Good morning and welcome to Aurinia's Aritinercept phase one study results conference call. Please be advised that a Q&A session will follow Aurinia's prepared remarks. You may be placed into question queue at any time by pressing star one 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 Aurinia. Please go ahead, sir.
Good morning. Thank you all for joining us to discuss the results from our Aritinercept phase I single ascending dose study. Our Aritinercept has been previously referred to as AUR200. 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 Aritinercept phase one study results. Greg?
Thank you, Peter. It's a pleasure speaking with you today about Aritinercept and the results of our phase I single ascending dose study. Aritinercept is a dual BAFF-APRIL inhibitor. It contains a BCMA-engineered extracellular binding domain optimized for superior affinity to BAFF and APRIL. Other dual BAFF and APRIL inhibitors use TACI-engineered extracellular binding domains. BCMA has a stronger natural affinity for APRIL than TACI. Aritinercept also contains an IgG4 Fc domain with no appreciable effector function. Other dual BAFF-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 Aritinercept results, just a few words on the important roles of BAFF 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 BAFF more targeted at differentiating and mature B cells and APRIL more targeted at plasma cells. Thus, targeting both BAFF and APRIL depletes a broader set of B cells, including plasma cells, than targeting a single cytokine. Aritinercept may prevent the activation of autoreactive B cells and reduce their numbers and associated immunoglobulins in the body, thereby reducing important drivers of B cell-mediated autoimmune diseases. Aritinercept has high binding affinity for both BAFF and APRIL. As you can see in this slide, when compared in in vitro studies to Atacicept and Telitacicept, two BAFF-APRIL inhibitors from other sponsors, Aritinercept has three- to eight-fold higher binding affinity. Additionally, as you can see in this slide, Aritinercept potently inhibits both BAFF- and APRIL-mediated B cell proliferation as compared to the competitor dual BAFF-APRIL inhibitors.
Compared to Atacicept and Telitacicept, Aritinercept is six- to fifty-three-fold more potent at inhibiting BAFF- and APRIL-mediated B-cell proliferation. On this slide, you can see our results in non-human primates. Aritinercept reduced the immunoglobulins IgA, IgM, and IgG by up to 76%, 67%, and 43%, respectively. Aritinercept was well tolerated with no adverse findings in any of the doses tested. Moving to our phase I results, we enrolled 61 healthy subjects in a standard single ascending dose study design. Subjects were treated with placebo or one of six subcutaneous doses of Aritinercept: 5, 25, 75, 150, 225, and 300 milligrams. You can see our safety results on this slide. Aritinercept was well tolerated at all dose levels tested. There were no treatment-related grade three 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 Aritinercept versus 13% of subjects who received placebo. All injection site reactions were grade one. Headaches, which occurred in 11% of subjects who received Aritinercept versus 7% of subjects who received placebo. Upper respiratory tract infection, which occurred in 7% of subjects who received Aritinercept versus 0% of subjects who received placebo. Back pain, which occurred in 4% of subjects who received Aritinercept versus 0% of subjects who received placebo. This slide depicts the pharmacokinetic curves of subcutaneous Aritinercept. A half-life of 6-8 days after a single dose in the target dose range was observed. On this slide, you can see the pharmacodynamic effects of Aritinercept treatment.
Single doses of Aritinercept 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 Aritinercept's effect on IgA compares favorably to that for BAFF-APRIL inhibitors from Vertex, Vera, and RemeGen, as well as Otsuka's anti-APRIL. On this slide, you can see the same comparison for IgM. Again, Aritinercept compares favorably. Finally, on this slide, you can see the same comparison for IgG with Aritinercept 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, Aritinercept was well tolerated at all dose levels that we tested, and single doses of Aritinercept led to robust and long-lasting reductions in immunoglobulins supportive of once-monthly dosing. Aurinia plans to initiate further clinical studies of Aritinercept 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 Aritinercept, 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. With that, let me ask the operator to now open up the line for Q&A. Operator?
Certainly. When conducting a question and answer session, if you'd like to be placed into the question queue, please press star one on your telephone keypad. We ask you, please ask one question and one follow-up. Once again, that's star one to be placed into the question queue, and please ask one question and one follow-up. Our first question is coming from Stacy Ku from TD Cowen, and your line is now live.
Hey there. Thanks so much for taking our questions and congratulations on the progress. Understanding you're not able to maybe talk about the clinical study 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? 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? The second question, 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, how are you thinking about that?
Thank you so much.
Hey, Stacy, thanks for the question. As you know, there's a lot of excitement about the BAFF-APRIL 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. 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 ease on dose selection. We're trying to leave it at that.
In terms of the doses we're intending to take forward, obviously, you know, Greg, I can kind of ask you maybe just to elaborate a little bit on that. You want to go, Greg?
Sure. Thanks. Thanks, Stacy, 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 ascending 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 that. We're very encouraged with the SAD results and the information it provides to inform the multiple ascending 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?
IP life on the product, we continue to file IP in and around the compound. We have not disclosed the full life on it, but know that we continue to add to the patent portfolio as early as the results that we are seeing from this SAD study. The other question was about, can you repeat the second question, Morrie?
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 Leerink 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 BAFF-APRILs, 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 Aurinia might be able to control their destiny in those indications in particular? What is the timeline to generate phase two data in these studies? We noticed that the 150 milligram dose group had almost three times as many patients. I was just wondering why that was.
On the indications, as we've already said, 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. 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. 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. Obviously, this is going to be important for everyone developing in this space moving forward. If everyone's hypothesis around the potential breadth and depth of indications works out, this could be a very large area. We're excited about that.
Greg, do you want to talk maybe just a little bit about the 150 milligram?
Sure, yeah. Thanks for the question. Going into the study, the development of the single ascending dose study, our allometric scaling relative to the non-human primate-based work we had done indicated or 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. That is why we "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. 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.
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. I had one question on the safety and one on the injection side. For the 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.
Greg, feel free.
I'm sure. Thank you, Peter. Yeah, so just specifically, obviously, this is a small study, so we did not observe any dose-dependent effects on upper respiratory tract infections, for example, where it was a very modest number of events. These were relatively mild and very self-limited, did not require any intervention. We were very encouraged by those, so 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. Transient, mild, benign.
That's great. My second question is regarding injection volume. Could you give us more color on that? The reason I ask is, do you think your drug also could be suitable for the self-administration at home?
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's ongoing, and we're confident that given the physiochemical properties of our Aritinercept 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 prefilled syringe or an autoinjector and a standard gauge needle. The hope would be that that could be administered at home as well.
That's great. Thank you very much for taking my question. Congrats again.
Thank you. We reached 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.