Executive Summary / Key Takeaways

• INmune Bio is a clinical-stage immunology company with three distinct therapeutic platforms: XPro (targeting neuroinflammation in Alzheimer's disease), CORDStrom (a mesenchymal stromal cell therapy for rare diseases like RDEB), and INKmune (a natural killer cell priming platform for cancer). The company is strategically repositioning its pipeline following recent clinical readouts.
• Despite XPro's Phase 2 MINDFuL trial not meeting its primary endpoint in the overall Alzheimer's population, a predefined subgroup with high inflammation showed promising cognitive, behavioral, and biological benefits, leading to a strategic pivot to seek partnerships for late-stage development and explore rare disease indications for XPro.
• CORDStrom is INmune Bio's most advanced program, with a clear path towards regulatory submission for Recessive Dystrophic Epidermolysis Bullosa (RDEB) in the U.K. (MAA by mid-2026) and the U.S. (BLA in 2026), bolstered by Orphan Drug and Rare Pediatric Disease Designations and demonstrated efficacy in reducing debilitating itch.
• The company faces significant liquidity challenges, with recurring net losses and negative cash flows raising substantial doubt about its ability to continue as a going concern, necessitating ongoing financing efforts and strategic partnerships to fund operations into Q4 2026.
• INmune Bio's technological differentiation lies in its precision medicine approach, focusing on reprogramming the innate immune system, and its robust, scalable manufacturing processes for cell therapies, which could provide a competitive edge in specific, underserved patient populations.

A New Chapter: Reprogramming Immunity in a Dynamic Market

INmune Bio Inc. (NASDAQ:INMB) is a clinical-stage biotechnology company focused on developing therapies that reprogram the patient's innate immune system to combat disease. Founded in 2015, the company has strategically built a pipeline around three distinct platforms: XPro, targeting neuroinflammation; CORDStrom, a mesenchymal stromal cell therapy; and INKmune, an NK cell priming platform. This foundational strategy positions INmune Bio in highly competitive yet potentially lucrative therapeutic areas, including Alzheimer's disease, rare genetic disorders, and oncology. The company's approach emphasizes precision medicine, aiming to match its therapies to specific patient pathophysiologies, a critical differentiator in an industry increasingly moving beyond "one-size-fits-all" treatments.

The biotechnology sector, particularly in neurodegenerative diseases and advanced cell therapies, is characterized by high barriers to entry, including stringent regulatory requirements, immense research and development costs, and the need for specialized manufacturing capabilities. These barriers, while challenging for smaller entities like INmune Bio, also serve to protect innovative approaches from rapid commoditization. INmune Bio operates amidst large, established pharmaceutical companies such as Bristol-Myers Squibb , Merck & Co. , Biogen , and Gilead Sciences (GILD), which possess vast resources, diversified portfolios, and extensive commercialization infrastructure. While these larger players dominate market share and exhibit robust financial performance, INmune Bio aims to carve out its niche through targeted, innovative therapies that address specific unmet needs.

Technological Edge: Precision and Scalability

INmune Bio's core competitive advantage stems from its differentiated technology platforms, each designed to precisely modulate the innate immune system.

The DN-TNF (XPro) platform utilizes dominant-negative technology to selectively neutralize soluble TNF (sTNF), a key driver of innate immune dysfunction. Unlike older, non-selective TNF inhibitors, XPro is designed to neutralize sTNF without affecting trans-membrane TNF (tmTNF) or TNF receptors, thereby avoiding broad immunosuppression. This selective mechanism is intended to target activated microglia and astrocytes in the brain that produce sTNF, which contributes to nerve cell loss, synaptic dysfunction, and impaired myelin repair in neurodegenerative conditions. In its Phase 1 Alzheimer's study, XPro demonstrated a significant decrease in p-tau217, a critical biomarker of Alzheimer's severity and progression. This specific biomarker reduction highlights XPro's potential to impact underlying disease pathology, a tangible benefit over therapies that may only address symptoms. The company's focus on neuroinflammation, a driver often overlooked by amyloid-centric approaches, positions XPro as a unique therapeutic option, particularly for patients with a strong inflammatory profile who may be ineligible for anti-amyloid therapies due to safety concerns like ARIA (amyloid-related imaging abnormalities), which XPro has not exhibited.

The CORDStrom platform represents a breakthrough in mesenchymal stromal cell (MSC) technology. It is an off-the-shelf, allogeneic product derived from pooled human umbilical cord mesenchymal stromal cells (HuMSCs). The proprietary screening, pooling, and expansion techniques allow for the creation of batch-to-batch consistent, scalable, cGMP manufactured cellular medicines. A key differentiator is the ability to tailor the final product for specific disease indications by selecting individual donor MSC seed stocks with optimal potencies for desired functional characteristics, such as wound healing or anti-inflammatory effects. For Recessive Dystrophic Epidermolysis Bullosa (RDEB), CORDStrom is formulated from MSCs with the best wound healing capacity and those that secrete cytokines to enhance wound repair and suppress itch. In the MissionEB trial, CORDStrom significantly reduced itch scores by over 27% at 6 months in patients with the most severe disease activity, a clinically meaningful reduction. This systemic approach contrasts with topical gene therapies for RDEB, which address only skin wounds and can even exacerbate itch. The company's emphasis on manufacturing consistency and cost-effectiveness from inception provides a significant operational advantage, aiming to deliver a commercially viable product at scale.

The Natural Killer Cell Priming Platform (INKmune) is designed to prime a patient's NK cells to eliminate minimal residual disease in cancer. INKmune converts inert resting NK cells into memory-like NK cells that actively kill cancer cells. This technology aims to be administered after cytotoxic chemotherapy to target residual disease, leveraging the patient's own immune system. The manufacturing processes for INKmune and CORDStrom are designed to be parallel, allowing for shared manufacturing platforms and rotational campaigns, which maximizes resource utilization and controls production costs as the company moves towards commercial supply. This operational synergy contributes to INmune Bio's efficiency in developing multiple cell therapies.

Financial Performance and Strategic Realignment

INmune Bio's financial performance reflects its status as a clinical-stage biotechnology company with significant investment in research and development. For the nine months ended September 30, 2025, the company reported a net loss of $40.70 million, an increase from $32.86 million in the comparable period of 2024. This was significantly impacted by an impairment charge of $16.51 million on acquired in-process research and development intangible assets during the second quarter of 2025. This impairment was a direct consequence of the strategic decision to halt immediate plans for XPro's development in Alzheimer's disease and other indications, following the Phase 2 MINDFuL trial's failure to meet its primary endpoint in the overall population.

Research and development expenses, a primary driver of the company's operational costs, decreased from $25.80 million in the first nine months of 2024 to $18.30 million in the same period of 2025. This reduction was largely due to the completion of the Alzheimer's clinical program, partially offset by increased compensation expenses related to employee terminations. General and administrative expenses also saw a slight decrease to $7.10 million from $7.40 million year-over-year. The company generated $1.20 million in other income, net, for the nine months ended September 30, 2025, primarily from interest income and gains on forgiveness of payables.

Liquidity and Capital Strategy

As of September 30, 2025, INmune Bio held approximately $27.7 million in cash and cash equivalents. Net cash used in operating activities for the nine months ended September 30, 2025, was $19.60 million. Despite recent financing activities, including a registered direct offering in June 2025 that generated approximately $17.4 million in net proceeds and $10.10 million in net proceeds from its At-The-Market (ATM) program, the company's recurring net losses and negative cash flows raise substantial doubt about its ability to continue as a going concern for one year following the issuance of its financial statements.

Management projects that current cash resources are sufficient to fund operations into Q4 2026. However, the company is actively evaluating various financing strategies, including equity and debt financings, government funding, collaborations, strategic alliances, and licensing arrangements. The potential for dilution to existing stockholders remains a significant risk if additional capital is raised through equity offerings. The company's ability to secure favorable terms for future financing is critical to sustaining its operations and advancing its pipeline.

Outlook and Strategic Initiatives

INmune Bio is at a pivotal juncture, with several key milestones anticipated across its platforms:

XPro (Alzheimer's Disease): Following the Phase 2 MINDFuL trial results, which showed benefits in a highly inflamed subgroup, INmune Bio is pursuing an accelerated regulatory pathway. The company expects to receive regulatory feedback from the FDA and minutes from its end-of-Phase 2 meeting in Q1 2026. This feedback is crucial for defining the path forward for a potential registration study and for advancing strategic funding and partnership discussions. Additional MRI data from the MINDFuL trial, expected in Q4 2025, could further support XPro's benefits in myelin, gray matter, and white matter. The company has also decided to re-evaluate XPro's potential beyond AD, focusing on rare diseases that offer shorter, faster pathways to market, rather than treatment-resistant depression.

CORDStrom (RDEB): This platform is on a rapid path to market. INmune Bio plans to file a Marketing Authorization Application (MAA) in the U.K. by mid-2026, followed by a Biologics License Application (BLA) with the FDA in 2026. The company anticipates hearing back from the FDA regarding the BLA by mid-2027 or later. CORDStrom has received Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation (ODD) from the FDA, making it eligible for a Priority Review Voucher (PRV) if approved by September 30, 2026, and offering seven years of market exclusivity post-approval. The company has completed technology transfer to a new cGMP manufacturing space in the U.K., ensuring readiness for commercial production.

INKmune (Prostate Cancer): The Phase I/II CaRe PC trial in metastatic castration-resistant prostate cancer completed its Phase II aspect ahead of schedule, meeting its primary safety endpoint and two of three secondary immunologic endpoints. The company plans to design a randomized Phase II trial in 2026, focusing on less advanced patient groups, as immunotherapies are generally more effective against minimal residual disease.

Competitive Positioning and Market Dynamics

INmune Bio's competitive strategy centers on its differentiated technology and precision medicine approach, aiming to address specific patient populations where larger competitors may have limitations or less targeted solutions.

In Alzheimer's disease, INmune Bio's XPro stands apart from anti-amyloid therapies like Biogen's (BIIB) lecanemab, which are approved for patients with none or one copy of the ApoE4 gene, often excluding ApoE4 homozygotes due to ARIA risk. XPro's safety profile, with no ARIA-related safety signals observed, positions it as a potential best-in-class or complementary therapy for these underserved patients, particularly those with high neuroinflammation. While Biogen has established market presence, INmune Bio's innovative targeting could capture a significant niche.

For RDEB, CORDStrom offers a systemic treatment for a systemic disease, a key differentiator from topical gene therapies that primarily address skin wounds. Mark Lowdell, INmune Bio's CSO, emphasizes that existing gene therapies do not provide a systemic solution and can even cause itch, a major complaint that CORDStrom significantly reduces. Furthermore, INmune Bio's focus on scalable and cost-effective cGMP manufacturing for CORDStrom could provide a pricing advantage in the ultra-rare disease market, where high costs are a significant barrier.

In oncology, INKmune's NK cell priming technology targets minimal residual disease, a strategy that could differentiate it from broader chemotherapy or established immunotherapies offered by giants like Bristol-Myers Squibb (BMY) or Merck (MRK). While these large players have extensive portfolios and robust cash flows, INmune Bio's agility and specialized focus on innate immunity could yield superior outcomes in specific cancer types or patient subsets. However, INmune Bio's earlier stage of development and smaller scale mean it lags in commercialization and overall financial efficiency compared to its larger, more diversified competitors.

Conclusion

INmune Bio is undergoing a significant strategic evolution, marked by both challenges and promising opportunities. The pivot for XPro in Alzheimer's disease, driven by a nuanced understanding of its Phase 2 data, underscores a commitment to precision medicine and efficient resource allocation. While the impairment charge for XPro's intangible assets highlights the inherent risks in drug development, the focus on a highly inflamed subgroup and exploration of rare disease pathways could unlock substantial value.

The CORDStrom platform stands out as the company's most advanced asset, with a clear regulatory pathway and the potential to become INmune Bio's first commercial therapeutic. Its systemic approach to RDEB, coupled with robust manufacturing capabilities and favorable regulatory designations, positions it strongly in a market with significant unmet needs. The INKmune program, with its refined strategy targeting earlier-stage cancers, further diversifies the company's pipeline. Despite ongoing liquidity challenges and the need for future financing, INmune Bio's commitment to innovative, immune-modulating therapies, coupled with a disciplined approach to development and manufacturing, provides a compelling, albeit speculative, investment thesis. The company's ability to execute on its upcoming regulatory milestones for CORDStrom and secure strategic partnerships for XPro will be critical determinants of its future success and its ability to deliver transformative therapies to patients.