Ionis Pharmaceuticals Inc at Leerink Partners Global Healthcare Conference Transcript

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

Question: Mani Foroohar - Leerink Partners - Analyst : Okay. I had a insightful moment. Beth, it's good to have you. You may be the only team that flew from better weather here to visit us in Miami. But before we go diving into details on pipeline, et cetera, let's talk a little bit on the balance sheet. I know this has been sort of an increasing topic, which is not surprising, as we approach one credit security on the balance sheet going into current status. Obviously, that's less of a concern for a company that has Ionis' fairly robust balance sheet as well as sort of opportunities to access capital. But it's something that comes up as, hey, how you think about strategy, convert versus other types of debt and sort of what the long-term complexion of the capital stack should look like?

Question: Mani Foroohar - Leerink Partners - Analyst : So let's slide from the balance sheet over to the income statement, operationally speaking. Let's talk a little bit about what we should expect from Tryngolza launch in terms of metrics as the launch progresses, both -- revenue, obviously. But also like how we should think about end market metrics, what you will be tracking internally and what we should expect in your quarterly reports as we evaluate the speed of launch, acceleration, et cetera?

Question: Mani Foroohar - Leerink Partners - Analyst : So while we're on that topic of patient populations. This is not the last patient population you're going to be studying here. Obviously, while FCS, there's tremendous unmet need, a lot in good to be done, with different price point than the eventual sHTG population. So how do you think about price when you're looking at two very different populations, price to value, what the metrics are? And operationally, how you transition from one model to another?

Question: Mani Foroohar - Leerink Partners - Analyst : You do have a competitor who is sort of following on in both these indications that is likely to be in FCS fairly briefly before you transition to the broader indication. How do you think about contracting price as a competitive lever in a world where you have an FCS and sHTG indication versus a competitor who is early on in an FCS launch?

Question: Mani Foroohar - Leerink Partners - Analyst : So I want to take this exact sort of dynamic -- well, a similar dynamic and move it to a different indication, we're playing, you're more of a fast follower, second, third to market dynamic in TTR. WAINUA has been launched, is an injectable, self-administrated, at-home therapy, competing with a market leader, which is an approved in office subcu in Amvuttra. Obviously, Amvuttra is priced for polyneuropathy, it has done quite well for Alnylam for some time. Presuming approval at the end of this month of cardiomyopathy, how do you think about potential price competition contracting? And how is this analogous or not analogous to the Tryngolza dynamic for you looking forward?

Question: Mani Foroohar - Leerink Partners - Analyst : So let's talk a little bit about CARDIO-TTRansform, your ongoing pivotal Phase 3 in that market. A little bit different of a design than HELIOS-B, which is Alnylam study. It's certainly different than [Attribute]. Reflecting in part the fact that you have AstraZeneca supporting you, so you have -- it's a different level of resources in any of these other players; talk to me about how the design of CARDIO-TTRansform informs a competitive position in the market you expect to launch into and into a partially genericized market.

Question: Mani Foroohar - Leerink Partners - Analyst : So we're touching on a fairly controversial debate there. So taking a step back, operationally, how does one reprice a higher-priced drug to a markedly lower price? And how is that different in an at-home administered drug or self-administered drug, this was at Part D, versus something given in office, whether it's subcu, IV, any kind of Part B? Mechanistically, how does that work? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 11, 2025 / 7:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at Leerink Partners Global Healthcare Conference

Question: Mani Foroohar - Leerink Partners - Analyst : One certainly hope so on behalf of patients.

Question: Mani Foroohar - Leerink Partners - Analyst : So I'm going to hop over to another large but complex and competitive rare disease market that Ionis will be entering on a stand-alone basis, which is donidalorsen and HAE. I'm going to ask something we talked about last night, which is based upon the work that you and your team have done, obviously, in prep for the launch deeply (inaudible) in this market. What is the churn rate for HAE patients on a prophylaxis therapy -- prophylactic therapy to a different prophylactic therapy on an annual basis?

Question: Mani Foroohar - Leerink Partners - Analyst : So we had a fairly stable duopoly. But there were some older -- frequently administered older therapies for HAE, but we frequently had supply issues because of plasma derivation. So we had a -- what was a fairly stable duopoly, which became a higher switch market with the introduction of a differentiated product, in this case, the oral. And now we're having a second differentiated product, a less frequently administered product with a different MOA in donidalorsen. Looking out beyond that, we have a gene editing approach currently in a pivotal study, as well as your own editing partnership with Metagenomi, which includes equity ownership. Talk to me how you think about not just the disruptive and churn driving opportunity that the introduction of donidalorsen offers, but also how you expect to participate in the eventual introduction of potentially onetime aspirationally, functionally curative, I'm trying to be careful here, not use the C word dangerously; genetic medicines into this market? How do we think about that sort of life cycle generational management of what's going to be a meaningful franchise for Ionis?

Question: Mani Foroohar - Leerink Partners - Analyst : So we're coming down the end of our end of our alloted time. We talked about a lot of different elements of the pipeline. We didn't get to Angelman, we didn't get to -- I know (inaudible).

Question: Mani Foroohar - Leerink Partners - Analyst : But let's talk about exactly that dynamic, the perfusion of other assets, which realistically would take a ton of capital to all move into Phase 3. How do we think about early= and mid-stage assets that live inside the Ionis pipeline, that should perhaps be partnered? And how do you decide what to partner, what not to partner? And to what extent does that lead into our very first question around managing sources of capital?