INmune Bio Inc.

greetings and welcome to the immune bio third quarter 2023 earnings call at this time all participants are in a listen only mode a question and answer session will follow the formal presentation if anyone should require operator assistance during the conference please press star and then zero on your telephone keypad as a reminder this conference is being recorded A transcript will follow within 24 hours of this conference call. At this time, it is my pleasure to introduce Mr. David Moss, CFO of ImmuneBio. David, the floor is yours.

Thank you, Claudia, and good afternoon, everybody. We thank you for joining us for ImmuneBio's third quarter 2023 financial results. With me on the call is Dr. RJ Tessie, CEO of ImmuneBio, and Dr. Mark Liddell, Chief Scientific Officer of ImmuneBio, We'll provide an update on IncBUNE, our memory-like natural killer cell oncology platform. Before we begin, I remind everyone that except for statements of historical fact, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Please see the forward-looking statements disclaimer on the company's earning press release as well as risk factors in the company's SEC filings, including our most recent quarterly filings with the SEC. There's no assurance of any specific outcome. Undue reliance should not be placed on forward-looking statements which speak only as of the date they are made as the facts and circumstances underlying these forward-looking statements may change. Except as required by law, Immune Bio disclaims any obligations to update these forward-looking statements to reflect future information events or circumstances. With that behind us, now I'd like to turn the call over to Dr. RJ Tessie, CEO of Immune Bio. RJ.

Thank you, David, and thank you, everyone, for joining the call. As usual, I will arrange my remarks to highlight the key takeaways for the third quarter and the subsequent period and include updates on our platform programs. I will start by reviewing our developments of EXPRO before passing it over to Mark Liddell, who will provide an update on IncMUNE. And then David Moss will conclude with a discussion of our financial results and provide an update on upcoming and new milestones. Then we move to Q&A. During the third quarter, our primary focus remained enrollment of patients into ADO2, our blinded randomized phase two trial in patients with early Alzheimer's disease with inflammation, and we focused on increasing our geographic footprint of that trial. We had notable success on both fronts. The MHRA, the UK equivalent of the FDA, approved our clinical trial application in August Five of the six sites in the UK are already screening and enrolling patients into ADO2. The UK is an ideal jurisdiction to expand our Alzheimer's disease trial, given it possesses one of the highest rates of Alzheimer's disease in the Western world, coupled with a robust for-profit medical research infrastructure. Recognition Health, our lead vendor in the UK, has five memory centers with a large Rolodex of clinical trial ready patients. This provides a ready pool of patients to screen for participation in the trial. Recognition Health has a history of enrolling a large number of patients and are incentivized to find the right patients to enroll in our program. Australia, where the trial is furthest advanced, continue to see patients who have completed the six month blinded trial opt in to the phase two open label extension program. We have also submitted regulatory dossiers to additional countries with the plan to have additional sites open soon. This leaves the US and the FDA. The FDA is the outlier here. We remain on track with the FDA to meet the conditions necessary to lift the clinical hold. We believe the hold will be lifted before the end of the year. There are two main themes from the just completed CTAD or Clinical Trials Alzheimer's Disease Meeting in Boston, earlier treatment and better treatments. As you can imagine, we heard a lot about the anti-amyloid therapies. Little new was presented and no matter how they cut the data, there is no change in safety or efficacy of the various anti-amyloid products. Unsurprisingly, a meta-analysis demonstrated all three drugs, aducanumab, lucanumab, and donamimab performed the same. This is shaping up to be an interesting marketing battle debating features, not benefits. In my opinion, the desire for earlier treatments is driven by the frustrating results from anti-amyloid monotherapy. That is, if the results of anti-amyloid drugs were better, there may be less talk about earlier treatment. Both of these themes, the limit efficacy of anti-amyloid drugs in the early treatment, play two ex-pro strengths. The universe of therapies for Alzheimer's disease is expanding. Targeting neuroinflammation is high on everyone's list. Dr. Howard Fillett, the chief scientific officer of the Alzheimer's Drug Discovery Foundation, highlighted the role of inflammation and aging and cognitive decline. In a recent Fierce Biotech interview, Dr. Fillett points out that at autopsy, beta amyloid is present in the brains of many elderly individuals that have died with normal cognitive functions. Only those, and this is the key point, only those with both amyloid and inflammation have dementia. In other words, the immune response to amyloid appears to drive nerve cell death and synaptic dysfunction that results in cognitive decline. His comments highlights our longstanding position. Without inflammation, there is no cognitive decline in patients with amyloid pathology. Combination therapy with the anti-amyloid drugs was much discussed at CTAD, but no data was presented. Once again, the desire for combination therapy reflects a frustration with the current results. Combination therapies, excuse me, must improve safety or efficacy, ideally both. Because the major safety problem with anti-amyloid class of drugs is neuroinflammation, we believe EXPRO plays a role in combination therapy. ImmuneBio has initiated preclinical studies testing combination therapy in animal models. I emphasize the combination therapy is preclinical and in no way dilutes our focus on the phase two trial currently enrolling patients. The discussion on early diagnosis focused on blood tests aiming to produce a simple, accurate, cost-effective triage system. Our view is simple. Cognitive decline is predicted by biomarkers of neuroinflammation and neurodegeneration. Blood amyloid is a biomarker of disease, the disease of Alzheimer's disease. Staging, by staging I mean the severity of the disease, requires a different set of biomarkers. In my opinion, and many of those at the meeting, the most promising duo is GFAP, was glial fibrillary acidic protein, a biomarker of astrocyte activation, and phospho-tau-217, a biomarker of neurodegeneration, are promising. Although we do not use GFAP or p-tau-217 as screening biomarkers for enrollment in the Phase I trial, They were measured as part of the biomarker response package. Both biomarkers decreased in patients after treatment with XPRO. We hope to show that this decrease correlates with clinical response in the Phase II trial. We are persistent in our belief that cognitive decline is the sum of synaptic dysfunction and nerve cell death. Phosphatau is an excellent measure of neurodegeneration, or nerve cell death in patients with Alzheimer's disease, measuring synaptic function is more complicated. A small group of Alzheimer's patients used a self-administered EEG using the novel system from Cumulus Neuroscience. The study confirmed in this small number of patients the feasibility of collecting high-quality EEG signals at home. The patients liked it, and there was evidence of benefit as demonstrated by acute and chronic changes changes in the P300 amplitude on EEG after treatment with EXPRO. Although the group is small and the data are early, we believe this work is further evidence of improved synaptic function after EXPRO treatment. And future work will correlate this activity with cognitive function and pharmacodynamic responses to DN-TNF. This type of home testing may be a key element to CNS drug development in the future. Two other applications of the DNT in a family of drugs are worth mentioning. New data using MbO3 to treat cancer will be presented at the 38th annual Society of Immunotherapy meeting in San Diego later this week. MbO3 has been shown to be an innate immune checkpoint inhibitor that down regulars SIRP-alpha. SIRP-alpha, that is S-I-R-P-alpha, is signal regulatory protein alpha. That is the macrophage side of the CD47 don't eat me signal. Down regulation of SIRP-alpha repolarizes immunosuppressive macrophages in the tumor microenvironment into M2 macrophages that directly kill and phagocytes tumors and improves ADCP, which is antibody-dependent cellular phagocytosis, a key but often ignored effector of anti-cancer antibody therapy. Recent data from the DMD program confirms the potency of the 10 kilodalton PSAR DNTNF in mouse models of the disease. As a reminder, the PSAR DNTNF compounds are the sons of Vexpro with similar biologic activity that allows immune biology to expand applications of the DN-TNF class of compounds beyond CNS. The goal of the MBO3 cancer program and the DMD program is to out-license these promising drugs. Some of you are wondering how a single drug, dominant negative TNF inhibitors, can be useful in the treatment of cancer and the treatment of Alzheimer's disease. Macrophage function is the glue that holds this story together. Microglia are tissue-based macrophages of the brain. TAMs, or tumor-activated macrophages, are tissue-based macrophages in the TME of cancer. In disease, chronic inflammation, shall we say, stuns the macrophages into not working. In the brain, chronic neuroinflammation causes the microglia to become dysfunctional, a dysfunctional phenotype that produces destructive cytokine, does not phagocytize cellular and myelin debris, and does not prune synapses appropriately. This results in nerve cell loss, demyelination, and synaptic dysfunction, the hallmarks of neurodegenerative disease, including Alzheimer's. DN-TNF converts the destructive microglia into a reparative cell type that promotes nerve cell survival, remyelination, and synaptic classivity. The remodeling and repair we have seen in the brains of patients with Alzheimer's disease treated with Expro reflect the normalization of microglial function caused by Expro. In cancer, soluble TNF produced by tumor cells causes expression of MUC4, SERP-alpha, and other immunosuppressive cytokines that polarize TAMs to an immunosuppressive phenotype that promotes and protects tumor growth and metastasis. These elements also promote resistance to immunotherapy. EXPRO neutralizes soluble TNF resulting in M2 macrophages that do not express SERP-alpha, kill tumor cells, promote ADCP. On the tumor, EXPRO down-regulates MUX4 to expose the tumor to immune attack. In summary, ExPRO improves the function of innate immune cells needed to defeat the ravages of neurodegenerative diseases of the brain and cancer, and the macrophage is the common denominator to these effects. I will now pass this to Mark Liddell, the founder and CSO of ImmuneVial, to update the progress on the InCMU program. Mark.