Immunic, Inc.

Good morning and welcome to Munich's fourth quarter and year-end 2021 earnings call. My name is Jessica Bru, Head of Investor Relations and Communications at eMunich. I will also be the moderator on today's call. Speaking on today's call are Dr. Daniel Fitt, our Chief Executive Officer and President, as well as Glenn Whaley, our Vice President Finance and Principal Financial and Accounting Officer. For the Q&A session of today's call, we also have our chief medical officer, Dr. Andreas Müller, on the call. Please note, all participants will be in listen-only mode, and this event is being recorded. After today's presentation, there will be an opportunity to ask questions. If you join the webcast via the Zoom platform, there are two ways to submit questions. You can either submit your questions in writing via the Q&A tool of the Zoom portal, or if you would like to speak with us directly, Please use the raise hand function of the Zoom portal to queue your question. If you join today's webcast by phone, please press star nine to queue your question. Before we begin, I would like to remind you that this presentation may contain forward-looking statements. Such statements can be identified by words such as may, will, expect, anticipate, estimate or words with a similar meaning. And such statements involve a number of risks and uncertainties that could cause Immunex's actual results to differ materially from those discussed here. Please note that these forward-looking statements reflect Immunix opinions only as of the date of this presentation and it undertakes no obligation to revise or publicly release the result of any revision to these forward-looking statements in light of new information or future events. Please refer to Immunix SEC filings for a more detailed description of the risk factors that may affect Immunix results and these forward-looking statements. I would now like to turn the call over to our CEO and President, Dr. Daniel Fitt, to begin the presentation. Daniel, please go ahead.

Yeah, thank you, Jessica. I would like to welcome everybody on Immunix year-end 2021 earnings call. I do not want to start this call without expressing our sympathy with the people in Ukraine and expressing our solidarity with them. Despite of these developments, earlier this morning we announced our financial results for the year end of December 31st, 2021, and highlighted recent activities as well as upcoming milestones to our clinical development pipeline. During today's call, we will talk through our fourth quarter 2021 and subsequent highlights, financial and operating results, as well as anticipated milestones. As Jessica noted before we close the call, you will have the opportunity to ask questions. 2021 was another year of tremendous achievements for Immunic, marked by significant clinical progress across key pipeline programs, clearing the way for several important data readouts this year that are potentially transformative for the company. Notably, during the fourth quarter, we enrolled the first patient in our Phase III insure program of Vitoflutimus calcium in patients with relapsing multiple sclerosis. We also completed enrollment in our Phase II Carlos I trial of Vitoflutimus calcium in patients with moderate to severe ulcerative colitis. We expect top-line data for the induction phase of the UC trial to be available in June of this year. For our second program, IMD-935, we reported positive unblinded safety, PK, and PD data from the healthy volunteer portion of our ongoing phase one trial. We also expanded the trial as planned to treat patients with moderate to severe psoriasis. Beyond this, we also initiated an open-label phase one dose escalation trial of IMU95 in metastatic CRPC and expect clinical safety data to be available in the third quarter of this year. Finally, we hope to see the first clinical data from the ZMED part of the ongoing phase one trial of IMU856 in the third quarter of this year and expect to initiate the third portion of the trial in patients with intestinal barrier functions associated diseases during the first half of this year. That quick overview set, let me now walk through the fourth quarter of 2021 and subsequent highlights in greater detail. Given the milestones we have achieved so far, our continued pace of development and ongoing interest in our therapeutic focus areas, in October, we appointed Patrick Walsh to the newly created role of Chief Business Officer. This is a key position within Immunic, and Patrick has already proven to be a valuable addition to the team as we work to realize the full potential of our clinical programs. Also in October, we started treating patients with moderate to severe psoriasis in Part C of our ongoing FAS1 trial of IMU935, representing the first time patients have been treated with our potentially best-in-class oral IL-17 inhibitor. To enable the rapid conduction of the trial, despite COVID-19 related limitations in Australia and New Zealand, where the trial is exclusively performed so far, we have early initiated measures to randomize patients faster. This includes a potential expansion of the trial to one or more countries in Europe. Based on our modified projections, we expect initial results from the psoriasis patient cohorts now to be available in the second half of 2022. Rounding out October's news, the key announcement was that we enrolled and randomized the last patient in our Phase 2 CalDOS-1 trial of VFK in patients with moderate to severe ulcerative colitis. At completion of patient recruitment, the trial had randomized a total of 263 patients into four arms, three active dose grams of 10 mg, 30 mg, and 45 mg, as well as placebo. We currently expect the top-line results of the induction phase to be available in June of this year. Backed by promising results from our previous Phase IIa entrance trial performed in UC and Crohn's disease patients, and the interim analysis of our CALDOS-1 trial published in September 2019, along with vitofrutimose calcium already established strong safety and tolerability profile, we believe that the drug could become a preferred oral treatment option for patients suffering from ulcerative colitis, an obvious alternative to biologics. In November, we enrolled the first patient in our Phase III Ensure trial of Vitoflutimus calcium in RMS. This was followed by enrollment of the first patient in the program's twin Ensure II trial two months later in January. We have targeted an enrollment of approximately 1,050 patients in each trial. Dosing will be either 30 milligram daily of Vitoflutimus calcium or placebo. The primary endpoint for both trials is time to first relapse up to 72 weeks. Enrollment in these twin phase three studies comes on the heels of initiating our supportive phase two CALIPER trial in progressive multiple sclerosis. Together with these programs mark a significant milestone for Immunic, in particular, as we have now initiated our first phase three program. As we have noted before, based on the strong activity observed in our Phase II emphasis trial in RMS and the drug's well-established safety and tolerability profile to date, we believe that the design of the INSURE program provides a straightforward path towards potential regulatory approval of Vitoflutimus calcium in RMS. Despite the limitations of currently approved therapies, the global MS market exceeds $23 billion, and VD-Fluidimus calcium is uniquely positioned to address the unmet need for MS patients. Moving on, in December, based on the strength of preclinical data highlighting the therapeutic potential of IMU935, To affect castration-resistant prostate cancer, we enrolled the first patient in an open-label phase 1 trial in this indication. The trial's principal investigator, Dr. Johann Sebastian de Bono, is one of the world's leading experts on the subject of CRPC. His expertise and deep understanding of the unique mechanism of action of IMU95 provides important corroboration of this program within the scientific and clinical communities. Also in December, we reported positive unblinded safety, tolerability, and PK data from the single and multiple ascending dose portions of our Phase I clinical trial of IMU95 in healthy volunteers. The data showed a very attractive profile for IMU95 and are consistent with our preclinical data supporting our vision of establishing IMU95 as the potentially best-in-class oral IL-17 inhibitor. Additionally, we announced newly available preclinical in vivo data confirming that IMU95 maintains normal thymocyte maturation in relevant acute and chronic mouse models. These data are consistent with previous preclinical in vitro data and support that we may have the first clinical stage RhoA gamma T inverse agonist, which circumvents thymocyte maturation issues. To our knowledge, such an outstanding selectivity hasn't been reported for any other raw gamma T inhibitor so far. More recently, just earlier this month, we strengthened our IP position with the receipt of notice of allowance for composition of meta patents covering IMU95 in the United States, in Europe, and in Australia. These patents provide patent protection into at least 2038, with further extension possible through potential PTE in the U.S. and SBC in Europe, respectively. Also in February, we presented preclinical data on the potent anti-inflammatory activity of Bifluorimus calcium at the 17th Congress of ECHO. Highlights included, first, that Vitoflutimose calcium reduces pro-inflammatory immune cell response by inducing regulatory macrophages, reducing pro-inflammatory cytokine secretion, and reducing T cell proliferation. Second, that Vitoflutimus calcium shows an additive to synergistic effect with anti-TNF antibodies. And finally, that DHO-DH is important in the fraction of cells that receive a strong immune stimulus and are highly metabolically active. In conjunction with the ECHO Congress, we also announced the blinded baseline characteristics of our Phase II CalDOS-1 trial of Vitoflutimus calcium in UCs. Patients in the trial had active, moderate to severe disease, and we were happy to see that only 17% of the patients were pre-treated with biologics. The trial employed a central independent reader to evaluate the endoscopy eligibility criteria. At baseline, 55% of patients had a modified Mayo endoscopy score of 3, and 45% of patients had a score of 2. We believe that these data of randomized patients and the methodology regarding endoscopic assessment used in the clinical and in the trial contributes to ensuring an optimized study readout. In our 10K file this morning, we also released final data of cohort two from our phase two emphasis trial of Idoflutimus calcimin RMS. We believe that this data set provides additional support for the previously determined dose selection for the ongoing Ensure and Caliper trials in RMS and PMS, respectively. Recall that our emphasis trial comprised two cohorts. Cohort one compared the efficacy and safety of 30 milligram or 45 milligram once daily Vitoflutimus calcium with placebo in RMS, while cohort two compared the efficacy and safety of 10 milligram once daily Vitoflutimus calcium with placebo in RMS. Full data from cohort one was published in the third quarter of 2020, while 12-week interim data from cohort 2 was released in the second quarter of 2021. In the newly available cohort 2 data set, the anti-inflammatory effects of VFCC at the 10 mg dose were observed to be lower than those found with the 30 mg VFCC dose. and the pooled cohort 1 and 2 data, providing further support for the selection of 30 milligram dose in the ongoing insured trials of RMS. The final cohort 2 data also provided evidence of dose-proportional neuroprotective activity For instance, the highest decrease of the biomarker serum neurofilament light chain was observed with 45 milligram dose of beta-fluidimus calcium versus placebo. With minus 26% median of difference between percentage change of serum neurofilament light chain, a substantial decrease was seen with a 30 milligram dose with minus 18%. while the smallest decrease was observed with 10 mg dose of cohort 2 with minus 9%. The 10 mg group of cohort 2 also showed a signal with respect to improvement in EDSS, consistent with those signals seen with the higher doses of cohort 1. However, all of these early signals need to be confirmed in larger patient populations with longer follow-up periods. Taken together, these observations suggest that higher doses, such as 45 mg BDF calcium, may be preferred doses for clinical trials in which neuroprotective effects are the main mechanism for improvement, such as in PMS. While the blinded treatment of cohort 1 was completed right before the COVID-19 pandemic started, final cohort 2 data provided additional evidence that ongoing beta-fluidimus calcium treatment may reduce the risk of COVID-19 infections. In the entire cohort 2 population of 59 patients, incidental COVID-19 infections in the active treatment group was 88.5%. We were less frequent than in the placebo group with 25%. Additionally, we recently obtained new preclinical data underlining that Vitoflutimus keratin shows potent anti-EBV activity at concentrations of 3.3 to 30 micromolar in a superinfection assay. A poster with the full data was presented at the Actions Congress in October. We also confirmed that Vitoflutimus calcium can be detected to a noteworthy degree in the CSF of animals after oral dosing. We believe that this finding suggests that Vitoflutimus calcium may be able to act directly within the central nervous system. For the next part of today's presentation, the financial overview, I would like now to hand over to

Thank you, Daniel. We will now review the financial and operating results for the year ended December 31st, 2021. Let me start with the cash overview. We ended the year with 86.9 million in cash and cash equivalents and also raised an additional 16.2 million through our at-the-market facilities so far in 2022. We anticipate this cash balance to be sufficient to fund operations through the first quarter of 2023. regarding the operating results. Research and development expenses for the year ended December 31st, 2021 were 61.1 million as compared to 38.6 million for the same period in 2020. The increase in costs for the full year reflect the continued ramp up of clinical expenses related to our three clinical programs, as well as increased personnel expenses related to the hiring of more people to support the company's growth. The increases were partially offset by decreased costs related to our Phase II clinical trial in COVID-19 that was finished in the first quarter of 2021 and a decrease in drug supply costs for IMU 856. General administrative expenses were $13.3 million for the year end of December 31st, 2021, as compared to $10.3 million for the same period last year. The increase in costs was primarily due to non-cash stock compensation expense as well as smaller increases in costs across numerous categories. Net loss for the year ended December 31, 2021 was approximately $92.9 million, or $3.93 per share, based on approximately 23.7 million weighted average common shares outstanding. compared to a net loss of approximately $44 million or $2.81 per share based on 15.7 million weighted average common shares outstanding for the same period in 2020. I would like to remind everybody that our 2021 net loss was impacted by the settlement agreement our subsidiary Immunic AG signed with 4SC AG in March 2021. Munic AG settled its remaining obligation of a 4.4% royalty on net sales of vitifuminous calcium for $17.25 million. The payment was made 50% in cash, 50% in shares of Munic stock. No further payment obligations remain between Munic and Forest CAG. With that, I'll turn the call back over to Daniel for an outlook on our upcoming clinical milestones. Daniel.