INMB Q1 2025: XPro yields robust early pTau217 cut in Phase I
- Compelling biomarker impact: The executives highlighted that XPro demonstrated a robust and early reduction in pTau217 in the Phase I study, a result that is unusual compared to other Alzheimer's disease treatments, suggesting a strong potential in addressing neuroinflammation in AD.
- Exclusive market opportunity in Alzheimer's: Management pointed out that XPro may be particularly beneficial for the subgroup of early Alzheimer's patients—especially APOE4 homozygotes—who are underserved by current anti-amyloid therapies due to regulatory labeling exclusions, presenting a differentiated market position.
- Differentiated systemic therapy for RDEB: In the Q&A, it was emphasized that CORDStrom, being a systemic treatment, could serve patients with RDEB beyond the limitations of approved gene therapies that only address localized skin wounds, indicating a broader therapeutic opportunity.
- Uncertainty in data robustness: The management acknowledged difficulty comparing XPro's impact on pTau217 with other approaches and noted that full data is still pending, which raises concerns about the consistency and reliability of its clinical effects .
- Limited historical context: The executives mentioned they haven't seen such early, robust changes in CSF in other studies, suggesting that the current data may be an outlier and could be challenging to replicate or benchmark against established treatments .
- Regulatory risk reliance: Although there is optimism that regulatory agencies will be receptive to pTau217, the sole reliance on this biomarker in the data package introduces uncertainty if regulatory expectations evolve or if the biomarker results are not as predictive as hoped .
| Metric | YoY Change | Reason |
|---|---|---|
Revenue | +31.6% (from $38K in Q1 2024 to $50K in Q1 2025) | Revenue increased by 31.6% YoY, likely reflecting improved market acceptance and higher sales that built on the Q1 2024 baseline, although specific drivers were not detailed in the documents. |
Total Operating Expenses | –9.7% (from $11,031K in Q1 2024 to $9,955K in Q1 2025) | Total operating expenses declined by 9.7% YoY, largely due to a 12.2% decrease in R&D expenses (falling from $8,693K to $7,639K) which indicates a strategic reduction in high-cost R&D spending building on the previous period’s higher expenditures. |
Net Loss | Improved by about 11.6% (from $11,025K in Q1 2024 to $9,739K in Q1 2025) | Net loss narrowed by approximately 11.6% YoY, which can be attributed to the reduction in R&D expenses and better cost control, improving the loss profile relative to the more burdensome expenses seen in Q1 2024. |
Cash and Cash Equivalents | –26% (from $26,002K in Q1 2024 to $19,337K in Q1 2025) | Cash and cash equivalents decreased by 26% YoY, reflecting higher cash usage in operations and a tighter liquidity position as the company built on the lower cash levels from Q1 2024, despite some financing inflows. |
Total Assets | –19% (from $46,833K in Q1 2024 to $37,801K in Q1 2025) | Total assets declined by nearly 19% YoY, primarily due to the reduced cash holdings and adjustments in the asset base that followed the prior period’s figures, indicating a contraction in the company's asset portfolio from Q1 2024 to Q1 2025. |
Total Stockholders’ Equity | +5% (from $28,224K in Q1 2024 to $29,673K in Q1 2025) | Total stockholders’ equity increased by roughly 5% YoY, which is notable given the net loss; this improvement is likely driven by the issuance of common stock and increased stock-based compensation that provided a boost despite operational losses from the previous period. |
| Metric | Period | Previous Guidance | Current Guidance | Change |
|---|---|---|---|---|
AD02 Top-line Data Release | Q4 2024 | Expected in June 2025, less than 100 days from the earnings call date | no guidance provided | no current guidance |
AD02 Trial Details | Q4 2024 | Enrolled 208 patients across 8 countries, with a focus on neuroinflammation biomarkers | no guidance provided | no current guidance |
INKmune Phase II Trial Enrollment | Q4 2024 | Expected to complete by the end of 2025 | no guidance provided | no current guidance |
INKmune Data Release | Q4 2024 | Open‐label trial data will be reported as it becomes available during 2025 | no guidance provided | no current guidance |
CORDStrom BLA Filing | Q4 2024 | Planned for the first quarter of 2026 | no guidance provided | no current guidance |
CORDStrom Potential Approval Timeline | Q4 2024 | Approximately 6 months after submission, targeting approval by September 2026 | no guidance provided | no current guidance |
Cash Runway | Q4 2024 | Cash is sufficient to fund operations through Q3 2025 | no guidance provided | no current guidance |
Additional Capital | Q4 2024 | Raised $5.4 million through the ATM since year-end 2024 and potential to raise approximately $30 million contingent on positive AD02 data | no guidance provided | no current guidance |
Commercialization Plans | Q4 2024 | For CORDStrom and XPro, the company plans to seek partnerships for distribution and marketing rather than building standalone capabilities | no guidance provided | no current guidance |
Pipeline Prioritization | Q4 2024 | Continued focus on CNS diseases, particularly Alzheimer's, while advancing cell therapy programs like INKmune and CORDStrom | no guidance provided | no current guidance |
| Topic | Previous Mentions | Current Period | Trend |
|---|---|---|---|
Alzheimer’s Disease Clinical Trials & Biomarker Strategy | Prior calls (Q2–Q4) highlighted the use of inflammatory biomarkers, EMACC as a cognitive endpoint, and patient enrichment strategies; pTau217 was notably absent in Q2–Q4 discussions | Q1 2025 added a strong focus on pTau217 with evidence of early CSF changes and reinforced the value of EMACC, differentiating their approach against anti‐amyloid therapies | Evolving focus: The strategy is advancing from general neuroinflammation and cognitive endpoints toward incorporating novel biomarkers (pTau217) to better characterize early Alzheimer’s disease response. |
Regulatory Uncertainty in Novel Endpoints and Biomarker Reliance | Q3 touched on regulatory concerns regarding endpoint acceptance (with discussion of matching the mechanism to patient pathology) while Q2 and Q4 provided little or no discussion on regulatory uncertainty | Q1 2025 explicitly discussed FDA uncertainty regarding novel endpoints such as EMAC (with fallback plans to use CDR) and reiterated the importance of pTau217 as a prognostic marker | Heightened focus: There’s an increased emphasis on proactively addressing regulatory uncertainties through clear contingency plans, reflecting a more cautious yet strategic regulatory approach. |
Trial Data Robustness and Reliance on Interim Results | Q2 emphasized a robust blinded interim analysis with “highest quality data” and Q3 reported strong third‐party validations, while Q4 promised a robust data package at top‐line readout | Q1 2025 reinforced the rigorous quality control measures—detailed patient enrollment (208 patients across 8–9 countries) and exhaustive data cleaning—to ensure the reliability of results | Consistent strength: The messaging around data robustness has remained positive and consistent across periods, reinforcing confidence in trial execution. |
Patient Enrollment and Trial Execution Challenges | Q2 described slow but selective patient enrollment using biomarkers; Q3 highlighted closing enrollment for rigorous global trials and addressed screening challenges; Q4 noted manageable dropout rates | Q1 2025 reiterated complex multinational enrollment (208 patients in 8–9 countries) and provided updates on trials like CaRe PC and CORDStrom, underscoring well-managed execution challenges | Steady management: Enrollment and execution challenges persist but are being effectively managed with rigorous quality control and strategic patient selection. |
INKmune Platform Innovation with Mechanism Uncertainty | Q2 provided detailed discussions on the platform’s mechanistic complexity (trogocytosis, key molecules, cytokine‐free advantages) while Q3 and Q4 largely focused on clinical progress and manufacturing without emphasizing uncertainty | Q1 2025 did not address mechanism uncertainty, suggesting a shift toward highlighting clinical and safety data over mechanistic debates | De‐emphasis: There is a move away from discussing mechanism uncertainties, likely to focus investor attention on clinical progress and scalability. |
CORDStrom Program for Systemic Therapy (RDEB and Broader Applications) | Q4 extensively detailed CORDStrom’s systemic approach for RDEB with regulatory and manufacturing milestones; Q2 and Q3 had little or no mention | Q1 2025 reaffirmed progress with clear regulatory milestones (BLA filing targeted for 2026), continuing to emphasize its potential for addressing systemic disease aspects of RDEB | Resurgence: After intermittent mentions, recent calls show renewed commitment and clearer regulatory pathways for CORDStrom, underlining its potential impact. |
External Partnership Dependency for Commercialization | Q4 clearly discussed partnering with external entities for distribution and marketing; Q3 briefly touched on self-administration features for an injectable asset; Q2 did not mention this topic | Q1 2025 did not explicitly mention external partnerships, indicating mixed messaging across periods | Variable focus: While external partnership dependency was stressed in Q4, it was not reiterated in Q1, suggesting ongoing evaluation of commercialization strategies. |
Operational Efficiency and Burn Reduction Strategies | Q3 mentioned an expected burn rate of approximately $4M for the next year, underscoring cost awareness; Q2 and Q4 did not provide details on this topic | Q1 2025 did not provide any updates on operational efficiency or burn reduction strategies | De‐emphasis: The focus on operational efficiency appears to have been scaled back after Q3, indicating a possible shift in priority or improved execution within ongoing operations. |
Emergence of New Indications (Treatment-Resistant Depression & mCRPC) | Q2 and Q3 introduced treatment-resistant depression (TRD) with plans for a Phase II trial and provided steady progress on the mCRPC (CaRe PC) trial; Q4 focused on mCRPC with updates on dosing and enrollment | Q1 2025 continued to update on the CaRe PC trial for mCRPC, while TRD was not mentioned | Selective emphasis: mCRPC remains a core emerging indication with ongoing trial progress, while mention of TRD has diminished in the latest period, possibly reflecting strategic prioritization. |
De-emphasis of Earlier Focus Areas (APOE4 Homozygote Targeting & Early Robust CSF Changes) | In prior periods (Q2–Q4) there was no explicit mention of de-emphasizing these focus areas, though patient selection based on inflammation was consistently noted | Q1 2025 maintained focus on these areas by highlighting the market potential for APOE4 homozygotes and robust CSF changes; no de-emphasis was communicated | Continuity: Earlier focus areas remain integral to the strategy, with no notable de-emphasis, underscoring a steady commitment to these markets. |
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Phase III Timeline
Q: When is Phase III starting?
A: Management indicated they plan to meet with the FDA for an end-of-Phase II discussion in Q4 2026 to design a larger Phase III trial, with sites ready in Europe and the U.S. to start enrollment quickly after data readout. -
XPro Outcome
Q: What if EMAC is strong but CDR less clear?
A: They explained that EMAC is the preferred tool for tracking subtle cognitive changes, whereas CDR tends to be a noisier measure. Despite seeing about 9% APOE homozygotes in the smaller trial, they expect this to be around 15% in larger studies, aligning with benchmarks from comparable trials. -
FDA Turnover
Q: Is FDA reviewer turnover a concern?
A: Management reassured investors that, despite turnover rumors, the FDA team remains on track. They have provided clear guidelines for validating endpoints like EMAC, suggesting no major disruptions in the review process. -
CDR Decline
Q: How much CDR reduction is needed?
A: They noted the trial was powered using conservative assumptions—mirroring the effect sizes (with a standard deviation around 1) seen in larger trials such as lecanemab and donanemab—implying a similar magnitude of decline should be sufficient over a 6‑month period. -
CORDStrom Enrollment
Q: What’s the plan for CORDStrom enrollment?
A: Management confirmed they are manufacturing a new U.S.-approved batch and plan to file an IND later this year, setting up an open-label trial in the U.K. and then expanding enrollment in the U.S. to further assess dosing. -
Regulatory Outlook
Q: How favorable is the RDEB regulatory landscape?
A: They view the recent gene therapy approval as positive and emphasize that CORDStrom offers a systemic treatment for RDEB, addressing broader disease aspects beyond localized skin applications. -
APOE Inflammation
Q: Are APOE4 patients inherently inflammatory?
A: Management described APOE4 as a risky gene that leads to earlier onset and faster progression of Alzheimer’s, suggesting its carriers are more prone to inflammation and have a shorter survival compared to other groups.
Research analysts covering Inmune Bio.