Ionis Pharmaceuticals Inc Donidalorsen Webcast: OASIS-HAE and OASIS-Plus: OLE + Switch Data Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Myles Minter - William Blair & Company, L.L.C. - Analyst : Hi. Thanks for taking the questions. One for Dr. Reidl and one may be for the company. Dr. Riedl, I was just wondering whether or not with the donidalorsen data in hand like you'd be convinced to put patients on dosing every two months instead of one month, which does look more efficacious from this data in our view. If you would I mean what type of HAE patient would you recommend for that extending dosing interval? And would you recommend maybe starting on once monthly and then switching to a once every two months if those were -- if those patients are well controlled, that's the first one. And then maybe for the company, we haven't really talked about CSL Garrett [testimab] in the competitive profile against that? I mean, how are you thinking about positioning against that product if that does receive approval by the end of the year? Thanks very much. Marc Riedl - University of California - Clinical Director, US HAEA Angioedema Center & Clinical Service Chief, Division of Allergy & Immunology Yeah, so I can start, happy to answer the question about treatments for patients. As you may know, I mean, HAE is such a variable condition and so it really is sitting down with each patient and making that shared decision discussing not only the multiple of treatment options, but the potentially different doses of medicine. So I think, well, it's very hard to characterize a certain type of patient that you might prescribe a specific medication for, I would agree with you that based on the data we have in hand, the Q4 week dosing looks to be perhaps more affected, at least in the short run. And I think, our rational strategy we may discuss with patients, if this is approved is to start, if that Q4 week dosing and that potentially move out to Q8 week dosing. That said, there are patients where the burden of treatment is very important to them, meaning that there -- it's important that they dose less often. So it's possible depending on the labeling and indication with the approval that one might in certain instances start with the Q8 week dosing and see how patients do. So I think it's very individualized to sort of encapsulate the answer, it'd be something we'd have to discuss with patients based on the data we have in hand.

Question: Myles Minter - William Blair & Company, L.L.C. - Analyst : Thanks for the questions. Congrats on the data.

Question: Yanan Zhu - Wells Fargo Securities, LLC - Analyst : Great. Thanks for taking our question. Congrats on the results. I have a question for the doctor and the question for the company. Question for the Dr. Riedl, with the data and with the Switch studies it results, what percentage of your current attack free patients would you expect initiate switching over, let's say, six months a period of six months? And then a question for the company, there is -- there seems to be a substantial difference in the baseline HAE attack rates for the donidalorsen groups versus the placebo group. I'm wondering how does that difference at baseline may have affected the attack reduction rate or reduction in attack rate -- attacks in a --on a primary endpoint. Thanks. Marc Riedl - University of California - Clinical Director, US HAEA Angioedema Center & Clinical Service Chief, Division of Allergy & Immunology And so to answer your question about the Switch patients, I'll be honest -- I'm notoriously bad at predicting what treatments patients will gravitate towards, because of all the factors that go into that decision. And so I'm not going to be able to provide you an estimate on what percentage of a certain group may transition if and when donidalorsen has on the market. What I can tell you and I what I think is interesting about the Switch study is that clearly there are patients interested in additional therapies, as was pointed out during the presentation. And I think we don't actually know why patients enroll in specific trials. We don't know the reasons for their enrollments in the Switch study. But one possibility, of course, is that people are not entirely satisfied with their treatment that they're on. And so there were those patients in the Switch study that were previously on lanadelumab and so -- well, I can't give you a percentage, it suggests that there are people on any and all of the current therapies that are interested in something -- in another option, including potentially donidalorsen. So I think there is interest it's just very hard to predict, what percentage of people will shift to be totally honest.

Question: Yanan Zhu - Wells Fargo Securities, LLC - Analyst : Very helpful. Brett, just to maybe clarify, I think what this might have meant is that had the patients on the equal footing in terms of baseline and the number for the placebo-adjusted attack rate could be even higher if that's the right interpretation?

Question: Yanan Zhu - Wells Fargo Securities, LLC - Analyst : Got it. Very helpful. Thank you.

Question: Jason Gerberry - BofA Global Research (US) - Analyst : Hey, guys, thanks for taking my question. Do you see this survey indication on preference for doni as a good indicator of a willingness to Switch? And what sort of resistance do you think you'll face from physicians when it comes to switching a patient that's under control? And then just -- I didn't see a percentage tax-free rate, which I know was a metric of interest to some I think tax zero was around 30% to 40% at the two different dose levels for Q4 week, if I have that right. So just wondering how you stack up on that metric. Thanks.

Question: Allison Bratzel - Piper Sandler & Co - Analyst : Hey, guys, good morning, congrats on the data and thanks for taking my question. Really just a follow-up on some of the prior discussion, probably for Kyle. Which is how do you anticipate the Switch data is going to resonate with both patients and with physicians? And just what are your plans to incorporate it into the launch marketing strategy. And I think a lot of us have viewed this as a historically like sticky market, is it your sense that the switching data and can help overcome that stickiness? And then just secondarily, could you talk to how you think the Switch data kind of strengthens your hand when you talk to -- when you have had initial conversations with payers? Thanks.

Question: Yaron Werber - TD Cowen - Analyst : Great. Thanks for taking my question, also congrats on the data. So I have two questions. One for the physician, please, and one to the company. I guess to the physician as the drug gets approved, in 12 months or so from now, with the filing, do you give us a sense kind of how do you think you're going to use it? Do you call patients to switch them, you give them the offer -- the option to switch? Do you use it in new patients immediately? And then for the company, the Q4 week data, as everybody sort of noted, looks better in the first 25 weeks. But as you stay on Q8 for longer those two begin to look sort of similar. Is that something that's going to be in the label? So both options are given and again, maybe even back to the physicians, do you treat everybody Q8 weeks? Or do you treat Q4 weeks and then switch to Q8 weeks? Sorry for all these questions. Thank you. Marc Riedl - University of California - Clinical Director, US HAEA Angioedema Center & Clinical Service Chief, Division of Allergy & Immunology So I can start, when new therapies come along, our practice is not to proactively contact patients, although this is a very well educated and aware patient population. So they often contact us when there's something new that comes along. They're very in tune with developments, we do though however, as we see people back in our clinical practice and we on average, we see these patients probably twice a year. If they're not doing well, we see them more often. Occasionally, we'll just see patients once a year if they're really doing well. But during their follow-up, one of our steps is to review what's new in the HAE space. And so that includes any new therapies that have been FDA approved and so that's a scenario where we discuss with them the new treatment option, the risks benefits and all the data that we've covered. And I do that very briefly. And that gives us an opportunity -- in the patient an opportunity to discuss whether they're interested in making a change in their management. So it sort of on a rolling basis in the year that follows these new medication approvals. And so that allows us, like I said, to incorporate change for patients who may want to Switch therapy. And of course, with new patients, we go over all of the options that are available at the time, including sometimes investigational drugs if patients are interested in clinical trials. So I would see this being discussed both with obviously existing treatment -- treated patients, but certainly with newly diagnosed patients also. without the prior written consent of Thomson Reuters. 'Thomson Reuters' and the Thomson Reuters logo are registered trademarks of Thomson Reuters and its affiliated companies.

Question: Yale Jen - Laidlaw & Company - Analyst : Good morning, and thank you for the question and congrats on the data. I just had two, one for doctor and one for the company. For the doctor that the secondary endpoint, the week 5 to 25. I'm just curious what's the a value or difference between that from one to the primary data of week 1 to 25? Marc Riedl - University of California - Clinical Director, US HAEA Angioedema Center & Clinical Service Chief, Division of Allergy & Immunology Yeah, I think this is mostly recognizing the mechanism of action of the medication, meaning that's as you block the production of pre kallikrein, you still have to use up the existing pre kallikrein which can take a couple of weeks a few weeks. And so the MOA at least even a mechanistic standpoint, you would expect it to be fully optimized or the pharmaco dynamic effect to be the greatest starting at about that month the five week. So I think it's a little hard to know because we don't have measurements earlier, than that it's possible that the drug could work faster. But I think that's the rationale for looking from 5 to 25 instead of 1 to 25 as the recognition that it would take from a mechanistic standpoint, it could take a couple of weeks for the effects to fully be realized in terms of knocking down those pre kallikrein levels.

Question: Yale Jen - Laidlaw & Company - Analyst : Okay, great. Thanks a lot again. Again congrats.

Question: Kostas Biliouris - BMO Capital Markets Corp. - Analyst : Hi, everyone. Thanks for taking my question and congrats on the data. A quick question from us on the Switch study, you mentioned that a 8% remaining in the study. So I was wondering if you can provide a little color around these 12%, that did not remain -- was not remaining in this study? Was the reason purely the attack rate well up or any other feelings that these patients had potentially made them suites back and any characteristics of these patients that made that drug not worked very well in these patient potentially. Thank you.

Question: Kostas Biliouris - BMO Capital Markets Corp. - Analyst : I get it. Very helpful. Thank you.

Question: Michael Ulz - Morgan Stanley & Co. LLC - Analyst : Hey, guys, thanks for taking the question and congrats on the data as well. Maybe just one on the Switch study. Looks like there was a slightly lower preference for donidalorsen, when patients switch from lanadelumab, it was around 72% compared to the other two agents, which were north of 90%. So just curious, any factors driving that you could maybe shed a little light on? Thanks.

Question: Michael Ulz - Morgan Stanley & Co. LLC - Analyst : Got it. Thank you.

Question: David Lebowitz - Citi Investment Research (US) - Analyst : Thank you very much for taking my question. Earlier in the call, you talked about how all the data across the Phase 2 OLE, the Switch study and of course, pivotal will be submitted. Which of these components, do you think a standard obviously the Phase 2 and 3 certainly, but which other components do you think actually stand it, reasonable chance of appearing in the label and which would you think would be a tougher debate with the agency?

Question: David Lebowitz - Citi Investment Research (US) - Analyst : Thank you for taking my questions. without the prior written consent of Thomson Reuters. 'Thomson Reuters' and the Thomson Reuters logo are registered trademarks of Thomson Reuters and its affiliated companies.