Aurinia Pharmaceuticals Inc

Good morning, and welcome to ARINIA's ARIT Intercept Phase 1 Study Results Conference Call. Please be advised that a Q&A session will follow ARINIA's prepared remarks. You may be placed at the question queue at any time by pressing star 1 on your telephone keypad, and we ask you please limit yourselves to one question and one follow-up. I will now turn the call over to Peter Greenleaf, Chief Executive Officer of ARINIA. Please go ahead, sir.

Good morning. Thank you all for joining us to discuss the results from our ARIT Intercept Phase 1 Single Ascending Dose Study. ARIT Intercept has been previously referred to as AUR 200. Joining me on the call today are Dr. Greg Keenan, our Chief Medical Officer, and Joe Miller, our Chief Financial Officer. Before beginning our discussion, I'd like to direct your attention to slide two, which contains important information regarding forward-looking statements. With that introduction, let me now turn the call over to Dr. Greg Keenan to walk you through the R-Tintercept Phase 1 study results. Greg?

Thank you, Peter. It's a pleasure speaking with you today about R-Tintercept and the results of our Phase 1 single ascending dose study. R-Tintercept is a dual BAP April inhibitor. It contains a BCMA-engineered extracellular binding domain optimized for for superior affinity to BAF and APRIL. Other dual BAF and APRIL inhibitors use TASI-engineered extracellular binding domains. DCMA has a stronger natural affinity for APRIL than TASI. RX-intercept also contains an IgG4-FC domain with no appreciable effector function. Other dual BAF-APRIL inhibitors use IgG1-FC domains IgG4 is considered the least inflammatory across the IgG subclasses, in part because it poorly activates the complement system. Before we talk about our RRT intercept results, just a few words on the important roles of BAF and APRIL in the immune system and why modulating these cytokines may be a good treatment approach for a wide range of autoimmune diseases. Both of these cytokines regulate B-cell survival and differentiation, with BAF more targeted at differentiating and mature B-cells, and APRIL more targeted at plasma cells. Thus, targeting both BAF and APRIL depletes a broader set of B-cells, including plasma cells, than targeting a single cytokine. ART Intercept may prevent the activation of autoreactive B-cells and reduce their numbers and associated immune globulins in the body, thereby reducing important drivers of B-cell-mediated autoimmune diseases. Aritintercept has high binding affinity for both BAF and APRIL. As you can see in this slide, when compared in in vitro studies to atacicept and telatacicept, two BAF APRIL inhibitors from other sponsors, aritintercept has three to eight-fold higher binding affinity. Additionally, as you can see in this slide, R-Atenercept potently inhibits both BAF and APRIL-mediated B-cell proliferation as compared to the competitor dual BAF-APRIL inhibitors. Compared to Atacicept and Telatacicept, R-Atenercept is six to 53-fold more potent at inhibiting BAF and APAL-mediated B-cell proliferation. On this side, you can see our results in non-human primates. R-Atenercept reduced the immunoglobulins IgA, IgM, and IgG by up to 76, 67, and 43% respectively. R-Atenercept was well-tolerated with no adverse findings in any of the doses tested. Moving to our phase one results, we enrolled 61 healthy subjects in a standard single ascending dose study design. Subjects were treated with placebo for one of six subcutaneous doses of our tintercept, 5, 25, 75, 150, 225, and 300 milligrams. You can see our safety results on this slide. R-intercept was well-tolerated, all dose levels tested. There are no treatment-related grade 3 or higher adverse events. There were no treatment-related serious adverse events, and there were no discontinuations due to treatment-related adverse events. There was one SAE, a concussion, due to a motor vehicle accident reported as not treatment-related. Adverse events that occurred in more than one subject were Injection site reactions, which occurred in 24% of subjects who received ART intercept versus 13% of subjects who received placebo. All injection site reactions were grade one. Headaches, which occurred in 11% of subjects who received ART intercept versus 7% of subjects who received placebo. Upper respiratory tract infection, which occurred in 7% of subjects who received ART intercept versus 0% of subjects who received placebo. and back pain, which occurred in 4% of subjects who received RRT intercept versus 0% of subjects who received placebo. This slide depicts the pharmacokinetic curves of subcutaneous RRT intercept, a half-life of six to eight days after a single dose in the target dose range was observed. On this slide, you can see the pharmacodynamic effects of ART intercept treatment. Single doses of ART intercept led to robust and long-lasting reductions in immunoglobulins. Specifically, mean reductions from baseline to day 28 of up to 48, 55, and 20% were observed for IgA, IgM, and IgG, respectively. Importantly, we believe these long-lasting pharmacodynamic effects support once-monthly dosing. On the next three slides, we provide some comparative results to provide context. Please note that these are cross-trial comparisons and therefore should be interpreted with caution. On this slide, you can see that our tintercepts effect on IgA compares favorably to that for BAF april inhibitors from Vertex, Vera, and Remigen as well as Otsuka's anti-APRIL. On this slide, you can see the same comparison for IgM. Again, R-T-intercept compares favorably. And finally, on this slide, you can see the same comparison for IgG, with R-T-intercept again comparing favorably. With this, I will turn the presentation back over to Peter.

Thanks, Greg. We're obviously very excited about these results. In summary, R-tintercept was well-tolerated at all dose levels that we tested, and single doses of R-tintercept led to robust and long-lasting reductions in immunoglobulins supportive of once-monthly dosing. Are any plans to initiate further clinical studies of R-tintercept in at least two autoimmune diseases in the second half of this year? We're very excited about the wide range of therapeutic possibilities for R-tintercept, But for competitive reasons, we'll not be disclosing further detail about our future plans at this time. We want to thank you all for joining us on today's call, and we look forward to taking your questions. So with that, let me ask the operator to now open up the line for Q&A. Operator?

Certainly. When are they conducting a question and answer session? If you'd like to be placed in the question queue, please press star 1 on your telephone keypad. we ask you to please ask one question and one follow-up. Once again, that's star one to be placed in the question queue, and please ask one question and one follow-up. Our first question is coming from Stacy Koo from TD Cal, and your line is now live.

Hey there. Thanks so much for taking our questions, and congratulations on the progress. So understanding you're not able to maybe talk about the clinical studies specifically that you're planning to do next, maybe can you comment on your current deliberations? Would you be wanting to stay within your current commercial infrastructure? So maybe a lupus or something in renal diseases? Or are you even thinking kind of more widely to think about maybe neuromuscular or even dermatology? So that's the first question. Just any kind of thoughts on what a potential clinical trial design would look like? And just to confirm, would this be phase 1A kind of concept? And then the second question is, if we could sneak one in, is if you've disclosed kind of doses you're planning to move forward, could you even, you know, looking at the safety, what are, how are you thinking about that? Thank you so much.

Stacey, thanks for the question. So, as you know, there's a lot of excitement about the BAFAPRIL inhibitor space at this stage, and I think a large part of that's because of the wide range of B-cell-mediated autoimmune diseases that are out there, which these potential compounds could be effective in. So as we said on the call, we plan to initiate clinical studies in at least two of these autoimmune diseases in the second half of the year. But for competitive reasons, we've made the decision not to disclose any more at this time. Obviously, there's alignment to our therapeutic area that's interesting. But also, as this space continues to widen, I think it's going to become more competitive on dose selection. So we're trying to leave it at that. In terms of the doses we're intending to take forward, obviously, Greg, I can kind of ask you maybe just to elaborate a little bit on that. You want to go, Greg?

Sure. Thanks. And thanks, Stacey, for the question. At this point, we're not prepared to indicate the specific dose level that our dose levels will take forward into the multiple assigning dose study. But I think it's fair to say when you see the evidence, specifically the kinetics of the drug, the higher doses performing well with regard to half-life on the one hand and with regard to the impact on pharmacodynamics on the other. It's definitely fair to say that in our single ascending dose study, we captured in a bracketed way doses that are very viable, and we're going to use the information from the SAD study to inform which dose or doses we take forward into MAD. But we're very encouraged with the SAD results and the information it provides to inform the multiple sending dose study.

Thank you. Next question today is coming from Maury Raycroft from Jefferies. Your line is now live.

Hi, good morning. Congrats on the update and thanks for taking my questions. Maybe just to, I think the data speak for itself for the most part. Wondering if you can just remind me what the IP life is for the drug and Also wondering strategically from a BD standpoint, would you consider running the studies on your own or potentially consider partnering these out?

So IP life on the product, we continue to file, you know, IP in and around the compound. So we haven't disclosed the full life on it, but know that we continue to add to the patent portfolio as early as, you know, the results that we're seeing from this stat study. And then second, the other question was about, can you repeat the second question, Maureen?

BD and whether you'd run the studies on your own or potentially partner out.

Yeah, no, our thought is we're going to take this study forward on our own. We don't need funding. Obviously, we've got good cash flows coming from operations, so our intention right now is to take this forward on our own.

Thank you. Next question today is coming from Joe Schwartz from Learing Partners. Your line is now live.

Great, thanks. Congrats on the nice data. I was wondering if you could just give us some insight into your thought process around what indications you're most likely to pursue. Is there anything which could give you a sustainable competitive advantage in any of them relative to other April baths, which there are many and they're all further ahead and a lot of different indications. Are there any indications that might be particularly well-suited where Aranea might, you know, be able to control their destiny in those indications in particular. And then what is the timeline to generate phase two data in these studies? And then we noticed that the 150 milligram dose group had almost three times as many patients. I was just wondering why that was.

Well, on the indications, as we've already said, you know, we've done a pretty extensive internal review on all the potential B-cell-mediated diseases, autoimmune diseases that we could potentially look at here. And I think in our initial assessment, we had upwards of 20 different potential targets you could go after. Obviously, the focus primarily has been centered as of late on IGAN and some emerging new areas. So we think Part of this is going to be a competitive process moving forward and why we're not disclosing more details on the two that we intend to move forward with. But obviously, this is going to be important for everyone developing this space moving forward. And if everyone's hypothesis around the potential breadth and depth of indications works out, this could be a very large area. So we're excited about that. Greg, do you want to talk maybe just a little bit about the 150 milligram?

Sure. Yeah. And thanks for the question. Going into the study, the development of the single ascendant dose study, are allometric scaling relative to the non-human primate Based work we had done indicators suggested that 150 milligrams or thereabouts was going to be an important dose to thoroughly explore to be able to understand the magnitude of impact on pharmacodynamic changes. So that's why we quote enriched that particular dose level. As we built it out, you can see for yourself the impact of that dose with fine precision relative to the other doses. And we think when we look at it now that it really helped inform our thinking of the firmness of the effect that we see both with regard to PD and really clarified and firmed up the kinetics of the drug in general. So it's basically a dose to explore very specific aspects of the pharmacodynamics and pharmacokinetics of the drug. Great. Thanks for the color.

Thank you. Next question today is coming from Arthur He from H.C. Wainwright. Your line is now live.

Hey, good morning, gentlemen. Congratulations on the data. It's very impressive, a single-dose immunoglobulin reduction. So I have one question on the safety and one on the injection side. So for safety, Greg, could you give us more color on the upper respiratory infection and also the back pain? Is this more has any dose dependent or lean towards the higher dose or it's more across the board?

Yeah, so I'm sure. Thank you, Peter. Yeah, so just specifically, you know, obviously this is a small study, so we didn't observe any dose-dependent effects on upper respiratory tract infections, for example, where it was a very modest number of events. And these were... relatively mild and very self-limited, did not require any intervention. So we were very encouraged by those and no dose effect there. With regard to back pain, the same thing goes for that. These were very transient events that resolved with essentially no intervention. So transient, mild, benign.

That's great. My second question is regarding injection volume. Could you give us more color on that? And the reason I ask is, do you think your drug also could be suitable for the self-administration at home?

Well, thanks for the question. Our formulation for early clinical studies is less concentrated than what will be our commercial formulation. Right now, our formulation development is ongoing, and we're confident that given the physiochemical properties of Arctintercept and our target dose range, our commercial formulation and the formulation we'll use in later stage clinical studies will enable a single monthly injection from either a pre-filled syringe or an autodirector and a standard gauge needle. And the hope would be that that could be administered at home as well.

That's great. Thank you very much for taking my question. And congrats again.

Thank you. We reach the end of our question and answer session. I'd like to turn the floor back over for any further closing comments.

We want to thank everybody for joining us on the call today, and we look forward to giving further updates moving forward. Thank you very much, and have a great day.

Thank you. That does conclude today's teleconference and webcast. We disconnect your line at this time, and have a wonderful day. We thank you for your participation today.