Core Insights - The article discusses the recent performance and outlook of Altimmue (ALT), particularly following the Phase IIb MASH data readout that negatively impacted the share price, suggesting that the selloff was more of a panic reaction rather than a justified market response [1]. Group 1: Company Overview - Altimmue (ALT) has experienced significant volatility in its share price due to recent clinical data releases, specifically the Phase IIb MASH data [1]. - The author believes that the market's reaction to the Phase IIb data was exaggerated, indicating potential for recovery and investment opportunity [1]. Group 2: Investment Strategy - The focus of the analysis is on identifying innovative companies in the biotech sector that are developing breakthrough therapies, which may present catalysts for potential acquisitions [1]. - The author leads an investment group, Compounding Healthcare, which provides resources such as model healthcare portfolios, newsletters, and daily watchlists to assist investors in making informed decisions [1].

Summary of Altimmune Conference Call Company Overview - **Company**: Altimmune - **Key Product**: Pemvidutide (Pemvi), a GLP-1 glucagon dual receptor agonist for treating serious liver diseases such as MASH (Metabolic Associated Steatotic Liver Disease), AUD (Alcohol Use Disorder), and ALD (Alcoholic Liver Disease) [1][2][3] Core Points and Arguments Product Development and Mechanism - Pemvidutide is designed to provide a balanced agonist effect on both glucagon and GLP-1 receptors, targeting liver health and metabolic benefits simultaneously [2][3] - The drug aims to treat MASH effectively by combining anti-inflammatory and anti-fibrotic effects with metabolic improvements [3][4] - Recent 24-week data showed significant improvements in MASH resolution, anti-fibrotic activity, and weight loss, preserving lean mass, which is crucial for the patient population [4][12] Competitive Landscape - The MASH treatment landscape is becoming competitive with large pharmaceutical companies acquiring advanced FGF21 assets and exploring combination therapies [5][6] - Altimmune believes its dual mechanism of action positions Pemvidutide favorably against competitors, as it combines both liver-targeting and metabolic benefits in one molecule [6][13] Clinical Data and Expectations - The 48-week study readout is anticipated in Q4, following a successful 24-week readout that demonstrated rapid MASH resolution and fibrosis improvement [2][16] - The company reported a 36% improvement in fibrosis without worsening MASH, although statistical significance was not achieved due to high placebo effects [17] - Non-invasive tests showed promising results, with a notable decrease in ELF scores, indicating effective treatment [17][19] Regulatory and Market Strategy - Altimmune is preparing for Phase III trials, with flexibility in endpoints to adapt to potential regulatory changes regarding biopsy requirements [32][34] - The FDA is engaged and supportive of advancing Pemvidutide, with a meeting scheduled to discuss the drug's development [18][33] Financial Position - Altimmune reported a strong financial position with approximately $211 million in cash at the end of the quarter, enabling continued development through 2026 and 2027 [50] Additional Important Insights - The tolerability of Pemvidutide is highlighted as a key differentiator, with a lower discontinuation rate compared to other glucagon GLP-1 receptor agonists [10][36] - The drug's ability to preserve lean mass during weight loss is particularly relevant for the aging population affected by MASH [12][44] - Altimmune is also exploring the use of Pemvidutide in AUD and ALD, leveraging its dual mechanism to address cravings and liver health simultaneously [41][42] Conclusion Altimmune is positioned strongly in the competitive landscape of liver disease treatments with Pemvidutide, showcasing promising clinical data and a robust financial foundation to support its ongoing development and regulatory strategy. The focus on dual mechanisms and tolerability may provide a significant advantage in treating MASH, AUD, and ALD.

Core Insights - Altimmune, Inc. announced significant 24-week efficacy and safety data from the IMPACT Phase 2b trial of pemvidutide for metabolic dysfunction-associated steatohepatitis (MASH), showing promising results in MASH resolution, weight loss, and anti-fibrotic activity [1][3][5] Group 1: Trial Results - The IMPACT Phase 2b trial demonstrated that pemvidutide achieved statistically significant MASH resolution without worsening fibrosis, with 58% and 52% of patients in the 1.2 mg and 1.8 mg groups respectively achieving this outcome compared to 20% in the placebo group [6] - Significant improvements were observed in secondary endpoints, including a reduction in liver stiffness measurement and Enhanced Liver Fibrosis score, with the 1.2 mg and 1.8 mg groups showing reductions of -3.7 kPa and -2.2 kPa respectively [6] - The trial also reported a normalization of liver fat content in 31% and 44% of patients in the 1.2 mg and 1.8 mg groups respectively, compared to only 4% in the placebo group [6] Group 2: Safety and Tolerability - Pemvidutide exhibited a favorable tolerability profile, with only 2% of placebo patients experiencing adverse events leading to treatment discontinuation, compared to 0% in the 1.2 mg group and 1% in the 1.8 mg group [6] - Serious adverse events were reported in 3% of placebo patients, 2% in the 1.2 mg group, and 4% in the 1.8 mg group, with no serious adverse events deemed related to the treatment [6] Group 3: Future Outlook - The final readout of longer-term non-invasive tests and weight loss from the IMPACT trial is anticipated in the fourth quarter of 2025, which will provide further insights into the efficacy of pemvidutide [7][10] - The FDA has granted Fast Track designations to pemvidutide for the treatment of MASH and alcohol use disorder (AUD), indicating significant unmet medical needs in these areas [10]

Group 1 - Citizens JMP analyst Jonathan Wolleben lowered the price target on Altimmune (ALT) to $14 from $15 while maintaining an Outperform rating on the shares [1] - The firm anticipates the oral late-breaking presentation of pemvidutide's Phase 2b data at the Liver Meeting, with 48-week data expected to be released this quarter [1]

Core Insights - Altimmune, Inc. announced significant results from the IMPACT Phase 2b trial of pemvidutide, demonstrating reductions in liver fibrosis and improvements in non-invasive tests compared to placebo at 24 weeks [1][2][5] Group 1: Trial Results - The AI-based pathology tool Liver Explore™ showed significant reductions in early, advanced, and total liver fibrosis areas with pemvidutide treatment compared to placebo at 24 weeks [2] - In the trial, 58% of patients achieved MASH resolution, indicating the efficacy of the glucagon/GLP-1 balanced approach in pemvidutide [5] - Statistically significant reductions in total liver fibrosis were observed, with 31% of patients in the 1.8 mg group achieving a ≥ 60% reduction compared to 8% in the placebo group [7] Group 2: Study Design - The IMPACT Phase 2b trial was a randomized, placebo-controlled, double-blind study involving 212 participants with biopsy-confirmed MASH and fibrosis stages F2 or F3 [6] - Participants were randomized to receive weekly subcutaneous doses of pemvidutide at either 1.2 mg, 1.8 mg, or placebo for 48 weeks, with key efficacy endpoints measured at 24 weeks [6] Group 3: Mechanism and Future Outlook - Pemvidutide is a novel investigational peptide with dual receptor agonist activity targeting both glucagon and GLP-1, aimed at treating MASH, AUD, and ALD [8] - The FDA has granted Fast Track designations for pemvidutide in treating MASH and AUD, highlighting the unmet medical need in these areas [9] - The final readout of the ongoing 48-week IMPACT trial is anticipated in the fourth quarter of 2025, which will include longer-term data on non-invasive tests and weight loss [9]

Financial Performance - Revenues for the three months ended September 30, 2025, were $5, unchanged from the same period in 2024[90] - The net loss for the three months ended September 30, 2025, was $19.01 million, a decrease of $3.83 million, or 17%, from a net loss of $22.85 million in 2024[90] - Revenues for the nine months ended September 30, 2025, remained unchanged at $15,000 compared to the same period in 2024[98] - Net loss for the nine months ended September 30, 2025, was $60.7 million, a decrease of $11.1 million, or 16%, from a net loss of $71.9 million in 2024[98] Expenses - Research and development expenses decreased by $4.8 million, or 24%, to $14.96 million for the three months ended September 30, 2025, compared to $19.80 million in 2024[93] - General and administrative expenses increased by $0.9 million, or 19%, to $5.90 million for the three months ended September 30, 2025, compared to $4.97 million in 2024[95] - Research and development expenses decreased by $14.4 million, or 23%, to $48.0 million for the nine months ended September 30, 2025, from $62.4 million in 2024[100] - General and administrative expenses increased by $1.7 million, or 11%, to $17.6 million for the nine months ended September 30, 2025[102] Other Income and Cash Flow - Total other income (expense), net decreased by $0.1 million, or 4%, for the three months ended September 30, 2025, compared to the same period in 2024[96] - Total other income (expense), net decreased by $2.2 million, or 35%, to $4.2 million for the nine months ended September 30, 2025[103] - Net cash used in operating activities was $48.1 million for the nine months ended September 30, 2025, compared to $61.6 million in 2024, reflecting a decrease of $13.5 million[116] - Net cash provided by financing activities was $125.7 million during the nine months ended September 30, 2025, primarily from the issuance of common stock[118] Financial Position - Cash, cash equivalents, restricted cash, and short-term investments totaled $210.8 million as of September 30, 2025[105] - The accumulated deficit as of September 30, 2025, was $622.1 million, indicating significant losses since operations commenced[106] - The company plans to continue pursuing additional equity or debt financing to address long-term capital needs for clinical trials[119] Clinical Trials and Designations - In a Phase 2b trial for MASH, 58% and 52% of subjects achieved MASH resolution with pemvidutide doses of 1.2 mg and 1.8 mg, respectively, compared to 20% for placebo (p<0.0001) at 24 weeks[77] - Mean weight loss in pemvidutide-treated subjects was 4.8% and 5.8% at the 1.2 mg and 1.8 mg doses, respectively, versus 0.5% in the placebo group (p<0.001) at 24 weeks[79] - The U.S. FDA granted Fast Track designation to pemvidutide for the treatment of alcohol use disorder (AUD) on August 19, 2025[83] - The RECLAIM Phase 2 trial for AUD has enrolled approximately 100 subjects, with topline results expected in 2026[84] - The RESTORE Phase 2 trial for alcohol-associated liver disease (ALD) is enrolling approximately 100 patients, with a primary endpoint of liver stiffness measurement change at Week 24[85] Accounting and Reporting - Management's Discussion and Analysis is based on unaudited consolidated financial statements prepared in accordance with U.S. GAAP[121] - There have been no changes in critical accounting policies and significant judgments since the Annual Report for the year ended December 31, 2024[122] - As a smaller reporting company, the company is not required to provide quantitative and qualitative disclosures about market risk[123]

Pemvidutide's Potential in Liver Diseases - Pemvidutide targets both liver and metabolic components with a differentiated 1:1 glucagon/GLP-1 ratio, showing potential in various steatotic liver diseases[10] - The IMPACT Phase 2b trial of Pemvidutide in MASH patients showed promising 24-week data, with 48-week data and an FDA meeting expected in Q4 2025[14] - Pemvidutide demonstrated a favorable tolerability profile with no dose titration, and a low rate of AEs leading to treatment discontinuation (1.2% in the 1.8 mg group)[55] MASH (NASH) Market and Clinical Data - The IMPACT Phase 2b trial enrolled 212 subjects with MASH (F2/F3), liver fat content ≥ 8%, and BMI ≥ 27.0 kg/m2, HbA1c < 9.5%[23] - Pemvidutide shows potential for best-in-class MASH resolution without worsening of fibrosis[24] - IMPACT data shows significant weight loss at 24 weeks, addressing an underlying cause of MASH[48] - In a Phase 2 obesity study, Pemvidutide demonstrated a lean loss ratio of 21.9% at 48 weeks, indicating class-leading lean mass preservation[52] AUD and ALD Programs - The RECLAIM Phase 2 trial enrollment for AUD is expected to be completed in Q4 2025, while the RESTORE Phase 2 trial for ALD was initiated in Q3 2025[14] - Approximately 66% of AUD patients have obesity or overweight, similar to ALD patients, making them potential targets for Pemvidutide treatment[60] - ALD patients are approximately 3 times more likely to have liver-related disease progression compared to MASH patients[65] Financial Position - The company reported $211 million in total cash as of September 30, 2025, with access to a $125 million credit facility[75] - The company's 9-month year-to-date operating expenses (OPEX) were $54.5 million[75]

Financial Data and Key Metrics Changes - Total cash as of September 30 was $211 million, representing a 60% increase from the beginning of the year [11] - R&D expenses for Q3 2025 were $15 million, down from $19.8 million in Q3 2024, primarily due to the timing of CRO development costs [12] - Net loss for Q3 2025 was $19 million or $0.21 per share, compared to a net loss of $22.8 million or $0.32 per share in Q3 2024 [13] Business Line Data and Key Metrics Changes - Direct costs related to Pemvidutide development in Q3 2025 included $9.2 million, with $3.7 million for the IMPACT phase 2b trial, $3.4 million for AUD and ALD startup costs, and $1.3 million for CMC [12] Market Data and Key Metrics Changes - Market research indicated that 70%-80% of surveyed physicians expressed a high likelihood to prescribe Pemvidutide based on its product profile [7] - Positive feedback from payers suggested broad coverage expectations across the EU for Pemvidutide [8] Company Strategy and Development Direction - The company is preparing for a scheduled end-of-phase two meeting with the FDA to review the proposed phase three MASH program [2][15] - Pemvidutide is positioned as a promising therapeutic candidate for MASH, AUD, and ALD, leveraging its dual mechanism of action [3][5] - The company aims to design a flexible phase three trial to adapt to potential regulatory changes regarding endpoints [20][21] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strength of the 24-week data supporting the upcoming discussions with the FDA [18][19] - The company anticipates continued weight loss and improvements in NITs at the 48-week mark, reinforcing the efficacy of Pemvidutide [20][35] Other Important Information - The company has raised $127 million through various capital sourcing options to support key development milestones [11] - A $400 million shelf registration and a new $200 million ATM facility were filed to enhance financial flexibility [12] Q&A Session Summary Question: Upcoming 48-week data from the phase two IMPACT trial - Management indicated that the end-of-phase two meeting with the FDA was based on the 24-week data, and the 48-week data would be submitted later [18][19] Question: Probability of using NITs or AI-based histological reading - Management noted ongoing discussions and increasing interest in NITs, with flexibility built into the phase three design to adapt to regulatory changes [25] Question: Advantages of AI-based biopsy reading - AI provides a more comprehensive evaluation of fibrosis with less variability compared to traditional histology, which is subject to human error [25][26] Question: Clinically meaningful endpoint for the RECLAIM trial - The primary endpoint for the RECLAIM trial is the number of heavy drinking days per week, with a focus on assessing changes from baseline [28][31] Question: Competitive positioning against Retatrutide - Management believes Pemvidutide's dual mechanism of action provides a competitive advantage in the MASH space compared to Retatrutide [64][65] Question: Progress on the oral formulation of Pemvidutide - The company is advancing its oral formulation program and plans to share more data as it progresses [70]

Loan Agreement Details - Borrower has requested Lenders to make available up to four tranches of term loans totaling $125 million[33]. - The Loan Agreement was initially made on May 13, 2025, and has been amended by Amendment No. 1 as of November 5, 2025[31][2]. - Each Borrower must execute and deliver the Amendment to Lender for it to become effective[14]. - The Amendment constitutes a legal, valid, and binding obligation of the Borrower[11]. - The Loan Agreement will continue in full force and effect except as expressly amended[13]. - The maximum term loan amount is set at $125 million[98]. - The initial facility charge payable to lenders is $150,000[78]. - The company plans to draw a Term Loan Advance of $15 million on the Closing Date as part of the Tranche 1 Advance[156]. - A subsequent Term Loan Advance of $20 million is scheduled to be drawn on or before the First Amendment Effective Date as part of the Tranche 2 Advance[157]. - The company may request up to $10 million in additional Term Loan Advances under the Tranche 3 Advances, with minimum increments of $5 million[158]. - Borrower may request up to two additional Term Loan Advances in minimum increments of $5,000,000, totaling up to $80,000,000[161]. - The principal balance of each Term Loan Advance will bear interest at a floating Term Loan Interest Rate based on the Prime Rate[164]. - Borrower will pay accrued but unpaid interest on each Term Loan Advance on the first Business Day of each month, starting the month after the Advance Date[165]. - A Prepayment Charge of 3.00% applies if the principal amount is prepaid within 12 months of the First Amendment Effective Date, decreasing to 0.00% thereafter[170]. - An End of Term Charge of 6.25% will be applied to the principal amount of Term Loan Advances upon certain events, including full prepayment[171]. - In the event of a payment default, a default interest of 4% will be charged on the past due amount[168]. - The maximum aggregate outstanding Term Loan Advances shall not exceed the Maximum Term Loan Amount as defined in the agreement[162]. - Borrower must submit an Advance Request at least one Business Day before the Closing Date and five Business Days before each Advance Date[163]. - All payments under the agreement must be made without setoff or deduction, regardless of any counterclaim[166]. Borrower Obligations - Borrower must pay all reasonable and documented out-of-pocket Lender expenses incurred through the date of the Amendment[15]. - Borrower has the corporate power and authority to execute and deliver the Amendment[10]. - The execution of the Amendment has been duly authorized by all necessary corporate actions on the part of Borrower[10]. - Borrower must deliver various documents, including executed Loan Documents and a legal opinion, prior to the Closing Date to satisfy conditions for the Loan[185]. - Each Loan Party must maintain good standing and be duly organized under applicable laws to avoid a Material Adverse Effect[192]. - Borrower must ensure that no defaults exist under any material agreements or instruments related to its indebtedness[197]. - The obligations of Lenders to make the Loan are contingent upon the Borrower's compliance with all terms and conditions set forth in the Loan Documents[188]. - Borrower must use best efforts to obtain landlord and bailee consents for locations holding significant collateral[190]. - Borrower is required to provide insurance certificates and other documentation within specified timeframes post-Closing Date[190]. Compliance and Legal Matters - No Event of Default has occurred and is continuing as per Borrower's representations[9]. - The Company must comply with Anti-Corruption and Anti-Terrorism Laws, including the U.S. Foreign Corrupt Practices Act and the USA PATRIOT Act[46][47]. - A Change in Control is defined as any person or group obtaining 49% or more of the voting power for the election of directors[54]. - The Company must maintain compliance with the Employee Retirement Income Security Act (ERISA) regulations[68]. - The Company is required to provide a Compliance Certificate as part of its obligations under the Agreement[58]. - The Agreement outlines the conditions under which an Event of Default may occur, impacting the Company's obligations[69]. - Borrower and its Subsidiaries are not classified as an "investment company" under the Investment Company Act of 1940[198]. - Borrower has complied with the Federal Fair Labor Standards Act in all material respects[199]. - Borrower and its Subsidiaries have obtained all necessary consents and approvals from Governmental Authorities to continue their businesses[199]. - There are no violations of Anti-Terrorism Laws by Borrower or its Subsidiaries[200]. - None of the funds provided under the Agreement will be used for activities violating Anti-Corruption Laws or for payments to government officials[200]. Financial Definitions and Conditions - The Loan and Security Agreement includes provisions for cash proceeds from public or private sales of Qualified Equity Interests, with specific definitions for net proceeds and partnerships[43]. - The Amortization Date is set for December 1, 2027, with potential extensions based on milestone achievements[45]. - The definition of "Borrower Products" includes all products and technologies currently being developed or sold by the Company[51]. - The definition of "Equity Interests" encompasses various forms of capital stock and ownership interests in the Company[68]. - The definition of "indebtedness" includes all obligations for borrowed money and capital lease obligations[76]. - The term "material agreement" includes contracts involving amounts exceeding $10 million[95]. - Permitted Indebtedness includes up to $1,000,000 outstanding at any time secured by specific liens, and trade creditor indebtedness not exceeding $250,000[107]. - Unsecured indebtedness is capped at $500,000 at any time outstanding, with reimbursement obligations related to letters of credit not exceeding $200,000[108]. - Investments in newly-formed subsidiaries are allowed, provided they enter into a Joinder Agreement or Guaranty promptly after formation[111]. - Investments by a Loan Party in any Immaterial Subsidiary for clinical trial expenses are limited to $2,500,000 in the aggregate[111]. - Permitted Royalty Transactions can yield up to 7% of worldwide net sales or revenue in any calendar year[115]. - Transfers of assets with a fair market value not exceeding $500,000 in the aggregate are permitted in any fiscal year[116]. - Liens securing claims of materialmen and other similar persons are allowed if not delinquent or being contested in good faith[113]. - Indebtedness incurred in the ordinary course of business for netting services and overdraft protections is permitted[108]. - Investments consisting of loans to employees for purchasing equity securities are capped at $500,000 in aggregate[110]. - Extensions, refinancings, and renewals of permitted indebtedness are allowed without increasing the principal amount[108]. - The aggregate balance in the deposit account must not exceed $42,000 at any time[70].

Core Insights - Altimmune, Inc. is approaching significant milestones in the development of pemvidutide for metabolic dysfunction-associated steatohepatitis (MASH) and alcohol use disorder (AUD) [2][12] - The company has strengthened its executive leadership team with key appointments to support its growth strategy [2][9] - Financial results indicate a robust cash position and a reduction in research and development expenses compared to the previous year [7][19] MASH Program Updates - The 48-week data from the Phase 2b IMPACT trial of pemvidutide is expected to be released before the end of 2025 [2][12] - An End-of-Phase 2 meeting with the FDA is scheduled for the fourth quarter of 2025 to discuss the proposed design of the Phase 3 trial [5][12] - The trial design may include flexibility to adapt based on regulatory discussions regarding non-invasive tests and AI-based biopsy readings [2] AUD and ALD Trials - The RECLAIM trial for pemvidutide in AUD has completed patient recruitment ahead of schedule, indicating strong interest in new therapies for this condition [9][12] - The RESTORE trial for pemvidutide in alcohol-associated liver disease (ALD) has also been initiated, with a focus on safety and efficacy [9][12] Executive Leadership Changes - Recent appointments include Dr. Christophe Arbet-Engels as Chief Medical Officer, Linda Richardson as Chief Commercial Officer, and Robin Abrams as Chief Legal Officer [2][9] - These leaders bring extensive experience in clinical development, commercial strategy, and legal compliance to the company [9] Financial Performance - As of September 30, 2025, the company reported cash, cash equivalents, and short-term investments totaling approximately $211 million, a 60% increase from $131.9 million at the end of 2024 [7][19] - Research and development expenses decreased to $15 million from $19.8 million year-over-year, reflecting a strategic focus on cost management [19] - The net loss for the quarter was $19 million, or $0.21 per share, an improvement from a net loss of $22.8 million, or $0.32 per share, in the same period in 2024 [19]