INmune Bio, Big Risk, Much Bigger Reward
The first drug company to breach $100B in sales?
We were years too early for INmune Bio (INMB), having covered the stock years back (here and here), but the Phase 2 trial results are now imminent, and this could very well be a game changer:
INmune Bio is a high-risk, high-reward speculative mid-stage biotech company on the cusp of releasing crucial Phase 2 Alzheimer's disease data for its lead asset, XPro1595, which is considered a highly intriguing mid-stage Alzheimer’s opportunity due to its unique mechanism and prior encouraging data.
XPro1595 is a "selective" TNF-alpha inhibitor that specifically targets and inhibits soluble TNF (sTNF), the form of TNF-alpha that induces inflammation and causes damage, while critically sparing transmembrane TNF (tmTNF), which is anti-inflammatory and reparative. At only ~27 kDa, it is significantly smaller than other TNF inhibitors like Humira and Enbrel (~150 kDa), allowing it to penetrate the brain/CNS effectively.
The small Phase 1b trial of XPro1595 showed consistently positive results including a reduction of over 30 cytokines in the cerebrospinal fluid (CSF), significant improvements in neuronal integrity proteins (e.g., neurofilament light, neurogranin, pTau-217), and positive changes in MRI imaging markers indicative of enhanced axonal integrity and decreased inflammation.
Two patients from the Phase 1b trial experienced "dramatic responses," regaining memory, cognition, and interest in life after treatment, and have remained stable for over three years on an expanded access program. While not expected to be a typical outcome for all patients, these highlight the potential for profound effects.
The Phase 2 MINDful trial, which completed enrollment in November 2024 with 208 early Alzheimer's patients, enriched for individuals with elevated biomarkers of neuroinflammation (hsCRP, HbA1c, ESR, or APOE4 allele) to enhance the likelihood of a positive outcome. The primary cognitive endpoint is the Early/Mild Alzheimer’s Cognitive Composite (EMACC), though the market will likely require positive and congruent results on the well-known CDR-SB for full market recognition.
The trial's goal is to demonstrate cognitive maintenance (halting decline), and it is well-powered to reach statistical significance if XPro1595 can deliver stable cognition while the placebo group declines as expected (e.g., a similar decline of about 0.6 points on the CDR-SB over 6 months seen in lecanemab's Phase 3 trial). Achieving a change approximately 0.3 points better than placebo on CDR-SB is estimated to reach statistical significance.
Approved non-selective TNF inhibitors have been associated with a dramatically reduced risk of Alzheimer’s disease in patients with inflammatory conditions. A small 2015 trial of etanercept (Enbrel) in Alzheimer's, despite its limitations, showed encouraging cognitive trends, providing incremental optimism for XPro1595. Furthermore, strong management confidence is indicated by insider participation in recent financings and a strategic warrant repurchase to minimize dilution.
Alzheimer's disease represents potentially the largest total addressable market in drug industry history, with an estimated 16.75M patients in Western countries with established healthcare systems. If successful, and assuming conservative peak penetration and pricing, the potential valuation for XPro1595 could reach several hundred billion dollars, on a yearly $30K treatment cost (higher in the US, lower in the EU).