[PART I — FINANCIAL INFORMATION](index=4&type=section&id=PART%20I.%20%E2%80%94%20FINANCIAL%20INFORMATION) This section presents the company's condensed consolidated financial statements and related disclosures [Item 1. Condensed Consolidated Financial Statements](index=4&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements) The financial statements show decreased assets, increased net loss, and significant cash reduction, raising going concern doubts [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets decreased to $48.3 million, driven by a significant cash drop, while liabilities and equity remained stable Condensed Consolidated Balance Sheet Highlights (in thousands of USD) | Balance Sheet Item | June 30, 2025 (unaudited) | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash | $2,207 | $8,002 | | Total current assets | $27,903 | $32,198 | | Total assets | $48,268 | $53,425 | | **Liabilities & Equity** | | | | Total current liabilities | $29,218 | $19,704 | | Total liabilities | $41,388 | $44,446 | | Total stockholders' equity | $6,880 | $6,494 | | **Total liabilities and stockholders' equity** | **$48,268** | **$53,425** | [Condensed Consolidated Statements of Operations](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) Net losses increased to $21.2 million for the six months, driven by higher operating expenses despite a slight revenue increase Statements of Operations Summary (in thousands of USD, except per share data) | Metric | Q2 2025 | Q2 2024 | 6 Months 2025 | 6 Months 2024 | | :--- | :--- | :--- | :--- | :--- | | Total revenue, net | $2,979 | $2,721 | $5,193 | $5,072 | | Total operating expenses | $10,986 | $9,918 | $22,621 | $20,484 | | Loss from operations | $(8,007) | $(7,197) | $(17,428) | $(15,412) | | Net loss | $(10,560) | $(9,628) | $(21,156) | $(18,996) | | Net loss per share | $(10.26) | $(2.66) | $(26.78) | $(7.80) | [Condensed Consolidated Statements of Cash Flows](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Cash decreased by $5.8 million, with $13.5 million used in operations and reduced financing activities Cash Flow Summary for Six Months Ended June 30 (in thousands of USD) | Cash Flow Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(13,509) | $(15,217) | | Net cash used in investing activities | $0 | $(16) | | Net cash provided by financing activities | $7,621 | $24,842 | | **Net increase (decrease) in cash** | **$(5,795)** | **$9,580** | | Cash at beginning of period | $8,002 | $6,469 | | **Cash at end of period** | **$2,207** | **$16,049** | [Notes to Condensed Consolidated Financial Statements](index=13&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Notes detail a going concern warning, revenue concentration, debt instruments, and equity transactions - The company has incurred recurring operating losses and has an accumulated deficit of **$367.4 million** as of June 30, 2025. Management has substantial doubt about the company's ability to continue as a going concern as current cash balances are not sufficient to fund operations for the next year[37](index=37&type=chunk)[38](index=38&type=chunk) - The company is highly dependent on two major customers, which accounted for **58%** and **30%** of total revenue for the three months ended June 30, 2025[53](index=53&type=chunk) - The company manages its operations through two segments: human health and animal health, with the human health segment focused on developing and commercializing products like Mytesi[36](index=36&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=78&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses plant-based medicines, OnTarget trial results, Gelclair launch, and critical liquidity concerns [Overview](index=78&type=section&id=Overview) Jaguar Health focuses on plant-based GI medicines, with mixed OnTarget trial results, a new Gelclair launch, and orphan disease development - The OnTarget Phase 3 clinical trial for prophylaxis of diarrhea in adult cancer patients did not meet its primary endpoint for all tumor types, but a prespecified subgroup analysis of breast cancer patients showed **statistical significance**[341](index=341&type=chunk) - The company entered into an exclusive 5-year in-license agreement for Gelclair, a prescription product for oral mucositis, and initiated its commercial launch in October 2024 to expand its cancer-related supportive care offerings[345](index=345&type=chunk) - Napo Therapeutics, a subsidiary, is focused on expanding crofelemer access in Europe for orphan diseases, initially targeting Short Bowel Syndrome (SBS-IF) and Microvillus Inclusion Disease (MVID)[346](index=346&type=chunk) [Results of Operations](index=91&type=section&id=Results%20of%20Operations) Revenue slightly increased, but operating expenses rose significantly due to sales and marketing for Gelclair, widening the operating loss Comparison of Results for Six Months Ended June 30 (in thousands of USD) | Item | 2025 | 2024 | Variance | Variance % | | :--- | :--- | :--- | :--- | :--- | | Total revenue | $5,193 | $5,072 | $121 | 2.4% | | Cost of product revenue | $1,042 | $857 | $185 | 21.6% | | Research and development | $6,995 | $7,965 | $(970) | (12.2)% | | Sales and marketing | $4,960 | $2,967 | $1,993 | 67.2% | | General and administrative | $9,624 | $8,695 | $929 | 10.7% | | Loss from operations | $(17,428) | $(15,412) | $(2,016) | 13.1% | | Net loss | $(21,156) | $(18,996) | $(2,160) | 11.4% | - The increase in Sales and Marketing expense was primarily due to a **$1.1 million** increase in personnel costs and a **$0.7 million** increase in direct marketing fees to support the Gelclair launch[414](index=414&type=chunk)[418](index=418&type=chunk) - The decrease in Research and Development expense was largely due to a **$0.9 million** reduction in clinical and contract manufacturing costs as the Phase 3 OnTarget Clinical Trial concluded[413](index=413&type=chunk)[415](index=415&type=chunk) [Liquidity and Capital Resources](index=103&type=section&id=Liquidity%20and%20Capital%20Resources) Cash reserves are critically low at $2.2 million, insufficient for future operations, necessitating additional funding to avoid curtailing activities - As of June 30, 2025, the company had cash of **$2.2 million** and an accumulated deficit of **$367.4 million**[438](index=438&type=chunk)[439](index=439&type=chunk) - Management acknowledges that current capital resources are not sufficient to fund the operating plan for at least one year, and if additional financing is not obtained, the company will need to curtail planned activities and reduce costs[439](index=439&type=chunk)[441](index=441&type=chunk) Cash Flow Summary for Six Months Ended June 30 (in thousands of USD) | Cash Flow Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(13,509) | $(15,217) | | Net cash provided by financing activities | $7,621 | $24,842 | | Net increase (decrease) in cash | $(5,795) | $9,580 | [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=107&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company states that quantitative and qualitative disclosures about market risk are not applicable - The company states that quantitative and qualitative disclosures about market risk are not applicable[458](index=458&type=chunk) [Item 4. Controls and Procedures](index=107&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were effective as of June 30, 2025 - Based on an evaluation as of June 30, 2025, the CEO and Principal Financial and Accounting Officer concluded that the company's disclosure controls and procedures were effective[460](index=460&type=chunk) - Management concluded that as of June 30, 2025, the company's internal control over financial reporting was effective based on the COSO 2013 framework[461](index=461&type=chunk) [PART II — OTHER INFORMATION](index=109&type=section&id=PART%20II.%20%E2%80%94%20OTHER%20INFORMATION) This section provides additional information including legal proceedings, risk factors, and equity security sales [Item 1. Legal Proceedings](index=109&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently subject to any material legal proceedings, though it may encounter routine legal actions - The company is not currently subject to any material legal proceedings[463](index=463&type=chunk) [Item 1A. Risk Factors](index=109&type=section&id=Item%201A.%20Risk%20Factors) Key risks include substantial minimum royalty payments starting in 2026 and potential FDA review delays impacting product approvals - The company's royalty interests require minimum royalty payments, totaling approximately **$36.0 million**, which will commence in 2026, potentially straining cash resources regardless of product sales levels[467](index=467&type=chunk)[468](index=468&type=chunk) - Disruptions at the FDA, including layoffs and the departure of senior scientists, could lead to slower review cycles and delayed approvals for the company's product candidates, materially harming the business[469](index=469&type=chunk)[472](index=472&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=111&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company conducted several unregistered equity sales, including common and preferred stock exchanges for debt, and issued warrants and convertible notes - Issued common stock and Series L and M Preferred Stock in multiple transactions to Iliad and Streeterville in exchange for reductions of outstanding royalty interest debt[473](index=473&type=chunk)[475](index=475&type=chunk)[480](index=480&type=chunk) - In a private placement on May 20, 2025, issued unregistered warrants to purchase up to **492,612** shares of common stock to institutional investors[476](index=476&type=chunk) - On June 24, 2025, completed a private exchange of approximately **$2.57 million** of new convertible promissory notes and new warrants for existing convertible notes[477](index=477&type=chunk)[478](index=478&type=chunk) [Item 6. Exhibits](index=114&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Quarterly Report on Form 10-Q, including certificates, warrants, agreements, and officer certifications

Summary of Conference Call Records Company Overview Clean Inc. (NASDAQ: CLNN) - Clean Inc. is a late-stage clinical biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, particularly ALS [1][2]. Sono Group NV (OTCQB: SEVCF) - Sono Group NV, through its subsidiary Sono Motors GmbH, is pioneering solar technology integration into commercial vehicles, aiming to revolutionize mobility by making every commercial vehicle solar [20][22]. Key Points from Clean Inc. Conference Call Core Insights - Clean Inc. met with the FDA in June to discuss the evaluation of neurofilament as a biomarker for ALS, which is indicative of neuronal damage [2][4]. - The company is leveraging a $45 million grant from the NIH to fund a study involving 180 ALS patients, with data collection starting next month [4][5]. - Clean Inc. aims to submit a new drug application (NDA) to the FDA by the end of the year, contingent on positive data regarding neurofilament levels and survival rates [6][7]. - A confirmatory Phase 3 clinical trial is planned, focusing on survival as the primary endpoint, with the first patients expected to start treatment by the end of this year [9][10]. Additional Insights - Neurofilament levels can indicate ALS progression before clinical symptoms appear, and Clean Inc. is the only company in a Phase 2 study showing a reduction in neurofilament [12][14]. - The company is also exploring other neurodegenerative diseases, including multiple sclerosis (MS), Parkinson's, and Huntington's disease, with ongoing discussions with the FDA regarding MS [15][17]. Key Points from Sono Group NV Conference Call Core Insights - Sono Group is focused on integrating solar technology into commercial vehicles, with a patent portfolio of nine granted patents and over 30 pending patents [24][25]. - The company has received orders from six large OEMs and expects significant revenue growth in Q3 and Q4, with an average revenue per unit projected to reach €8,000 [29][30]. - Sono Group aims to uplist to a major national exchange, enhancing visibility and liquidity, which is expected to drive long-term shareholder value [32][34]. Additional Insights - The company has won a green innovation award and received national type certification for solar bus kits in Germany, simplifying the installation process across fleets [27][28]. - The solar solutions are designed to work across various vehicle types, including diesel, hybrid, and electric, providing immediate CO2 reductions and cost benefits [25][33]. - The management team emphasizes a commitment to sustainability, with employees actively participating in eco-friendly practices [31]. Conclusion Both Clean Inc. and Sono Group NV are positioned in innovative sectors with significant growth potential. Clean Inc. is advancing in the biopharmaceutical space with a focus on ALS, while Sono Group is leading in solar mobility solutions for commercial vehicles. Both companies are preparing for critical developments in the near future, including regulatory submissions and market expansions.

Clinical Development & Regulatory - Initial proof-of-concept results show crofelemer reduced Total Parenteral Nutrition (TPN) in patients with MVID and SBS-IF by up to 27% and 12.5% respectively[20], potentially modifying disease progression in intestinal failure patients[17] - Crofelemer achieved statistically significant improvement in monthly responder analysis in a prespecified subgroup of adult patients with breast cancer from the OnTarget Phase 3 study[23] - The company plans to meet with the FDA in Q2 2025 to discuss submitting a supplemental NDA for crofelemer for adult breast cancer patients on targeted therapy[21] - Napo Therapeutics is pursuing accelerated marketing PRIME authorization from the European Medicines Agency (EMA) for TPN reduction for MVID, as there are no alternative treatments[67] Commercial & Financial - Jaguar Health is a commercial-stage company with approximately $12 million in annual net revenue[13] - The company estimates the U S market revenue potential for Mytesi for HIV-related diarrhea to be approximately $30-$50 million in gross annual sales[27] - The global Short Bowel Syndrome (SBS) market is projected to reach $4.6 billion by 2027, with a CAGR of 26% from 2020 to 2027[27] - Net Q1 2025 revenue was approximately $2.2 million, a decrease of approximately 6% versus net Q1 2024 revenue of approximately $2.4 million and 37% versus net Q4 2024 revenue of approximately $3.5 million[110] Strategic Initiatives - Magdalena Biosciences, a joint venture focused on mental health illnesses, is valued at $5 million based on initial funding of $1 million from One Small Planet[103] - The company plans to pursue a Priority Review Voucher (PRV) for NP-300, with PRVs having sold for values ranging from $67 million to $350 million in past transactions[10, 97]

Financial Data and Key Metrics Changes - Total net revenue for the company's prescription products was approximately $2.2 million in Q1 2025, a decrease of approximately 6% compared to $2.4 million in Q1 2024 and a 37% decrease from $3.5 million in Q4 2024 [27] - Loss from operations increased by $1.2 million from $8.2 million in Q1 2024 to $9.4 million in Q1 2025 [28] - Net loss attributable to common shareholders increased by approximately $1.2 million from $9.2 million in Q1 2024 to $10.4 million in Q1 2025 [28] Business Line Data and Key Metrics Changes - Mytesi prescription volume increased by approximately 1.8% in Q1 2025 compared to Q1 2024 but decreased by approximately 13.5% compared to Q4 2024 [27] - Dispensed prescriptions for Mytesi and Profelymer increased by approximately 2% in Q1 2025 compared to Q1 2024, indicating increased demand [5] Market Data and Key Metrics Changes - Short bowel syndrome affects approximately 10,000 to 20,000 people in Europe and a similar number in the United States, qualifying for orphan designation [19] - MVID is an ultra-rare condition with an estimated prevalence of just a couple hundred patients globally [19] Company Strategy and Development Direction - The company is focusing on the convergence of key catalysts that are expected to enhance value for stakeholders, including paradigm-shifting medicines and mechanisms of action [6] - There are ongoing proof of concept trials for crofelemer in both pediatric and adult patients with rare diseases, which are expected to yield results throughout 2025 and into 2026 [21] - The company is also exploring business development opportunities related to its product CANALIVIA CA1 for chemotherapy-induced diarrhea in dogs, aiming to expand its approval [31] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the multiple expected near-term catalysts throughout 2025 and early 2026, viewing them as potentially transformative for stakeholders [30] - The company is committed to enhancing collaborations and licensing deals to support late-stage products and programs [30] Other Important Information - The initial proof of concept results for crofelemer showed a reduction in TPN by up to 27% for MVID patients and 12.5% for pediatric SBS patients, which could modify disease progression [12] - The FDA has granted a Type C meeting to discuss the responder analysis for breast cancer patients in the on-target study, indicating a pathway for making profelymer available for cancer therapy-related diarrhea [23] Q&A Session Summary Question: What are the expected catalysts for the company in the near term? - Management highlighted multiple expected catalysts throughout 2025 and early 2026 that are viewed as important for enhancing value for stakeholders [30] Question: How does the company plan to address the unmet needs in the supportive care area for cancer treatment? - The company is focusing on addressing the supportive care needs for cancer treatment, particularly related to diarrhea, which can impact treatment outcomes [25]

Financial Data and Key Metrics Changes - The total net revenue for the company's prescription products was approximately $2.2 million in Q1 2025, a decrease of about 6% compared to $2.4 million in Q1 2024 and a 37% decrease from $3.5 million in Q4 2024 [25] - Loss from operations increased by $1.2 million from $8.2 million in Q1 2024 to $9.4 million in Q1 2025 [26] - Net loss attributable to common shareholders increased by approximately $1.2 million from $9.2 million in Q1 2024 to $10.4 million in Q1 2025 [26] Business Line Data and Key Metrics Changes - Mytesi prescription volume increased by approximately 1.8% in Q1 2025 compared to Q1 2024 but decreased by approximately 13.5% compared to Q4 2024 [26] - Dispensed prescriptions for Mytesi and Profelymer increased by approximately 2% in Q1 2025 compared to Q1 2024, indicating increased demand for treatments [5] Market Data and Key Metrics Changes - Short bowel syndrome affects approximately 10,000 to 20,000 people in Europe and a similar number in the United States, qualifying for orphan designation [19] - MVID is an ultra-rare condition with an estimated prevalence of just a couple hundred patients globally [19] Company Strategy and Development Direction - The company is focusing on the convergence of key catalysts that are expected to be transformational for stakeholders, including paradigm-shifting medicines and mechanisms of action [5] - There are ongoing proof of concept trials for crofelemer in both pediatric and adult patients with rare diseases, with results expected throughout 2025 and into 2026 [21] - The company is exploring expedited regulatory approval pathways for its products, including the FDA's breakthrough therapy program [19] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the multiple expected near-term catalysts throughout 2025 and early 2026, viewing them as important and potentially transformative [27] - The management highlighted the significance of the initial proof of concept results for crofelemer, which could modify disease progression for patients with intestinal failure [12] Other Important Information - The company is also pursuing business development opportunities related to its product CANALIVIA CA1, which is conditionally approved for chemotherapy-induced diarrhea in dogs [28] - The management emphasized the importance of addressing supportive care needs in cancer treatment, as diarrhea can impact treatment outcomes [24] Q&A Session Summary Question: What are the expected catalysts for the company in the near term? - Management highlighted multiple expected catalysts throughout 2025 and early 2026 that are viewed as important for stakeholders [27] Question: How does the company plan to address the regulatory pathways for its products? - The company is exploring expedited regulatory approval pathways, including the FDA's breakthrough therapy program and EMA's PRIME program [19]

Series L Preferred Stock Structure - The Series L Preferred Stock consists of 200 shares with a par value of $0.0001 per share[27]. - The Stated Value of the Series L Preferred Stock is set at $25,000[22]. - The Corporation has the authority to issue a total of 4,464,011 shares of preferred stock[2]. - The Series L Preferred Stock can be issued for cash or exchange of other securities[2]. - The Series L Preferred Stock will initially be issued in book-entry form[27]. Voting Rights and Preferences - Each share of Series L Preferred Stock will have voting rights on an as-converted basis, with the voting power determined by the Stated Value divided by the Minimum Price[29]. - The maximum percentage of voting rights for any Holder is capped at 9.99% of the Corporation's outstanding shares of Common Stock[30]. - The Corporation is authorized to fix the rights and preferences of the Series L Preferred Stock[2]. Dividends and Returns - Holders of Series L Preferred Stock will not be entitled to receive any dividends[28]. - Series L Preferred Stock accrues a Preferred Return of 0% for the first 2 years, 10% for years 3 and 4, and 15% thereafter[38]. - The Preferred Return is payable quarterly within five trading days after each calendar quarter[40]. Liquidation and Redemption - The Liquidation Amount for Series L Preferred Stock includes the Stated Value plus any accrued but unpaid Preferred Return[32]. - The Corporation may redeem Series L Preferred Stock at the Liquidation Amount, payable in Common Stock based on the Redemption Ratio[45]. - In a Deemed Liquidation Event, the Corporation cannot proceed unless the Merger Agreement allocates consideration to Series L Preferred Stock as specified[34]. - If an Event of Default occurs, the Required Holders can force the Corporation to redeem all Series L Preferred Stock at a price equal to the Stated Value plus any accrued and unpaid Preferred Return[65]. - The Redemption Price will be paid in Common Stock, calculated based on the Floor Price[66]. - The Corporation will allocate 15% of all Licensing Fees to redeem Series L Preferred Stock in Common Stock[61]. - Any shares of Series L Preferred Stock that are exchanged or redeemed will be automatically cancelled and will not be reissued[77]. Corporate Governance and Compliance - The issuance of Series L Preferred Stock is subject to Stockholder Approval as required by Nasdaq rules[23]. - The Corporation will not issue or sell Equity Securities resulting in net proceeds exceeding $15 million without prior consent from Required Holders[51]. - The Corporation cannot increase authorized shares of Common Stock or Preferred Stock without Required Holders' consent[52]. - The Corporation will not consummate a Fundamental Transaction without prior consent from Required Holders[60]. - The Corporation must ensure that its Common Stock remains listed on major exchanges until a Fundamental Transaction occurs[50]. - The Corporation may declare an "Event of Default" if it fails to comply with any covenant or obligation, with a cure period of 30 days after notice[64]. - Holders have the right to seek injunctive relief to prevent the Corporation from issuing Common or Preferred Stock unless Series L Preferred Stock is redeemed in full[67]. - The Corporation must reimburse Holders for reasonable expenses incurred in enforcing their rights, including attorneys' fees[69]. - Amendments to the terms of Series L Preferred Stock require the consent of at least a majority of the outstanding shares[78]. Notices and Legal Proceedings - Notices must be delivered in writing and are effective upon transmission or receipt as specified[70]. - The governing law for this Certificate is the State of Delaware, and all legal proceedings must be commenced in Delaware Courts[71].

Clinical Trials and Drug Development - The OnTarget study for crofelemer did not meet its primary endpoint for all tumor types, but showed statistical significance in the subgroup of breast cancer patients, with 183 out of 287 participants being breast cancer patients [323]. - Jaguar is conducting two Phase 2 studies for crofelemer targeting SBS-IF and MVID, with data expected in early 2026 [335]. - Preliminary results from the pediatric IIT of crofelemer in Abu Dhabi were presented at the ELITE PED-GI Congress, indicating ongoing research in rare pediatric diseases [332]. - The company is supporting three proof-of-concept trials and conducting two Phase 2 studies for crofelemer, with the first POC IIT results expected in Q2 2025 [331]. - Jaguar holds global unencumbered rights for crofelemer, Mytesi, and Canalevia-CA1, with several drug product opportunities backed by Phase 2 and POC evidence from human clinical trials [346]. Financial Performance - The company reported a net loss of $10.6 million for the three months ended March 31, 2025, compared to a net loss of $9.4 million for the same period in 2024, reflecting a 13.1% increase in losses [347]. - Total revenue decreased by 5.8% from $2.351 million in Q1 2024 to $2.214 million in Q1 2025, with product revenue declining by 7.7% [372]. - Gross product sales decreased from $3.419 million in Q1 2024 to $3.183 million in Q1 2025, a decline of 6.9% [376]. - License revenue increased to $43,000 in Q1 2025, attributed to a new license agreement with Gen Ilac Ve Saglik Urunleri Sanayi Ve Ticaret, A.S. [375]. - As of March 31, 2025, the company had total stockholders' equity of $830,000 and an accumulated deficit of $356.9 million [347]. Expenses and Cost Management - Research and development expenses were $3.730 million for Q1 2025, down 13.5% from $4.312 million in Q1 2024 [372]. - Sales and marketing expenses surged by 72.8%, increasing from $1.443 million in Q1 2024 to $2.493 million in Q1 2025 [372]. - General and administrative (G&A) expenses rose by $516,000, or 11.8%, from $4.4 million in 2024 to $4.9 million in 2025, mainly due to higher legal services and personnel costs [385]. - Total cost of product revenue increased by $85,000, or 19.8%, from $430,000 in 2024 to $515,000 in 2025, driven by higher material costs and outsourced contract manufacturing services [378]. - Research and development (R&D) expenses decreased by $582,000, or 13.5%, from $4.3 million in 2024 to $3.7 million in 2025, largely due to reduced clinical and contract manufacturing costs [380]. Cash Flow and Financing Activities - Cash provided by financing activities for the three months ended March 31, 2025, was $4.966 million, a decrease from $12.268 million in 2024, indicating reduced capital inflow [403]. - As of March 31, 2025, the company had cash of $5.7 million, which is insufficient to fund its operating plan for at least one year [392]. - Net cash provided by financing activities for the three months ended March 31, 2025, was $5.0 million, consisting of $3.4 million from Convertible Notes and $1.8 million from shares issued in an At the Market offering [409]. - Net cash provided by financing activities decreased by $7.3 million in 2025, primarily due to a decline in proceeds from the ATM offering, which totaled $11.3 million in the prior period [410]. - For the three months ended March 31, 2025, net cash used in operating activities was $7.3 million, resulting from a net comprehensive loss of $10.9 million [404]. Strategic Partnerships and Collaborations - Jaguar entered into a 5-year exclusive in-license agreement with Venture Life for the commercialization of Gelclair in the US, which was launched in October 2024 [325]. - Jaguar is seeking a partner to fund the expanded development of Canalevia for non-infectious diarrhea in dogs, addressing an estimated six million cases annually in the US [342]. - The joint venture Magdalena focuses on developing plant-based medicines for mental health, with an exclusive license to Jaguar's library of 2,300 medicinal plants [343].

Summary of Jaguar Health's Conference Call Company Overview - **Company Name**: Jaguar Health - **Subsidiaries**: Napo Pharmaceuticals, Napo Therapeutics (Italy) - **Key Personnel**: Lisa Conte (Founder, President, CEO), Praveen Chetovetti (Chief Scientific Officer) Industry Focus - **Primary Focus**: Development of treatments for rare diseases, specifically intestinal failure conditions such as Microvillous Inclusion Disease (MVID) and Short Bowel Syndrome (SBS) - **Key Product**: Crofelemer, aimed at reducing the need for Total Parenteral Nutrition (TPN) in patients with intestinal failure Core Points and Arguments 1. **Proof of Concept Results**: Initial results from a study show that crofelemer reduced TPN in MVID patients by up to 27% and by 12.5% in SBS patients, indicating a significant impact on patient care [5][6][16] 2. **Market Potential**: The market for SBS is estimated to exceed $5 billion, with MVID representing a smaller but significant opportunity due to its ultra-rare nature [31][56] 3. **Regulatory Pathways**: The company is pursuing PRIME designation from the European Medicines Agency, which could expedite the approval process for crofelemer [26][47] 4. **Clinical Trials**: Ongoing trials include two investigator-initiated studies and two placebo-controlled Phase II trials, with results expected in 2025 and 2026 [17][18][46] 5. **Collaboration with Experts**: The company has established relationships with key opinion leaders and clinical investigators in pediatric gastroenterology, enhancing its research credibility [17][21][22] Additional Important Content 1. **Patient Impact**: The reduction in TPN is crucial for improving the quality of life for patients with intestinal failure, who often face high morbidity and mortality rates [35][36] 2. **Cost of Care**: A typical patient on lifelong TPN costs approximately $500,000 annually, highlighting the financial burden of these conditions [35] 3. **Cognitive Development Concerns**: There are ongoing discussions about the cognitive impacts of TPN on pediatric patients, with hopes that improved oral absorption through crofelemer could enhance neurodevelopment [75][82] 4. **Commercial Strategy**: Jaguar Health plans to maintain U.S. commercialization while seeking partnerships for international markets, particularly in rare disease segments [78] Conclusion Jaguar Health is positioned to make significant advancements in the treatment of rare intestinal failure diseases through innovative drug development and strategic collaborations, with promising early results from clinical trials indicating a potential breakthrough in patient care and market opportunity.

Financial Data and Key Metrics Changes - The company's net revenue for 2024 increased approximately 20% to about $11.7 million compared to $9.8 million in 2023 [6][40] - Total net revenue for Q4 2024 was approximately $3.5 million, representing a 53% increase from Q4 2023's $2.3 million and a 13% increase from Q3 2024's $3.1 million [6][40] - Loss from operations decreased from $34.3 million in 2023 to $30.8 million in 2024 [41] - Net loss attributable to common shareholders decreased from $41.3 million in 2023 to $38.5 million in 2024 [42] Business Line Data and Key Metrics Changes - Mytesi prescription volume increased approximately 3.9% in 2024 compared to 2023 [41] - Mytesi prescription volume increased by about 9.4% in Q4 2024 over Q4 2023 [41] Market Data and Key Metrics Changes - The company is focusing on rare diseases and supportive care for cancer patients, particularly targeting intestinal failure and cancer therapy-related diarrhea [10][32] Company Strategy and Development Direction - The company is pursuing multiple near-term catalysts expected in Q2 2025, which are viewed as significant and value-enhancing [7][43] - The focus is on developing crofelemer for rare diseases and expanding Mytesi's indications to include cancer therapy-related diarrhea [26][36] Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of upcoming catalysts and the potential for significant collaborations and licensing deals [13][43] - The company is optimistic about the potential for crofelemer to receive fast-track designations from regulatory agencies due to the lack of approved treatments for certain conditions [25][27] Other Important Information - The company is conducting ongoing proof-of-concept trials for crofelemer in rare diseases, with initial results expected in Q2 2025 [21][22] - The company has developed a novel formulation of crofelemer specifically for patients with intestinal failure, which differs from the commercialized version [30][29] Q&A Session Summary - No specific questions or answers were provided in the content regarding the Q&A session [46]

Product Development and Indications - Jaguar Health, Inc. focuses on developing prescription medicines for gastrointestinal distress, with its lead product crofelemer approved for noninfectious diarrhea in adults with HIV/AIDS[22]. - Crofelemer is being developed for multiple indications, including cancer therapy-related diarrhea, irritable bowel syndrome, and orphan diseases like microvillus inclusion disease[22][45]. - The OnTarget Phase 3 clinical trial of crofelemer did not meet its primary endpoint but showed statistically significant improvement in breast cancer patients, indicating potential for prophylaxis of chemotherapy-related diarrhea[26]. - Crofelemer received Orphan Drug Designation from the FDA for microvillus inclusion disease in February 2023, enhancing its development prospects in rare diseases[44]. - The OnTarget trial included patients with 10 different tumor types, emphasizing the broad applicability of crofelemer in cancer treatment[25]. - Jaguar is conducting three proof-of-concept trials and two Phase 2 studies of crofelemer for short bowel syndrome (SBS) and microvillus inclusion disease (MVID) in various regions, with results expected throughout 2025[46]. - NP-300 is in development for symptomatic relief of moderate-to-severe diarrhea, with a focus on bacterial, viral, and parasitic infections, including cholera[106]. - The company is developing a pipeline of prescription drug candidates to address unmet needs in gastrointestinal health, with several backed by clinical trial evidence[84]. Market Opportunities - Oral mucositis affects up to 40% of chemotherapy patients, with 90% incidence in head and neck cancer patients, highlighting a significant market opportunity for Gelclair[43]. - The global SBS market exceeded $568 million in 2019 and is projected to reach $4.6 billion by 2027, indicating significant market potential for crofelemer[50]. - Jaguar estimates that nearly 250,000 newly diagnosed cancer patients in 2020 could be eligible for targeted therapies, representing a substantial market for crofelemer[29]. - The global market for chemotherapy-induced nausea and vomiting (CINV) drugs is projected to reach $4.3 billion by 2031, with Mytesi targeting the significant unmet need in this area[73][91]. - Mytesi's target market in the US is estimated to generate approximately $50 million in gross annual sales, with no direct competition[91]. - Jaguar estimates that US veterinarians see approximately six million cases of acute and chronic diarrhea in dogs annually, indicating a substantial market for canine diarrhea treatments[67]. Intellectual Property and Patents - The company holds approximately 193 patents related to crofelemer, with most not expiring until 2027-2031, ensuring strong intellectual property protection[68]. - Jaguar has approximately 194 issued patents, providing significant barriers to entry for generic competition for Mytesi, with coverage extending until 2031[78][79]. - Napo owns patents for treating HIV-associated diarrhea and related conditions, with US patents expiring on October 31, 2031[123]. - The company retains a portfolio of patents covering formulations and treatment methods related to Mytesi and other products[122]. - The company has issued patents for treating diarrhea-predominant irritable bowel syndrome, with expiration dates estimated for April 30, 2027[123]. Regulatory and Approval Processes - The FDA's review process for new drug applications (NDAs) typically takes about 10 months from filing, with a goal of 12 months for completion[138]. - The FDA may require a risk evaluation and mitigation strategy (REMS) as part of the NDA filing to ensure the drug's benefits outweigh its risks[140]. - The FDA may impose post-approval requirements such as Phase 4 clinical trials to assess a drug's safety and effectiveness after commercialization[149]. - The EMA provides orphan medicines marketing authorization incentives, allowing for expedited regulatory procedures for drugs addressing unmet medical needs[153]. - Conditional marketing authorization can be granted based on less comprehensive clinical data if the immediate availability of the medicine outweighs the risks[159]. - The approval process for new animal drugs involves either the NADA or ANADA process, ensuring safety and effectiveness[218]. Joint Ventures and Collaborations - The company signed a 5-year in-license agreement with Venture Life Group for Gelclair, an FDA-approved oral mucositis product, and launched it in the US in October 2024[40]. - An agreement with Quadri Pharmaceuticals grants exclusive rights for Mytesi commercialization in Bahrain, Kuwait, Qatar, Saudi Arabia, UAE, and Oman, pending regulatory approval[100]. - The company has a distribution agreement with Knight Therapeutics for Mytesi in Canada and Israel, with potential payments up to approximately $18 million based on regulatory and sales milestones[101]. - Napo has a license agreement with Napo Therapeutics for the development and commercialization of crofelemer and NP-300 in the EU and specific non-EU countries[126]. Research and Development Initiatives - Jaguar's joint venture, Magdalena Biosciences, focuses on developing natural prescription medicines for mental health, starting with ADHD in adults[53]. - The ETI initiative supports the discovery of novel medicines from psychoactive plants, targeting mood disorders and neurodegenerative diseases, which affect hundreds of millions globally[58]. - The proprietary library includes over 2,300 medicinal plants, supporting the company's drug development efforts[120]. - The company is focused on reducing risks in product development by confirming unmet medical needs and generating protocols for FDA discussions[103]. Veterinary Medicine - The FDA has conditionally approved Canalevia-CA1, the only veterinary drug for treating canine inflammatory diarrhea (CID), which is now available through multiple distributors in the US[60]. - Canalevia-CA1 received MUMS designation from the FDA for treating chemotherapy-induced diarrhea (CID) in dogs, indicating potential for market expansion in veterinary medicine[81].