Q4 2021 Immunic Inc Earnings Call

Jessica Breu: My name is Jessica Breu, Head of Investor Relations and Communications at Immunix. I will also be the moderator on today's call.

My name is Jessica <unk> head of Investor Relations and communications at the Munich I would also be the moderator on today's call.

Jessica Breu: Speaking on today's call are Dr. Daniel Vitt, 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 Mueller, 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.

Speaking on today's call are adopted and exit our chief Executive Officer, and President as well as Glenn <unk>, 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 Mueller on the call.

Please note all participants will be in listen only mode and this event is being recorded.

After todays presentation, there will be an opportunity to ask questions. If you join the webcast via the <unk> platform. They are two way to submit questions you can eat or submit your questions in writing via the Q&A till after two quarters or if you would like to speak with US directly. Please use the raise hand function of the <unk> question.

Jessica Breu: If you joined 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 questions.

Jessica Breu: If you joined today's webcast by phone, please press star 9 to queue your questions. 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 immunosexual results to differ materially from those discussed here. Please note that these forward-looking statements reflect Immunics' 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.

If you joined today's webcast by phone. Please press Star nine took 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 similar meaning and such statements involve a number of risks and uncertainties that could cause actual results to differ materially from those disk.

Just here.

Please note that these forward looking statements reflect immunity opinion opinions only as of the date of this presentation and in undertakes no obligations to revise or publicly release the results of any revision to these forward looking statements in light of new information or future events.

Jessica Breu: 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 Vitt, to begin the presentation. Daniel, please go ahead.

Please refer to the Munich SEC filings for a more detailed description of the risk factors that may affect in your next results in these forward looking statements.

I would now like to turn the call over to our CEO and President of Fidelity is set to begin the presentation. Daniel Please go ahead.

Daniel Vitt: Yeah, thank you, Jessica. I would like to welcome everybody on Immunics year-end 2021 earnings. I do not want to start this call without expressing our sympathy with the people in Ukraine and expressing our solidarity. Solidarity with them.

Yes, Thank you Jessica.

I would like to welcome everybody home in the next year and 2021 earnings call.

I do not want to start this call with all the expressing our sympathy with the people in Ukraine.

And express it goes lower solitary.

Solidarity with them.

Daniel Vitt: Despite all 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 in 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, 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.

Despite all these developments earlier this morning, we announced our financial results for the year end.

Of December 31, 2021, and highlighted recent activities as well as upcoming milestones to our clinical development pipeline.

Daniel Vitt: Notably, during the fourth quarter, we enrolled the first patient in our Phase III Ensure program, Ophedia Flutimus Calcium, in patients with elapsing mitral visceral. We also completed enrollment in our Phase II Carlos I trial of edifutimus calcium in patients with moderate to severe positive 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, IMU95, 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.

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 it was announced the opportunity to ask questions.

Yeah.

Daniel Vitt: Beyond this, we also initiated an open label, Phase 1, dose escalation trial of I-95 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 Z-MAP part of the ongoing Phase 1 trial of IMU-856 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.

2021 was another year of tremendous achievements for <unk>.

Mark by significant clinical progress across key pipeline programs.

Clearing the way for several important data readouts this year.

Potentially transformative for the company.

Notably during the fourth quarter, we enrolled the first patient in our phase III and short program will be deployed in Wisconsin in patients with <unk> screws.

We also completed enrollment in the.

Phase II Carlos one trial of.

<unk> <unk> in patients with moderate to severe onset of colitis.

We expect topline data for the for the induction phase of UC trial to be available in June of this year.

Okay.

Our second program <unk>, we've 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 <unk> 95.

In metastatic CRC 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 this part of the ongoing phase one trial of <unk> hundred six 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.

This year.

Okay.

Daniel Vitt: That quick overview set, let me now walk through the fourth quarter 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 key therapeutic focus areas, in October, we appointed Patrick Walsh to the newly created role of Chief Business Officer.

That quick overview, let me now walk through the fourth quarter 2021, and subsequent highlights in greater detail.

Daniel Vitt: 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 phase 1 trial of IMU-935, representing the first time patients have been treated with our potentially best-in-class oral IL-17 inhibitor. To enable the rapid conduction of a 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.

Given the milestones we have achieved so far our continued pace of development and ongoing interest in our key therapeutic focus areas in October we appointed Patrick Walsh.

The newly created role of Chief business Officer.

This is a key position within the Munich, 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 of our ongoing first month trial of <unk> <unk>, representing the first time patients have been treated with our potentially best in class <unk> inhibitor.

To enable the rapid conduct 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 .

Daniel Vitt: 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 randomize the last patient in our phase two, CALDOS-1 trial of vidofluminous calcium 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 arms of 10mg, 30mg and 45mg, as well as placebo.

Based on our modified predictions, we expect initial results from the <unk> patient cohorts nor to be available in the second half of 2022.

Rounding out October we use the key announcements was that we enrolled.

And randomized the last patient in our phase III <unk> trial of video fruitless catch them in patients with moderate to severe ards or discrete items.

At completion of patient recruitment the trial had randomized a total of 263 patients into four amps three active dose of 10 milligram 30, milligram and 45 milligram as well as placebo.

Daniel Vitt: We currently expect the top line and the size of the induction phase to be available in June. Backed by promising results from our previous phase 2a entrance trial performed in UC and Crohn's disease patients and the interim analysis of our CALGOS-1 trial published in September 2019, along with Ritofutimus calcium's already established strong safety and tolerability profile, we believe that the drug could become a preferred oral treatment option for patients suffering from asthma colitis In November, we enrolled the first patient in our face-free and short trial of the de-future. This was followed by enrollment of the first patient in the programs to ensure two trials two months later in January. We have targeted an enrollment of approximately 1,050 patients in each trial. Closing will be either 30mg daily of beta-fluidimus calcium or placebo.

We currently expect the top line the songs of the induction phase to be available in June of this year.

Backed by promising results from our previous phase Iia entrants trial.

Formed in UC, and Crohn's disease patients and the interim analysis of our cargoes one trial.

<unk> in September 2019, along with better food and Wisconsin already established strong safety and Tolerability profile, we believe that the drug could become a preferred oral treatment option for patients suffering from us with colitis and <unk> alternative to biologics.

In November we enrolled the first patient in our phase III and short trial of food in Wisconsin, and our image.

This was followed by enrollment of the first patient in the programs to ensure two trial two months later in January .

We are targeting targeted an enrollment of approximately 1050 patients in each trial.

Dosing will be EBIT, 30, milligram daily, albeit the fruit in Wisconsin for placebo.

Daniel Vitt: The primary endpoint for both trials is time to first relapse up to 72 weeks. Enrollment in these twin phase 3 studies comes on the heels of initiating our supportive phase 2 caliper trial in progressive multiple sclerosis. Together with these programs.

The primary endpoint for both trials is time to first relapse up to 72 weeks.

Enrollment in these two phase III studies comes on the heels of initiating our supportive phase III <unk> trial and progressive multiple sclerosis took.

Together with these programs.

Daniel Vitt: Mark a significant milestone for Immunic, in particular, as we have initiated our first face-weep. As we have noted before, based on the extraordinary ability observed in our phase two emphasis trial in RMS and the drug Swedish capitalist saved in probability profile to date, we believe that the delineation of the insurance program provides a straightforward cross towards potential regulatory approval of Vittofutimus calcium in RMS. Despite the limitations of currently approved therapies, the global MS market exceeds 23 billion dollars, and Vita Flutimus Calcium is uniquely positioned to address the unmet need for MS. Moving on, in December, based on the strength of preclinical data highlighting the therapeutic potential of IMU-95 to affect castration-resistant prostate cancer, we enrolled the first patient in an open-label, phase one trial of this medication. The trial's principal investigator, Dr. Johann Sebastian De Bono, is one of the world's leading experts on the subject of CRPC.

Mark a significant milestone for <unk> music in particular as we have now initiated our first phase III program.

As we have noted before based on the strong activity observed in our phase II emphasis trial in RMS and the drug sweat established safety and Tolerability profile to date.

We believe that the design of the insured program provides a straightforward cost.

Towards potential regulatory approval of <unk> in our image.

Despite the limitations of currently approved therapies, the global <unk> market exceeds $23 billion and video food in Wisconsin 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 IME months defiance.

To affect castration resistant prostate cancer, we enrolled the first patient in an open label Phase one trial in this indication.

The trial's principal investigator Dr. <unk> as one of world's leading experts on the subject of <unk>.

Daniel Vitt: His expertise and deep understanding of the unique mechanism of action of Immunantify provides important cooperation from this program within the scientific and clinical community. Also in December, we reported positive unblinded safety, tolerability, and PK data from the single and multiple ascending dose portions of all phase one clinical trials of IMU-95 in healthy volunteers. The data showed a very attractive profile for IMU-95 and are consistent with our preclinical data supporting our vision of establishing IMU-95 as the potentially best in glance at IS-17 inhibitors.

<unk> expertise and deep understanding of the unique mechanics of action of <unk> five provides important cooperation.

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 all phase one clinical trial of <unk> hundred 95 from the healthy volunteers.

The data showed a very attractive profile for IMAX define and are consistent with our preclinical data supporting our vision of establishing <unk> hundred 95, as the potentially best in class.

17 inhibitor.

Daniel Vitt: Additionally, we announced newly available pre-clinical in vivo data confirming that IMUN-95 maintains normal thymocyte maturation in relevant acute and chronic mouse models. These data are consistent with previous pre-clinical in vitro data and support that we may have the first clinical stage rho-gamma-T inverse agonist which circumvents thymocyte maturation issue. To our knowledge, such an outstanding selectivity hasn't been reported for any other raw gamma T inhibitors so far. More recently, just earlier this month, we strengthened our IP position with the receipt of notice of allowance for composition of matter patents covering IMU-95 in the United States, in Europe, and in Australia.

Additionally, we announced newly available preclinical in vivo data confirming that aiman ninety-five maintains normal time, aside maturation and 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 drug I'm actually inverse agonist, which circumvents tomo assignment duration issues.

To our knowledge such an outstanding selectivity Hasnt been reported for any other <unk> inhibitor so far.

Okay.

More recently just earlier this month, we strengthened our IP.

<unk> position with the receipt of notice of allowance for a composition of matter patents covering <unk> 95 in the United States and Europe and in Australia.

Daniel Vitt: These patents provide patent protection into at least 2038 with further extension possible through potential PTE in the US and SPG in Europe, respectively. Also in February, we presented preclinical data on the potent anti-inflammatory activity of B. calcium at the 17th Congress of ECOWAS. Highlights included first, that vidofluidin-most calcium reduces pro-inflammatory immune cell responses by inducing regulatory macrophages, reducing pro-inflammatory cytokine secretion, and reducing T-cell proliferation.

These patents provides patent protection into at least 2038 with further extension possible through potential PGE and the U S and SPC and Europe , respectively.

Also in February we presented preclinical data of the potent anti inflammatory activity of your floating Wisconsin.

At the 17th Congress of Echo.

Highlights included first but with a food most couch some reduces pro inflammatory immune cell response by inducing regulatory macrophages, reducing pro inflammatory cytokines accretion any use reducing T cell proliferation.

Daniel Vitt: Second, the videofloodymost calcium shows an additive to the logistic effect with anti-DNS antibodies. And finally, the DH-ODIH is important in the fraction of cells that receive a strong immune stimulus and are highly metagogically active. In conjunction with the ECHA Congress, we also announced the blinded baseline characteristics of our phase 2 CALDOS1 trial of ediflutimus calcium in use. 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 male endoscopy score of 3 and 45% of patients had a score of 2.

Second the video truly most CASM shows in additive to synergistic effect with anti TNF antibodies.

And finally that <unk> is important in the fraction of cells that received a strong immune stimulus and a highly metabolically active.

In conjunction with the Echo Congress, we also announced the blinded baseline characteristics of our phase III <unk> trial of <unk> in Wisconsin and UC.

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.

Trial employed a central independent reader to evaluate the endoscopy eligibility criteria at.

At baseline, 55% of patients had a modified Mayo endoscopy score of three and 45% of patients had a score of two.

Daniel Vitt: We believe that these data of randomized patients and the methodology regarding endoscopic assessment used in the clinical, And the triad contributes to ensuring an optimized study readout. In our 10K flight this morning, we also released final data of cohort 2 from our Phase 2 Ampest Strike of the Dufurimus Charoetim and Arame. 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 TMS respectively. Recall that our emphasis is try to comprise two courts.

We believe that these data of randomized patients and the methodology regarding endoscopic assessment used in the clinical.

And the trial contributes to ensuring an optimized study readout.

Okay.

In our 10-K filed this morning, we also released final data of cohort two from our phase II emphasis trial fully Ms. Johnson Rms.

We believe that this data set provides additional support for the previously determined dose.

Dose selection for the ongoing insured <unk> and RMS and Pms, respectively.

Daniel Vitt: Go ahead one, compare the efficacy and safety of 30 milligram or 45 milligram one daily. We flew the most calcium with placebo in RMS. Why cohort two compare the efficacy and safety of 10 milligram one daily. We flew the most calcium with placebo in RMS.

Recall that our emphasis trial comprised two cohorts cohort one compared the efficacy and safety of 30 milligram or 45 milligram once daily Redefault in Wisconsin with placebo in Rms.

Cohort to compare the efficacy and safety of 10 milligram.

Once daily beta food Muscocho with placebo in Rms.

Daniel Vitt: Full of data from cohort one was published in the third quarter of 2020, while 12-week interim data from cohort two was released in the second quarter of 2021. In the newly available COHORT2 data set, the anti-inflammatory effects of VFC with a 10mg dose were observed to be lower than those found with a 30mg VFC dose, and the Poole cohort one and two data, providing further support for the selection of 30 milligram those and the ongoing insured threat of RMS. The final cohort 2 data also provided, evidence of dose-proportioned neuroprotective activity. For instance, the highest decrease of the biomarker serum neurofilament light chain was observed at 45 milligram dose of beta-flutimose calcium versus placebo.

Full data from cohort one was published in the third quarter of 2020, while 12 week interim data from cohort two was released in the second quarter of 2021.

And the newly available cohort two data sets the anti inflammatory effects of meaningfully, Wisconsin with the 10 milligram dose were observed to be lower than those fund with the 30 milligram ridiculous truly most calcium dose.

And the Pud cohort, one and two data providing further support for the selection of 30 milligram dose in the ongoing and shoe excellence of RMS.

The final cohort two data also provided.

Evidence of dose proportional neuroprotective activity.

For instance, the highest decrease of the biomarker.

Philip Nadeau from Atlas Sheen was observed with 45 milligram dose of better fruit in Wisconsin versus placebo with a minus 26% median of difference between percentage change of serum.

Daniel Vitt: 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 milligram dose of COVID-2 with minus 9%. The 10-milligram group of cohort 2 also showed a signal with respect to improvement in EDSF 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.

<unk> light chain, a substantive decrease was seen with a 30 milligram dose with minus 18%, while the smallest decrease was observed with 10 milligram dose of cohort two with minus 9%.

The 10 milligram group of cohort two also showed a signal with respect to improvement in Etfs consistent with dose signal seen with the higher doses of cohort. One. However, all of these early signals need to be confirmed and doctoral patient populations with non op loss periods.

Daniel Vitt: Taken together, these observations suggest that higher doses, such as 45 mg VDF 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 401 was completely completed right before the COVID-19 pandemic started, Final Core II data provided additional evidence that ongoing use of the Wisconsin treatment may reduce the risk of COVID-19 infections. In the entire Core II population of 59 patients, incidental COVID-19 infections occurred in the active treatment group were 88.5%.

Taken together these observations suggest that higher doses, such as 45 milligram with the Florida, Wisconsin, maybe preferred doses for clinical trials in which they are protected.

The main Mccann has room for improvement such as Mpls.

Yeah.

While the blinded treatment of cohort one was completely right before was completed right before the COVID-19 pandemic started final cohort two data provided additional evidence that ongoing redo. The most constant treatment may reduce the risk of COVID-19 infections.

The entire cohort two population of 59 patients incident until COVID-19 infections in the active treatment group.

Daniel Vitt: We are less frequent than in the placebo group with 25%. Additionally, we recently obtained new preclinical data underlining that VFK shows potent anti-EBV activity at concentrations of 3.3 to 30 µmol, in a super infection. A poster with a full data was presented at the Actions Congress in October. We also confirmed that medial flutemose calcium can be detected, to a noteworthy degree in the CSF of animals after oral dosing. We believe that this finding suggests that vidoflutimus calcium may be able to act directly within the central nervous system.

Was 88, 5%, we are less and less.

Less frequent than in the placebo group with 25%.

Additionally, we recently obtained new preclinical data underlining that media fully most callison shows potent anti <unk> activity at concentrations of three 3% to 30 micro molar.

Super interaction SC.

A poster with a full data was presented at the actions Congress in October .

We also confirmed that <unk>, most capstone can be detected.

Noteworthy to REIT in the CSF of animals. After oral dosing, we believe that this finding suggests in vitro food in Wisconsin, maybe able to act directly within the central nervous system.

Glenn Whaley: For the next part of today's presentation, the financial overview, I would like now to hand over to Glenn. 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.

For the next part of today's presentation, the financial overview I would like now to hand over to Glen.

Glenn Whaley: We anticipate this cash balance to be sufficient to fund operations through the first quarter of 2020, based on operating results. Research and Development Expenses for the year ended December 31, 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 reflects 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.

Thank you Daniel.

I will now review the financial and operating results for the year ended December 31 2021.

Glenn Whaley: The increases were partially offset by decreased costs related to our Phase 2 clinical trial in COVID-19 that was finished in the first quarter of 2021 and a decrease in drug supply costs for IMU-851. General and administrative expenses were $13.3 million for the year-end of December 31, 2021, as compared to $10.3 million for the same period last year.

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 facility. 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 31, 2021, or <unk> $61 1 million as compared to $38 6 million from the same period in 2020.

The increase in cost 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 III clinical trial in COVID-19 that was finished in the first quarter of 2021 and a decrease in drug supply cost for <unk> <unk> six.

General and administrative expenses were $13 3 million for the year ended December 31, 2021, as compared to $10 3 million for the same period last year.

Glenn Whaley: The increase in cost was primarily due to non-cash stock compensation expense as well the smaller increases in cost across the 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 share is outstanding for the same period in 2020.

The increase in cost was primarily due to noncash stock compensation expense as well as a 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 eight.

$2 81 per share based on $15 7 million weighted average common shares outstanding for the same period in 2020.

Glenn Whaley: 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. AG settled its remaining obligation of a 4.4% royalty on net sales of vitifumulus calcium for $17.25 million. The payment was made 50% in cash, 50% in shares of the Immunic spot. No further payment obligations remain between Immunic and Forestier. With that, I'll turn the call back over to Daniel for an outlook on our upcoming clinical milestones. Daniel.

I would like to remind everybody that our 2021 net loss was impacted by the settlement agreement our subsidiary in Munich AG side with for FCA in March 2021.

Munich AG subtle thats remaining obligation of a four 4% royalty on net sales.

<unk> calcium for $17 5 million.

The payment was made 50% cash 50% in shares of <unk> stock.

No further payment obligations remain between the Munich and for our CAGR.

With that I'll turn the call back over to Daniel for an outlook on our upcoming clinical milestones Daniel.

Daniel Vitt: Thank you, Glenn. As mentioned in the beginning of the call, we have a very exciting year, 2022, with several significant milestones coming up, and I'm happy to walk with all these. One of our most important milestones in 2022 will be the readout of our phase 2 caldose 1 trial in patients with moderate to severe ulcerative colitis. We currently expect the top line results of the induction phase to be available in June of this year.

Thank you Glenn as mentioned in the beginning of the call. We have a very exciting year 2022, with several significant milestones coming up and I'm happy to walk utilities.

Okay.

One of our most important muscles in 2022 will be the readout of our phase two <unk> trial in patients with mortgages to be a positive colitis.

Currently expect the topline results of the induction phase to be available in June of this year.

Daniel Vitt: For our phase one clinical trial of IMU95, we expect initial results from the third portion in patients with moderate to severe psoriasis to be available in the second half of this year. The initial data will provide us with the first important look at IV-95's safety and efficacy profile in this patient population. In addition, we expect initial safety data from our Phase 1 dose escalation trial of IMU-925 in progressive metastatic CRPC to be available in the third quarter of this year.

For our phase one clinical trial of our new 95, we expect initial results from the third portion in patients with moderate to severe psoriasis to be available in the second half of this year the.

The initial data will provide us with the first important look at I mean, 95 safety and efficacy profile in this patient population.

In addition, we expect initial safety data from all phase one dose escalation trial of <unk> 95 in progressive metastatic CRC to be available in the third quarter of this year. As a reminder, the trial is designed to establish a recommended phase two dose and to assess safety tolerability and tumor activity by markets and so on.

Daniel Vitt: As a reminder, the trial is designed to establish a recommended Phase 2 dose and to assess safety, tolerability, anti-tumor activity, biomarkers, and pharmacokinetics of IMU-925 in this patient cohort. Finally, we anticipate unblinded safety data from the single and multiple ascending dose permits of the Phase I clinical trial of IMU-856 in healthy volunteers in the third quarter of 2022, followed by the initiation of the third portion of the trial in patients with intestinal barrier function-related diseases, as expected, in the first half of 2022. This brings us to the end of our formal presentation. Jessica, please open the call for the Q&A session. Thank you, Daniel.

Michael Kinetics of <unk> 95 in this patient cohort.

Finally, we anticipate unblinded safety data from the single and multiple ascending dose permits of the phase one clinical trial of <unk> hundred six in healthy volunteers in the third quarter of 2022.

And initiation of a third portion of the trial and patients with intestinal barrier function associated diseases is expected in the first half of 2022.

This brings us to the end of our formal presentation. Jessica Please open the call for the Q&A session.

Thank you Danielle we will now begin the question and answer session was done Atlantan Andreas as a reminder, each under webcast slide assume platform to wait to submit questions. You can either submit your questions in writing by at the Q&A to our fiscal quarter or if you would like to speak with US directly. Please use the raise hand function after some.

Jessica Breu: We will now begin the question and answer session with Daniel, Glenn, and Andreas. As a reminder, if you joined 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 your hand function of the Zoom portal to queue your questions.

So to your question is he joined today's webcast by phone. Please press star 9% to your question.

Jessica Breu: If you joined today's webcast by phone, please press star 9 to queue questions. At this time, we will pause momentarily to assemble our rooms. Our first question comes from Jesse Faux at Piper Sandler. Jesse, please unmute yourself and go ahead.

At this time, we will pause momentarily to assemble <unk>.

Our first question comes from Joseph <unk> at Piper Sandler Jesse Please unmet yourself I'm go ahead.

Andreas Mueller: Hi, team. Thanks for taking our questions. We've just got one for Yasmeen. I had a few on how those based on the demographics on Friday, what do you guys expect to see the rates for clinical remission and doskyty? And what aspects of the baseline do you expect to drive down placebo responses? Hi Jess, this is Andreas.

Thanks for taking our questions.

Hum.

Okay.

Just on the baseline demographics on Friday, what do you guys expect for clinical remission in endoscopy.

And one aspect of the baseline do you expect to drive Ahmed.

Andreas Mueller: Thank you very much for the question. I think we were very happy to provide you with the data with the baseline characteristics because we believe we have worked hard to find a patient population where we have a very good chance of showing the properties of INU838 in the right setting in ulcerative colitis patients. The baseline data showed that we had an active population. You can see this, for example, in the fecal care protecting data but also in the amount of patients or proportion of patients that had a very high stool frequency and had blood in their stool to a very large degree, almost in every patient population, outside of these two occurrences.

Hi, Jeff This is Andreas.

Sure.

Thank you very much for the question I think we were very happy to provide you the data with the based on characteristics because we believe.

We have worked hard to find a patient population where we have.

A very good chance of showing.

The properties of IV <unk> in the right setting.

Ulcerative colitis patients.

The.

The baseline data showed that we had an active population.

You can see this for example in the FICO cut protecting data, but also in the.

The amount of patients our proportion of patients that had very high stool frequency and heads.

Our blood and stool to a very large degree almost at every.

After all of this tool.

Our currency, so I think that.

Andreas Mueller: So I think that... To my mind, the high activity seen in the baseline, I think is the major driver for giving the drug a chance to show activity in this trial. On top of it, I think since the primary endpoint is a composite out of the endoscopic healing and symptomatic remission, we are also very happy that, More than 60%, almost 60% of these patients had a mild endoscopy score of 3, which is also, I think, important to limit the placebo response in any IBD trial, because it is known that in IBD you have a placebo response, including sometimes for endoscopy, and having patients with a very extensive baseline disease in endoscopy, I think, allows us to limit the placebo response as well.

To my mind, the high activity seen in the baseline I think is the major driver for giving the drug a chance to show.

Activity in this trial on top of it I think.

Since the primary endpoint is a composite out of.

The endoscopic healing and symptomatic remission, we are also very happy that.

60% of more than 60% almost 60% of these patients had a mile endoscopy score of three which is also I think important to limits.

Placebo response, and any IBD trial because.

It is known that IV IBD you have.

A placebo response, including sometimes for endoscopy and having.

Patients with a very extensive.

Baseline disease, and Endoscopy I think allows us to.

Andreas Mueller: So overall, I think we've been quite happy with the baseline data that we have presented, and we believe that this enables us to have, Give our drug a chance to really shine in this study. And I hope that just, I, addressed all of your questions on all of your aspects. Yes, thank you, Andrea. I had one more follow up. And on the face, if there's if there will be a phase three, do you plan on running it yourself or with a partner? I think that's too early to tell.

To limit the placebo response as well so overall I think we've been quite happy with the baseline data that we presented and we believe that this enables us to have.

Given our drug a chance to really shine in this.

In this study.

And I hope to adjust.

Address all of your questions on all gas specs.

Yes, Thank you and I had one more follow up.

And on the fifth third.

Thanks, Steve.

Do you plan on running it yourself or with a partner.

Andreas Mueller: We do, however, are in the middle of preparing, of course, what phase three would look like. We're having a lot of very close discussions with our medical advisors in IBD. We are very happy that we have a very large and also very well-known group of medical advisors for our IBD program. And over the years, we really have had a very close relationship with them.

I think that's too early to tell.

We do however.

In the middle of preparing of course, how AK steel will look like.

We are having a lot of very tight discussions with our medical advisers in IBD.

We are very happy that we have a very large and also very well known group of medical advisers for our IBD program and.

Over the years, we really have had a very close relationship with them.

Andreas Mueller: And basically, in anticipation of the study readout, we have had a lot of ongoing discussions with them that target also, I think, the positioning of the drug, given what happened in IBD treatment over the last year or so, with the repositioning of the JAK inhibitors basically behind, more or less, as a medication, behind biologics as a medication of last resort. And also, I think we want to understand a little bit whether Ozanimod, the newest entrance into the market, has more or less been observed to be in the same position as JAKs for IBD patients as well.

Basically in anticipation for the <unk> study readout of course have a lot of ongoing discussions with them that target also I think.

The positioning of the drug given what happened in <unk>.

In IBD treatment over the last year or so.

With the repositioning of.

The JAK inhibitors, basically behind more or less.

Medications, they're behind biologics.

Medication of last resort and also I think we wanted to understand a little bit.

<unk> launched the newest entrants into the market had.

More or less.

The observed to be in the same positioning is jaques.

For for IBD patients as well.

Andreas Mueller: And I think that also there's discussion about the positioning of a drug that has a placebo-like or a very favorable safety profile in IBD patients as compared to these previous entries of other oral drugs. How does this change the perception and also positioning of the drug?

And I think that that also there's discussion about the positioning of a drug that has a.

<unk>.

Placebo like.

There is a favorable safety profile in IBD patients as compared to the previous entries of other oral drugs how does this change.

The perception and also positioning of the drug I think that was also very important to us in terms of planning.

Andreas Mueller: I think that is also very important to us in terms of planning a phase three trial. So this is all ongoing, but I think it's too early to tell. How we do it, because I think you need the data for that as well, and also with whom we do it, whether alone or with a partner. I think that's still open. Thank you so much, Andreas. [inaudible] Thank you, Jeff. Thank you, Jesse. Our next question comes from Andreas Agouridis at WETOCEAN. Andreas, please unmute yourself and go ahead. Good morning. Can you guys hear me?

<unk> III trial. So this is ongoing but I think it's too early to tell.

How are we how we do it because I think we need the data for that as well.

And also.

With whom we're doing it.

Loan with a partner.

That's still open.

Okay. Thank you so Martin.

Thank you Joseph thank.

Thank you Jesse.

Yeah.

Our next question comes from Andreas <unk> at Wedbush.

Andreas just under just thoughts on go ahead.

unknown: Yes. Good morning. We have two quick ones from us. So from the full emphasis trial results, could you please provide, Mayank Mamtani, Glenn Whaley, Jessica Breu, Daniel Vitt, William Wood, Nathanael Charoensook, Glenn Whaley, Jessica Breu, Daniel Vitt, William Wood, Nathanael Charoensook, All right. No, thank you, Andreas.

Alright, good morning can you guys Larry yes, good morning.

Alright. Thanks.

Two quick ones from us.

So from the fall emphasis trial results.

Could you provide.

So maybe some of your thoughts on the.

Explanations on the license reduction in regions.

For a more robust changing the nerf elements concentrations at 45, <unk> compared to 30, Megs and then Jess.

I don't know if I missed it earlier you mentioned the delay in part C finished.

Horizon trial, just additional color there would be appreciated thank you.

Andreas Mueller: I will address the first question maybe first and then maybe let Daniel talk a little bit about Part C for IMU-935. So in the emphasis trial, which is, I think, for everybody to understand, is the Phase II trial of IMU-838 in relapsing-remitting MS, where we had reported fantastic results from the Core 1 with 30 and 45 mg. We added a Core 2 that explored 10 mg and placebo to really understand a little bit better the dose response curve.

Alright. Thank you address I will address the first question, maybe first and then maybe.

Daniel.

Talk a little bit about the party for annualized three five so Andy emphasis trial, which is I think for everybody to understand is that phase two trial of <unk> hundred eight in relapse and remitting, Ms, where we had reported fantastic results from the core at 1% to 30 or 45 milligram.

We added a cohort two that explored 10 milligram.

And plus Ebola to really understand a little bit better the dose response curve and we have published the interim analysis with week 12 data.

Andreas Mueller: And we published the interim analysis with Week 12 data in early 2021, which confirmed, I think, the dose for relapsing-remitting MS that we are using in Phase III, 30 mg. So I think, first of all, the data in the Core 2 readout now that we published today this morning is confirming, I think, our conclusions about dosing. What was interesting, which I also find personally very interesting, is that from previous DH, and ODH drugs in MS, they have a particular strength in the long-term readouts on the variables that are responsible for the long-term outcome of patients, specifically disability worsening and brain atrophy. So things that are related probably more in terms of the EDSS readout, how much disability you acquire over time in the long term for these MS patients.

In early 2021, which confirmed I think.

The dose for a relapsing Ms, but they are using in phase III 30 milligram. So I think first of all the.

Andreas Mueller: And the interesting thing that I find very interesting personally is that in cohort 2 data with 10 milligrams, you see a substantial effect in EDSS, and you see a substantial effect in, for example, disability worsening. All in all, I think that the study is too small and doesn't have a long enough follow-up to really draw conclusions. However, I think it gives us a first hint that I think the effect of IMU838 on disability accumulation over time is potentially.

The data in the cord to readout now that we've published today this morning.

Confirming I think our conclusions for the dosing.

What was interesting, which I also find personally very interesting is that.

The new debt from from previous DH DH draw.

A drug in Ms that they have a particular strength.

On the on the long term readouts on the on the variables that are responsible for the long term outcome of patients specifically disability worsening and brain atrophy, so things that are.

Related probably more in it.

Terms of the eds estimate out of how much visibility you acquire over time in the long term for these MF patients.

And did the interesting thing that I find very interesting personally is that in the cohort two data with 10 milligram youll see a substantial effect in.

In Etfs and you see a substantial effects.

In for example visibility worst names this is all.

I think that the study is too small and has doesn't have a long enough follow up to really make conclusions. However, I think it gives us a first hint that.

I think the effect of <unk> hundred eight.

On disability accumulation over time.

It's potentially.

Andreas Mueller: Again, I think the parallel to other DH or DH trucks is very strong, whereas the, you know, the anti-inflammatory effect that is more or less related to lesion reduction, I think it is very strong at 30 milligrams, but we haven't seen a strong effect as much on an attend the ground, though. So I think there's some.

Again I think.

And very much in parallel to other <unk> is very strong whereas the.

And tie inflammatory effects.

That is more or less related to lesion reduction I think.

Is very strong at 30 milligrams, but we haven't seen a strong effect as much in the 10 milligram dose. So I think there are some.

Andreas Mueller: These results confirm that a drug like IMU-838, in terms of efficacy, will likely have its strength in neuroprotective effects and effects that are measured in disability accumulation or potentially also in brain atrophy. In that respect, I think these data are very exciting as compared to just having anti-inflammatory effects. I think that's very important, I think, for the positioning of the drug in the future as well. So I'll hand over to Daniel regarding Part C and Part D. Maybe just one comment on what you said, Andreas. I think for us, it was really a positive surprise to see the EDSS data from the 10 milligram core.

This this really these results confirm that a drug like <unk> in terms of efficacy, we will likely have a strength.

The neuroprotective effects and protect and effects.

Our measured in disability accumulation or potentially also in brain atrophy and in that respect I think these data are very exciting as compared to just having the anti inflammatory effects.

<unk>.

I think that's very important I think for the positioning of the drug in the future as well.

So I'll hand, it over to Daniel regarding the parks preliminary not regarding maybe just let him comment to what you said Andreas I think for US. It was really a positive surprise to see the EES as data from the 10 milligram cohort. This was unexpected honestly and I think that speaks for the strengths. We have we have seen here.

Daniel Vitt: And I think that speaks for the strength we have seen here relating to NFL data and so forth and all of that. So, but let's come to 95 on your second question. I think it's an obvious question.

Relating to NFL data and so forth and entitlement, so, but let's come to $95 to the second question I think it's an obvious question I think we are it will be full of our philosophy of being transparent being early and if you know us for some time, we usually try to react early if we if we see things not 100% aligned with our expectation.

Daniel Vitt: I think we follow our philosophy of being transparent and being early. And if you know us for some time, we usually try to react early if we see things not 100 percent aligned with our expectations. And therefore, we decided quite early.

And therefore, we decided quite early.

Daniel Vitt: This patient cohort of 95 tried just recently started. So but we felt if we really don't want to have substantial delays, we should consider adding another country just to have a broader set of dermatologists contributing patients. So that's something we decided and everyone to share that with the market. I would not call it a delay.

Patients in cohort ultimately five tranches recently started so.

But we felt if we really don't want to have substantial delays we should add.

Okay consider adding.

Another country to that just to have a broader set of dermatologist contributing patients. So.

So thats something we decided that we want to share them with the market.

Call It a delay.

Yeah.

Okay, all right I appreciate it guys. Thank you I'll step back in the queue.

Daniel Vitt: OK. Thank you, Andrea. The next question comes from Gobind Singh at JMP. Govind, please unmute yourself and go ahead. Gobind?

Thank you Andreas.

Our next question comes from Goldman thing JMP Gulf.

unknown: Working? Yes. Great. Sorry about that.

Kelvin please on mute yourself and go ahead.

Okay.

Yeah.

unknown: Well, congrats on the pipeline progress. I guess my question would be, if I heard you guys correctly, I think there is the announcement that the interim results from the Phase 3 MS trials and the Phase 2 MS trial for progressive MS, those are... Those are new and happening this year, so I was just wondering if you're hearing anything from your clinical sites that might add some color around the enrollment speed, and can you remind us what the bar is in terms of whatever kind of clinical results you're going to be presenting? What would be, you know, results that you guys would be excited and continue development? Hi, Goldman.

Goldman.

Yes.

Great sorry about that.

Congrats on the pipeline progress My my I guess my question would be if I heard you guys correctly I think there is.

The announcement that the interim results from the phase III trials.

The phase two MF trial for progressive Msos or it.

It doesn't.

Happening this year. So just wondering if you're hearing anything from your clinical sites.

To add some color around the the.

The enrollment speed and then can you remind us what the bar is in terms of.

Every kind of clinical results youre going to be presenting.

Could be.

Results that you guys will be excited and then continued feldman.

Andreas Mueller: I'm not sure I totally understand the remark about the timing of the interim analysis for phase two and three. I have not seen anything in our releases that would even talk about the interim analysis, so I'm not sure. Maybe that was a misunderstanding with some of the things.

Yes, I <unk> I am not sure.

Totally understand.

<unk>.

Remark about the timing of the interim analysis for phase II and III.

I have not seen anything in our releases that would even talk about the interim analysis. So I'm not sure maybe there was a misunderstanding with some of the things so.

Andreas Mueller: So just to confirm, the phase two study in progressive MS will have its interim readout when half of the planned patients, we have 450 patients, there are 225 patients on goal, and these 225 patients have reached week 24 to have enough data because we will basically report on neurofilament data as the interim readout. And then for the phase three trials, we said that we would have an interim analysis for phase three in relapsing MS when half of the events, meaning relapses, have occurred in this study. It's... In terms of the phase 3 interim readout, we have to look at the number of events and the frequency of events in this trial. And It's way too early to do this.

Just to confirm.

The phase two study in progressive Ms will have its interim readout.

When half of the planned patients we have 450 patients with <unk> 275 patients enrolled and these 275 patients have reached.

We have 24 to have enough data because we will basically report on newer filament data as the interim readout and then for the Phase III trials. We said that we will have an interim analysis for the phase III in relapsing Ms. When half of the events, meaning with axis have occurred.

In this study.

It's <unk>.

In terms of the phase III interim readout, we have to look at the number of events.

And the frequency of events in this trial and it's way too early to do so.

There's really no.

Andreas Mueller: So there's really no, A more precise timing of the interim analysis that I can give you at the moment. We need a little bit more enrollment for that and a little bit more follow-up on these patients. But just to confirm, none of these interim analysis is expected in 2022.

<unk>.

A more precise timing of the.

The interim analysis that I can give you at the moment, we need a little bit more enrollment for that in a little bit more follow up on these patients and but just to confirm none of these interim analysis is expected in 2002.

Andreas Mueller: The other questions about, I think, enrollment, I think we are very happy to have seen a good enrollment now in all of our MS studies, which are recruiting. All of our, we have three studies that are recruiting, the phase two study in progressive MS, and then ensure one and two, which are in relapsing MS, and they're recruiting very well, and actually progressing with them as anticipated. So I think at this point, that's the only. Update, I can give you. Thank you for that. I think that was my bad on the milestone slide there.

The other questions about I think enrollment I think we.

We're very happy to have seen.

A good enrollment now and in all of our MF studies are recruiting all of our tier three.

Studies that are recruiting the phase III study in progressive Ms and then ensure one and two which are.

In relapsing, Ms and they are recruiting very well.

Actually.

Progressing as anticipated so I think at this point thats the only.

unknown: Just one follow-up for me as well. On the MS studies, there are some recent studies that have actually been coming out about the role of EBV in MS. It's becoming more and more, it looks like, a causative relationship.

Update I can give you.

Thank you for that.

I think that was my bad.

The milestone slide there.

Just one follow up for me as well on that.

And that study is with there is some recent studies that have actually been coming out about the role of EBV and and then thats, becoming more and more it looks like that's.

Andreas Mueller: And you presented some data, I think, recently, and today you reminded the audience about your data and EBV with 838. Can you just help us connect the dots here in terms of how you think this is going to play out and if you could relate that at all to the BTKs or any of the other CD20s or any of the other drugs that are popular commercially or in development and if they have any role in EBV, that would be great. Yeah, I think that's a very good question.

Positive.

Our relation and you presented some data I think recently and today you reminded the audience about.

Your data and EBV with.

Three eight can you just help us connect the dots here in terms of how you think this is going to play out and if you could relate at all to the <unk> or any of the other.

The 20th or any of the other drugs that are.

Popular commercially or in development and if they have any role on ABB that'd be great. Thank.

Andreas Mueller: And we've been, as a team, very excited about seeing more data and more information coming out about the role of EBV in MS. And there was always kind of a suspicion that EBV plays a role, and I think it's become a lot more concrete now what the role of EBV is. So, I think the study that made the most splash, I think, in public, was the study of several thousands of U.S. military personnel that were followed over, I think, 25 years or so, and looked at how many of those developed MS and what basically was known about their health status before that.

Thank you Yeah Goldman I think Theres a very good question, we have been as a team very excited about seeing more.

Data and more information coming out about the role of EBV and EMS and there was always Congress, especially at ABB plays a role.

And I think it became a lot more concrete now what's the role of Ebitdas. So I think the <unk>.

Study that made the most splash I think in public is that there was the study in several thousands of.

U S military that before or not.

I think 25 years or so.

And looked at how many of those developed EMS and what basically was known about the health status.

That before that and the interesting thing was.

Andreas Mueller: And the interesting thing was… This study, for the first time, could make a clear link between an EBV infection that becomes neurotropic, meaning you see, before the, with the EBV infection, you see an increase of neurofilament at the same time, and those patients who have an increase in neurofilament at the time of EBV infection develop MS. And those, of course, I think 98% or so of the population has an EvVN, or made an EvVN infection. But those who had an EvVN infection, and which was not neurotropic, that basically did not show a neuro filament increase, basically did not develop EvVN. So I think there's now clear length between the EvVN infection, having a neurotropism of that EvVN infection and developing MS. So that's the answer.

This study for the first time could make a clear link between an EBV infection.

That becomes neuro tropic, meaning you see before the answer with the EBV infection is an increase of your filament at the same time and those patients who have an increasingly our filament at the time of EBV infection develop EMS.

And those of course, I think 98% or so of the population is hasnt unions, Amit and EBV infection, but those who hadn't EBV infection, and which was not newer tropics.

Basically did not show a neuro filament increase basically did not develop DVD. So I think there is a clear link between the EBITDA infection, having a neuro tropism of depth EBV infection and developing EMS. So thats the answer it doesn't.

Andreas Mueller: It doesn't necessarily have to say that EvV plays a role during the disease, it's the onset. But then there was also very interesting data that came out, probably had made less of a splash, but I think we're as equally important by a Stanford group, also in February, a published in February of 22, that showed that they looked at the CSS. So they found that first of all, they have, plasma blasts in the CSF at that time of relapse that are actually producing cross-reactive antibodies. And that's the oligoclonal bands. The cross-reactive means there's actually FNR1 antibodies, but they're cross-reactive to an antigen on glia, microglia in the brain that's clearly linked to neuronal destruction.

Necessarily have to say that ABB plays a role during during this disease.

The onset, but then there was also very interesting data that came out probably had less of a splash, but I think as equally important by a central group also in February our published in February of 'twenty, two that showed that.

They looked at the CSF.

It's a terrible of spinal fluids of patients during relapse.

And it was always known that the CSF of patients in relapse contain some older Gopro more bands of immunoglobulin, but David a lot more <unk> analysis, where this all of Oklahoma band of.

Of Immunoglobulins comes from one of this so they have found that first of all.

Do you have.

Plasma glass in the CSF at that time of relapse that actually producing cross reactive antibodies and thats. The OLED OLED, Oklahoma events. The cross reactive means theres actually <unk> antibodies, but that cross reactive to a.

To E antigen.

Unclear microglia in the brain that is clearly linked to new enrollment destruction and so these cross reactive antibodies are increased.

Andreas Mueller: And so these cross-reactive antibodies are increased, produced by these plasma blasts. The interesting thing, you ask about different interventions that probably could influence, you know, these plasma blasts. The interesting thing is that these plasma baths were shown to be CD20 negative, which is kind of important because we're always thinking of EBV infections as these viruses are hiding in B cells. And you would think that, for example, CD20 and really have a EBV-free B-cell recovery.

Used by these plasmablast. The interesting thing you asked about different interventions that probably could influence. This plasmablast. The interesting thing is that this plasma boss of are shown to be CD 20 negatives.

Which is kind of important because we're always thinking of EBV infection.

As these viruses are hiding in B cells, and you would think that for example, CD 20.

Anti CD 20 therapies or <unk>.

The effective and eliminating edd because they eliminate T cells.

At least from this publication that is Plasmablast CD 20 negative they concluded that.

You have to find other sorry.

Andreas Mueller: We believe it's very exciting for us because it could open the possibility of using, for example, IMU-838 with an established, broad antiviral activity and also EBV activity to help in terms of EBV-free recovery, for example, when you think about de-escalation after CD20 therapies and so forth. I think this is all hypothetical at this point, but I think the hints that we get from this publication are very exciting for a drug like IMU-838.

<unk> therapeutic strategies to really have a EBV free b cell recovery. That's also as we believe it's very exciting for us because it could open the possibility of using for example, <unk> hundred eight.

Established broad antiviral activity and also a <unk> activity.

To help in terms of.

<unk> recovery for example, then you're thinking about the escalation of the CD <unk> therapies, and so forth I think.

This is all hypothetical at this point, but I think the hint that we get from this publication.

I think a very exciting for a drug like <unk>.

Andreas Mueller: It just needs a little bit of time to spread, I think, the scientific community and probably a few more confirmations of this, but at least the data that came out about EBV was very exciting for Munich and for Vita Flutimus Calcium. Thank you. Thanks, Govind. Our next speaker is Matt Kaplan of Landbrook, Thomas. Matt please aren't going to just stop and go ahead. Hi, good morning. Can you hear me?

It just needs a little bit of time to spread I think the scientific community and probably.

A few more confirmations.

Of this but at least the data that came out about ABB look very exciting for our Munich and for Vida fluid most kelson.

Thank you.

Thanks Kelvin.

Our next speaker is Matt Kaplan of Ladenburg Thalmann, mattress unmet yourself and go ahead.

unknown: Great. Well, congrats on the progress. Just a quick follow-up to the last question. If we remain on that topic, how does the concentration that you studied and saw in vitro, in terms of the 3.3 to 30 micromolar, correlate with the concentration that you're seeing with 838 in vivo and in the CSF in the central nervous system since you're getting across the bubbling barrier?

Hi, Good morning can you hear me, yes, good morning, good morning, Brian .

Great well congrats on the progress just a quick follow up to the last question.

And if we remain on that topic.

How does the concentration that you studied in <unk> and <unk>.

In vitro in terms of.

$3 three to 30 micro molar.

Correlate with the concentration that you're seeing.

With 838, <unk> and the CFO .

In the central nervous system.

You're getting getting across the blood brain barrier.

unknown: Ahmed, so I think, thank you for this question. I think we have seen a lot of splash by companies that do B.D.K. inhibitors, claiming that they're the only drugs that really have a centrally acting medication format. And we always suspected that that statement is probably not entirely correct as some of these smaller molecules should enter the CSF and the central component as well.

Hi, Matt So I think thank you for this question I think we have seen.

A lot of splashed Fi.

Companies that do PTK inhibitors, claiming.

Claiming that they're the only drugs that really have a centrally acting.

The medication formats, and we always suspected thats.

That statement is probably.

Not entirely correct as some of these smaller molecule should enter the.

Andreas Mueller: So, these are preliminary data. We're working on expanding this and having more data and confirming a little bit closer to the human situation what concentrations we'll get. To answer your question really fully, I think that you have, you know, are these concentrations enough to make a meaningful contribution also in terms of efficacy from the central component when you look at the relationship between serum concentrations and CSF concentrations.

The CSF in the central component as well so.

These are preliminary data we are working on expanding doesn't having more data and confirming a little bit more closer to the human situation.

What concentrations of our debt.

To answer really fully your question I think that you have is that are these.

Concentrations enough to make a.

A meaningful contribution also in terms of efficacy from the central components.

Andreas Mueller: We see that we're at least on par, I think, with the data that were published with the BDK inhibitors, and we actually believe that the BDK inhibitors are not that unique in terms of being a small molecule to act in the central component as a central compartment and that it may not be what sets them apart. So I think that, to me, was the main rationale for showing these rat data. But we will continue to generate data that will show that, I think, IMU-838 or Vita Flutimus have access to the central compartment as well. Okay, very good.

When you look at the.

The relationship between serum concentrations.

Concentrations in CSF concentrations, we see that.

Or at least on par I think with the data that were published lifted PTK inhibitors, and we actually believe that.

<unk> inhibitors are not that unique in terms of being as a small molecule too to act in the central component in central compartment and.

And.

It may.

And not be what sets them apart so I think that to me.

The main rationale for.

It's showing the.

This rat data, but.

We will continue to to generate data that will show that I think <unk> has access to the central compartment as well.

Andreas Mueller: And then a question in terms of data that we should be looking for in the psoriasis cohort for 9.3.5 in the second half of this year. Can you give us a sense in terms of what you're looking for potentially in the efficacy profile of the drug and what you're modeling there and what we should be expecting? Yeah, so I think we'll take a little bit. We're learning a little bit from history.

Okay very good and then.

A question in terms of data that you are that we should be looking for in the psoriasis.

Our cohort 495 in the second half of this year.

Can you give us a sense in terms of what youre looking for potentially in the efficacy profile of the drug and what you're what you're modeling there.

Should be expecting.

Yes, so I think.

Andreas Mueller: History in terms of the different drugs that had a full phase two program in psoriasis, where you look at how quickly, for example, things like the PASI score change over time. Usually, phase two trials are done with a 12-week endpoint or a three-month endpoint. And you see that after four weeks or after one month, you have a half maximum effect in terms of PASI as compared to three months. So I think you have the good news is that I think you can very well estimate what the change in PASI score, not in PASI 75 or so, but in the actual PASI score, what the change in actual PASI score, the average change should be.

We will take a little bit.

We're learning a little bit from history.

The history in terms of the.

Different drugs that.

Had a full phase II program in psoriasis, where you look at how quickly for example, things like deposit score change over time.

Usually the phase III trials are done with a 12 week endpoint or three months endpoint.

And you see that after four weeks. After one month, you have a half maximal effect in terms of possibly as compared to three months. So I think you have.

The good news is I think you can very well estimate.

The change in positive score not not in deposits of $75 or so.

The actual policies for what the change in <unk> score the average change should be.

Andreas Mueller: And so when we look at this, I think you see that maybe the IL-17 antibodies, IL-23 antibodies, they're on the range of 30% to 35% change that they have at week four. With Vitae Pharmaceuticals, the raw gamma inhibitor some years ago, they found in their trial in moderate to severe psoriasis patients, I think they had two dose groups.

And <unk>.

So when we look at this I think.

You see that maybe.

Our 17 antibodies IL 23 antibody as they do on the range of 30% to 35% change that they have at week four.

With Vijay pharmaceuticals, with gamma inhibitor or some years ago Dave.

They've found in there.

Trial in moderate to severe.

Andreas Mueller: And I think one dose group was somewhere around 20% change of PASI. And the higher dose was, I think, 28% change in PASI. So I think that's also the expectations that we have for our drug, that we want to show that we're in the same range, somewhere between the Vitae compound and the IL-17-23 antibodies. Of course, we measure much more in this trial. We do biomarkers, we have a skin biopsy where we do immunohistochemistry.

So as these patients I think that two dose groups and I think one dose group of somewhere between somewhere around 20% change of party.

And the higher doses I think 28% change in policy. So I think that's also the expectations that we have for our drugs that we want to show that we are in the same range.

Somewhere between the VJ compounds empty.

Our $17 23 antibodies of course, we measure much more in this trial, we do biomarkers.

Skin biopsy, where we do immuno histochemistry, we look at other clinical scores like for example in each component, which I think is very important also to seat to see early efficacy.

Andreas Mueller: We look at other clinical scores, like, for example, an itch component, which I think is very important also to see early efficacy. But the PASI score is usually the most well-recognized assessment in psoriasis, and everybody knows this.

And so.

But the deposit score is really different.

<unk> well recognized.

Andreas Mueller: And that's why I think it's also, for us, I think it's the most visible outcome of this trial, probably. And then when other comment to your first question, I think if you're guarding the coverage, I think it was also referring to the EVV activity. Yes, we were surprised that just by accident, basically we have seen this benefit for preventing COVID-19 and it was a small courtside and everything, but I think it was a quite remarkable surprising difference between the active placebo group on COVID underlining the broad antiviral activity and that also stood into. So for EBV, the concentration should be the same range and therefore we believe that that's covered and the top levels really cover that in vitro data, which represented. Okay, great.

Assessment in psoriasis and everybody knows this and Thats why I think it's also for US I think it's the most visible outcome of this trial.

And then one other.

Comment.

Your first question I think you are cutting the coverage I think it was also referring to the <unk> activity.

Yes, we were surprised that just by accident basically we have seen this benefit for preventing COVID-19 in the Midwest, a small cohort size and everything but I think it was occurring.

Remarkably surprising difference between the active and placebo group uncovered underlining the broad antiviral activity and that also shipped into for ABB.

The concentrations within the same range and therefore, we believe that thats comfort in the trough levels really cover that.

In vitro data, which we presented.

Andreas Mueller: And just this last question, in terms of the recent announcements and invasion of Ukraine, what's your exposure in terms of your clinical development programs in Ukraine? So, of course, that has been some concern to us over the last weeks already. Yes, I mean, it was an event that, of course, surprised the world, but I think we had looked at that.

Okay, Great and just last question in terms of with the recent announcements.

Innovation.

You can't.

Your exposure in terms of your clinical development.

Our programs and in Ukraine.

So.

Of course, that's that has been some concern to us over the last weeks already.

I mean it was a.

An event at all.

Andreas Mueller: What we can say is that the CALDO study, our study in ulcerative colitis, is completely unaffected. And the reason for that is that we have been very specific of doing the data cleaning for all of the data up to week 10, which is our primary endpoint, as quickly as possible. We have done all the monitoring visits, so that is all done. We basically have these data and, of course, it's not unblinded.

Of course, the price the world, but I think we had looked at what we can say is that.

Cargoes study our study in ulcerative colitis is completely unaffected and the reason for that is that.

We had done.

We have been very specific of doing the data cleaning for all of the data up to week 10, which is our primary endpoint as quickly as possible. We have done all the monitoring visits so that's all done we basically.

Have these data and of course, there's nothing underlying that so they have patients that are in extended deduction. So we can unwind the study yet.

Andreas Mueller: So, there are patients that are in extended induction, so we can't unblind the study yet, and that will go up to week 22. But all of the data that go to the primary endpoint are already cleaned, sourced, and verified. So, in CALDO, we actually have no exposure.

And that will go up to week 22, but <unk>.

All of the data that goes into the primary endpoint the already cleaned sourced out of verified so in condos we have.

Andreas Mueller: Ukraine has been part of other studies, of course, especially the DMS studies are done in Ukraine as well. We have also started with countermeasures. You know, really, I think we have to look a little bit at the dynamic situation. And, of course, this is a very unfortunate situation, but we have to monitor this. What kind of long-term repercussions this has for doing clinical trials in Ukraine? We have implemented some countermeasures ahead of time.

Actually no exposure.

Ukraine had been part of other studies of course, our specialty CNS studies are done in Ukraine as well.

We have also started with complementary.

Really I think we have to.

Look a little bit at the this is a dynamic situation and of course.

This is very unfortunate situation, but we have to more than two quarters.

Andreas Mueller: And we anticipate that given the, I mean, it's hard to expect at this early time but how long this and how severe this conflict will be. But I think the best thing we can do at this time is to monitor the situation day by day. Thanks, Matt. Next is Zegbe Jala of Roth Capital. Zegbe, please unmute yourself and go ahead.

What kind of.

Long term repercussions of this house for doing clinical trials in Ukraine.

We have implemented some countermeasures ahead of time.

Have to just see how this develops and we anticipate that.

That's something that.

Yeah.

Given the I mean is it.

Hard to expect.

At this early time.

How long does and how severe this conflict there will be but.

I think.

The best thing, we can do it at this time.

One is on the situation day by day.

Okay. Thank you.

Thanks, Matt.

And next is.

The dollar of Roth capital. Please go.

unknown: Good morning, guys. Thanks for taking my questions. And clearly, a nice cadence of data readouts ahead. So I know CalDOS is probably going to be a significant focus investor.

Go ahead.

Good morning, guys. Thanks for taking my questions and clearly a nice cadence of data Readouts ahead. So Cal Dallas is probably going to be a significant focus investors I just had a couple of questions.

First one is I know the study enrolled biologically 90, and biologically creature and patients. So should we expect to see very different efficacy profiles in these patients and then similarly as you would also expect to see differences in efficacy profile featuring at patients so different.

Andreas Mueller: So just had a couple of questions. I think the first one is, I know the study enrolled biologically naive and biologically pretreated patients. So should we expect to see very different efficacy profiles in these patients? And then similarly, she would also expect to see differences in efficacy profiles between patients with different baseline ME or scores coming into the study. And so this, this, of course, I can only take the history because this this can differ from drug to drug, occasionally based on the mechanism of action.

Baseline <unk> coming into the study.

Okay.

As all of this of course.

I can only take the history because.

This is Ken.

Differ from Dr drop occasionally based on the mechanism of action traditionally I think the.

Andreas Mueller: Traditionally, I think the biologically experienced patient has shown less of a response to active treatment than the biologically naive patient. So that's, I think, the general wisdom in IBD. Let's say it this way. And so that includes a lot of biologically naive patients, which is, to me, good news because it gives the drug the chance to really show good activity versus placebo. In my mind. Thank you.

Biologically experienced patients had shown less of.

Response to active treatment than the biologic naive patients so thats I think the.

The general Wisdom, and IBD, let's say it this way.

So that includes.

A lot of biologic naive patients I think very consistent.

Consistent with the likely positioning of this drug.

As to me is good news because it gives it the direct a chance to really show.

Good.

Activity versus placebo to nine months.

Andreas Mueller: And then just another follow-up here. What are your thoughts regarding the differences in the MOA of Ozanamide versus IMU-A3, and what would you expect to see in terms of time to response between the two different drugs in the induction phase? So I, you know, Ozanimod as an S1P modulator has a very different, of course, mechanism of action, and you can see this on several things. I, for example, you see a, so S1P modulators basically more or less trap lymphocytes in lymph nodes or in other lymphatic tissue and leads to a lowering of, basically leads to lymphopenia in blood, and you can see the effect very clearly in all of the trials, and that's part of the mechanism of action, which leads, of course, to, for example, infections, virus reactivations, because you limit the ability of the immune system to respond.

Well, Yeah, and then I guess another follow up here what are your thoughts regarding that defense to the MLA.

<unk> Bancshares, Inc.

And what would you expect to see in terms of time to response to.

Thank God.

Thanks.

So.

Yes.

<unk> is an excellent key modulator has a very different of course mechanism of action and you can see this on.

On several things.

For example, <unk>.

Okay.

So S&P modulators basically.

Basically more or less track lymphocytes in and lymph nodes are in.

And other than fat tissue and leads to a lowering of basic.

Basically the user Lymphopenia and blood.

And.

You can see the effect very clearly and all of the trials and that's part of the mechanism of action.

Which leads of course to for example infections virus reactivation because your limits.

Andreas Mueller: There's also now, just at ECHO last week, there were presentations, for example, how vaccination efficacy and tumor response against SARS-CoV-2 infection is much lowered for patients using Ozanimod. All of this is not the case for INU-838 because they have very different mechanism of action. We have a very selective effect only on what we call the bad guys of the immune system, so the hyperactivated immune cells that are causing the autoimmune disease, and we leave the basically innate immune system and the immune response against infections completely unaffected, and we have seen this now in several trials where we've seen that the rate of infections, for example, versus placebo control is not increased, and some of the studies, it was actually slightly decreased, so I think that made it to the differences in MOAs. Daniel.

Ability of D.

Immune system to respond that is also now just at Echo last week presentations for example, vaccination efficacy in tumor response against Sars Cov two.

Infection is much lower for patients.

Using <unk>.

All of this is not the case for <unk> because they are very different mechanism of action. We have a very selective effect only on what we call. The bad guys of the immune system yes.

The hyper activated immune cells that are causing the autoimmune disease autoimmune disease.

And believe me.

Basically innate immune system and immune response against infections completely unaffected and we have seen those mellon several trials.

<unk> assumed that the rate of infections for example versus placebo control.

Has not increased.

Some of the studies that was actually.

Slightly decrease so I think that made it to the differences in <unk>.

Andreas Mueller: Hello. The Phase 2 study and Phase 3 study, I think, used an induction period of eight weeks in asthma. I hope I'm correct. I've seen so many presentations last week that echo that I'm at an age where I can be confused sometimes, but I think it's eight weeks. So we use 10 weeks. It's something that sometimes doesn't make a lot of difference whether it's eight or 10 weeks because often these curves in clinical trials in terms of response also have this kind of exponential curve. Most of the effect happens in the early weeks or the early two or four weeks.

Eddie.

The phase two study in phase III study I think use an induction period of eight weeks and as Johnny but I hope I am correct.

So many presentations last week echo that.

I'm at an age where I can be confused sometimes but I think it's eight weeks.

We use 10 weeks.

It's something that sometimes is.

Doesn't make a difference whether it's eight or 10 weeks because.

Often these curves in clinical trials in terms of response also have this kind of.

Exponential curve most of the effect happens.

Andreas Mueller: And the way you define the induction period often is to give the chance for the drug to work in all of the patients, maybe patients that are responding slower. We know from our Phase 2a trial, an entrance trial in corticosteroids-dependent patients, that the ability to withdraw corticosteroids was very quick. Within the first two weeks, I think you could lower the baseline dose to 20% of the baseline dose. So this is all published.

In the early weeks are in the early two or four weeks.

And the way you define induction gate often this is what gives us the chance for the drug to work in all of the patients may be patients that are responding slower we know from our phase Iia trial entrants trial and corticosteroids.

Pendant patients that the ability to withdraw corticosteroids was.

It was very quick within the first two weeks I think you could lower.

Andreas Mueller: So we believe that also our mechanism of action leads to a very good and fast onset of the disease. And again, the time points, eight or 10 weeks, really don't make a lot of difference. It's just that in a clinical trial, you want to give the drug a chance to work in most patients. Thanks, Andreas, and I don't want to put words into your mouth, so just for clarification here, you do expect a fast onset of action, and then in terms of the magnitude of response, do you expect that to be similar, or should we be looking at it more as a composite, meaning the efficacy and safety balance, because you did mention how you expect the safety rate to come out better on safety?

220% of the baseline dose.

So this is all published but.

So we believe that also the.

Our mechanism of action that leads to a very good and fast onset of <unk>.

Of the disease and the.

Again, the time points eight or 10 weeks is really doesn't make a lot of difference is just that.

In a clinical trial you want to give the drug a chance to also work in <unk>.

Most of the patients.

Yeah.

Thanks, Andres and I don't want to put words in came out so just a quick clarification here.

Expect a fast onset of action and then in terms of the magnitude of response do you expect that to be similar or should we be looking at it more as a composite more at the efficacy safety balance because you didn't mention how we expect it to come out better on our safety. So I think.

Andreas Mueller: So, I think maybe to start with the back, the last statement. I would totally agree that we always expect to be the safest drug in any indication. Yes, clearly. I think that we have learned now, and we're very happy about it. And that's basically the foundation on which we build our efficacy results. And the fast onset of action, I think that's also... Yeah, fast onset of action.

Maybe just start with the back the last statement I would totally agree that we always expect to be the safest drug in any indication yes.

Yes.

I think that we have learned now and we're very happy about this and Thats basically the foundation on which we build our efficacy results.

Andreas Mueller: I think we have, yeah, we have the data from the entrance trial that actually would indicate a very fast onset of this mechanism of action, what the expected efficacy results are. I think Ozanimod, especially in phase 2, hasn't shown, you know, overwhelming efficacy results if you look at other drugs. So you always look at this clinical remission, which endpoint that is very similar to or identical to what we have here in this trial.

And swap onset of excellent.

So, yes fast onset of action I think.

We have.

Data from an entrance Violet <unk> indicated very fast onset of.

This mechanism of action.

What the expected efficacy results I think lasagna.

Especially in phase III Hasnt Sean.

Overwhelming.

As a result, if you look at other drugs. So you always look at is clinical remission, which endpoint that is very similar to our identical to what we have here this trial.

Andreas Mueller: And for some reason, we call it differently, but it was on the suggestion of the FDA. We call it a composite out of endoscopic healing and symptomatic remission, which is exactly the same definition as everybody's using for clinical remission.

For some reason they call it differently, but it wasn't on the suggestion of the FDA.

We call it a composite out of <unk>.

Andreas Mueller: And you've seen that you have, you know, data, let's say for tofacitinib, where I have only, you know, 3 or 6%, depending on the dose difference between active and placebo. And then you have the best drugs that probably have like a 25% difference between active and placebo. And usually, we look at the differential between active and placebo. That's important. Ozanimod was more on the medium end.

Endoscopic healing and symptomatic remission, which is exactly the same definition as everybody is using for clinical remission and you've seen that you have.

Data, let's say for Tofacitinib, where have only.

Three of our 6% depending on the dose difference between active and placebo and then you have the best drugs that probably have like 25% difference between active and placebo and usually look at the differential between active and placebo. That's important is that.

And even with us more on the.

Andreas Mueller: I think there's like 13% difference, if I remember well. But I think we would like to come out with a strong efficacy. And we have talked to our medical advisors. And I think very consistently, for your safety profile, I think you have to have around 50% of difference between active and placebo to really have an outstanding efficacy. Thank you.

Medium and I think it was like 13% difference or amount of well.

But I think we would like.

I'd like to come out with a strong efficacy and we have talked to our.

Medical advisors, and I think very consistently they say for for your safety profile I think.

You have to have.

Around 50% of difference between active and placebo to really have outstanding efficacy.

Andreas Mueller: And then just a couple of quick follow-ups here. So for folks that kind of like to change the goalposts, assuming that the data from the induction phase comes out really good, you know, how do you think that do you risk the maintenance phase of the study? And then is it possible to make changes to the maintenance phase based on some things that you do observe in the induction phase? So the last question is very easy.

Thank you and then just.

Just a couple quick follow ups here, so first off that kind of like it changed at all post the human that paid off in the induction phase comes out very good and how do you think that de risks. The magnitude is of the study and then is it possible to make changes to the maintenance base based on some things.

<unk> yeah.

Andreas Mueller: No, the protocol is fixed. And also, we do re-randomization for the maintenance phase, which is kind of usual in many IBD trials, because you expect that a maintenance dose may be lower than an induction dose because here you in the induction phase you take sick patients very quickly from active disease to non-active disease whereas the in the maintenance phase you maintain the non-active disease and that has been done in several trials you know opacitinib for example also at a very different dosing for the maintenance phase so the re-randomization is important.

<unk>. Thank you Sir.

Last question is very easy no.

The protocol is fixed and also we do re randomization for the maintenance space, which is kind of usual and many IBD trials.

Because you expect that.

Maintenance dose may be lower than in reduction dose because here you in the induction phase you take sick patients very quickly from active disease to non active disease, whereas the in the maintenance space you maintain the non active disease and that has been done in several trials.

Andreas Mueller: In terms of going to phase three the induction data are really important data and this will decide whether you can go into phase three. The a phase two study and that has been shown by many other trials doesn't necessarily have to include the maintenance phase and many phase two trials have not. We have decided to include the maintenance phase for the reason that we want that in phase three you have to show not only induction but also maintenance of effect so it is obligatory in phase three and we want to learn a little bit more about phase three planning statistical effect size and so forth and that's why we included this in the phase two trial as well but I would not first of all the readout that we have in June for the induction data does not include maintenance data because the maintenance is ongoing at that time but also it will be available thereafter but it's more or less a tool for phase three planning rather than a full-fledged efficacy readout for this study for the phase two study. Thanks guys and I'll save my final questions for a follow-up call as I know we're approaching the hour here. Thank you again.

But it didn't it for example, also that has a very different dosing for the automated and stay so you re randomization is important.

In terms of going to phase III.

Induction data are really important data and this will decide whether.

You can go into phase III.

A phase II study and that has been shown by many other trials doesn't necessarily have to include the maintenance space and many phase II trials have not we have decided to include a maintenance phase for the reason that we want that in phase III you have to show not only induction, but also maintenance of effect. So it is it is.

<unk> in phase III, and we want to learn a little bit more about phase III planning statistical effect size and so forth and that's why we included it in the phase II trial, as well, but I would not first of all the.

The readout of the have in June for the induction data does not include maintenance data because the maintenance is ongoing at that time.

But also it will be available after but it's more or less a tool for phase III planning rather than a full fledged efficacy readouts for this study for the phase two study.

Thanks, guys and I'll save my final question for a follow up call is I know, we're approaching vre and thank you again.

Thanks, Okay. Thank you I'll take this so.

unknown: So we have two more questions in the queue. The next one is Subbalan Pachapayappan at H2Rainwright. Subbalan, please unmute yourself and go ahead. Good morning. Can you hear me okay?

So we have two more questions in the queue.

Next one.

<unk> at H C. Wainwright prove allow me please go.

unknown: Yes. Good morning. Hi, awesome.

Go ahead.

Good morning can you hear me Okay, yes, good morning.

Andreas Mueller: Congrats on your progress. So to start off the discussion with respect to your CALDOS-1 trial design, I see that the 83% of the enrolled patients were biologically naive and 17% had prior biologic exposure. So I'm just curious whether the intention is to position IMU-935 after immunosuppressants, but before TNF-alpha inhibitors in the UC treatment paradigm. So I think, I would not draw that conclusion, but I think that would be a wonderful positioning, to be quite honest.

Hi, Awesome Congrats on your progress so to start off the discussion with respect to your calendars, one trial design I see that the 83% of the enrolled patients were biologically nave and 17% had prior biologic exposure. So I'm just curious whether the intention is to position <unk> 935 after.

Immunosuppressants, but before TNF alpha inhibitors and their UC treatment paradigm.

So I think I would not draw that conclusion, but I think that would be a wonderful position to be behind us.

Andreas Mueller: In the discussion, I said that we have a lot of ongoing discussions with our medical advisors, that includes, of course, discussion on positioning. And over the last. 3, 4, 5 years.

In the discussion I had said that we have.

A lot of other ongoing discussions with our medical advisers, but that includes of course discretional positioning.

Andreas Mueller: There have been several oral drugs that went into very approved or in late stage approval process for ulcerative colitis and, There was always the discussion where they should position. They always, they aimed for the positioning to basically prior to biologics and after immunomodulators. And none of them really has achieved it and had to do with the safety profile.

And over the last.

345 years, there have been several oral drugs that went into very approved <unk> and <unk>.

Late stage the approval process for <unk>.

Ulcerative colitis and <unk>.

There was always the discussion whether it should position the OLED the aimed for the positioning that basically prior to biologics and after immuno modulators and none of them. It really has achieved has to do with the safety profile and the.

Andreas Mueller: And the FDA was very specific now about all of the JAK inhibitors, and they actually named not only Topaz-Petrin, but they were very specific that this will apply the same positioning from their point of view, regulatory positioning, would apply to really only after at least one biological failure. So it's more or less also seen in the minds of the gastroenterologist as a medication of last resort. This will apply to all of the JAKs, including Uparicitinib. That is specifically mentioned in that FDA communication as well. Ozanimod also has a considerable amount of safety challenges as well.

After it was very specific now, but all of these JAK inhibitors and they actually named.

Not only top as stated on a deliver very specific debt. This will apply the same positioning from DAP under their regulatory positioning would apply to really only after at least one biological failures. So it's more or less also seen in the minds of the gastroenterology.

<unk> the role of this as a medication of last resort and this will apply to all of the.

Jackson, including <unk>.

That is specifically mentioned and that FCA communication as well.

<unk> also has a considerable amount of safety challenges as well.

Andreas Mueller: And... Gastroenterologists see this as a disappointing entry into the UC market and the IBD market that will probably also end up with more or less the same positioning as Jack's, which leaves kind of that therapeutic white space, just what everybody wanted to be, completely open. The drug that has good safety, so you can use it early and use it in many patients early on in their disease, right after you use 5-ASA and corticosteroids and before you use biologics.

Customer end of August <unk>.

Disappointing entry entity Youll see marketed IBD market. It will probably also end up with a more or less the same positioning as Jack's which leaves kind of that therapeutic with a white space just what everybody wanted to be completely open day.

The drug that is.

<unk> has a good safety. So you can use it early and use it in many patients early on in their disease right. After you used five five years.

And corticosteroids.

Andreas Mueller: And I think that's, in our discussions with medical experts, they see as exciting for this program. 83% Biologically Naive is a, I think is a measure of maybe some of the countries and so forth that we were in. It was not intentional.

And before you use biologics.

And I think that's when in our discussions with medical experts Stacy is exciting.

For this for this program.

83%.

Biologically nave is a.

I think as a measure of maybe some of the countries and so forth that we're in.

It was not intentional I think the outcome is but it is not intentional.

Andreas Mueller: I think we welcomed it, but it was not intentional. Got it. Thanks for the clarification. There is a French company called Inventiva.

Got it thanks for the clarity.

Daniel Vitt: It's also developing oral Rho Gamma inverse agonist, and that's currently in phase 2B trial in psoriasis patients. So can you outline how your IMU-935 is differentiated from Inventiva's oral Rho Gamma agonist, inverse agonist? Thank you. That's a good question.

So there is a French company called <unk>, It's also developing or roll gamma inverse agonism. That's currently in phase two b trial in psoriasis patients. So can you outline how youre IMMU 135 is differentiated from inland gave us oral drug gamma agonist inverse agonist.

Daniel Vitt: And I'm not sure if this refers to CDeroGant, which is now in phase two by AbbVie, if you get it right. So this was originally developed by Inventiva, if you get it right. That molecule is, I think, an interesting compound now in phase two. We have published a lot of data on our drug, and it comes with more data than ever published for the at-the-imagine molecule about modern action in selectivity, exposure, PK, safety, and so on.

Thank you that's a good question.

I'm not sure.

If this refers to a severe again, which is now in phase III, but we if you get it right. So this was originally developed by them and T bifurcated right.

That molecule is I've seen.

An interesting component no interest too.

We have published a lot of data on lower demand.

Tons of more data than ever published for the upbeat.

And then tivo molecule.

Motive action selectivity exposure PK safety and so forth, we're quite convinced that we have the best in class molecule, but let's wait a little bit until.

Daniel Vitt: We're quite convinced that we have a best-in-class molecule, but let's wait a little bit until we get more data on fossil deuterium, and especially I would like to point to the publication we made in December, which you can find on the homepage.

More data for severe event.

And the specifics I would like to point to the to the publication we made in.

In December .

You can find it on the homepage there was an update on the specific activity of hard rock.

Daniel Vitt: There was an update on the specific selectivity of our drive. So then we selectively suppress IL-17 or Th17 polarization differentiation. We suppress IL-17 in a very potent fashion in human lymphocytes but with a totally absence of impact at time of self-maturation.

So then we selectively suppressed IL 17 line 17 will receive some differentiation with Chris IL 17, and a very important first in human lymphocytes.

Daniel Vitt: We have not seen any other company publishing such data. So we believe that this is a quite unique feature for us. Great. And with respect to your ongoing metastatic CRPC trial, what do you need to see to move the program forward? And what are your go and no-go considerations?

Totally absence of impacting time was that maturation, we have not seen any other company publishing such data. So we believe that this is a unique feature for our drug.

Okay.

Right on.

With respect to your ongoing metastatic CRP C trial, what do you need to see to move the program forward and what are you going noga concentrations.

Andreas Mueller: So this is phase one in CRPC, and we look at this as a phase one trial where, I think, most importantly, we want to escalate the dose, which is something that you want to do in oncology indications. And the dosing, of course, in oncology is expected to be quite different from immunology indications. And then, of course, you also want to have maybe a first hint that things are happening.

So this is the phase one.

And <unk> and we look at this as a phase one trial, where I think most importantly, we want to escalate dose, which is something that you want to do in oncology indications.

And.

Which ended dosing of course in oncology is expected to be quite different from immunology indications.

And then of course, you also want to have maybe a first hint of.

Andreas Mueller: I wouldn't call it efficacy. I would call it more that you have an effect that you can translate into some sort of efficacy in future trials. And that's, I think, what we call the expected phase two dose. It's a dose that is large enough to still be safe, but it's large enough to cause biological effects that could translate into clinical activity in future trials.

The things are happening.

I wouldn't call it efficacy I would call it more that youll have a effect that Doug.

Then you could translate into.

Into some sort of efficacy in future trials and that's I think what we call expected phase II dose a dose that is large enough.

Still be safe, but it's large enough to cause biologically.

Andreas Mueller: And you've seen this in some other phase one trials in oncology, where you're not looking for systematic efficacy yet, but you're looking for biological effects that you can see at this dose that you can translate into efficacy in a phase two trial. Okay, one final question from me. I know you spoke about interim analysis for your phase three ensure program. So I'm just curious.

Biologically effects that could translate into clinical activity in future trials.

You have seen this in some some other phase one trials in oncology.

Yes.

Looking for systematic efficacy yet, but you are looking for biologically effects that you can see at a desk that you can translate into efficacy in a phase II trial.

Andreas Mueller: I know you'll be assessing event rates, but will you be looking at other endpoints as well during the interim analysis period? No, we're not looking at endpoints, actually, in the interim analysis. We're looking at events rates and basically more or less the hazard ratio of events rates, just whether our assumption, what hazard ratio, We get in this trial will be confirmed by this interim analysis. And really, the idea is that you have to make assumptions here that drive the number of patients needed for this trial.

Okay. One final question from me.

You spoke about interim analysis for your phase III ensure program. So I'm just curious I know you'll be assessing even traits, but would you be looking at other endpoints as well during the interim analysis period now.

Now looking at endpoints actually the interim analysis, we're looking at advanced rates and basically the more or less a hazard ratio of events rates, yes, whether our assumption what hazard ratio.

We get in this trial.

There will be confirmed by this interim analysis.

And really the idea is that.

You have to make assumptions here.

Andreas Mueller: I think we know from phase two already that, of course, you have an effect on lesions, you have an effect on relapse activity, even in the small population, but we need to see that our assumptions for the hazard ratio was the same. So we're not really assessing any specific endpoints in the interim analysis for the phase three. We're looking at the hazard ratio and see how this translates into patient population or patient numbers needed.

Drive the number of patients needed for Australia, I think we know from phase II already that of course, you have an effect on lesions you have an effect on relapse activity, even the small population, but we need to.

<unk> see that our assumptions for the hazard ratio was the same so we're not really assessing any specific endpoints in the interim analysis of the phase III. We're looking at the hazard ratio and see how this translates into patient population or if the patient numbers needed.

That's it from me thanks for taking my questions and congrats on your progress.

Andreas Mueller: That's it from me. Thanks for taking my questions and congratulations on your progress. Thank you, Bhubhalan. And finally, we have Nath Charoensook, apologies if I pronounce this incorrectly, at SVB Learning. Nath, please unmute yourself and go ahead.

Thank you <unk>.

And finally, we have net Karin so apologies.

I pronounced this incorrectly and SBB leerink net piece, unlike yourself and go ahead.

unknown: Hi, this is Matt, on for Tom Smith from SGB. We have two quick questions here. So the first one regarding the phase three intra trial, was what's the thinking behind the 18 month time point and the use of time to first relapse at the primary endpoint, and have a quick follow up. You said 18 months endpoints? Yeah, everyone come.

Hi, This is Matt on Photonics last from S&P, we have two quick questions here.

First one regarding the factory and for trial on what's the thinking behind the 18 month time point and again at all times with Barstool, App, Apple pie and client and have a quick follow up.

Yeah.

Andreas Mueller: Okay, 72 weeks. Yep. Yeah, yeah. The idea of the 72-week... Pull up here.

You said 18 months endpoint.

Yes.

Oh, Okay, sorry until week, yes, yes, yes.

Yes.

The idea of the 72 week.

Andreas Mueller: I think it is looked at in terms of, being a placebo-controlled trial, getting enough. Having enough chance for enough relapses to happen in a longer follow-up period but having the follow-up period short enough to be able to do a placebo-controlled trial in as many countries as possible. So that's the short answer.

<unk>.

Follow up here I think is.

Is looked at in terms of.

Being a placebo controlled trial getting enough.

Having enough chance for enough relapses to happen a longer follow up period, but having the full hour periods short enough to be able to do a placebo controlled trial in as many countries as possible. So thats the short answer.

Andreas Mueller: And then time to first relapse us, time to first relapse us. The regulators ask for a relapse, related endpoints in a phase 3 study, and that's been traditionally also done in all the other trials. The guidances actually give you a choice of analyzed relapse rate, ARR, which was traditionally used in phase 3 trials, or time to first relapse. Time to first relapse has become more interesting as relapse rates in MS patients are very well documented to go down over the last two decades and considerably going down, so that ARR assessment becomes more and more difficult to do with a reasonable number of study populations.

And then time to Farhan.

Tangibles relapse.

The regular regulators asked for a relapse.

Related endpoints in a phase III study.

And Thats been traditionally also done and all the other trials.

The guidance is actually.

Andreas Mueller: So I think there have been actually published reports that compare these two endpoints and basically really highlight the advantages of time to first relapse as an endpoint for relapse, at it. Um, and another question regarding the phase two CAUDOS1 trial, could you remind us quickly again, like what are the specific efficacy thresholds and clinical improvement to view this as a positive data? So I think the, What we, you mean in terms of statistical planning, just wanted to understand our statistical assumptions more or less, what, how we look at the sample? Yes.

Give you a choice of annualized relapse rate <unk>, which was traditionally used in phase III trials or time to first relapse.

Time to first relapse has become more interesting as well.

Relapse rates in MF patients.

Very well documented to go down over the last two decades and considerably going down so that our assessment becomes more and more difficult to do with a reasonable number of.

Of study population. So I think they have been actually published reports of compare these two endpoints.

Basically really highlight the advantages.

Time to first relapse.

Endpoint for relapse.

Okay.

Got it.

And another question regarding the <unk> one trial can you remind us quickly about what artist co formulate.

Efficacy threshold and clinical equivalent to deal with F. A pocket dataset.

So I think.

So what we do.

You mean in terms of statistical planning just wanted to understand our statistical assumptions more or less.

Andreas Mueller: So we have made statistical assumptions that are very much in line with what I just outlined as the expected delta. And we also made assumptions, of course, for the we had to make some assumptions for the placebo response. Yes, so we know that all of the, for clinical remission, and there's a, there's good summaries now available, and you can look at other trials, the placebo response is basically 10% or less, often considerably less.

Hobbies.

Central idea.

Yes.

The threshold or the bar for success here, yes, so we have made.

Statistical assumptions that are very much in line, what I just outlined as the expected Delta.

And.

We also made assumptions of course for the we have to make some assumptions 40 placebo response. So we know that all of these for the pre clinical remission and that is it.

Andreas Mueller: And we have basically been conservative and basically assumed also a placebo response of 10%, and then basically added the delta. And we also assumed, for example, a dropout rate of 20%, and then we came up with basically 240 patient sample size that we needed. So we've actually, recruited 263. We had very good success, especially at the end of the trial, recruiting very fast. So we had a little bit over recruitment.

This summary is now available and you look at other trials.

Placebo responses is basically 10% or less often considerably less.

And we have basically been conservative and basically assumed also a placebo response of 10% and then basically out of the Delta.

We also assumed for example, a dropout rate.

Of 20% and then we came up with basically the 240 patient.

The sample size that we needed so we are actually.

Recruited 263, we had very good success, especially at the end of the trial recruiting very fast so we had a little bit or recruitment and also the I think we haven't seen the dropout rate, we have seen less drop out so we feel very comfortable that.

Andreas Mueller: And also, I think we haven't seen the dropout rate; we have seen less dropout. So we feel very comfortable that the statistical assumptions, I think will lead us to success in this trial. And if it comes to effect, so maybe a comment from my end, if you look at the whole, the many molecules which are used there and also the biologics, if you have something like the effect size of a little bit or something like that, this would be a success, of course.

I think the statistical assumptions.

It will lead us to success in this trial.

If it comes into effect size, maybe comment from my end, if you look on the whole market.

The plenty molecules, which are used here and also on the biologics. If you have some things like the effect size that will be delayed a month or something like that this.

Andreas Mueller: And I think the biggest challenge in the last couple of years has been more as Andreas elaborated on the safety concerns for drugs like JAK inhibitors, which were unexpected and, I think, limiting their use there, specifically in this big gap between the current baseline medications like mesosilanes and steroids and so forth and the antibodies.

This would be a successive quarters and I think the biggest challenge in the last couple of years was more as Andre elaborated on the safety concerns for drug slate of JAK inhibitors, which were unexpected.

Unexpected NSA and limiting the use there.

<unk>.

This big gap between the.

The current baseline medications, like Netherlands lines, and steroids, and so forth and the antibodies.

Daniel Vitt: Got it. Thanks again for answering the question. Thank you, Nath. And thanks to everyone for your great questions. This concludes our question and answer session. I would like to turn the conference back over to Daniel for any closing remarks. Sure. Thank you, Jessica, and thanks to today's attendees for your insightful questions. We are very excited about the progress we achieved last year and the value inflection points we anticipate this year, including the phase two ulcerative colitis data for beta-fludenosperms in June, and the initial patient data for MU95 in the second half.

Got it and thanks again for your question.

Thank you Matt.

And thanks to everyone for you Greg.

Daniel Vitt: With that, I would like to close this call. Thank you very much for joining, and we're happy to answer any additional questions one-on-one. Also, from my side, thank you for joining Munich's fourth quarter and year-end 2021 earnings call today. The conference has now concluded. You may now disconnect.

Good question.

And this concludes our question and answer session I would like to turn the conference back over to Denis for any closing remarks.

Sure.

Thank you Jessica.

Thanks to today's attendees for your insightful questions we have.

Very excited about the progress we achieved last year and the value inflection points, we anticipate this year, including the phase III onset of colitis data will be defeated in Wisconsin in June and the initial patient data from <unk> 95 in the second half.

With this I would like to close today's call. Thank you very much for joining.

To answer any additional questions one of them.

Also from my side. Thank you for joining and your next fourth quarter and year end 2021 earnings call. Today. The conference has now concluded you may now disconnect.

Yeah.