results to differ materially[13](index=13&type=chunk) - Kezar assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, except as required by law[13](index=13&type=chunk)

Zetomipzomib in Autoimmune Hepatitis (AIH) - The PORTOLA Phase 2 study evaluated zetomipzomib in AIH patients with relapsed disease or inadequate response to prior therapy [16] - In a pre-specified subgroup of patients on steroid-based therapy (n=21), 36% (5/14) of zetomipzomib-treated patients achieved a steroid-sparing complete biochemical remission (CR) by Week 24, compared to 0% (0/7) in the placebo arm [18] - In the Intent to Treat (ITT) population (n=24), 31.3% (5/16) of zetomipzomib-treated patients achieved a steroid-sparing CR by Week 24 versus 12.5% (1/8) in the placebo arm [18] - The PORTOLA results support a registrational program in AIH, a disease affecting approximately 100,000 patients in the US [17, 21] - The company plans to present PORTOLA results at a major medical conference in the second half of 2025 [43] Zetomipzomib in Lupus Nephritis (LN) - In the MISSION Phase 2 study, 35% of LN patients achieved a complete renal response (CRR) following 25 weeks of treatment without induction therapy [48, 50] - In the PALIZADE Phase 2 study, over 40% of patients achieved a UPCR ≤0.5 at Week 25 in the 60 mg zetomipzomib dose group [48] - The MISSION Phase 2 study showed an 83% median reduction in UPCR from baseline to Week 29 (4 weeks post-EOT) [50] - In the PALIZADE trial, the median percent change in UPCR from baseline at Week 25 was -67% in the Zetomipzomib 60mg group [54] Safety and Tolerability - In the PORTOLA study, the most common treatment emergent adverse events (TEAEs) were injection site reactions (ISRs) and systemic injection reactions (SIRs), all of which were Grade 1 or Grade 2 [18]

Key Takeaways from Kezar Life Sciences (KZR) 2025 Conference Company Overview - **Company**: Kezar Life Sciences - **Focus**: Development of zetomipsumab (Zito), the first selective inhibitor of the immunoproteosome in clinical development, targeting autoimmune hepatitis (AIH) [5][6] Industry Context - **Market Opportunity**: Approximately 100,000 patients in the United States suffer from AIH, with no new treatments in over three decades [5][6] - **Competitive Landscape**: No other drugs currently in development for AIH; Novartis discontinued its Phase II study last year [6] Core Product Insights - **Mechanism of Action**: Zito modulates immune responses without inducing cell depletion or immunosuppression, targeting all arms of the immune system [7][8] - **Clinical Data**: - In the Portola study, over 30% of Zito patients achieved steroid-free remission, a significant improvement compared to the placebo group [14][15] - Median duration of response for complete remission was just under 7 months, exceeding expectations [15] Safety and Regulatory Considerations - **Partial Clinical Hold**: The company is under a partial clinical hold due to safety concerns from a lupus nephritis study, which resulted in fatalities [20][22] - **Safety Profile**: Zito showed a favorable safety profile in AIH patients compared to lupus nephritis patients, with no disease flares reported in the AIH study [24][32] Future Development Plans - **Next Steps**: The company plans to submit a comprehensive safety summary to the FDA to lift the partial clinical hold and initiate a pivotal study for AIH [25][39] - **Study Design**: The pivotal study is expected to be similar to the Portola study, focusing on steroid-dependent second-line AIH patients [41][42] Market Potential and Pricing Strategy - **Addressable Patient Population**: Estimated 40,000 to 60,000 second-line AIH patients in the U.S. [56] - **Pricing Strategy**: Comparable to drugs for primary biliary cholangitis, potentially around $150,000 per year, leading to a blockbuster market opportunity [58] Intellectual Property and Exclusivity - **Patent Expiration**: Current composition of matter patent for Zito is expected to expire in 2039, with potential for orphan drug designation providing additional market exclusivity [61][62] Financial Position - **Cash Reserves**: The company reported $114 million in cash, sufficient to navigate key inflection points and fund upcoming trials [64] Key Inflection Points - **Upcoming Milestones**: - Lifting of the clinical hold - Alignment with the FDA on the next trial design - Potential partnerships for global market expansion [63][59] Conclusion Kezar Life Sciences is positioned to address a significant unmet need in the treatment of autoimmune hepatitis with its innovative drug Zito. The company is navigating regulatory challenges while preparing for pivotal studies that could unlock substantial market potential.

Core Viewpoint - Kezar Life Sciences, Inc. (KZR) has received an upgrade to a Zacks Rank 2 (Buy), indicating a positive outlook driven by rising earnings estimates, which significantly influence stock prices [1][4][6]. Earnings Estimates and Stock Performance - The Zacks rating system focuses on a company's changing earnings picture, with the Zacks Consensus Estimate tracking EPS estimates from sell-side analysts [2]. - Changes in earnings estimates are strongly correlated with near-term stock price movements, largely due to institutional investors adjusting their valuations based on these estimates [5][7]. - For Kezar Life Sciences, the Zacks Consensus Estimate for the fiscal year ending December 2025 is projected at -$8.19 per share, reflecting a 27.5% change from the previous year [9]. Zacks Rating System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a strong historical performance, particularly for Zacks Rank 1 stocks, which have averaged a +25% annual return since 1988 [8]. - The upgrade of Kezar Life Sciences to a 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][11].

Financial Performance - The company reported a net loss of $16.6 million for the three months ended March 31, 2025, compared to a net loss of $21.7 million for the same period in 2024, reflecting a decrease of $5.1 million [118]. - Total operating expenses for the three months ended March 31, 2025, were $17.7 million, down from $23.7 million in the same period of 2024, a decrease of $6.0 million [118]. - Net cash used in operating activities for Q1 2025 was $17.2 million, compared to $22.9 million in Q1 2024, indicating a decrease of 25% [133][134]. - The net loss for Q1 2025 was $16.6 million, with non-cash charges of $2.5 million, including $2.8 million for stock-based compensation [134]. Research and Development - Research and development expenses decreased to $12.2 million for the three months ended March 31, 2025, down from $17.2 million in the same period of 2024, primarily due to a $3.4 million reduction in clinical expenses [111][119]. - The company is focusing its clinical development efforts on zetomipzomib for the treatment of autoimmune diseases, having discontinued development of KZR-261 and the PALIZADE trial [114]. Financial Position - The accumulated deficit as of March 31, 2025, was $451.1 million, indicating significant ongoing operating losses since inception [105][124]. - The company had $114.4 million in cash, cash equivalents, and marketable securities as of March 31, 2025, which is expected to meet projected operating requirements for at least the next 12 months [123][125]. - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities totaling $114.4 million [143]. - The average maturity of cash equivalents and marketable securities was approximately three months, with the longest maturity being nine months [143]. - The company maintains a diversified investment portfolio with a maximum credit exposure limit of 10% to any one issuer, except for U.S. Treasury and Federal Agencies [145]. - Approximately $0.6 million of cash and marketable securities were located in Australia, with expenses generally denominated in U.S. dollars [146]. - A 10% change in current exchange rates would not have a material effect on the company's consolidated financial results [146]. Funding and Financing - The company has no products approved for commercial sale and does not expect to generate revenue from product sales in the near future [107][108]. - The company has a loan agreement with Oxford Finance providing up to $50.0 million in borrowing capacity, with the initial tranche of $10.0 million funded [126]. - Future funding requirements will depend on various factors, including the progress and costs of clinical trials, regulatory approvals, and the ability to attract and retain qualified personnel [128]. - The company requires additional financing to fund working capital and pay obligations, with no committed external sources of funding currently available [132]. - Interest income decreased by $1.0 million to $1.4 million for the three months ended March 31, 2025, compared to $2.4 million in the same period of 2024, primarily due to a decrease in cash equivalents and marketable securities [121]. Cash Flow - Cash provided by investing activities was $13.7 million in Q1 2025, down from $20.4 million in Q1 2024, primarily due to maturities of marketable securities [137]. - Net cash used in financing activities for Q1 2025 was $1.3 million, primarily from loan repayments, with no financing activities reported in Q1 2024 [138].

Financial Performance - Cash, cash equivalents, and marketable securities totaled $114.4 million as of March 31, 2025, down from $132.2 million as of December 31, 2024, primarily due to cash used in operations[9] - Net loss for Q1 2025 was $16.6 million, or $2.27 per basic and diluted common share, compared to a net loss of $21.7 million, or $2.98 per basic and diluted common share, for Q1 2024[9] - Total stockholders' equity decreased to $103.1 million as of March 31, 2025, from $116.9 million as of December 31, 2024[12] - Total operating expenses for Q1 2025 were $17.6 million, down from $23.7 million in Q1 2024[13] Research and Development - Research and development (R&D) expenses for Q1 2025 decreased by $5.0 million to $12.2 million, compared to $17.2 million in Q1 2024, due to decreased clinical activities following the termination of the PALIZADE trial[9] - In the PORTOLA Phase 2a clinical trial, 36% of zetomipzomib-treated patients achieved a complete biochemical response and clinically significant steroid taper, compared to 0% of placebo patients[5] - The median duration of response in zetomipzomib patients achieving a complete response was 27.6 weeks, with no disease flares reported during the study[5] - The PORTOLA trial enrolled 24 patients, randomized (2:1) to receive 60 mg of zetomipzomib or placebo for 24 weeks[8] - The median urine protein-to-creatinine ratio (UPCR) was reduced by 79% from baseline in patients receiving 60 mg of zetomipzomib[6] General and Administrative Expenses - General and administrative (G&A) expenses for Q1 2025 decreased by $1.1 million to $5.4 million compared to $6.5 million in Q1 2024, primarily due to reduced legal and professional service expenses[9]

Financial Data and Key Metrics Changes - The Portola trial enrolled 24 patients, with 21 in a prespecified subgroup on steroid therapy. 36% of patients receiving zetomipsemib achieved complete biochemical remission by week 24 compared to none in the placebo arm [4][16] - The safety profile of zetomipsemib was favorable, with most treatment-emergent adverse events being grade one and two, primarily related to injection site reactions [5][19] Business Line Data and Key Metrics Changes - The trial demonstrated that responses to zetomipsemib were durable, with no flares reported for patients achieving complete remission [4][16] - 20 patients completed the double-blind treatment period, with 16 eligible for the open-label extension, indicating a strong continuation of treatment [11] Market Data and Key Metrics Changes - Autoimmune hepatitis affects nearly 100,000 patients in the United States, with a significant unmet need for effective treatments [5][21] - The trial results suggest that zetomipsemib could transform the treatment landscape for autoimmune hepatitis, which currently lacks additional therapeutic options [7][21] Company Strategy and Development Direction - The company aims to respond to the FDA regarding the partial clinical hold on the Portola study and plans to align with regulatory bodies for a potential registrational study of zetomipsemib in autoimmune hepatitis [51] - Future studies may mandate steroid tapering as a key endpoint, reflecting a commitment to improving treatment protocols [61] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the data from the Portola study, highlighting the potential for zetomipsemib to address the needs of patients with autoimmune hepatitis [22][51] - The management acknowledged the challenges in designing a phase three study due to the lack of regulatory precedent but emphasized the importance of biochemical remission and histologic improvement as endpoints [80] Other Important Information - The trial included an open-label extension for some patients, with ongoing data collection to assess long-term outcomes [11][51] - The company highlighted the need for new agents in the treatment of autoimmune hepatitis, as current therapies have significant side effects and limited efficacy [21][47] Q&A Session Summary Question: Concerns with zetomipsemib and lupus nephritis - Craig Lammert noted that injection site reactions were minor and manageable, with no significant safety concerns observed in the Portola study [56][57] - Christopher Kirk added that systemic injection reactions were consistent with previous studies, indicating a tolerable safety profile [59] Question: Biochemical remission without steroid taper - Christopher Kirk explained that the protocol suggested but did not mandate steroid tapering, with physicians making decisions based on individual patient responses [61] - Craig Lammert emphasized the real-world challenges in managing autoimmune hepatitis and the need for a more rigorous approach in future studies [63][64] Question: Infection rates in the trial - Divya Rao inquired about the higher infection rates in the placebo arm, to which Christopher Kirk responded that overall infection rates were consistent with previous trials [67] - Gideon Hirschfield noted that corticosteroids are a significant risk factor for infections, highlighting the unmet need for better therapies [70] Question: Clinical meaningfulness of the data - Craig Lammert discussed the importance of reducing liver test abnormalities and corticosteroid dependency, emphasizing the potential impact on patient quality of life [76] - Gideon Hirschfield agreed, stating that the trial population reflected patients struggling to control their disease, and the results indicated a meaningful biological effect [78] Question: Designing a phase three study - Christopher Kirk acknowledged the lack of regulatory guidance but emphasized the need for alignment with the FDA on trial design and endpoints [80]