Q4 2021 Eledon Pharmaceuticals Inc Earnings Call

March 24, 2022

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Greetings and welcome to you I'll, let dawn pharmaceuticals fourth quarter and full year 2021, operating and financial results Conference call.

Operator 2: Greetings, and welcome to Eledon Pharmaceuticals' Q4 and full year 2021 operating and financial results conference call. At this time, all participants are on a listen-only mode. A question and answer session will follow the formal presentation. If you'd like to ask a question, you may press star one on your telephone keypad. If anybody should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded today, 24 March 2022. I would now like to turn the conference call over to Paul Little, Chief Financial Officer of Eledon. Please go ahead.

Operator: Greetings, and welcome to Eledon Pharmaceuticals' Q4 and Full Year 2021 Operating and Financial Results Conference Call. At this time, all participants are on a listen-only mode. A question and answer session will follow the formal presentation. If you'd like to ask a question, you may press star one on your telephone keypad. If anybody should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded today, 24 March 2022. I would now like to turn the conference call over to Paul Little, Chief Financial Officer of Eledon. Please go ahead.

Greetings and welcome to Elladon Pharmaceutical's fourth quarter and full year 2021 Operating and Financial Results conference call.

At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation.

At this time all participants are in a listen only mode.

A question and answer session will follow the formal presentation.

If you'd like to ask a question, you may press star 1 on your telephone keypad.

If you'd like to ask a question you May press star one on your telephone keypad.

If anybody should require operator assistance during the conference, please press star zero on your telephone keypad.

If anybody should require operator assistance during the conference. Please press star zero on your telephone keypad.

As a reminder, this conference is being recorded today, March 24, 2022.

As a reminder, this conference is being recorded today March 24th.

2022 .

I would now like to turn the conference call over to Paul Little, Chief Financial Officer of Elladon. Please go ahead.

I'd now like to turn the conference call over to Paul Little Chief Financial Officer of Eligon. Please go ahead.

Good afternoon, and thank you for joining <unk> fourth quarter and full year 2021, operating and financial results Conference call.

Paul Little: Good afternoon, and thank you for joining Eledon's Q4 and full year 2021 operating and financial results conference call. I am joined on today's call by David-Alexandre Gros, Chief Executive Officer, Steven Perrin, President and Chief Scientific Officer, and Jeff Bornstein, Chief Medical Officer. Earlier today, Eledon issued a press release announcing financial results for the Q4 and full year ended December 31, 2021. You may access the release under the investors tab on our company's website at eledon.com. Before we begin, I would like to remind everyone that statements made during this conference call relating to Eledon's expected future performance, future business prospects or future events or plans may include forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995.

Paul Little: Good afternoon and thank you for joining Elladon's fourth quarter and full year 2021 Operating and Financial Results conference call.

Paul Little: I am joined on today's call by David Alexander-Groh, Chief Executive Officer, Steve Perrin, President and Chief Scientific Officer, and Jeff Bornstein, Chief Medical Officer. Earlier today, Eladon issued a press release.

I am joined on today's call by David Alexandra grow Chief Executive Officer, Steve Perrin, President and Chief Scientific Officer, and Jeff Bornstein, Chief Medical Officer.

Earlier today <unk> issued a press release.

Paul Little: announcing financial results for the fourth quarter and full year ended December 31st, 2021. You may access the release under the Investors tab on our company's website at Elladon.com.

Announcing financial results for the fourth quarter and full year ended December 31, 2021, you may access the release under the investors tab on your compete on our company's website at Amazon Dot Com.

Paul Little: Before we begin, I would like to remind everyone that statements made during this conference call relating to Elladon's expected future performance, future business prospects, or future events or plans may include forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995.

Before we begin I would like to remind everyone that statements made during this conference call relating to <unk> expected future performance future business prospects or future events or plans may include forward looking statements as defined under the private Securities Litigation Reform Act of 1995.

Paul Little: All such forward-looking statements are intended to be subject to the safe harbor protection provided by the Reform Act. Actual outcomes and results could differ materially from those forecasts due to the impact of many factors beyond the control of Eledon. Eledon expressly disclaims any duty to provide updates to its forward-looking statements, whether as a result of new information, future events, or otherwise. Participants are directed to the risk factors set forth in Eledon's reports filed with the US Securities and Exchange Commission. It's now my pleasure to pass the call to Eledon CEO, Dr. David-Alexandre Gros.

Paul Little: All such forward-looking statements are intended to be subject to the Safe Harbor Protection provided by the Reform Act.

All such forward looking statements are intended to be subject to the safe Harbor protection provided by the Reform Act.

Actual outcomes and results could differ materially from those forecast due to the impact of many factors beyond the control of all the data.

Paul Little: Actual outcomes and results could differ materially from those forecasts due to the impact of many factors beyond the control of Al-Adam.

<unk> expressly disclaims any duty to provide updates to its forward looking statements whether as a result of new information future events or otherwise participants are directed to the risk factors set forth in <unk> reports filed with the U S Securities and Exchange Commission.

Paul Little: Eladon expressly disclaims any duty to provide updates to its forward-looking statements, whether as a result of new information, future events, or otherwise.

Paul Little: Participants are directed to the risk factors set forth in Eladon's reports, followed with the U.S. Securities and Exchange Commission.

Speaker Change: It is now my pleasure to pass the call to Eldon CEO , Dr. David Alexander-Groh, DA.

It is now my pleasure to pass the call to Al Dor CEO , Dr. David Alexander grow D.

Yeah.

David Alexander-Groh: Thank you, Paul, and thank you all for joining the call today.

Thank you Paul and thank you all for joining the call today.

David-Alexandre Gros: Thank you, Paul, and thank you all for joining the call today. I'm pleased to report on the continued progress here at Eledon in Q4 2021 and into 2022, as we look ahead to a transformative year. We have assembled an exceptional team here, and we are all committed to realizing the broad therapeutic potential of Tegoprubart, formerly known as AT-1501. We recently announced the United States Adopted Names Council assigned Tegoprubart as the unique non-proprietary or generic name for AT-1501. This is the name that we will now use going forward. In 2022, we are executing our strategy to explore the breadth of Tegoprubart's potential by evaluating the molecule in up to four open label clinical trials across three therapeutic areas. Neurodegeneration, focusing on ALS, transplantation, focusing on kidney and islet cell transplantation, and autoimmunity, focusing on IgA nephropathy.

I'm pleased to report on the continued progress here at Ala Don in the fourth quarter of 2021 and into 2022 as we look ahead to a transformative year.

David Alexander-Groh: I'm pleased to report on the continued progress here at Elladon in the fourth quarter of 2021 and into 2022 as we look ahead to a transformative year.

David Alexander-Groh: We have assembled an exceptional team here, and we are all committed to realizing the broad therapeutic potential of Tagoprubart, formerly known as AT50.

We have assembled an exceptional team here and we are all committed to realizing the broad therapeutic potential up to go for Bart.

Formerly known as a T 15 O one.

David Alexander-Groh: We recently announced the United States Adopt-a-Names Council assigned to Go-Provart as the unique non-proprietary or generic name for AT-1501. This is the name that we will

We recently announced the United States adopted names Council assigned to go for Bart as the unique non proprietary or generic name for a 2015 O. One.

This is the name that we will now use going forward.

In 2022, we are executing our strategy to explore the breadth has to go through barts potential.

David Alexander-Groh: In 2022, we are executing our strategy to explore the breadth of the GoPro BART's potential.

David Alexander-Groh: by evaluating the molecule in up to four open-labeled clinical trials across three therapeutic areas, neurodegeneration,

By evaluating the molecule in up to four open label clinical trials across three therapeutic areas.

Neuro degeneration, focusing on a L. S transplantation, focusing on kidney in islet cell transplantation and auto immunity focusing on Iga nephropathy.

David Alexander-Groh: transplantation focusing on kidney and islet cell transplantation, and autoimmunity focusing on IgA nephropathy.

Before I turn over the call to Steve for additional details on each of these programs.

David-Alexandre Gros: Before I turn over the call to Steve for additional details on each of these programs, I'll provide a high-level update of our recent progress. In December of last year, we completed enrollment of the fourth and final cohort in our phase 2a study of tegoprubart in adults with ALS. We recently completed dosing and visits for all subjects in the study, and we thus remain on track to meet our goal and report out top-line data from this study in Q2. Turning to transplantation, we received regulatory clearance to initiate a phase 1b clinical trial in the United Kingdom, evaluating tegoprubart as a replacement for tacrolimus as an immunosuppressive regimen component for persons undergoing kidney transplantation. With this clearance, we are working on adding additional sites to the phase 1b clinical trial, which previously received regulatory clearance in Canada.

David Alexander-Groh: Before I turn over the call to Steve for additional details on each of these programs, I'll provide a high-level update.

I'll provide a high level update of our recent progress.

Steve Perrin: In December of last year, we completed enrollment of the fourth and final cohort in our Phase 2a study of togoprobart in adults with ALS.

In December of last year, we completed enrollment of the fourth and final cohort in our phase Iia study of to go for Bart in adults with a L. S.

We recently completed dosing in visits for all subjects in the study.

Steve Perrin: We recently completed dosing and visits for all subjects in the study.

Steve Perrin: and we thus remain on track to meet our goal and report out top-line data from this study in the second quarter of the year.

And we thus remain on track to meet our goal and report out top line data from this study in the second quarter of the year.

Turning to transplantation, we received regulatory clearance to initiate a phase <unk> clinical trial in the United Kingdom evaluating to go for Bart as a replacement for tanker limas as an immunosuppressive regimen component for persons undergoing kidney transplantation.

Steve Perrin: Turning to transplantation, we received regulatory clearance to initiate a phase 1B clinical trial in the United Kingdom, evaluating to goprobart as a replacement for tacrolimus as an immunosuppressive regimen component for persons undergoing kidney transplantation.

Steve Perrin: With this clearance, we are working on adding additional sites to the Phase 1b clinical trial which previously received regulatory clearance in Canada. Also

With this clearance we are working on adding additional sites to the phase <unk> clinical trial, which previously received regulatory clearance in Canada.

I'll also in kidney transplantation.

David-Alexandre Gros: Also in kidney transplantation, the US FDA requested last year that we conduct a non-human primate study evaluating tegoprubart monotherapy in the prevention of allograft rejection. While the trial is still ongoing, we have now transplanted all four animals and are happy to report our preliminary observations showing that to date, monotherapy tegoprubart successfully prevented transplant rejection in a manner consistent with both historical anti-CD40 ligand antibodies, as well as with our prior experience with tegoprubart in a non-human primate islet cell transplantation model. Next, we received IND clearance from the FDA to proceed with a Phase 2 clinical trial to assess tegoprubart for the prevention of allograft rejection in patients undergoing islet cell transplantation for the treatment of type 1 diabetes.

Steve Perrin: The U.S. FDA requested last year that we conduct a non-human primate study evaluating to go ProBart monotherapy in the prevention of allograft rejection.

The U S. F D. A requested last year that we conduct a nonhuman primate study evaluating to go for Bart mono therapy, and the prevention of allograft rejection.

While the trial is still ongoing we have now transplanted all for animals.

Steve Perrin: While the trial is still ongoing, we have now transplanted all four animals.

Steve Perrin: and are happy to report our preliminary observations showing that to date monotherapy to goprobar successfully prevented transplant rejection in a manner consistent with both historical anti-CD40 ligand antibodies.

And are happy to report our preliminary observations showing that to date mono therapy to go for bars successfully prevented transplant rejection in a manner consistent with both historical anti CD 40 ligand antibodies as well as with our prior experience with to go for Bart.

Steve Perrin: as well as with our prior experience with togoprobart in a non-human primate islet cell transplantation model.

In a nonhuman primate islet cell transplantation model.

Next we received <unk> clearance from the F. D. A to proceed with a phase Iia clinical trial to assess to go for Bart for the prevention of allograft rejection in patients undergoing islet cell transplantation for the treatment of type one diabetes.

Steve Perrin: Next, we received ID clearance from the FDA to proceed with a phase two-way clinical trial to Sestagoprubart for the prevention of allograft rejection in patients undergoing islet cell transplantation for the treatment of type 1 diabetes.

Steve Perrin: And finally, we received regulatory clearance in Australia, New Zealand, and Malaysia to initiate a phase 2A clinical trial evaluating to go for the treatment of IgA nephropathy.

And finally, we received regulatory clearance in Australia, New Zealand and in Malaysia to initiate a phase Iia clinical trial evaluating to Gopro Bart for the treatment of Iga nephropathy.

David-Alexandre Gros: Finally, we received regulatory clearance in Australia, New Zealand, and Malaysia to initiate a Phase 2 clinical trial evaluating tegoprubart for the treatment of IgA nephropathy, and we plan to expand the study into up to eight additional countries this year. I'll close by reiterating that 2022 is shaping up to be a transformative year for us, highlighted by multiple clinical trial catalysts, beginning with our ALS trial data readout in Q2, and followed by initial data readouts from our open label studies in renal transplantation, islet cell transplantation, and IgAN late this year. We look forward to sharing updates on our trials and further demonstrating tegoprubart's therapeutic potential. With that, I'll now turn the call over to Steven Perrin, our President and Chief Scientific Officer, to provide more details on our development programs. Steve?

Steve Perrin: And we plan to expand the study into up to eight additional countries this year.

And we plan to expand the study into up to eight additional countries. This year.

Okay.

Steve Perrin: I'll close by reiterating that 2022 is shaping up to be a transformative year for us, highlighted by multiple clinical trial catalysts.

I'll close by reiterating that 2022 is shaping up to be a transformative year for us highlighted by multiple clinical trial catalysts, beginning with our AOS trial data readout in the second quarter and followed by initial data Readouts from our open label studies in renal.

Steve Perrin: beginning with our ALS trial data readout in the second quarter, and followed by initial data readouts from our open label studies in renal transplantation, islet cell transplantation, and IGAN late this year.

Can I, let cell transplantation and I'll again late this year.

Steve Perrin: We look forward to sharing updates on our trials and further demonstrating the GoProBART's therapeutic potential.

We look forward to sharing updates on our trials and further demonstrating to gopro <unk> therapeutic potential.

Yeah.

With that I'll now turn the call over to Steve Perrin, Our President and Chief Scientific officer to provide more details on our development programs.

Steve Perrin: With that, I'll now turn the call over to Steve Perrin, our President and Chief Scientific Officer, to provide more details on our development programs.

Steve.

Thank you D a.

Steven Perrin: Thank you, DA. I'll begin my program updates with ALS, our most advanced clinical indication currently in a phase 2a study. Previous researchers found the co-stimulatory pathway to be an overactive pathway involved in more than half of people with ALS, and preclinical work has demonstrated that stopping or delaying immune system activation by the inhibition of CD40 ligand can improve muscle function, slow disease progression, and improve survival in an ALS animal model. This provides a strong scientific rationale for the development of tegoprubart in this indication. Our ALS trial is a 12-week open-label dose-escalating study with 13 sites in the United States and Canada. Enrollment in the fourth and final cohort was completed in December, and dosing recently completed for all subjects, which will allow us to report top-line data from all subjects in the study in Q2 2022.

Steve Perrin: Thank you, DA. I'll begin my program updates with ALS, our most advanced clinical indication currently in a phase 2a study. Previous researchers found the co-stimulatory pathway to be an overactive pathway involved in more than half of people with ALS, and preclinical work has demonstrated that stopping or delaying immune system activation by the inhibition of CD40 ligand can improve muscle function, slow disease progression, and improve survival in an ALS animal model. This provides a strong scientific rationale for the development of tegoprubart in this indication. Our ALS trial is a 12-week open-label dose-escalating study with 13 sites in the United States and Canada. Enrollment in the fourth and final cohort was completed in December, and dosing recently completed for all subjects, which will allow us to report top-line data from all subjects in the study in Q2 2022.

I'll begin my program updates with ALS, our most advanced clinical indication currently in a phase Iia study.

Steve Perrin: I'll begin my program updates with ALS, our most advanced clinical indication, currently in a phase 2a study.

Steve Perrin: Previous research has found the co-stimulatory pathway to be an overactive pathway involved in more than half of people with ALS, and preclinical work has demonstrated that stopping or delaying immune system activation by the inhibition of CD40 ligand can improve muscle function, slow disease progression, and improve survival in an ALS animal model.

Previous researchers pharma costumer Tory pathway to be an overactive pathway involved in more than half of people with ALS and preclinical work has demonstrated that stopping or delaying immune system activation by the inhibition of C. 40, ligand can improve muscle function slow disease progression and improve survival and <unk>.

Loss animal model. This provides a strong scientific rationale for the development of <unk> in this indication.

Steve Perrin: This provides a strong scientific rationale for the development of teguioprubat in this indication.

Steve Perrin: Our ALS trial is a 12-week, open-label, dose-escalating study with 13 sites in the United States and Canada.

Our <unk> trial is a 12 week open label dose escalating study with 13 sites in the United States and Canada.

Steve Perrin: Enrollment in the fourth and final cohort was completed in December .

Enrollment in the fourth and final cohort was completed in December .

And dosing recently completed for all subjects, which will allow us to report topline data from all subjects in the study.

Steve Perrin: and dosing recently completed for all subjects, which will allow us to report top-line data from all subjects in the study, and the second quarter.

In the second quarter of 2022.

Steve Perrin: Data from this study will include safety and tolerability of Tay-Go-Proobart, as well as multiple categories of biomarker endpoints, with each subject serving as their own control by comparing changes from base.

Steven Perrin: Data from this study will include safety and tolerability of tegoprubart, as well as multiple categories of biomarker endpoints, with each subject serving as their own control by comparing changes from baseline. In the first category of biomarkers, we'll assess CD40 ligand target engagement because mechanistically inhibiting CD40 ligand function has profound effects on B-cell maturation, antibody production, and antibody class switching. We anticipate we'll be able to assess the inhibition of CD40 ligand target engagement by tegoprubart with biomarkers of B-cell function. The second category of biomarkers are changes in pro-inflammatory chemokines and cytokines upregulated in people living with ALS. There is a long history of ALS data describing increases of pro-inflammatory signals in circulation, including TNF-α, MCP-1, IL-6, IL-1β, C-reactive protein, and EN-RAGE.

Steve Perrin: Data from this study will include safety and tolerability of tegoprubart, as well as multiple categories of biomarker endpoints, with each subject serving as their own control by comparing changes from baseline. In the first category of biomarkers, we'll assess CD40 ligand target engagement because mechanistically inhibiting CD40 ligand function has profound effects on B-cell maturation, antibody production, and antibody class switching. We anticipate we'll be able to assess the inhibition of CD40 ligand target engagement by tegoprubart with biomarkers of B-cell function. The second category of biomarkers are changes in pro-inflammatory chemokines and cytokines upregulated in people living with ALS. There is a long history of ALS data describing increases of pro-inflammatory signals in circulation, including TNF-α, MCP-1, IL-6, IL-1β, C-reactive protein, and EN-RAGE.

Data from this study will include safety and Tolerability of Teco prove art as well as multiple categories of biomarker end points with each subject serving as their own control by comparing changes from baseline.

Steve Perrin: In the first category of biomarkers, we'll assess CD40 ligand target engagement because mechanistically inhibiting CD40 ligand function has profound effects on B cell maturation, antibody production, and antibody class.

And the first category of Biomarkers will assess CD 40 ligand target engagement, because mechanistically inhibiting CD 40 ligand function has profound effects on b cell maturation antibody production and the antibody class switching.

We anticipate we'll be able to assess the inhibition of C. D 40 ligand target engagement by Chico for Bart with Biomarkers will be so function.

Steve Perrin: We anticipate we'll be able to assess the inhibition of CD40 ligand target engagement by to go provide with biomarker.

Steve Perrin: The second category of biomarkers are changes in pro-inflammatory chemokines and cytokines upregulated in people living with ALS.

The second category of Biomarkers or changes in pro inflammatory chemo kinds of cytokines up regulated in people living with a L. S.

There was a long history of L. S data, describing increases a pro inflammatory signaling and circulation, including TNF Alpha.

Steve Perrin: There is a long history of ALS data describing increases of pro-inflammatory signals in circulation, including TNF-alpha, MCP-1, IL-6, IL-1-beta.

C P. One IL six IL one beta.

C reactive protein they didn't reach.

Steve Perrin: We anticipate that in subjects with elevated levels, a blocking of CD40 ligand will result in an overall decrease of these pro-inflammatory markers and circuit.

Steven Perrin: We anticipate that in subjects with elevated levels, the blocking of CD40 ligand will result in an overall decrease of these pro-inflammatory markers in circulation. Finally, we will also assess exploratory endpoints, including changes in ALS Functional Rating Scale or ALSFRS, the levels of neurofilament light chain in circulation. We deem these exploratory endpoints given the uncertainty that 12 weeks of therapy is sufficient time to see an effect on these endpoints. I will add that seeing an effect on neurofilament light chain would particularly be promising because of this biomarker's association with neuron health. Moving on to our renal transplant program. CNIs have been shown to be beta cell toxic, thus causing new onset diabetes, and neurotoxic, thus causing neurological symptoms, including tremors. They also lead to hair loss and are associated with increased risk of heart disease, as well as increases in infections and malignancies.

Steve Perrin: We anticipate that in subjects with elevated levels, the blocking of CD40 ligand will result in an overall decrease of these pro-inflammatory markers in circulation. Finally, we will also assess exploratory endpoints, including changes in ALS Functional Rating Scale or ALSFRS, the levels of neurofilament light chain in circulation. We deem these exploratory endpoints given the uncertainty that 12 weeks of therapy is sufficient time to see an effect on these endpoints. I will add that seeing an effect on neurofilament light chain would particularly be promising because of this biomarker's association with neuron health. Moving on to our renal transplant program. CNIs have been shown to be beta cell toxic, thus causing new onset diabetes, and neurotoxic, thus causing neurological symptoms, including tremors. They also lead to hair loss and are associated with increased risk of heart disease, as well as increases in infections and malignancies.

We anticipate that in subjects with elevated levels of blocking of CD 40 ligand will result in an overall decrease of these pro inflammatory markers in circulation.

Steve Perrin: Finally, we will also assess exploratory endpoints, including changes in ALS Functional Rating Scale, or ALS-FRS, the levels of neurofilament light

Finally, we will also have sex exploratory endpoints, including changes in ALS functional rating scale or alysa for us.

The levels of neuro filament light chain in circulation.

Steve Perrin: and we deem these exploratory endpoints, given the uncertainty.

We deem these exploratory endpoints given the uncertainty.

Steve Perrin: that 12 weeks of therapy is sufficient time to see an effect on these.

The 12 weeks of therapy is sufficient time to see an effect on these endpoints, but I will add that seeing an effect on neuro filament light chain were particularly be promising because of this Biomarkers Association with neuron health.

Steve Perrin: But I will add that seeing an effect on neurofilament light chain would particularly be promising because of this biomarker's association with neuron health.

Moving onto a renal transplant program.

C&I has had been shown to be beta cell toxic, thus, causing new once a diabetes.

Steve Perrin: CNIs have been shown to be beta cell toxic, thus causing nuance at diabetes.

Steve Perrin: neurotoxic, thus causing neurological symptoms, including tremors.

Toxic, thus, causing neurological symptoms, including tremors payoffs.

Steve Perrin: They also lead to hair loss and are associated with increased risk of heart disease as well as increases in infections and malignancies.

They also lead to hair loss and are associated with increased risk of heart disease as well as increases in infections and malignancies.

Steven Perrin: Additionally, the chronic utilization of CNIs to prevent graft rejection has been associated with nephrotoxicity in up to 30% of patients after 1 year, up to 50% of patients after 5 years, and up to 100% of patients after 10 years, which can paradoxically shorten graft survival in the same organs that CNIs are being taken to protect. By improving the safety and tolerability of first-line immunosuppression, we believe that tegoprubart has the potential to both improve patient quality of life and overall morbidity in the near term, as well as ultimately improve graft survival rates in the longer term. We received regulatory clearances in both Canada and the United Kingdom to conduct a phase 1b clinical trial of tegoprubart in kidney transplantation.

Steve Perrin: Additionally, the chronic utilization of CNIs to prevent graft rejection has been associated with nephrotoxicity in up to 30% of patients after 1 year, up to 50% of patients after 5 years, and up to 100% of patients after 10 years, which can paradoxically shorten graft survival in the same organs that CNIs are being taken to protect. By improving the safety and tolerability of first-line immunosuppression, we believe that tegoprubart has the potential to both improve patient quality of life and overall morbidity in the near term, as well as ultimately improve graft survival rates in the longer term. We received regulatory clearances in both Canada and the United Kingdom to conduct a phase 1b clinical trial of tegoprubart in kidney transplantation.

Steve Perrin: Additionally, the chronic utilization of CNI's to prevent graft rejection has been associated with nephrotoxicity up to 30% of patients after one year, up to 50% of patients after five years, and up.

Additionally, the chronic utilization of C&I strawberry and graft rejection has been associated with nephrotoxicity up to 30% of patients. After one year up to 50% of patients after five years and up to a 100% of patients. After 10 years, which can paradoxically shortened graft survival and the same organs, let's see in ours are being taken to protect.

Steve Perrin: which can paradoxically shorten graft survival in the same organs that C and I's are being

Act.

Steve Perrin: By improving the safety and tolerability of first-line immunosuppression, we believe that tegoprubart has the potential to both improve patient quality of life and overall morbidity in the near term, as well as ultimately improve grass survival rates in the longer term.

By improving the safety and Tolerability of first line immunosuppression, we believe that <unk> has the potential to both improve patient quality of life and overall morbidity and the nurse in the near term as well as ultimately improve graft survival rates in the longer term.

We received regulatory clearances in both Canada, and the United Kingdom to conduct a phase <unk> clinical trial of gate to gate provide in kidney transplantation.

Steve Perrin: We received regulatory clearances in both Canada and the United Kingdom to conduct a phase one B clinical trial of TGAPRIVOT and kidney transplantation.

Steve Perrin: This open label study is planning to enroll 6 to 12 patients undergoing renal transplant.

Steven Perrin: This open label study is planning to enroll 6 to 12 patients undergoing renal transplant, with primary endpoints of safety and pharmacokinetics. As well as exploratory endpoints, including biopsy-proven acute rejection, change in eGFR, and biomarkers of inflammation and kidney rejection. Our goal is to demonstrate that tegoprubart can be safely utilized to replace CNIs as part of first-line immunosuppressive therapy in solid organ transplantation and prevent acute and long-term solid organ transplant rejection without the use of CNIs. We are currently looking to enroll our first patients and look forward to providing available data from this open label clinical study later this year. In parallel to this clinical trial, and as requested by the FDA as a prerequisite to a potential future US kidney transplant IND, in H2 2021, we initiated a non-human primate kidney transplant study with tegoprubart as a monotherapy.

Steve Perrin: This open label study is planning to enroll 6 to 12 patients undergoing renal transplant, with primary endpoints of safety and pharmacokinetics. As well as exploratory endpoints, including biopsy-proven acute rejection, change in eGFR, and biomarkers of inflammation and kidney rejection. Our goal is to demonstrate that tegoprubart can be safely utilized to replace CNIs as part of first-line immunosuppressive therapy in solid organ transplantation and prevent acute and long-term solid organ transplant rejection without the use of CNIs. We are currently looking to enroll our first patients and look forward to providing available data from this open label clinical study later this year. In parallel to this clinical trial, and as requested by the FDA as a prerequisite to a potential future US kidney transplant IND, in H2 2021, we initiated a non-human primate kidney transplant study with tegoprubart as a monotherapy.

This open label study is planning to enroll six to 12 patients undergoing renal transplant.

With primary endpoints of safety and pharmacokinetics as well as exploratory endpoints, including biopsy proven acute rejection change in Egfr and biomarkers of inflammation and kidney rejection.

Steve Perrin: primary endpoints of safety and pharmacokinetics, as well as exploratory endpoints, including biopsy-proven acute rejection, change in EGFR, and biomarkers of inflammation and kidney.

Steve Perrin: Our goal is to demonstrate that tegoprobar can be safely utilized to replace CNI's as part of first-line immunosuppressive therapy and solid organ transplantation and prevent acute and long-term solid organ transplant rejection without the use of

Our goal is to demonstrate that <unk> can be safely utilized to replace <unk> as part of first line immunosuppressive therapy, and solid organ transplantation and prevent acute and long term solid organ transplant rejection without the use of <unk>.

Steve Perrin: We are currently looking to enroll our first patients and look forward to providing available data from this open-labeled clinical study later this year.

We are currently looking to enroll our first patients and look forward to providing available data from this open label clinical study later this year.

In parallel to this clinical trial and as requested by the FDA as a prerequisite to a potential future U S. Kidney transplant. Indeed in the second half of 2021, we initiated a nonhuman primate kidney transplant study with <unk> as a monotherapy.

Steve Perrin: In parallel to this clinical trial, and as requested by the FDA as a prerequisite to a potential future U.S. kidney transplant IND, in the second half of 2021, we initiated a non-human primate kidney transplant study with Teguiprubart as a monotherapy.

Steven Perrin: The agency agreed that untreated animals would not be required given the large body of historical data demonstrating acute rejection in 6 to 8 days post-transplant in the absence of immunosuppression. As of today, we are pleased to share preliminary observations showing that monotherapy tegoprubart successfully prevented transplant rejection in all 4 animals in a manner consistent with both historical anti-CD40 ligand antibodies and with our prior experience with tegoprubart in an islet cell transplant model. Data collection from the study is ongoing, and we'll provide an update on the study results when the complete data set is available. Based on the data to date, this study further supports the strong preclinical evidence of anti-CD40 ligand antibodies, including tegoprubart, for the use of prevention of allograft transplant rejection.

Steve Perrin: The agency agreed that untreated animals would not be required given the large body of historical data demonstrating acute rejection in 6 to 8 days post-transplant in the absence of immunosuppression. As of today, we are pleased to share preliminary observations showing that monotherapy tegoprubart successfully prevented transplant rejection in all 4 animals in a manner consistent with both historical anti-CD40 ligand antibodies and with our prior experience with tegoprubart in an islet cell transplant model. Data collection from the study is ongoing, and we'll provide an update on the study results when the complete data set is available. Based on the data to date, this study further supports the strong preclinical evidence of anti-CD40 ligand antibodies, including tegoprubart, for the use of prevention of allograft transplant rejection.

The agency agree that untreated animals would not be required given the large body of historical data demonstrating acute rejection in six to eight days post transplant and the absence of immunosuppression.

Steve Perrin: The agency agreed that untreated animals would not be required given the large body of historical data demonstrating acute rejection in six to eight days post-transplant in the absence of immunosuppression.

Steve Perrin: As of today, we are pleased to share preliminary observations showing that monotherapy Tegoprubart successfully prevented transplant rejection in all four animals in a manner consistent with both historical anti-CD40 ligand antibodies.

As of today, we are pleased to share preliminary observations showing that monotherapy <unk> successfully prevented transplant rejection at all for animals in a manner consistent with both historical anti CD 40, ligand antibodies and with our prior experience with Teco pool, Barton and islet cell transplant model.

Steve Perrin: And with our prior experience with Chagall-ProBarton and islet cell transplantation...

Steve Perrin: Data collection from the study is ongoing and we'll provide an update on the study results when the complete data set is available.

Data collection from this study is ongoing and we will provide an update on the study results when the complete data set is available.

Steve Perrin: Based on the data to date, this study further supports the strong preclinical evidence of anti-CD40 ligand antibodies, including Tegoprubac for the use of prevention of allograft transplant rejection.

Based on the data to date. This study further supports the strong preclinical evidence of anti CD 40, ligand antibodies, including to Gopro bought for the use of prevention of Allograph transplant rejection.

Turning to islet cell transplantation, we are focusing on people living with high risk type one diabetes, who are on chronic treatment with exogenous insulin who experience severe swings in blood glucose levels hypoglycemic on awareness and associated Comorbidities.

Steven Perrin: Turning to islet cell transplantation, we are focusing on people living with high-risk Type I diabetes who are on chronic treatment with exogenous insulin and who experience severe swings in blood glucose levels, hypoglycemic unawareness, and associated comorbidities. Clinical trials conducted by the Immune Tolerance Network, as well as islet cell transplant experience in other countries, have demonstrated that islet cell transplants in patients with difficult-to-control Type I diabetes can maintain glycemic balance, reinstate metabolic control, and in some cases, even eliminate the need for exogenous insulin. However, the current use of calcineurin inhibitors, or CNIs, in the prevention of islet cell transplant rejection poses challenges, as CNIs are toxic towards transplanted islets, potentially resulting in significant islet cell loss post-transplant, and thus potentially leading to the requirement for multiple islet cell transplants in order to reduce insulin dependence and improve hypoglycemic unawareness.

Steve Perrin: Turning to islet cell transplantation, we are focusing on people living with high-risk Type I diabetes who are on chronic treatment with exogenous insulin and who experience severe swings in blood glucose levels, hypoglycemic unawareness, and associated comorbidities. Clinical trials conducted by the Immune Tolerance Network, as well as islet cell transplant experience in other countries, have demonstrated that islet cell transplants in patients with difficult-to-control Type I diabetes can maintain glycemic balance, reinstate metabolic control, and in some cases, even eliminate the need for exogenous insulin. However, the current use of calcineurin inhibitors, or CNIs, in the prevention of islet cell transplant rejection poses challenges, as CNIs are toxic towards transplanted islets, potentially resulting in significant islet cell loss post-transplant, and thus potentially leading to the requirement for multiple islet cell transplants in order to reduce insulin dependence and improve hypoglycemic unawareness.

Steve Perrin: Turning to islet cell transplantation, we are focusing on people living with high-risk type 1 diabetes.

Steve Perrin: who are on chronic treatment with exogenous insulin and who experience severe swings in blood glucose levels, hypoglycemic unawareness, and associated comorbidities.

Steve Perrin: Clinical trials conducted by the Immune Tolerance Network as well as islet cell transplants experienced in other countries have demonstrated that islet cell transplants in patients with difficult-to-control type 1 diabetes can maintain glycemic balance, reinstate metabolic control, and in some cases,

Clinical trials conducted by the immune tolerance network as well as islet cell transplants experience in other countries have demonstrated that islet cell transplant in patients with difficult to control type one diabetes can maintain glycemic balance reinstate metabolic control.

And in some cases, even eliminate the need for exhaustion of insulin.

Steve Perrin: However, the current use of current calcineurin inhibitors or CNIs in the prevention of islet cell transplant.

However, the use of the current use of current kelson earn inhibitors or <unk> in the prevention of violence, all transplant rejection poses challenges CNI are toxic towards transplanted islands potentially resulting in significant island, so loss post transplant, and thus potentially leading to the requirement for multiple wireless sole tranche.

Steve Perrin: poses challenges as C and I's are toxic towards transplanted islets.

Steve Perrin: potentially resulting in significant islet cell loss post-transplant.

Steve Perrin: and thus potentially leading to the requirement for multiple islet cell transplants in order to reduce insulin dependence.

In order to reduce insulin dependence and improve hypoglycaemic on awareness.

Steven Perrin: In October 2021, we presented additional non-human primate data at the International Pancreas and Islet Transplant Association World Congress, showing a non-human primate model of islet cell transplanted animals treated with tegoprubart versus those treated with standard of care, including CNIs. The results demonstrated longer graft survival, better graft function and glycemic control, and post-transplant weight gain, indicating better overall health in animals treated with tegoprubart. Also, in Q4 of 2021, we announced FDA clearance of our IND, which allows us to pursue development of tegoprubart in islet cell transplant in the United States. While not only opening up a new geography for this indication, this regulatory clearance represents the first US-approved IND for a therapeutic in islet cell transplantation.

Steve Perrin: In October 2021, we presented additional non-human primate data at the International Pancreas and Islet Transplant Association World Congress, showing a non-human primate model of islet cell transplanted animals treated with tegoprubart versus those treated with standard of care, including CNIs. The results demonstrated longer graft survival, better graft function and glycemic control, and post-transplant weight gain, indicating better overall health in animals treated with tegoprubart. Also, in Q4 of 2021, we announced FDA clearance of our IND, which allows us to pursue development of tegoprubart in islet cell transplant in the United States. While not only opening up a new geography for this indication, this regulatory clearance represents the first US-approved IND for a therapeutic in islet cell transplantation.

Steve Perrin: In October 2021, we presented additional non-human primate data at the International Pancreas and Islet Cell Transplantation World Congress, showing a non-human primate model of islet cell transplanted animal.

In October 2021, we presented additional nonhuman primate data at the international Pancreas, and islet cell transplantation World Congress, showing a nonhuman primate model of violence, all transplants at animals treated with <unk> versus those treated with standard of care, including Cni's the results demonstrated longer graft survival.

Steve Perrin: treaty with Tegelprobat versus those treaty with standard of care, including CNI.

Steve Perrin: The results demonstrated longer graft survival, better graft function, and glycemic control.

So better graph function and glycemic control and post transplant, waking, indicating better overall health and animals treated with Teikoku Barton.

Steve Perrin: post-transplant weight gain indicating better overall health in animals treated with Tegel.

Also in the fourth quarter of 2021, we announced FDA clearance of our IND, which allows us to pursue development of takeover Barton I would so transplant in the United States.

Steve Perrin: Also in the fourth quarter of 2021, we announced FDA clearance of our IND which allows us to pursue development of tegobrevartin islet cell transplant in the United

Steve Perrin: Well, not only opening up a new geography for this indication, this regulatory clearance represents the first U.S. approved IND for a therapeutic and islet cell transplantation. Importantly, the IND represents a

Well not only opening up a new geography for this indication. This regulatory clearance represents the first U S approved IMD for a therapeutic and I'll, let cell transplantation.

Steven Perrin: Importantly, the IND represents a similar dosing level as we are using in our current ex-US transplantation studies and expect to use in future kidney transplantation studies. Primary endpoints will include safety and tolerability, glucose control, insulin independence, reduction of HbA1c, graft survival, and graft function. We will also be assessing hypoglycemic unawareness events as well as renal function. We expect to open our US site in the middle of the year and to report available data from this open label study late this year. I'll wrap up with our program in IgA nephropathy, or IgAN. IgAN is the leading cause of glomerulonephritis, a chronic autoimmune condition resulting in progressive kidney damage. Onset usually occurs in younger adults, often while the patient's in their twenties, and is characterized by the presence of protein in the urine.

Steve Perrin: Importantly, the IND represents a similar dosing level as we are using in our current ex-US transplantation studies and expect to use in future kidney transplantation studies. Primary endpoints will include safety and tolerability, glucose control, insulin independence, reduction of HbA1c, graft survival, and graft function. We will also be assessing hypoglycemic unawareness events as well as renal function. We expect to open our US site in the middle of the year and to report available data from this open label study late this year. I'll wrap up with our program in IgA nephropathy, or IgAN. IgAN is the leading cause of glomerulonephritis, a chronic autoimmune condition resulting in progressive kidney damage. Onset usually occurs in younger adults, often while the patient's in their twenties, and is characterized by the presence of protein in the urine.

<unk> the R&D represents a similar dosing level.

Steve Perrin: we are using in our current U.S. transplantation studies and expect to use in future kidney transplants.

As we are using in our current ex U S transplantation studies and expect to use in future kidney transplantation studies.

Steve Perrin: Primary endpoints will include safety and tolerability, glucose control, insulin independence.

Primary end points will include safety and Tolerability glucose control insulin independence reduction of HBA, when see graft survival and graft function.

Steve Perrin: reduction of HbA1c, graft survival, and graft function.

Steve Perrin: We will also be assessing hypoglycemic and awareness events as well as.

We will also be assessing hypoglycemic on awareness events as well as renal function.

Steve Perrin: We expect to open our U.S. site in the middle of the year and to report available data from this open-label study later.

We expect to open our U S site in the middle of the year and to report available data from this open label study late this year.

Steve Perrin: I'll wrap up with our program in IgE nephropathy or IgE.

I'll wrap up with our program in Iga nephropathy or IGN.

Steve Perrin: Igaine is the leading cause of glomerulonephritis, a chronic autoimmune condition resulting in progressing kidney.

<unk> is the leading cause of glomerulonephritis, a chronic autoimmune condition, resulting in progressing kidney damage.

Steve Perrin: Onset usually occurs in younger adults, often while the patient's in their 20s, and is characterized by the presence of protein in the urine.

It usually occurs in younger adults often while the patients in their twenties and is characterized by the presence of protein in the urine.

Steven Perrin: Currently, approximately 40% of patients will progress to end-stage renal disease within 15 to 20 years, indicating a significant unmet need because the treatment for end-stage renal disease is lifelong dialysis or kidney transplant, both of which bear significant patient and healthcare system costs. We believe there is a strong mechanistic rationale for pursuing CD40 Ligand inhibition in IgAN, since tegoprubart has the potential ability to modify disease progression by reducing immune complex formation, immune cell infiltration, and subsequent complement activation in the kidney. We recently received regulatory clearance to initiate a phase 2a clinical trial of tegoprubart in the treatment of IgAN in Australia, New Zealand, and Malaysia, with plans to expand the study in Europe, North America, and Asia in the coming months.

Steve Perrin: Currently, approximately 40% of patients will progress to end-stage renal disease within 15 to 20 years, indicating a significant unmet need because the treatment for end-stage renal disease is lifelong dialysis or kidney transplant, both of which bear significant patient and healthcare system costs. We believe there is a strong mechanistic rationale for pursuing CD40 Ligand inhibition in IgAN, since tegoprubart has the potential ability to modify disease progression by reducing immune complex formation, immune cell infiltration, and subsequent complement activation in the kidney. We recently received regulatory clearance to initiate a phase 2a clinical trial of tegoprubart in the treatment of IgAN in Australia, New Zealand, and Malaysia, with plans to expand the study in Europe, North America, and Asia in the coming months.

Currently approximately 40% of patients will progress to end stage renal disease within 15 to 20 years, indicating a significant unmet need because the treatment for end stage renal diseases lifelong dialysis or kidney transplant, both of which bear significant patients and health care system cost.

We believe there is a strong mechanistic rationale for pursuing city 40 ligand inhibition in Oregon since to go prove out has the potential ability to modify disease progression by reducing immune complex formation immune cell infiltration and subsequent complement activation in the kidney.

Steve Perrin: We believe there is a strong mechanistic rationale for pursuing CD40 ligand inhibition in IgAN since tegoprobart has the potential ability to modify disease progression by reducing immune complex formation, immune cell infiltration, and subsequent complement activation.

Steve Perrin: We recently received regulatory clearance to initiate a phase two-way clinical trial of tegoprobar in the treatment of IGAN in Australia, New Zealand, and Malaysia.

We recently received regulatory clearance to initiate a phase Iia clinical trial of <unk> in the treatment of IGN in Australia, New Zealand and Malaysia with plans to expand the study in Europe , North America, and Asia in the coming months.

Steve Perrin: plans to expand the study in Europe , North America, and Asia in the coming.

Steve Perrin: Planned Phase 2a is an open-label study expected to enroll up to 42 patients with a confirmed diagnosis of IgAN and significant...

Steven Perrin: The planned phase IIa is an open-label study expected to enroll up to 42 patients with a confirmed diagnosis of IgAN and significant proteinuria. Patients will be subsequently enrolled in two different dose cohorts and receive tegoprubart by IV infusion. The primary endpoint will be percent reduction in proteinuria at 24 weeks compared to baseline. We are in the process of opening up sites in multiple countries and recruiting our first patients. We look forward to providing initial data from this open-label phase IIa study later this year. With that, I'll now turn the call over to Paul for a financial update.

Steve Perrin: The planned phase IIa is an open-label study expected to enroll up to 42 patients with a confirmed diagnosis of IgAN and significant proteinuria. Patients will be subsequently enrolled in two different dose cohorts and receive tegoprubart by IV infusion. The primary endpoint will be percent reduction in proteinuria at 24 weeks compared to baseline. We are in the process of opening up sites in multiple countries and recruiting our first patients. We look forward to providing initial data from this open-label phase IIa study later this year. With that, I'll now turn the call over to Paul for a financial update.

The planned phase II is an open label study expected to enroll up to 42 patients with a confirmed diagnosis of IGN and significant proteinuria pace.

Steve Perrin: Patients will be subsequently enrolled in two different dose courts and receive Tegelprobarbiotin infusion.

Patients will be subsequently enrolled in two different dose cohorts and receive teco rhubarb pie of infusion.

The primary endpoint will be percent reduction in proteinuria at 24 weeks compared to baseline.

Steve Perrin: The primary end point will be percent reduction in protein urea at 24 weeks compared to.

Steve Perrin: We are in the process of opening up sites in multiple countries and recruiting our first patient.

We are in the process of opening up sites in multiple countries and recruiting our first patients. We look forward to providing initial data from this open label Phase III study later this year.

Steve Perrin: We look forward to providing initial data from this open-label face-to-face study later this year. With that, I'll now turn the call.

With that I'll now turn the call over to Paul for our financial update.

Steve Perrin: In addition to the financial results summarized in our press release, you can find additional information in our Form 10-K , which we will file later today.

Thank you Steve in addition to the financial results summarized in our press release, you can find additional information in our Form 10-K , which we will file later today.

Paul Little: Thank you, Steve. In addition to the financial results summarized in our press release, you can find additional information in our Form 10-K, which we will file later today. The company reported a net loss of $8.8 million, or $0.59 per share for the three months ended December 31, 2021, compared to a net loss of $5.9 million or $2.13 for the same period in 2020. Research and development expenses were $6.2 million for the three months ended December 31, 2021, compared to $3 million for the comparable period in 2020, which is an increase of $3.2 million.

Steve Perrin: The company reported a net loss of $8.8 million, or $0.59 per share, for the three months into December 31, 2021, compared to a net loss of $5.9 million, or $2.13, for the same period in 2020.

Company reported a net loss of $8 8 million or <unk> 59 per share for the three months ended December 31, 2021, compared to a net loss of $5 9 million or $2 13 for the same period of 2020.

Steve Perrin: Research and development expenses were $6.2 million for the three months ended, December 31, 2021, compared to $3 million for the comparable period in 2020, which is an increase of $3.2 million. The increase in R&D spend primarily reflects an increase in clinical development costs and costs related to the production of clinical trial materials as we advance Tegel-PUBART into Global Phase I and Phase II clinical trials.

Research and development expenses were $6 2 million for the three months ended December 31, 2021, compared to $3 million for the comparable period in 2020, which was an increase of $3 2 million. The increase in R&D spend primarily reflects an increase in clinical development costs and costs related to the production.

Paul Little: The increase in R&D spend primarily reflects an increase in clinical development costs and costs related to the production of clinical trial materials as we advance tegoprubart into global phase 1 and phase 2 clinical trials. I'll turn to a few key financial metrics for the full year to date. The company reported a net loss of $34.5 million or $2.33 per share for the year ended December 31, 2021, compared to a net loss of $22.8 million or $15.72 per share in 2020. R&D expenses were $23.7 million for the year ended December 31, 2021, compared to $6.1 million for 2020, an increase of $17.6 million.

Of clinical trial materials, as we advance <unk>, Bart and two global phase, one and phase II clinical trials.

Speaker Change: I'll turn to a few key financial metrics for the full year to date. The company reported a net loss of $34.5 million, or $2.33 per share, for the year ended December 31st, 2021, compared to a net loss of $22.8 million, or $15.72 per share, in 2020.

I will turn to a few key financial metrics for the full year to date. The company reported a net loss of $34 5 million or $2 33 per share for the year ended December 31, 2021, compared to a net loss of $22 8 million or $15 72 per share in 2020.

Speaker Change: R&D expenses were $23.7 million for the year ended December 31, 2021, compared to $6.1 million for 2020, an increase of $17.6 million.

R&D expenses were $23 7 million for the year ended December 31, 2021, compared to $6 1 million for 2020, an increase of $17 6 million.

Speaker Change: The increase in the research and development spend primarily reflects an increase in clinical development costs and costs related to the production of clinical trial materials as we continue to advance our technical proof of art program.

Paul Little: The increase in research and development spend primarily reflects an increase in clinical development costs and costs related to the production of clinical trial materials as we continue to advance our tegoprubart programs. G&A expenses were $13.1 million for the year ended December 31, 2021, compared to $10.1 million for 2020, an increase of $3 million. The increase in G&A spend primarily reflects an increase in stock-based compensation costs and other personnel costs associated with increased headcount and an increase in other general operating expenses. This cost was partially offset by a decrease in merger-related costs of $2.9 million that we incurred in 2020 as a result of the Anelixis acquisition.

The increase in research and development spend primarily reflects an increase in clinical development costs and cost related to the production of clinical trial materials as we continue to advance our <unk> programs.

Speaker Change: G&A expenses were $13.1 million for the year ended December 31, 2021, compared to $10.1 million for 2020, an increase of $3 million. The increase in G&A spend primarily reflects an increase in stock-based compensation costs and other personnel costs associated with increased headcount and an increase in other general operating expenses.

G&A expenses were $13 1 million for the year ended December 31, 2021, compared to $10 1 million for 2020, an increase of 3 million. The increase in G&A spend primarily reflects an increase in stock based compensation costs and other personnel costs associated with increased headcount and an increase in <unk>.

Other general operating expenses.

Speaker Change: This cost was partially offset by a decrease in merger-related costs of $2.9 million that we incurred in 2020 as a result of the Analexis acquisition.

This cost was partially offset by a decrease in merger related costs of $2 $9 million that we incurred in 2020 as a result of the <unk> acquisition.

We ended the year with approximately $84 8 million in cash and cash equivalents, which we expect to be sufficient to fund operations. As currently planned into 2024, thereby allowing us to generate clinical data across all four of our currently planned trials and.

Paul Little: We ended the year with approximately $84.8 million in cash and cash equivalents, which we expect to be sufficient to fund operations as currently planned into 2024, thereby allowing us to generate clinical data across all four of our currently planned trials and still have over one year of cash on hand. With that financial update, let me turn the call back over to DA.

Speaker Change: We ended the year with approximately $84.8 million in cash and cash equivalents, which we expect to be sufficient to fund operations as currently planned into 2024, thereby allowing us to generate clinical data across all four of our currently planned trials and still have over one year of cash on hand.

Still have over one year of cash on hand.

Speaker Change: With that financial update, let me turn the call back over to DA.

That financial update let me turn the call back over to da.

Thanks, Paul.

David-Alexandre Gros: Thanks, Paul. In summary, we are proud of the progress we have made across our programs and look forward to catalyst-rich 2022, beginning with a top-line readout of our phase 2A ALS trial in Q2. We have secured regulatory clearances and are well-positioned to begin our evaluation of tegoprubart in three additional distinct indications in renal and islet cell transplantation, and IgAN. With cash to fund operations into 2024, we are well-capitalized to move these programs forward and closer to patients in need. We look forward to providing clinical updates through the remainder of the year and to building upon the strong base of evidence for targeting the CD40 Ligand pathway to transform therapeutics for patients undergoing organ or cellular transplantation or living with autoimmune disease or ALS. With that, I will now ask the operator to begin our Q&A session. Operator?

DA: In summary, we are proud of the progress we have made across our programs and look forward to Catalyst-Rich 2022, beginning with a top-line readout of our Phase 2a ALS trial in the second quarter.

In summary, we are proud of the progress we have made across our programs and look forward to catalyst rich 2022, beginning with the top line readout of our phase Iia ALS trial in the second quarter.

We have secured regulatory clearances and are well positioned to begin our evaluation and to go per box.

DA: We have secured regulatory clearances and are well-positioned to begin our evaluation and to go provide.

In.

Three additional distinct indications in renal and I'll, let cell transplantation and again.

DA: three additional distinct indications in renal and islet cell transplantation and IGAMS.

With cash to fund operations into 2024, we are well capitalized to move these programs forward and closer to patients in need.

DA: With cash to fund operations into 2024, we are well capitalized to move these programs forward and closer to patients in need.

DA: We look forward to providing clinical updates through the remainder of the year and to building upon the strong base of evidence for targeting the CD40 ligand.

We look forward to providing clinical updates through the remainder of the year and to building upon the strong base of evidence for targeting the CD 40 ligand pathway to transform therapeutics for patients undergoing oregon or seller transplantation or living with autoimmune disease or <unk>.

DA: to transform therapeutics for patients undergoing organ or cellular transplantation.

DA: or living with autoimmune disease or ALS.

Yes.

DA: With that, I will now ask the operator to begin our Q&A session.

With that I'll now ask the operator to begin our Q&A session.

Operator.

Speaker Change: Thank you. Ladies and gentlemen, at this time, we will be conducting a question and answer session. If you'd like to ask a question, you may press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key.

Operator 2: Thank you. Ladies and gentlemen, at this time, we will be conducting a question and answer session. If you'd like to ask your question, you may press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. Our first question comes from the line of Rami Katkhuda with LifeSci Capital. Please proceed with your question.

Operator: Thank you. Ladies and gentlemen, at this time, we will be conducting a question and answer session. If you'd like to ask your question, you may press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. Our first question comes from the line of Rami Katkhuda with LifeSci Capital. Please proceed with your question.

Thank you.

Ladies and gentlemen at this time and we will be conducting a question and answer session. If you'd like to ask a question you May press star one on your telephone keypad.

Confirmation tone will indicate your line is in the question queue.

You May press Star two if you would like to remove your question from the Q4 participants using speaker equipment. It may be necessary to pick up your handset before pressing that starkey.

Speaker Change: Our first question comes from the line of Rami Kakuda with Lifestyle Capital. Please proceed with your question.

Our first question comes from the line of Remy Cuda with lifestyle capital. Please proceed with your question.

Hey, guys. Thanks for taking my questions. A couple of quick ones for me that I get in AOS are pro inflammatory biomarkers elevated and all patients who are just rapid progresses and has the correlation between these inflammatory biomarkers and clinical outcomes been evaluated before.

Rami Katkhuda: Hey, guys. Thanks for taking my questions. A couple of quick ones from me. I guess in ALS, are pro-inflammatory biomarkers elevated in all patients or just rapid progressors? And has the correlation between these inflammatory biomarkers and clinical outcomes been evaluated before?

Rami Kakuda: But I guess in ALS, are pro-inflammatory biomarkers elevated in all patients or just rapid progressors, and has the correlation between these inflammatory biomarkers and clinical outcomes been evaluated before?

Speaker Change: Hey, Rami, great to talk to you. For the question on ALS, let me turn that over to...

Hey, Rami great to talk to you for the question on a L. S. Let me turn that over to Steve.

David-Alexandre Gros: Hey, Rami. Great to talk to you. For the question on ALS, let me turn that over to Steve.

Oh, Hey, Rami.

Steven Perrin: Hey, Rami. Levels of pro-inflammatory markers have been reported in about 80% of people living with ALS, but it does not appear to be associated with progression rate, at least not in a way that's statistically meaningful that I've seen. There also has not been a study with therapeutic intervention with a priori biomarker plans to look at pro-inflammatory markers and see how a therapeutic treatment changes them. We're one of the first to be doing that.

Rami Kakuda: Yeah, so levels of pro-inflammatory markers have been reported in about 80% of people living with ALS, but it does not appear to be associated with progression rate.

Steve Perrin: Hey, Rami. Levels of pro-inflammatory markers have been reported in about 80% of people living with ALS, but it does not appear to be associated with progression rate, at least not in a way that's statistically meaningful that I've seen. There also has not been a study with therapeutic intervention with a priori biomarker plans to look at pro-inflammatory markers and see how a therapeutic treatment changes them. We're one of the first to be doing that.

Yeah, so levels of pro inflammatory markers have been reported in about 80% of people living with ALS, but it does not appear to be associated with progression rate at.

Rami Kakuda: at least not in a way that's statistically meaningful that I've seen. There also has not been a study with therapeutic intervention with a priori biomarker plans to look at pro-inflammatory markers and see how a therapeutic treatment changes them. So we're one of the first to be doing that.

At least not not in a way that's statistically meaningful data that I've seen.

There also has not been a study.

With therapeutic intervention with a priori.

Biomarker plans to look at pro inflammatory markers and see how a therapeutic treatment changes for them. So we're one of the first to be doing that.

Got it and then shifting gears, a little but for both kidney in islet cell transplantation can you kind of remind us how many patients worth of data you are looking to gather before you'd look at share results.

Rami Katkhuda: Got it. Shifting gears a little, but for both kidney and islet cell transplantation, can you kind of remind us how many patients worth of data you're looking to gather before you'd look to share results?

Rami Kakuda: gears a little, but for both kidney and islet cell transplantation, can you kind of remind us how many patients' worth of data you're looking to gather before you'd like to share results?

Sure. So for both of those indications will share the results that we have.

David-Alexandre Gros: Sure. For both of those indications, we'll share the results that we have, towards the end of the year. What's nice with these indications, and it's true across IgAN, islet cell, and kidney transplantation, is that even a small number of patients can be meaningful, and data can be generated quite quickly. For IgAN, we're looking at 24 weeks of data, and for islet cell or kidney transplantation, data even as short as 90 days can be meaningful. We expect to have probably a handful of patients in the kidney transplantation trial, in low single digits in islet cell.

Speaker Change: Sure, so for both of those indications, we'll share the results that we have.

Speaker Change: towards the end of the year. What's nice with these indications, and it's true across IGAN, islet cell, and kidney transplantation is that even a small number of patients can be meaningful, and data can be generated quite quickly. So, for IGAN, we're looking at 24 weeks of data.

Towards the end of the year, what's what's nice with these indications it's true cross.

Across all again islet cell and kidney transplantation is that even a small number of patients can be meaningful and data can be generated quite quickly. So for <unk>. We're looking at 24 weeks of data.

Speaker Change: and for islet cell or kidney transplantation.

And for islet cell or kidney transplantation.

Yeah.

Speaker Change: Data even as short as 90 days can be meaningful.

Data, even as short as 90 days can be meaningful.

Okay.

Speaker Change: So, we expect we expect to have probably a handful of patients in the kidney transplantation trial and the low single digits in an islet cell.

So we expect we expect to have.

A handful of patients in the kidney transplantation trial.

Uh huh.

Low single digits in an outlet center.

Yeah.

Got it thank you guys.

Rami Katkhuda: Got it. Thank you, guys.

Our next question comes from the line of Thomas Smith with SBB Leerink. Please proceed with your question.

Operator 2: Our next question comes from the line of Thomas Smith with SVB Leerink. Please proceed with your question.

Operator: Our next question comes from the line of Thomas Smith with SVB Leerink. Please proceed with your question.

Speaker Change: Our next question comes from the line of Thomas Smith with SVB Lyrinc. Please proceed with your question.

Okay.

Thomas Smith: Hey, guys. Good afternoon. Thanks for taking the questions. Just a couple on ALS. I guess, can you just walk us through any remaining gating steps here to the top line data? Like, is it mainly just data scrubbing and analyses, or is there still some degree of data collection that's ongoing or any other, you know, steps that are outstanding there? And then, can you talk a little bit about the data that you expect to report at the top line versus data that either might not be available for the top line or that you're thinking about saving for presentation in a scientific forum?

Thomas Smith: Hey guys, good afternoon. Thanks for taking the questions. Just a couple on on ALS. I guess you just walk us through any remaining game steps here to the top line data. Is it mainly just data scrubbing and analysis or is there still

Hey, guys. Good afternoon, thanks for taking the questions just a couple on an.

So I guess can you just walk us through any remaining gating steps here to the top line data is it mainly just data scrubbing and analyses or is there still.

Thomas Smith: some degree of data collection that's ongoing or any other, you know, steps that are outstanding there. And then can you talk a little bit about the data that you expect to report at the top line versus data that either might not be available for the top line or that you're thinking about saving for presentation in a scientific forum?

Some degree of data collection is ongoing or any others.

That are outstanding there and then.

Can you talk a little bit about the data that you expect to report at the topline versus data that either might not be available for the top line or that you're thinking about saving for presentation at a scientific forum.

Yeah.

Yes.

Alright.

David-Alexandre Gros: Right. Thanks for the question. Let me turn that over to Steve and Jeff.

Speaker Change: Thanks for the question. Let me turn that over to

Thanks for the question, let me turn that over.

Steve and Jeff.

I mean, Jeff why don't you why don't you comment on the data collection and timing for last subject being dose et cetera.

Steven Perrin: I mean, Jeff, why don't you comment on the data collection and timing for, you know, last subject being dosed, et cetera?

Steve Perrin: I mean, Jeff, why don't you comment on the data collection and timing for, you know, last subject being dosed, et cetera?

Speaker Change: I mean, Jeff, why don't you comment on the data collection and timing for, you know, last subject being dose, et cetera.

Jeff Bornstein: All right. Thank you, Steve. We've completed dosing and actually just completing follow-up on the patients in the final cohort of the study. There's no further intervention and no further data collection that is required at this point. It is now a matter of finalizing data entry, data cleaning, and generation of the final tables, figures, and listings. We anticipate having all of that in the near term and then being able to analyze the data and then disclose it.

Alright, Thank you Steve.

Jeff Bornstein: All right, thank you, Steve. So, we've completed dosing and actually...

So we've completed we've completed dosing in actually.

Just completing follow up on the patients in the final cohort of the study.

Jeff Bornstein: just completing follow-ups on the patients in the final cohort of the study.

Jeff Bornstein: And so, there's no further intervention and no further data collection that is required at this point. It is now a matter of data, finalizing data entry, data cleaning, and generation of data.

And so there is no further intervention and no further data collection that is required at this point. It is now a matter of.

Data finalizing data entry data cleaning and generation of the.

Jeff Bornstein: final table figures and listings. So we anticipate having all of that.

A final table figures in listings so we.

We anticipate having all of that.

Jeff Bornstein: in the near term and then being able to analyze the data and then disclose it.

In the near term and then being able to analyze the data and then disclose.

Yeah, and just to just add one comment to that Tom is I mean, the cohort four as Jeff just indicated just came down so there is.

Steven Perrin: Yeah. Just to add one comment to that, Tom, I mean, the cohort four, as Jeff just indicated, just came down. There is, you know, bio samples that still need to be sent out, processed for biomarkers, et cetera. There is a little. There's no more sample collection involved in the study 'cause the last subject was dosed in last visit. There is still some data collection that's going to happen with external vendors.

Steve Perrin: Yeah. Just to add one comment to that, Tom, I mean, the cohort four, as Jeff just indicated, just came down. There is, you know, bio samples that still need to be sent out, processed for biomarkers, et cetera. There is a little. There's no more sample collection involved in the study 'cause the last subject was dosed in last visit. There is still some data collection that's going to happen with external vendors.

Speaker Change: Yeah, and just to just add one comment to that, Tom, is, I mean, the cohort for, as Jeff just indicated, just came down. So there is, you know, bio samples that still need to be sent out, processed for biomarkers, etc. So there is a little, there's no more sample collection involved in the study because the last subject was dosed in last visit, but there's still some data collection that's going to happen with external vendors.

<unk> samples would still need to be sent out process for biomarkers et cetera. So there there is a little there's no more sample collection involved in the study because the last subject was dosed in Las visit but there are still some day.

Data collection, that's going to happen with external vendors.

Okay. Great. That's helpful. And then can you comment a little bit I guess just in terms of your expectations for the data that you think will be available for topline versus maybe some of the the datasets that you anticipate.

Speaker Change: Okay, great. Yeah, that's helpful. And then can you comment a little bit, I guess, just in terms of your expectations for the data that you think will be available for top line versus maybe some of the data sets that you anticipate either wouldn't be available or that you would look to save for a presentation in a scientific forum?

Thomas Smith: Okay, great. Yeah, that's helpful. Then can you comment a little bit, I guess, just in terms of your expectations for the data that you think will be available for top line versus maybe some of the data sets that you anticipate either wouldn't be available or that you would look to save for a presentation in the scientific forum?

Either wouldn't be available or that you would look to stay for a presentation at a scientific forum.

Yeah.

Steve.

Steven Perrin: Dave? I mean, our intention, I think, is primary endpoint of the study, as you know, was safety tolerability, and obviously we're looking at drug levels and pharmacokinetics. This was our first multiple ascending dose study. In addition to that, as you know, we're looking at multiple different biomarker arms, and we intend to correlate the biomarker arms with drug levels, et cetera. We kind of need a completed and compiled data package, right, to be able to interpret our biomarker data. I mean, obviously we'd love to aggregate all of that data and after the top line data's written up and the CSR is done, we'd obviously love to present this at a scientific conference.

David-Alexandre Gros: Dave?

Yeah.

Steve Perrin: I mean, our intention, I think, is primary endpoint of the study, as you know, was safety tolerability, and obviously we're looking at drug levels and pharmacokinetics. This was our first multiple ascending dose study. In addition to that, as you know, we're looking at multiple different biomarker arms, and we intend to correlate the biomarker arms with drug levels, et cetera. We kind of need a completed and compiled data package, right, to be able to interpret our biomarker data. I mean, obviously we'd love to aggregate all of that data and after the top line data's written up and the CSR is done, we'd obviously love to present this at a scientific conference.

I mean, our intention I think as I mean primary endpoint of the study as you know a safety Tolerability and obviously, we're looking at drug levels and pharmacokinetics. This was our first multiple ascending dose study.

Speaker Change: I mean, our intention, I think, is, I mean, primary endpoint to the study, as you know, was safety, tolerability, and obviously, we're looking at drug levels and pharmacokinetics. This was our first multiple assembly.

Speaker Change: In addition to that, as you know, we're looking at multiple different biomarker arms and we intend to correlate the biomarker arms with.

In addition to that as you know, we're looking at multiple different biomarker arms, and we intend to correlate the biomarker arms with drug levels et cetera. So we kind of need a complete isn't compiled data package right to be able to interpret our biomarker data.

Speaker Change: drug levels, et cetera, so we kind of need a completed and compiled data package, right, to be able to interpret our biomarkers.

I mean, obviously, we'd love to aggregate all of that data and after the topline data is.

Speaker Change: I mean, obviously we'd love to aggregate all of that data and after the top line data is, you know, written up and the CSR is done, we obviously would love to present this at a sign.

Written up in the CSR is done we'd obviously, we'd love to present this at a scientific conference.

Speaker Change: But we'll come back and we will report out on our belayed impact, the biomarker and

But we'll come back and we will report out on our on our end I believe genpact.

David-Alexandre Gros: We'll come back, and we will report out on our ability to impact the biomarker endpoints that we've been talking about.

The biomarker endpoints that we've been talking about.

Speaker Change: And then just one, maybe one other question on the non-human primate data and understanding, you know, you just have the preliminary observations, but there, any sort of comment or anything you can say on how this data set looks relative to other published CD40 renal transplant data in non-human primates?

Okay great.

Thomas Smith: Okay, great. Then just one, maybe one other question on the non-human primate data and understanding, you know, you just have the preliminary observations, but are there any sort of comment or anything you can say on how this data set looks relative to other published CD40 renal transplant data in non-human primates?

And then just one maybe one other question on.

The non human primate data and understanding you just had the preliminary observations, but there.

Any sort of comment or anything you can say on how this data set looks relative to other published CD 40, renal transplant data in nonhuman primates.

Okay.

David-Alexandre Gros: I think the study, as we mentioned, is still ongoing. To date, all four animals have been transplanted. As we mentioned, you know, if you don't treat animals with any immunosuppression, the animals will reject and die typically within seven days. Now all four of our animals are out multiple times that time period. What we're seeing today is consistent with what's been historically published and shown with anti-CD40 ligands, as well as with experience that we've had with tegoprubart specifically in the islet cell transplant non-human primate model.

I think the this study as we mentioned is still ongoing.

Speaker Change: The study, as we mentioned, is still ongoing, but to date, all four animals have been transplanted.

But to date.

All four animals have been transplanted.

Speaker Change: As we mentioned, you know, if you don't treat animals with any immunosuppression, the animals will reject and die typically within seven days.

As we mentioned you know if you.

If you don't treat animals with any immuno suppression.

The animals will reject and die typically within seven days and now all four of our animals are out multiple times that time period.

Speaker Change: And now, all four of our animals are out multiple times that time period. And so, what we're seeing today is consistent with what's been historically published and shown with anti-CD40 ligands, as well as with experience that we've had with Tagopru bards specifically in the islet cell transplant non-human primate model.

And so what we're seeing today is consistent with what's been historically published and shown.

With anti CD 40 law against as well as with experience that we've had with to go put BARDA specifically.

The islet cell transplant nonhuman primate model.

Okay.

Okay, Great got it alright, thanks, guys I.

Thomas Smith: Okay, great. Got it. All right. Thanks, guys. Appreciate you taking the questions.

Speaker Change: Okay, great. Got it. All right. Thanks, guys. Appreciate you taking the question. Yeah, just, you know, we're excited by this data, and we feel that it's, you know, we've met the goal of the study, which was to show that to go PruBart, even as monotherapy, was able to significantly inhibit solid organ rejection.

I appreciate you taking the question Yeah. Just you know we're we're excited by this data and.

David-Alexandre Gros: Yeah. Just, you know, we're excited by this data, and we feel that it's, you know, we've met the goal of the study, which was to show that tegoprubart, even as monotherapy, was able to significantly inhibit solid organ rejection.

And we feel that it's you know we've met the goal of the study which was to show that to go for Bard.

Even as monotherapy.

Was able to significantly inhibit.

Solid organ rejection.

Got it thanks, Steve I appreciate it.

Thomas Smith: Got it. Thanks. See ya. Yeah, appreciate it.

Speaker Change: Our next question comes from the line of Matt Kaplan with Lattenberg-Dowman. Please proceed with your question.

Our next question comes from the line of Matt Kaplan with Ladenburg Thalmann. Please proceed with your question.

Operator 2: Our next question comes from the line of Matt Kaplan with Ladenburg Thalmann. Please proceed with your question.

Operator: Our next question comes from the line of Matt Kaplan with Ladenburg Thalmann. Please proceed with your question.

Matt Kaplan: Hey guys, thanks for taking the question and congrats on the initial results from the non-human primate study. I guess starting there with respect to, I guess, next steps.

Matt Kaplan: Hey guys, thanks for taking the question and congrats on the initial results in the non-human primate study. I guess starting there with respect to I guess next steps and your thoughts on interaction with the FDA and potentially on moving forward in the US, what given the top line results that you initial results that you have in NHP study?

Hey, guys. Thanks for taking my question and.

And congrats on the initial results from the non human Primate study I.

I guess, starting there with respect to I guess next steps in and your thoughts on.

Matt Kaplan: thoughts on interaction with the FDA and potentially moving forward in renal transplant in the U.S. given the top-line results for you, initial results that you have.

Interaction with the FDA.

And potentially are moving forward in renal transplant.

What given given the topline herself to you initial results that you Havent HP study.

Yeah.

Great Hey, Matt. Thank you for the question in.

Matt Kaplan: Hey, Matt, thank you for the question. In terms of our future interactions with agency, as we've mentioned, we feel that we've shown that the GoproBart, even as monotherapy, can prevent.

David-Alexandre Gros: Great. Hey, Matt, thank you for the question. In terms of our future interactions with agency, you know, as we've mentioned, we feel that we've shown that tegoprubart even as monotherapy can prevent rejection in a kidney transplantation model. What we're going to do next is finish the study. We expect to complete the study next quarter and be able to fully analyze the data, including things such as PK, anti-drug antibody, and the like. As you know, in parallel, we're going to be getting our data from the ALS study. With regards to future interactions with agency, the agency would obviously ask to see all of the available data.

In terms of our future interactions with agency.

And as we've mentioned we feel that we've shown that to go for Bard, even as monotherapy can.

Prevent.

Matt Kaplan: can prevent rejection in a kidney transplantation model. What we're going to do next is finish the study. So we expect to complete the study next quarter and be able to fully analyze the data, including things such as PK, anti-drug antibody, and the like.

It can prevent rejection in kidney transplantation model.

We're going to do next is finish the study. So we expect to complete the study next quarter and be able to to analyze fully analyze the data.

Including things such as PK anti drug antibody and alike.

Matt Kaplan: As you know, in parallel, we're going to be getting our data from the ALS study.

As you know in parallel we're going to be.

Getting our data from the ALS study.

Matt Kaplan: So, with regards to future interactions with the agency, the agency would obviously ask to see all of the available data, and as such, you know, we would first complete, fully complete our non-human primate study, in parallel, get our ALS data, and then use that to go back to the agency and have a discussion around next steps for kidney transplantation.

So with regards to future interactions with the agency.

The agency would obviously ask to see all of the available data.

David-Alexandre Gros: As such, you know, we would first fully complete our non-human primate study, in parallel, get our ALS data, and then use that to go back to the agency and have a discussion around next steps for kidney transplantation.

And as such.

We would first complete fully complete our non human primate study in PAH.

<unk> levels get our ALS data and then use that to go back to the agency and have a discussion.

Around next steps for for kidney transplantation.

Okay. That's that's helpful. Thank you and then all of that data is coming in as we've discussed next.

Matt Kaplan: Okay. That's helpful. Thank you.

Speaker Change: That's helpful, thank you. But all of that data is coming in, as we've discussed, next quarter.

David-Alexandre Gros: All of that data is coming in, as we've discussed, next quarter. This is in the near term.

Next quarter. So this is this is in the near term.

Matt Kaplan: Great. You know, with the top line data for ALS, you know, as you said, expected in Q2, can you give us, maybe for Steve, kind of a sense in terms of what you're looking for in the biomarkers? I guess maybe specifically, what you would expect to see from a pharmacodynamic point of view, CD40 target engagement, and what we should look for there.

Great.

Speaker Change: And then, you know, with the top-line data for ALS, you know, as you said, it...

And then you know with the topline data for AOS as you said expected second quarter.

Speaker Change: second quarter. Can you give us, maybe for Steve, kind of a sense in terms of what you're looking for in in the biomarkers, I guess maybe specifically

Can you give us maybe for Steve kind of a sense in terms of what you're looking for in the Biomarkers I guess, maybe specifically.

What you would expect to see from a from a dynamic point of view CD 40 target engagement in what.

Steve Perrin: what you would expect to see from a pharmacodynamic point of view, CD40 target engagement and what we should look for there?

What we should look for there.

Steve Your question, Matt I mean, when you go through some of the past are the primary arm of the biomarker study, which is as important as knocked on a pro inflammatory markers.

David-Alexandre Gros: Steve?

Steven Perrin: Yeah. Great question, Matt. I mean, as we said in the past, the primary arm of the biomarker study, which is important, is knock down pro-inflammatory markers. You know, there's many publications and literature showing upregulation of pro-inflammatory markers in people with ALS. CD40 Ligand inhibition should directly be able to modulate those levels of pro-inflammatory markers through modulating B-cell and T-cell activation. That's really the primary objective. I mean, in addition to that, obviously target engagement is part of that. Many of the markers that I'm referring to are involved in CD40 Ligand activity, such as chemokines like CXCL13 that's expressed by activated B cells. So those are the important outcomes. I mean, obviously we'd like to see some other relationships like a PD effect, a dose response effect.

Steve Perrin: Yeah. Great question, Matt. I mean, as we said in the past, the primary arm of the biomarker study, which is important, is knock down pro-inflammatory markers. You know, there's many publications and literature showing upregulation of pro-inflammatory markers in people with ALS. CD40 Ligand inhibition should directly be able to modulate those levels of pro-inflammatory markers through modulating B-cell and T-cell activation. That's really the primary objective. I mean, in addition to that, obviously target engagement is part of that. Many of the markers that I'm referring to are involved in CD40 Ligand activity, such as chemokines like CXCL13 that's expressed by activated B cells. So those are the important outcomes. I mean, obviously we'd like to see some other relationships like a PD effect, a dose response effect.

Speaker Change: Great question, Matt. I mean, as we said in the past, the primary arm of the biomarker study, which is important, is knock down a pro-inflammatory marker.

Speaker Change: You know, there's many, many publications and literature showing up-regulation of pro-inflammatory markers in people with ALS, and CD40 ligand

There's many many publications in the literature, showing upregulation of pro inflammatory markers and people with a loss.

And C D 40 ligand inhibition.

Speaker Change: should directly be able to modulate those levels of pro-inflammatory markers through modulating B-cell and T-cell activity.

Should directly be able to modulate those levels of pro inflammatory markers through modulating b cell and T cell activation.

So that's really the primary objective I mean in addition to that obviously target engagement as part of that many of the markers that I'm, referring to we're involved in.

Speaker Change: So that's really the primary objective. I mean, in addition to that, obviously, target engagement is part of that. Many of the markers that I'm referring to are involved in CD40 ligand activity, such as chemokines like CXCL13 that's expressed by activated B cells.

C D 40 ligand activity such as <unk> like <unk> 13, that's expressed by activated T cells.

Speaker Change: So those are the important outcomes. I mean, obviously we'd like to see some other relationships like a PD effect, a dose response effect. But until we see the data, it's hard to understand what we're looking for there.

So those are the important outcomes I mean, obviously, we'd like to see some other relationships like our PD effect of dose response effect.

Steven Perrin: Until we see the data, it's hard to understand what we're looking for there.

Steve Perrin: Until we see the data, it's hard to understand what we're looking for there.

But until we see the data its hard to understand what we're looking for there.

Mhm.

Matt Kaplan: I guess, with respect to the exploratory endpoints, I guess neurofilament light chain, would you expect to potentially see a dose effect there as well?

I guess.

Speaker Change: respect to the exploratory endpoints, I guess neurofilament might.

With respect to the exploratory endpoints I guess north light chain would you expect to potentially see I E.

Speaker Change: would you expect to potentially see a dose effect there as well?

Dose effect, there as well.

I mean any effect on <unk> would be a really grand Slam home run sort of speak right. I mean, it's a fairly short study, it's only 12 weeks.

Steven Perrin: I mean, any effect on neurofilament light chain would be a really grand slam home run so to speak, right? I mean, it's a fairly short study. It's only 12 weeks. Neurofilament light chain is a surrogate of neuron health. At least that's what we're hypothesizing based on existing data that as neurons get sick and they die, part of their cell cytoskeleton ends up leaking from the CSF into circulation, and neurofilament light chain has been a marker of that, not only in ALS, but also in Alzheimer's, multiple sclerosis, and other neurodegenerative diseases. You know, that is kind of the best outcome we could expect, is to see some change in neurofilament light chain and to have that be associated with a dose response and correlate with inflammatory biomarker changes.

Steve Perrin: I mean, any effect on neurofilament light chain would be a really grand slam home run so to speak, right? I mean, it's a fairly short study. It's only 12 weeks. Neurofilament light chain is a surrogate of neuron health. At least that's what we're hypothesizing based on existing data that as neurons get sick and they die, part of their cell cytoskeleton ends up leaking from the CSF into circulation, and neurofilament light chain has been a marker of that, not only in ALS, but also in Alzheimer's, multiple sclerosis, and other neurodegenerative diseases. You know, that is kind of the best outcome we could expect, is to see some change in neurofilament light chain and to have that be associated with a dose response and correlate with inflammatory biomarker changes.

Speaker Change: I mean, any effect on neurofilament light chain would be a really grand slam home run, so to speak, right? I mean, it's a fairly short study. It's only 12 weeks.

Speaker Change: Neurofilament light chain is a surrogate of neuron health, as the neurons, at least that's what we're hypothesizing based on existing data, that as neurons get sick and they die, part of their cytoskeleton ends up leaking from the CSF into circulation, and neurofilament light chain has been.

Nerf <unk> light chain as a surrogate of neuro on health as the neurons at least that's what we're hypothesizing based on existing data that is neurons get sick and they die part of their cytoskeleton ends up leaking from the CSF into circulation of neuro filament light chain as Pam.

Speaker Change: a marker of that not only in ALS but also in Alzheimer's, multiple sclerosis, and other

Mark rollout not only inhaled hospital also in Alzheimers multiple sclerosis and other.

Speaker Change: neurodegenerative diseases. So, you know, that is kind of the best outcome we could expect is to see some change in neurofilament light chain, and to have that be associated with the dose response and correlate with inflammatory biology.

<unk> the German diseases. So you know about that as kind of the best outcome. We can expect us to see some change in euro filament light chain and to have that be associated with a dose response in correlate with inflammatory biomarker changes.

Speaker Change: that's like the perfect outcome if you can get there. But in a 12-week study, it's pretty short, whether we'd be able to see changes in NFL and or even clinical.

Steven Perrin: That, that's like the perfect outcome if you can get there. In a 12-week study, it's pretty short, whether we'd be able to see changes in NfL and/or even clinical endpoints at this point.

Steve Perrin: That, that's like the perfect outcome if you can get there. In a 12-week study, it's pretty short, whether we'd be able to see changes in NfL and/or even clinical endpoints at this point.

The perfect outcome. If you can get there in a 12 week study, it's pretty short whether we'd be able to see changes in NFL and or even clinical endpoints at this point.

Great great.

Matt Kaplan: Great. Last question in terms of progress with the islet cell transplant program. Any in terms of patient enrollment there.

Speaker Change: And last question in terms of progress with the, I would say, transit.

And our.

Last question in terms of progress with the islet cell transplant program.

Speaker Change: program in terms of patient enrollment.

Any.

In terms of patient enrollment there.

He has not enrolled the patient yet.

David-Alexandre Gros: We have not enrolled a patient yet. I think the key thing across our programs is to open up sites. You know, as we think about the studies, we continue to be confident that we'll be able to enroll our trials. What we've done is to really budget for a number of sites that we think is going to be appropriate for us to begin to get patients and get data by the end of the year. That's true really across the trials. Now in islet cell transplant specifically, we're looking to open up our second site, so the US site.

Speaker Change: We have not enrolled a patient yet. I think the key thing across our programs is to open up sites.

I think the key thing across our programs is to open up sites.

Speaker Change: And it's, since you know, as we think about the studies, we continue to be confident that we'll be able to enroll our trials.

And it's.

As you know.

As we think about the studies, we continue to be confident that we'll be able to enroll our trials.

Speaker Change: And what we've done is to really to budget for a number of sites that we think is going to be appropriate.

And what we've done is to.

So really to budget for a number of sites that we think is going to be appropriate.

Speaker Change: for us to begin to get patients and get data by the end of the year. And that's true really across the trough.

For us to begin to get patients and get data by the end of the year and Thats true really across across the trials.

Speaker Change: So now, in islet cell transplants specifically, we're looking to open up our second site, so the U.S. site. That site should be open in about the middle of the year, which would then allow a second site to potentially bring in patients into the trial.

So now in islet cell transplant specifically.

We're looking to open up our second site. So the U S site.

David-Alexandre Gros: That site should be open in about the middle of the year, which would then allow a second site to potentially bring in patients into the trial. Since, you know, meaningful data can be had in that trial in 90 days, since typically within 90 days, one can see how well the transplanted cells are doing, if the patient is able to control their diabetes and if the patient's able to be insulin free. We expect, once we're able to enroll patients to be able to get that data quite quickly.

Site should be opened in about the middle of the year.

Which would then allow a second site to potentially bringing patients into the trial.

So since we have meaningful data can be had in that trial in 90 days typically within 90 days, one can see how well the transplanted cells are doing it.

Speaker Change: So, since, you know, meaningful data can be had in that trial in 90 days, since typically within 90 days one can see how well the transplanted cells are doing.

Speaker Change: if the patient is able to control their diabetes and if the patient is able to be insulin free.

If the patient is able to two.

To control their diabetes and if the patient is able to be insulin free.

Speaker Change: We expect once we're able to enroll patients to be able to get that data quite quickly.

We expect our at once we're able to enroll patients to be able to get that data quite quickly.

Okay, great. Thanks for the added detail.

Matt Kaplan: Okay, great. Thanks for the added detail.

Yeah.

David-Alexandre Gros: Thank you.

Speaker Change: Thank you. Sir, there are no further questions in the queue. I'd like to hand the call back to management for closing remarks.

Thank you Sir there are no further questions in the queue I'd like to hand, the call back to management for closing remarks.

Operator 2: There are no further questions in the queue. I'd like to hand the call back to management for closing remarks.

Operator: There are no further questions in the queue. I'd like to hand the call back to management for closing remarks.

Speaker Change: Thank you, Operator, and thank you all for joining us on today's call. We have an exciting year ahead of us, and we look forward to keeping you updated on all of our progress. Have a

Thank you operator, and thank you all for joining us on today's call. We have an exciting year ahead of us and we look forward to keeping you updated on all of our progress have a great evening.

David-Alexandre Gros: Thank you, operator, and thank you all for joining us on today's call. We have an exciting year ahead of us, and we look forward to keeping you updated on all of our progress. Have a great evening.

Speaker Change: Ladies and gentlemen, this does include today's teleconference. Thank you for your participation. You may disconnect your lines at this time, and have a wonderful day.

Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation you may disconnect. Your lines at this time and have a wonderful day.

Operator 2: Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation. You may disconnect your lines at this time, and have a wonderful day.

Operator: Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation. You may disconnect your lines at this time, and have a wonderful day.

Okay.

Yes.

Okay.

Matt Kaplan: Okay.

David-Alexandre Gros: Okay.

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