Summary of Immune Bio's Mindful Phase Two Topline Data Conference Call Company and Industry - **Company**: Immune Bio - **Industry**: Alzheimer's Disease Treatment Key Points and Arguments Trial Overview - The MINDFUL trial is a double-blind, placebo-controlled Phase II trial evaluating Xpro for early Alzheimer's disease in patients with biomarkers of inflammation [6][14] - The trial included a modified intent to treat population of 200 patients, with a focus on a biologically defined group of 150 patients with early Alzheimer's disease confirmed by amyloid positivity and at least one biomarker of inflammation [10][11] Results and Efficacy - Xpro was found to be safe for early Alzheimer's patients and showed potential effectiveness in a defined patient population [6][12] - The primary endpoint was not met in the overall modified intent to treat population, but a consistent benefit was observed in the subgroup of patients with two or more biomarkers of inflammation [11][20] - The effect size for the primary endpoint (EMAC) was 0.27, indicating a meaningful benefit in cognition for the targeted patient group [19][20] - Positive effects were also noted on secondary endpoints related to behavior and disease-relevant biomarkers in the blood, including p tau 217 [11][19] Safety Profile - Xpro demonstrated a favorable safety profile with no deaths and no cases of ARIA (Amyloid-Related Imaging Abnormalities) reported [17][22] - The most common adverse event was injection site reactions, occurring in 80% of patients receiving Xpro, but these were manageable and did not lead to significant complications [25][28] Future Development Plans - Immune Bio plans to explore partnership opportunities and prepare for an end-of-phase two meeting with the FDA to discuss regulatory pathways and potential breakthrough designation [7][85] - The company aims to confirm EMAC as a primary cognitive endpoint with the FDA, which could facilitate a more efficient Phase III trial design [48][79] Market Implications - The trial results suggest a potential path forward for Xpro as a best-in-class therapy for early Alzheimer's disease, particularly in patients with neuroinflammation [14][28] - Immune Bio is committed to advancing Xpro's development and addressing the needs of Alzheimer's patients and their caregivers [82][85] Additional Important Content - The trial faced challenges with patient screening, leading to the exclusion of 50 patients who were not confirmed to have Alzheimer's disease [52][68] - The company emphasized the importance of biomarkers in understanding disease progression and treatment efficacy, noting that p tau 217 is gaining recognition as a significant prognostic indicator [44][70] - Immune Bio acknowledged the need for effective therapies for Alzheimer's, highlighting the trial's contribution to understanding neuroinflammation's role in the disease [28][82]

Core Insights - The Phase 2 MINDFuL trial of XPro™ in early Alzheimer's Disease (AD) patients with inflammation biomarkers did not meet the primary cognitive endpoint in the modified intent-to-treat (mITT) population, but showed cognitive, behavioral, and biological benefits in a predefined subgroup of amyloid-positive patients with two or more inflammation biomarkers [1][3][4] Group 1: Trial Results - The MINDFuL trial enrolled 208 participants with early-stage AD, assessing XPro™'s potential to slow cognitive decline by targeting neuroinflammation [4] - In the predefined subgroup of amyloid-positive early AD patients with two or more inflammation biomarkers (n=100), XPro™ demonstrated a cognitive benefit on the primary endpoint EMACC (effect size: 0.27) and a behavioral benefit on the Neuropsychiatric Inventory (effect size: -0.24) [7] - A biological benefit was observed in blood levels of pTau217 (effect size: -0.20), indicating a positive impact on AD pathology [7] Group 2: Safety and Tolerability - XPro™ treatment was well-tolerated and safe, with no occurrences of ARIA-E or ARIA-H reported [2][7] - The most common adverse events were injection site reactions, occurring in 80% of the XPro™ group compared to less than 20% in the placebo group [7] - There were no deaths or drug-related hospitalizations during the trial, indicating a favorable safety profile [7] Group 3: Future Plans - The company plans to submit for Breakthrough Therapy designation with the FDA and will present additional analyses at the Alzheimer's Association International Conference (AAIC) in July 2025 [2][10] - The company aims to engage regulatory authorities in the UK, EU, and other regions to define the path for a pivotal trial to support XPro™ approval in early AD [14]

Core Insights - The article emphasizes the importance of understanding the science behind biotech investments to avoid pitfalls in the industry [1] Group 1 - The author has a PhD in biochemistry and extensive experience analyzing clinical trials and biotech companies [1] - The mission is to educate investors on the scientific aspects of biotech businesses [1]

Core Viewpoint - INmune Bio Inc. has announced a registered direct offering of 3,000,000 shares of its common stock at a price of $6.30 per share, aiming to raise approximately $19 million in gross proceeds for working capital and general corporate purposes [1][2]. Group 1: Offering Details - The offering is expected to close on or about June 30, 2025, pending customary closing conditions [2]. - A.G.P./Alliance Global Partners is acting as the sole placement agent for the offering [2]. - The offering is made under an effective shelf registration statement previously filed with the SEC [3]. Group 2: Company Overview - INmune Bio Inc. is a clinical-stage biotechnology company focused on developing treatments targeting the innate immune system [5]. - The company has three product platforms: - The Dominant-Negative Tumor Necrosis Factor (DN-TNF) platform, which is in clinical trials for Mild Alzheimer's disease, Mild Cognitive Impairment, and treatment-resistant depression [5]. - The Natural Killer Cell Priming Platform, which includes INKmune® for cancer treatment, currently in trials for metastatic castration-resistant prostate cancer [5]. - The CORDStrom™ platform, which recently completed a trial for recessive dystrophic epidermolysis bullosa [5].

Core Viewpoint - INmune Bio Inc. is set to present top line data from the Phase 2 MINDFuL trial focused on early Alzheimer's Disease during a conference call on June 30, 2025 [1][2]. Group 1: MINDFuL Trial Details - The MINDFuL trial is an international, blinded, randomized Phase 2 study involving patients with early Alzheimer's Disease (AD) who exhibit biomarkers of elevated neuroinflammation [3]. - Participants in the trial must have at least one of four inflammation biomarkers: elevated CRP, HgbA1c, ESR, or ApoE4 allele, and they receive either XPro™ or placebo in a 2:1 ratio for 6 months [3]. - Cognitive endpoints for the trial include EMACC and CDR, with XPro™ administered as a once-a-week subcutaneous injection [3]. Group 2: XPro™ Overview - XPro™ is a next-generation inhibitor of tumor necrosis factor (TNF) that selectively neutralizes soluble TNF without affecting trans-membrane TNF or TNF receptors [4]. - The drug aims to reduce neuroinflammation, potentially benefiting patients with neurological diseases [4]. Group 3: Company Background - INmune Bio Inc. is a publicly traded clinical-stage biotechnology company focused on developing treatments targeting the innate immune system [5]. - The company has three product platforms, including the Dominant-Negative Tumor Necrosis Factor (DN-TNF) platform, which is in clinical trials for Mild Alzheimer's disease, Mild Cognitive Impairment, and treatment-resistant depression [5][6]. - Other platforms include the Natural Killer Cell Priming Platform and the CORDStrom™ program, which targets chronic inflammation and cancer [5][6].

Pipeline Highlights - XPro: Phase 2 Alzheimer's trial fully enrolled with top-line cognition results expected in June 2025[5], Phase I data showed a 222% increase in Contactin-2 and a 56% decrease in Neurogranin after 12 weeks of treatment[23] - CORDStrom: Completed blinded randomized trial in Recessive Dystrophic Epidermolysis Bullosa (RDEB) with US BLA submission planned for 2026[5], targeting a > $1 billion peak sales opportunity in the US, UK, and EU[50] - INKmune: Phase I dose escalation cohorts complete, with ongoing Phase 2 Metastatic Castrate Resistant Prostate Cancer (mCRPC) data readouts in 2025[5] XPro (Alzheimer's Disease) - TNF inhibitors reduce the risk of developing AD by 60% based on epidemiological studies of over 60 million cases[15] - Phase I results showed dose-dependent reduction of CSF biomarkers of neuroinflammation in AD patients[16] CORDStrom (RDEB) - CORDStrom is potentially the first systemic therapy for RDEB, with itch benefit as a key differentiating factor[50] - Mission EB trial: 30 pediatric patients with RDEB were treated in a double-blind, randomized, placebo-controlled cross-over design clinical trial[52, 56] INKmune (Cancer) - INKmune converts resting NK cells to cancer-killing memory-like NK cells[5, 73]

Analyst’s Disclosure:I/we have a beneficial long position in the shares of INMB either through stock ownership, options, or other derivatives. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.Seeking Alpha's Disclosure: Past performance is no guarantee of future results. No recommendation or advice is being given as to whether any investment is suitable for a partic ...

Core Insights - INmune Bio, Inc. is collaborating with Virginia Commonwealth University to study the effects of Traumatic Brain Injury (TBI) on Alzheimer's disease (AD) and the potential of XPro™ treatment to mitigate these effects [1][2][4] - The study indicates that TBI increases amyloid deposition and neuroinflammation, which are linked to AD progression, and that XPro™ significantly reduces amyloid formation and improves brain function [1][3][4] Group 1: Study Findings - TBI leads to a transient increase in TNFR1, BACE1, and Aβ42 expression in the hippocampus, peaking three days post-injury [3] - Administering XPro™ shortly after TBI inhibits solTNF/TNFR1 activity, preventing elevations in TNFR1, BACE1, Aβ42, and caspase-3 levels [3] - XPro™ treatment reduces intracellular neuronal amyloid accumulation and improves neurological outcomes in treated animals [3][4] Group 2: Implications for Alzheimer's Disease - The findings suggest that targeting TBI-induced solTNF/TNFR1 signaling could mitigate Aβ42 production and neuronal loss, linking TBI and AD [2][4] - XPro™ is positioned as a promising treatment to reduce AD pathology risk following TBI, particularly for the elderly population at risk for dementia [4] Group 3: Company Overview - INmune Bio, Inc. is a clinical-stage biotechnology company focused on developing treatments that target the innate immune system to combat diseases [6][7] - The company has three product platforms, including XPro™, which is in clinical trials for Mild Alzheimer's disease and other conditions [7]

Core Insights - INmune Bio, Inc. (NASDAQ: INMB) reported Q1 2025 business and financial results on May 8th, 2025, surpassing analyst estimates [1] - The company is on track to share results of its ongoing projects, indicating progress in its research and development efforts [1] Financial Performance - The financial results for Q1 2025 showed a positive trend, with the company beating analyst expectations [1] Research and Development - INmune Bio focuses on novel Cell & Gene Therapies (CGT) aimed at addressing various clinical needs, showcasing its commitment to innovation in the biotechnology sector [1]

Financial Data and Key Metrics Changes - The net loss attributable to common stockholders for Q1 2025 was approximately $9.7 million, compared to approximately $11 million for the same period in 2024, indicating an improvement [26] - Research and development expenses totaled approximately $7.6 million for Q1 2025, down from approximately $8.7 million in Q1 2024 [26] - General and administrative expenses remained stable at approximately $2.3 million for both Q1 2025 and Q1 2024 [26] - As of March 31, 2025, the company had cash and cash equivalents of approximately $19.3 million, which is expected to fund operations through Q3 2025 [27] Business Line Data and Key Metrics Changes - The company is preparing to report top-line results from the MINDFUL phase two trial in early Alzheimer's disease, expected in mid to late June 2025 [6][27] - The market opportunity for EXPAREL in early Alzheimer's disease has increased to nearly 70% of early AD patients, up from the previously estimated 40% [7][8] - The safety profile of EXPAREL remains excellent, with no reports of adverse events in the ongoing trial [9] Market Data and Key Metrics Changes - The approval of mecanumab in the EU and UK excludes patients with two copies of the APOE4 gene, creating an unmet need for EXPAREL therapy in this subgroup [10][11] - The evolving biomarker landscape in Alzheimer's disease, particularly the significance of p-tau217, is expected to enhance the company's market position [12] Company Strategy and Development Direction - The company is focused on targeting neuroinflammation in Alzheimer's disease, positioning itself as a leader in this area [81][82] - Plans for the Kordstrom program include filing a Biologics License Application (BLA) in 2026 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB) [17][24] - The company aims to transition manufacturing processes to optimize production for both Kordstrom and Inkmune, ensuring cost-effectiveness and regulatory compliance [24] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming MINDFUL trial results, believing they will significantly impact the treatment landscape for early Alzheimer's disease [16][81] - The company is optimistic about the regulatory environment for rare disease treatments, particularly following recent FDA comments [18][24] Other Important Information - The company has successfully transitioned its drug supply logistics for Inkmune to a US-based contractor, Cryoport, to ensure trial completion [21] - The company is also preparing for an IND submission for Kordstrom in the US, with manufacturing of a new batch of products using US-approved cord donors starting soon [73] Q&A Session Summary Question: Can you walk us through the next steps for the program assuming a positive readout in June? - Management indicated that they would defer specific timelines until after the FDA meeting, aiming to move quickly to open sites and enroll patients [32][33] Question: Can you comment on the FDA review team for your program? - Management believes that the FDA has remained on track and that the review team is stable, although they cannot predict future outcomes [36] Question: How do you think investors will react if EMAC hits but CDR is equivocal? - Management emphasized that EMAC is the primary driver for cognitive changes, and they expect correlations with CDR, which is a more blunt instrument [46][49] Question: Are APOE4 patients inherently inflammatory? - Management confirmed that APOE4 carriers tend to have earlier onset and faster progression of Alzheimer's disease, indicating a link to inflammation [62] Question: Are you still on track to initiate the twelve-month open-label trial for Cordstrom mid this year? - Management confirmed they are following FDA guidance and expect to submit an IND late this year, with plans for a follow-on trial in the US [73][74]