Aurinia Pharmaceuticals Inc. (AUPH) Earnings Call Transcript & Summary

Greetings, and welcome to the Aurinia Pharmaceuticals AURORA Renal Sub-study top line results webcast. [Operator Instructions] As a reminder, this conference is being recorded. It's now my pleasure to turn the conference over to your host, Jamie Harrell, Investor Relations for Aurinia Pharmaceuticals. Thank you. You may begin.

Thank you, operator, and thank you all for joining today's call and webcast to discuss the top line results from the AURORA renal sub-study. This morning, Aurinia issued a press release announcing the top line results from the AURORA 1 and AURORA 2 renal sub-study. For more information and to see the slides being shared on today's call, please refer to the Investor Relations Corporate Presentations section of the auriniapharma.com website. Now during this call, Aurinia may make forward-looking statements based on current expectations. These forward-looking statements are subject to a number of significant risks and uncertainties, and actual results may differ materially. Please note that all statements made during today's call are current as of today, April 5, 2023, unless otherwise noted and are based upon information currently available to us at this time. Except as required by law, Aurinia assumes no obligation to update any such statements. Now let me turn the call over to Aurinia's recently appointed Chief Medical Officer, Dr. Greg Keenan. Greg?

Great. Thank you, Jamie, and it's a pleasure to speak with everyone today. I am Greg Keenan, the CMO for Aurinia, and it's a pleasure to speak with you. I'm going to be talking about our renal biopsy sub-study, which was performed within the AURORA 1 and AURORA 2 trials. I'd like to provide some background for our renal biopsy sub-study. LUPKYNIS has been shown to have higher rates of remission and response over 3 years in placebo-controlled clinical trials against the background of the then current standard of care, while preserving renal function without typical first-generation calcineurin inhibitor clinical manifestations of toxicity. First-generation calcineurin inhibitors or CNIs, including tacrolimus and cyclosporine have been shown to cause irreversible histopathologic kidney damage, including arteriolar hyalinosis, interstitial fibrosis, tubular atrophy and glomerular sclerosis. The clinical utility of LUPKYNIS, a novel second-generation CNI for the treatment of adults with active lupus nephritis has been established. Last year, we reported the results of the AURORA 2 long-term extension, which demonstrated improved proteinuria and stable eGFR as well as safety of long-term LUPKYNIS treatment in LN. However, the renal tissue level impact of LUPKYNIS has not been demonstrated to date. The top line results that I'll be presenting shortly from the biopsy sub-study provide our first observations into the renal tissue level impact of LUPKYNIS. To assess the biopsies conducting the sub-study, we used a scoring methodology with a validated NIH systematic approach to assessing disease activity, including histologic measures of disease activity, inflammation and chronicity, irreversible kidney damage and scarring associated with end-stage kidney disease. On this slide, we understand a little bit more about the first-generation calcineurin inhibitors that have been shown to be associated with nephrotoxicity and subsequent kidney injury. Most data on CNI nephrotoxicity pertain to cyclosporine A, a compound that has been available for a long period of time. Acute CNI nephrotoxicity is manifested as acute kidney injury, which is hemodynamic and largely reversible after reducing the dose. Chronic CNI nephrotoxicity is observed in chronic progressive kidney disease and is hugely irreversible. Other kidney disease effects of CNIs include tubular dysfunction and rarely a thrombotic microangiopathy that can lead to acute kidney allograft loss. A similar pattern of kidney injury to that of those exposed to cyclosporin has been seen in those using tacrolimus, thereby suggesting a drug class effect. I call your attention to the table on the right of the slide, which shows that even in non-kidney transplant, such as liver, lung or heart for which a first-generation CNI is used for transplant rejection prevention, there is evidence of the incidence of chronic kidney injury over time. The long-term safety of first-generation CNI and non-lupus enterprise conditions has created questions regarding the safety associated with long-term use of LUPKYNIS in LN patients. Notably, LUPKYNIS is a second-generation CNI without a therapeutic drug monitoring requirement. Several studies suggest LUPKYNIS does not possess many of the clinical safety considerations associated with the first-generation CNI. For example, regarding lipid levels, cyclosporine has been associated with rapid and clinically important increases in serum lipid levels. LUPKYNIS has not been observed to be associated with these increases. In fact, it has been shown to reduce inflammatory lipids. Additionally, LUPKYNIS does not impact mycophenolate levels. This contrasts with cyclosporin, which is demonstrated to cause a reduction in mycophenolate levels. Regarding electrolyte impact, first-generation CNI may cause kidney tubular damage as seen by hypomagnesemia, and hyperkalemia. LUPKYNIS, when used in treatment of lupus nephritis has shown little or no impact. Tacrolimus has been demonstrated to be associated with hyperglycemia, diabetes and islet cells death. LUPKYNIS has not been demonstrated to have similar associations. Finally, the last remaining open question is the risk for CNI-induced chronic nephrotoxicity. This phenomenon has been demonstrated with both tacrolimus and cyclosporin. Clinically, to date, LUPKYNIS treatment has demonstrated the ability to stabilize the slope of the eGFR estimated glomerular filtration rate in lupus nephritis patients. However, there's been no evidence generated to address tissue level findings in those treated with LUPKYNIS. I'd like to present some examples of the characteristic histopathology associated with CNI nephrotoxicity. In Panel A on the left, we see light microscopic histopathology in a cyclosporin-induced lesion of fibrosis and atrophy and a kidney. The 2 arrows indicate areas of increased scarring and fibrosis. In Panel B, we see evidence of both arteriolar and subendothelial hyaline deposits in white and yellow arrows, respectively. And finally, in Panel C, we see evidence of segmental glomerulosclerosis, again, in an individual who is exposed to CNI. Now that we have that context, I'll take the opportunity to present the top line results of the AURORA biopsy sub-study. For background, AURORA 1 is a 357 patient Phase III 1-year lupus nephritis study comparing LUPKYNIS to placebo with a background of the then standard of care, mycophenolate and low-dose steroids. AURORA 2 is the Phase III double-blind 2-year continuation study of AURORA 1. 216 patients enrolled in AURORA 2, and the evidence generated has provided LUPKYNIS exposure data for up to 3 years duration. In the study schematic of the AURORA program, you can see the overall study design and duration. Importantly, you'll notice approximately 6 months into the participation in the AURORA 2 study, a follow-up biopsy was obtained in those study subjects that consented to participate in the sub-study. Let me review the study methods for the LUPKYNIS renal biopsy sub-study. 26 patients in all agreed to participate in the biopsy sub-study. 10 in the active control arm were receiving then standard of care and 16 were in the LUPKYNIS arm. Approximately 18 months after initiation of treatment in the AURORA program, participating patients underwent a follow-up kidney biopsy. Biopsies were processed utilizing standard procedures. Biopsy slides were subsequently evaluated and scored by expert centralized renal histopathologist at a specialized renal pathology laboratory according to the updated 2018 ISN RPS guidelines. I'd like to review the demographics and clinical outcomes of the sub-study. In this cohort, the patient demographics are very similar to the overall patient population that participate in AURORA 1 study when reviewed by age, sex, race, pretreatment eGFR and pretreatment baseline urinary protein creatinine ratio levels. These similarities are evident in the table presented to the right. Importantly, the sub-study population demonstrated clinical and safety results consistent with that observed in the overall AURORA 1 and 2 populations. As mentioned, the LUPKYNIS biopsy study utilized the NIH International Society for Nephrology Renal Pathology Society Scoring System. This system consists of an activity index and the chronicity index. The activity index has 6 unique items and is scored from 0 to 24. The conicity Index has 4 unique items and is scored from 0 to 12 as depicted in the table. On this slide, you can see the biopsy sub-study histologic results. I've provided Box and Whisker plots of the 2 populations at baseline in approximately 18 months of follow-up. In the left panel, you can see the activity scores, on the right, the chronicity scores. What we see regarding activity scores is that the active control arm at baseline improves over 18 months of exposure. LUPKYNIS-treated subjects demonstrate equivalent responsiveness over the same time frame. In the chronicity index, essentially no change in either population is observed. That is in the LUPKYNIS treatment arm, we see no evidence of the development of CNI nephrotoxicity manifestations. Let me emphasize, no evidence of the development of CNI nephrotoxicity manifestations. So to summarize, long-term use of first-generation calcineurin inhibitors such as cyclosporine and tacrolimus have been reported to cause a variety of acute findings, including renal dysfunction, glucose dysregulation, hyperkalemia, hypomagnesemia, MMF drug-drug interactions and serum lipid elevations. Irreversible renal damage due to progressive tubulo-interstitial injury and glomerulosclerosis have been associated with chronic first-generation CNI exposure. LUPKYNIS has been shown to have higher rates of remission and response over 3 years in controlled clinical trials against the backdrop of standard of care while preserving renal function without typical first-generation calcineurin clinical manifestations of nephrotoxicity. The biopsy sub-study involving a representative cohort of the AURORA study population demonstrated results consistent with the established clinical safety and efficacy of LUPKYNIS, a novel second-generation CNI. The NIH disease activity score, a histologic measure of kidney inflammation decreased substantially in both arms compared to baseline. The NIH chronicity score, a histologic measure of irreversible kidney damage and scarring assessed for evidence of end-stage kidney disease and remain stable. This is notable given the absence of chronic CNI nephrotoxicity observed in those sub-study subjects treated with LUPKYNIS. The total of the clinical and safety evidence in conjunction with these observations further differentiates LUPKYNIS from first-generation CNIs. Results are to be presented on this particular study at an upcoming scientific meeting. In the meantime, we intend to submit these results to applicable regulatory authorities. With that, I'd like to hand the call back over to Jamie for some closing remarks. Jamie?

Thanks, Greg. As you heard throughout the presentation, we are encouraged with the initial top line results from the LUPKYNIS biopsy sub-study. We believe these data further reinforce the safety and efficacy of LUPKYNIS in the treatment of active lupus nephritis patients. As Dr. Keenan mentioned, we plan to share these data with the health care community at upcoming medical meetings, such as the Congress of Clinical Rheumatology scheduled for May 4 through to 7, 2023, in Florida. In addition, we plan to communicate these data with the appropriate regulatory authorities as well. At this time, I want to thank everyone for joining us today and for more information or if you have additional questions, please feel free to reach out to those of us at Aurinia, including using the contact information form available on our corporate website. Operator?

Thank you. This will conclude today's call.