INmune Bio Inc.

Greetings and welcome to the Immune Bio fourth quarter 2020 earnings conference call. At this time, all participants are on 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 zero on your telephone keypad. As a reminder, this conference call 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, co-founder and CFO of ImmuneBio. David, the floor is yours.

Thank you, Rob, and good afternoon, everybody. We thank you for joining us for the call for ImmuneBio's fourth quarter 2020 financial results. With me on the call is Dr. RJ Tessie, CEO and co-founder of ImmuneBio, who will provide a business update. Before we begin, I remind everybody that except for statements of historical facts, 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 earnings press release as well as risk factors in the company's SEC filings. including our most recent quarterly filing 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 of the facts and circumstances underlying these forward-looking statements may change. Except as required by law, Immune Bio disclaims any obligation to update these forward-looking statements to reflect future information events or circumstances. With the forward-looking statements behind us, now I'd like to turn the call over to Dr. RJ Tessie, co-founder, CEO of Inubio. RJ.

Thank you, David, and thank you, everyone, for joining the call. I will arrange my remarks to highlight the key takeaways for the fourth quarter, year-to-date, and provide updates on our platform programs before I pass it back to David to discuss our financial results and upcoming milestones. Then we will move to Q&A. I'll start with our DN-TNF platform, beginning with EXPRO-59, which we are developing for Alzheimer's disease, and other CNS indications where neuroinflammation plays an important role. The clear highlight since our last quarterly update was data we reported on January 21st from our phase one trial of EXPRO in patients with Alzheimer's disease. ImmuneBio's data-driven hypothesis is that neuroinflammation results in synaptic loss and neurodegeneration, that is nerve cell death, in patients with Alzheimer's disease. Synaptic loss and neurodegeneration is the cause of cognitive decline in these unfortunate patients. Finally, we believe the control of neuroinflammation by Expo 1595 will help repair synaptic dysfunction, decrease neurodegeneration, and prevent progressions of cognitive decline. Last July, we announced interim data demonstrating that EXPRO 1595 reduced neuroinflammation by an average of 40% in the arcuate fasciculus, a white matter tract important for learning and memory in patients with Alzheimer's disease. Neuroinflammation was assessed using MRI to measure white matter-free water, a validated biomarker of neuroinflammation. The small preliminary data set included six patients, three in a low and high dose group, treated with Expro for 12 weeks. As a reminder, the phase one trial is a neuroinflammation trial in patients with Alzheimer's disease. At that time, based on the quality of the data, we committed to initiating a phase two clinical trial in Alzheimer's disease by the end of 2021. we remain committed to that goal. On January 21st, we provided additional data from nine patients who had completed the 12-week treatment period with Expro 1595. The group included the original three patients who received weekly subcutaneous injections of 0.3 milligram per kilogram of Expro 1595, and now six patients who received one milligram per kilogram once a week. These are the low and high dose groups respectively. We wanted to accomplish two goals with the data release in January. First, we wanted to connect the dots between white matter-free water measured by MRI, a validated but new biomarker of neuroinflammation, with traditional biomarkers of neuroinflammation, namely CSF cytokines. The second goal was to determine if the downstream consequences of decreasing neuroinflammation in this small group of intensively studied patients mirrored what was seen in the extensive animal data using external models of neurodegeneration. To accomplish the first goal, we used the O-Link platform to measure 47 inflammatory chemokines and cytokine levels in the CSF of patients. CSF, by the way, is cerebral spinal fluid that is obtained by lumbar puncture. But to measure those levels in the CSS of patients before and after three months of EXPRO 1595 therapy, the cytokines all decreased significantly. For example, CCL2, excuse me, CCL7, a chemokine that really mirrors what happens with soluble TNF, decreased by 47% after 12 weeks. of expo therapy, and you can see this in the slide. The decrease in the white matter-free water and the decrease in the inflammatory chemokines and cytokines correlated closely on the next slide, and you can see that the R-squared value is greater than .7, which is a highly statistically significant correlation despite a small number of patients. What this means for the future is that the MRI, using MRI to measure white matter-free water, at least when looking at neuroinflammation, may be able to replace CSF and lumbar puncture. That's what the future holds. The results presented so far have really met the primary goal of phase one study, that is to demonstrate that EXPRO-1595 decreases neuroinflammation in patients with Alzheimer's disease. We've clearly shown this. Now on to the second question. The second question is, what are the downstream consequences of decreasing neuroinflammation in patients with Alzheimer's disease? We used two biomarker platforms to provide insight into the consequences of the decreasing neuroinflammation. The first was Proteome Biosciences PMT Calibrator to study the changes in the CSF proteome in the Alzheimer's patients before and after 12 weeks of expo therapy. This is a big data analysis of the CSF proteome that revealed that decreasing neuroinflammation led to a significant change in multiple Alzheimer disease related pathways, including the immune inflammatory response pathway, the CNS neuronal function and injury pathway, and the dendritic spine morphogenesis synaptic plasticity pathway. Notably, the analysis found an 80% decrease in neurodegeneration markers, such as neurofilament-like chain and visin-like protein 1, and significant changes in connectin-2 and neurogranin both proteins associated with neuroplasticity. To get a drug approved in Alzheimer's disease, you must demonstrate that the treatment decreases the rate of cognitive decline compared to placebo. This trial does not attempt to really meet those standards as a primary endpoint. It's a small open labeled dose escalation trial. but there is important information included in the data set. The data, albeit preliminary in nine patients, show that only one patient had progression of their disease during the three-month study. Put another way, eight of nine patients were stable or had improved cognition over the three-month period. Finally, six of the patients, all in the high-dose group, have been enrolled in a nine-month extension study. That is, they basically were allowed to continue their treatment for nine months after they had finished three months on study. These patients receive safety labs, cognitive testing, MRI scans every three months. Three patients have already had a year of therapy, and two of these have been approved for a special access program by the Australian government to allow continued treatment of their Alzheimer's disease with Expro 1595. We continue to study these patients, and you will hear more about them in the future. In summary, this short trial in a small number of patients clearly shows that Expro 1595 quickly decreases neuroinflammation, resulting in positive changes in the CSF proteome and in MRI scans using very sophisticated measures that you will see an example of if you go back to the KOL webinar. All of this correlates with what we've seen in animal models. We remain committed to starting a blinded, randomized, placebo-controlled Phase II clinical trial in the second half of the year. We have a bit more work to do before we release the precise design of the Phase II trial. And we continue to enroll patients in the ongoing phase one trial and continue to mine the extensive data set that we have and are generating. What we have learned and are learning from these patients will prove invaluable as we design the best possible phase two trial for the development of EXPRO 1595 in Alzheimer's disease. A second CNS trial we plan to initiate this year is in treatment-resistant depression, or TRD. In September, we announced that we were awarded a large, up to a $2.9 million grant from the SBIR grant from the NIH to support a phase two trial of EXPRO 1595 in patients with treatment-resistant depression. We will conduct this trial in collaboration with two of the world's pioneers in the field, Professor Andy Miller and Associate Professor Jen Felger, both at Emory University. Dr. Miller is the pioneer in the role of neuroinflammation in depression, having described the problem in the early days of interferon therapy for cancer. Then going on to publish the first study demonstrating that targeting TNF improves depressive symptoms in patients with elevated biomarkers of inflammation. In addition, Dr. Felger discovered that the connectivity between two measures of the brain, as measured by MRI, that are vital for feelings of pleasure and motivation, are lost in depressed patients with inflammation. Our hypothesis is once again simple. Expo 1595 will decrease neuroinflammation, improve clinical symptoms, and restore connectivity between these vital regions of the brain. as measured by clinical criteria and by MRI. TRD, treatment resistant depression, is a neuroinflammation program that leverages a lot of what we're learning during the phase one trial in Alzheimer's disease. As with the AD trial, the TRD trial, we use biomarkers of inflammation to confirm diagnosis, enroll patients, and determine response to ex pro therapy. The use of biomarkers is a novel approach to psychiatric drug development. We believe the use of biomarkers will improve the efficiency of drug development in the field, and we believe we will lead that revolution. Treatment-resistant depression remains an area of significant unmet need. In the US, an estimated 7 million patients with major depressive disorder are resistant to current therapies, most often defined as having failed two prior lines of treatment. Current treatment strategies require treatment-resistant patients to cycle through multiple therapies in an attempt to find one that works. We hope to introduce precision into the diagnosis and treatment selection by using biomarkers to identify patients and track their progress. These two programs highlight a key advantage of the EXPRO 1595 platform. EXPRO decreases neuroinflammation. Neuroinflammation is a key pathology across a number of neurodegenerative and psychiatric diseases. A quick review of the more than 60 publications on our website will give you an idea of the breadth of the opportunity for EXPRO 1595 and CNS. Alzheimer's disease and treatment-resistant depression are the first, but not the last, of our programs in CNS. Turning now to Queller, our COVID-19 program for treating cytokine storm. Last quarter, we went into some detail on how the cytokine storm lands many COVID-19 patients in the hospital and why we believe targeting soluble TNF as the master cytokine is potentially more effective, a more effective approach at suppressing this dysregulated immune response. In November, we announced that the first patient had been enrolled in the Phase II trial of Queller for the treatment of pulmonary complications of COVID-19. The double-blind randomized placebo-controlled trial will enroll 366 patients high-risk COVID-19 patients in two equal-sized cohorts. One cohort is the placebo or the standard of care cohort. The other is standard of care plus Queller. They'll be given a one milligram per kilogram subcutaneous injection at enrollment. A second dose of Queller may be given a week later if the patient remains hospitalized. The primary study endpoint, and I'll remind you that this trial was written with the FDA, they really dictated the design and the endpoints of the trial. Primary endpoint is the need for mechanical ventilation during the 28 days following admission to the hospital and enrollment to the study. Secondary endpoints include things like transfer to the ICU, new onset of neurologic, cardiovascular, thromboembolic, or renal disease, and death. The first 100 patients, randomized into the study will inform a go-no-go decision by the Data Safety Monitoring Board. If the DSMB recommends the trial continue, the remaining 266 patients will be enrolled. We hope to reach that go-no-go decision by the end of second quarter. Turning now to IncMune, our NK cell priming platform. NK cells are cells of the innate immune system that play a crucial role role in cancer outcomes given their ability to target residual disease, the cause of cancer relapse. Incomune restores the function of the patient's own NK cell to attack their residual disease. We believe that by eliminating residual disease, Incomune should improve survival in cancer patients. This year, we plan to initiate a single center phase 1 trial in high-risk MDS patients that's myelosplastic syndrome, a precursor to acute myeloid leukemia that primarily affects elderly patients. This trial is set to run in the UK. The UK, like the rest of the world where we would do clinical development, has had restrictions on the startup of new clinical studies because of the strains of the pandemic on their healthcare systems. We are ready to enroll patients. When the NHS, the National Health Service, which is the UK health system, gives us the green light, we will initiate the trial that will include at least nine patients with the opportunity to expand both the number of centers and the number of patients. Finally, we had previously announced that MBO3, our oncology program, has been delayed due to COVID-19. We hope to initiate a phase two trial in MUC4 positive cancer once the pandemic has been controlled. Although this program is clinically dormant, laboratory research on the combination of MbO3 with tyrosine kinase inhibitors in MUC4 expressing tumors continues. Similarly, our Livnate program for NASH will not begin a phase two until the pandemic is completely controlled. We hope to have more clarity on these programs once we have reached herd immunity in the U.S. and the danger of these viral variants is understood. I will now turn it back to David Moss, immune bio CFO to discuss the financial results and upcoming announcements. David?