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Inside Sionna’s Bid To Normalize CFTR Function · Lab to Lives

• 0:32
  SPEAKER_01: Welcome to another episode of Transformation and Trials.
• 0:34
  SPEAKER_01: Today we're going to dive into a very exciting topic.
• 0:38
  SPEAKER_01: We're going to look at what it takes to build a company in a breakthrough field.
• 0:42
  SPEAKER_01: We're going to look at both uh the science side of things, but also the actual company building.
• 0:47
  SPEAKER_01: I'm very excited to have two guests with me in the studio.
• 0:50
  SPEAKER_01: One is uh Charlotte McKee, and I also have Mike Clunin.
• 0:54
  SPEAKER_01: And Charlotte and Mike, would you mind just saying a couple words to my listeners about uh what you currently do?
• 0:59
  SPEAKER_00: Go ahead, Charlotte.
• 1:00
  SPEAKER_00: You can go first.
• 1:01
  SPEAKER_02: Yes, I'm Charlotte McKee.
• 1:02
  SPEAKER_02: I'm the chief medical officer of Siona Therapeutics.
• 1:06
  SPEAKER_02: We are a biotech company based in the U.S.
• 1:09
  SPEAKER_02: focusing on cystic fibrosis.
• 1:11
  SPEAKER_00: And I'm Mike Kloonan.
• 1:12
  SPEAKER_00: I'm the CEO of Siona.
• 1:14
  SPEAKER_00: I've been here now a little over four years.
• 1:16
  SPEAKER_00: And as Charlotte said, we are focused on revolutionizing the treatment of cystic fibrosis.
• 1:20
  SPEAKER_00: We're going after a very differentiated target, different than what the standard of care goes after.
• 1:24
  SPEAKER_00: And it's been a journey that has actually gone back over 15 years when you think about where Siona came from, which I'm sure we'll get into later in the conversation.
• 1:31
  SPEAKER_01: Very much looking forward to that.
• 1:33
  SPEAKER_02: Where are you dialing in from today?
• 1:35
  SPEAKER_02: I'm at Siona's offices in Waltham, Massachusetts.
• 1:38
  SPEAKER_00: And I'm in the home office just outside of that, because I'm in need of Massachusetts.
• 1:42
  SPEAKER_01: Awesome.
• 1:43
  SPEAKER_01: I am in Copenhagen today.
• 1:45
  SPEAKER_01: Nice.
• 1:46
  SPEAKER_01: Well, I would be curious to hear more about what is the current state of assistive fibrosis treatment.
• 1:52
  SPEAKER_02: So the current state, we are in a world where maybe 90% plus of people with CF, which is a genetic disease, a severe, potentially fatal genetic disease, 90% plus of patients have at least the possibility of using a relatively new class of medications called CFTR modulators.
• 2:17
  SPEAKER_02: These are currently approved medicines that improve the function of the CFTR protein.
• 2:25
  SPEAKER_02: CFTR is the protein that goes wrong in CF.
• 2:29
  SPEAKER_02: That's it's an ion channel that conducts chloride and then water and mutations in the gene for CFTR are what cause CF.
• 2:40
  SPEAKER_02: And so one company, Vertex, where I used to work, I used to lead the CF clinical group at Vertex.
• 2:47
  SPEAKER_02: One company so far has been able to develop small molecules or pills that improve the function of CFTR.
• 2:57
  SPEAKER_02: And so there are still a small population of patients that don't have CFTR modulators approved, but for the vast majority of people, there is some CFTR modulator approved.
• 3:10
  SPEAKER_02: Now, as good as that has been, most of those patients who can use CFTR modulators don't yet have normal CFTR function.
• 3:21
  SPEAKER_02: And we know that through the CFTR biomarker of sweat chloride.
• 3:26
  SPEAKER_02: So while the approved modulators have improved the function of CFTR, and as a result, have improved clinical outcomes, lung function, long-term outcomes, we know from the epidemiology and from the real-world data that most of those people are not yet at normal.
• 3:47
  SPEAKER_02: And that is the opportunity or the possibility that we are working towards with this differentiated target that is not directly addressed by any of the approved CFTR modulators called NBD1.
• 4:02
  SPEAKER_02: That's a part of the CFTR protein that is most deranged or dysfunctional in the most common mutation in CF 508 DM.
• 4:15
  SPEAKER_02: So that's what we're working on.
• 4:17
  SPEAKER_02: And we really hope to move the needle significantly on what is the current standard of care.
• 4:24
  SPEAKER_01: That is an amazing development.
• 4:26
  SPEAKER_01: But also sounds like a lot has happened within this uh field, but a lot more is yet to come.
• 4:32
  SPEAKER_00: That's right.
• 4:32
  SPEAKER_00: That's our goal.
• 4:33
  SPEAKER_01: And maybe Mike, then I can ask you, how does one uh actually build a company that can deliver true the drug potential of uh revolutionizing this treatment?
• 4:42
  SPEAKER_00: Yeah, and I should take you back to the history as I sort of alluded to the upfront, because it really is a journey now that's been about 15 years in the making.
• 4:49
  SPEAKER_00: So when we're Siona, we spun out of Synofi back in late 2019.
• 4:54
  SPEAKER_00: But the science behind our programs goes all the way back to GenZyme, as I said, well over a decade now.
• 4:59
  SPEAKER_00: And when Synofi merged with GenZime, the programs continued at Synofi.
• 5:03
  SPEAKER_00: And at one point in time, these programs were the largest research programs within Synofi.
• 5:08
  SPEAKER_00: So a big effort was put in against these from GenZime to Synofi.
• 5:12
  SPEAKER_00: And then we benefit from that.
• 5:13
  SPEAKER_00: So we spun out in 2019 really because of a strategic shift that happened at Synofi at that time.
• 5:18
  SPEAKER_00: They were starting to deprioritize some of their rare diseases that came from GenZime.
• 5:23
  SPEAKER_00: And fortunately for us, they gave our two co-founders the opportunity to find and build a company on their own before they did a in light or outlicensing uh endeavor on these programs.
• 5:33
  SPEAKER_00: And so that's how Siona came to be back in 2019.
• 5:36
  SPEAKER_00: It was spun out of Sinofi.
• 5:38
  SPEAKER_00: The seed capital was put in that time from three different organizations, TPG, RA Capital, and the Cystic Fibrosis Foundations.
• 5:46
  SPEAKER_00: We sit here and now four to five years later since Siona was formed, we have multiple programs in the clinic.
• 5:52
  SPEAKER_00: We're going after this challenging target in NBD1, as Charlotte said, but we've made significant strides of getting that much closer to having an opportunity to dose patients now as we move into phase two later this year.
• 6:02
  SPEAKER_00: But we wouldn't be where we are, right?
• 6:04
  SPEAKER_00: From because of the investment that was made between Genzyme, Sonophi, and now Siona, we are in this position to really potentially be drugging the undruggable.
• 6:12
  SPEAKER_00: That was the label that NBD one had for many, many years.
• 6:15
  SPEAKER_00: So that is the legacy of the company.
• 6:18
  SPEAKER_00: That is in many ways why we are where we are today, because it's a very challenging target.
• 6:21
  SPEAKER_00: We wouldn't be here without the perseverance, the level of investment that was made prior to Siona forming.
• 6:26
  SPEAKER_00: And then since Siona formed, right, we were a hyper-focused CF company.
• 6:31
  SPEAKER_00: So we took the science that emerged from Genzyme and Sinofi.
• 6:34
  SPEAKER_00: We've advanced multiple compounds into the clinic as we've talked about.
• 6:37
  SPEAKER_00: We have a very rich and deep portfolio now across several targets, including NBD-1 and a couple of others that we can use in combination.
• 6:44
  SPEAKER_00: But we've really built this in a very disciplined way, right?
• 6:47
  SPEAKER_00: Raising the capital.
• 6:48
  SPEAKER_00: And we can we can talk through the financing strategy and how we've done that.
• 6:51
  SPEAKER_00: We've hired a world-class group of leaders, both that understand CF but rare disease, but we've been very disciplined in how we've built the organization as well as we've had success, you know, we've built the organization to the next stage.
• 7:03
  SPEAKER_00: And then we've tried to build a culture, right, that really embraces the things that Tar Charlotte talked about.
• 7:08
  SPEAKER_00: We're going after something that is very transformational, but our North Star has always been a focus on the patients.
• 7:14
  SPEAKER_00: How can we provide more options for patients, provide potentially new and differentiated options for them?
• 7:20
  SPEAKER_00: And that's what ultimately drives us today, right, to continue to move these programs forward to get even closer to hopefully benefiting patients in the future.
• 7:28
  SPEAKER_01: I would be curious to learn more about the development of your clinical programs.
• 7:31
  SPEAKER_01: What are some of the tricky things about working within this specific area?
• 7:35
  SPEAKER_02: Well, maybe I'll start with one of the things that is not tricky and one of the things that has been a huge advantage.
• 7:41
  SPEAKER_02: First of all, I will say we have been a partner from the very beginning.
• 7:46
  SPEAKER_02: Going back to the Genzyme days, the CF Foundation.
• 7:49
  SPEAKER_02: It's a very large advocacy organization and funding organization in CF.
• 7:54
  SPEAKER_02: And so we've had the privilege and the opportunity of being, as Mike alluded to, deeply partnered with them from the beginning.
• 8:00
  SPEAKER_02: And so that's actually been something that has really helped us and that's allowed us to have a deep partner in discussing study design and opportunities and the unmet need.
• 8:12
  SPEAKER_02: There is also in cystic fibrosis a very predictive in vitro assay called the CFHBE or human bronchial epithelial cell assay that's been leveraged for the approved modulators very effectively.
• 8:28
  SPEAKER_02: Our scientists have been running this assay.
• 8:31
  SPEAKER_02: It's an assay that was developed by academics way, way back in the day.
• 8:35
  SPEAKER_02: And so our scientists have learned and worked on it, run it very rigorously.
• 8:40
  SPEAKER_02: And so that's actually another de-risking element to working on this very challenging target and allowing us to get an early read on and de-risking read on both what whether things are working, these complex drugs that our scientists are discovering, whether it's working, and then how much we have to put into the body in order to predict that we'd have a clinically meaningful benefit.
• 9:09
  SPEAKER_02: And so we've been able to leverage that really effectively through our trials that are now the precursor, as Mike said, to getting, you know, just we're just on the verge of starting our first studies in people with CF, phase two studies.
• 9:25
  SPEAKER_01: That's very exciting.
• 9:26
  SPEAKER_01: I'm also curious about the fact that the CF Foundation has been so much involved.
• 9:30
  SPEAKER_01: I have not seen that before.
• 9:32
  SPEAKER_01: Tell me more about how did that uh partnership uh come to be.
• 9:35
  SPEAKER_00: Yeah, as I said, it actually goes back to the really the genesis of these programs all the way back at Gen Zime.
• 9:40
  SPEAKER_00: The Cystic Gibrosis Foundation provided funding even at Gen Zyme at that time.
• 9:44
  SPEAKER_00: They stayed connected to the programs and continued to fund some of the programs through Sinofi.
• 9:48
  SPEAKER_00: And then when we spun out, as I said, they took a seed financing round, they were involved in the seed financing round that they took equity, right?
• 9:55
  SPEAKER_00: And so they've been a financial partner, but also a collaboration and strategic partner for us, right?
• 10:02
  SPEAKER_00: It goes beyond just the economics that the CFF has provided to the organization.
• 10:06
  SPEAKER_00: They fundamentally believe in what we're trying to do, create more options for patients, a first in class, a differentiated approach, including NBD-1.
• 10:14
  SPEAKER_00: And we use them, you know, we're very fortunate to leverage a lot of the expertise the CFF has, right?
• 10:19
  SPEAKER_00: They've got a tremendous amount of resources and knowledge in the space, commitment to the community, and and the clinical trial network that we rely on that Charlotte can get into as well.
• 10:28
  SPEAKER_00: So it's a very deep relationship that we've had that goes back many, many years.
• 10:32
  SPEAKER_00: And I will say they're an excellent partner.
• 10:34
  SPEAKER_00: Of all of the not-for-profit organizations I've worked with, they are they are top class, right?
• 10:39
  SPEAKER_00: They're they're way up there with anybody in terms of how organized they are, how sophisticated they are, and thinking about what the needs of the patients are and how to deliver innovative medicines.
• 10:47
  SPEAKER_00: It's it's really been a pleasure, honestly, to work with them in the time that I've been here now for four years.
• 10:52
  SPEAKER_00: I've really valued the partnership.
• 10:53
  SPEAKER_00: And I know Charlotte can speak to the same thing.
• 10:55
  SPEAKER_02: I I would actually say, you know, interestingly enough, the CF Foundation was actually instrumental in the approved modulators as well as an early funders, partners, and the European cystic fibrosis groups and those networks are fantastic as well.
• 11:11
  SPEAKER_02: And really, you know, we're just so lucky in many ways, and you know, to be able to leverage those deep research and clinical networks, both in the US but also in Europe, Australia, Canada, and elsewhere.
• 11:24
  SPEAKER_01: It must be very hard not to be patient-centric when uh the patients themselves are so deeply ingrained into the the development of the drugs.
• 11:32
  SPEAKER_01: Right.
• 11:33
  SPEAKER_02: I'm a lung transplant pulmonologist originally, and so I have this deep appreciation for how meaningful an improvement in in these patients' quality of life and lifespan can be.
• 11:46
  SPEAKER_02: So it's not hard at all.
• 11:48
  SPEAKER_01: I would also be curious with starting a brand new organization and trying to build it from the ground up, what has been your journey?
• 11:56
  SPEAKER_01: Like what has been the steps that you have taken to kind of start building something that has a scientific background, but it has to eventually evolve into a product that is ready to hit the market?
• 12:06
  SPEAKER_00: Our journey has been very similar.
• 12:07
  SPEAKER_00: Charlotte and I joined very weeks apart, right, from each other.
• 12:09
  SPEAKER_00: So we've been on the same journey, which has been a pleasure.
• 12:12
  SPEAKER_00: And if you again, if you go back, what really started, I think, the journey for both Charlotte and I was the science behind these programs and the fact that NBD-1 created this opportunity to do something very, very different and novel.
• 12:23
  SPEAKER_00: And so it really attracted, I think, both of us to this company.
• 12:26
  SPEAKER_00: And then what we and then this opportunity, right, to positively disrupt the CF market for the benefit of patients was very, very unique.
• 12:34
  SPEAKER_00: And we had a great set of investors, including the CFF, as I said.
• 12:38
  SPEAKER_00: And we just had this great opportunity, not only to do something very meaningful in CF, but as you said, Ivana, to build a company, right?
• 12:45
  SPEAKER_00: When I joined, I think I was Employee 11 and Charlotte was Employee 12.
• 12:48
  SPEAKER_00: It was something along those lines.
• 12:50
  SPEAKER_00: We joined a very small research organization, and we've been able to obviously advance now into the clinic.
• 12:56
  SPEAKER_00: And as I think about this last four-year journey, there was a couple of key points I'd say in time that has led us to where we are today.
• 13:03
  SPEAKER_00: So one was bringing in the right people, right?
• 13:06
  SPEAKER_00: So we built the company over time.
• 13:07
  SPEAKER_00: We're now over 50 people, right?
• 13:09
  SPEAKER_00: Which may still sound small, but relative to where we came from, it's it's kind of exponential growth, right?
• 13:14
  SPEAKER_00: And you're trying to really make sure you're hiring the right people, not only for capabilities and experience, but for what they bring in terms of the culture and that their North Star aligns to what ours is in terms of the patient and our values.
• 13:26
  SPEAKER_00: We share the same values.
• 13:27
  SPEAKER_00: And we've been very fortunate.
• 13:28
  SPEAKER_00: We have a great group of people that have joined us, very talented people, but also share some of those softer things that I mentioned before in terms of value and commitment to the patients.
• 13:36
  SPEAKER_00: That's key.
• 13:37
  SPEAKER_00: And then at the same time, what you have to then do is how do you support the growth of the company, even when you're having success, you've got to finance the company, right?
• 13:44
  SPEAKER_00: So we were very thoughtful in how we approached the financing strategy and how we finance the company.
• 13:49
  SPEAKER_00: In the four plus years, we did our series B financing back in 2022, where our existing syndicate invested and we brought in some very high-quality new investors into that mix.
• 13:59
  SPEAKER_00: And then we did in our Series C about two years later, where again we expanded the syndicate, raised the capital to help us continue to invest in the clinical trials as we move these programs forward.
• 14:08
  SPEAKER_00: And then, as you may have seen, we just recently completed our IPO back in February of this year, right?
• 14:13
  SPEAKER_00: Which was a very important decision.
• 14:14
  SPEAKER_00: You don't take that decision lightly to move from a private company to a public company and all of that entails, but it was a really a great opportunity for us to provide additional capital into the company that now gives us capital runway into 2028, right?
• 14:28
  SPEAKER_00: So that gets us well beyond some of those next inflection points that we'll talk about in terms of the clinical trials that we're doing and enables us to turn those cards over and see the data and really gives us flexibility now, lots of strategic optionality to build in based on the IPO and the quality of the investors that we brought in.
• 14:44
  SPEAKER_00: So it's it's really a combination of bringing in the town at the right time, the right people, being very thoughtful and disciplined in your financing strategy.
• 14:52
  SPEAKER_00: And then there's execution, right?
• 14:53
  SPEAKER_00: There's the execution piece of this, which Charlotte and her team have had a critical part of that, right?
• 14:57
  SPEAKER_00: We've moved from that research organization, as I said, into preclinical.
• 15:01
  SPEAKER_00: Then we had our first compound in the clinic, and now we've got multiple programs in the clinic.
• 15:05
  SPEAKER_00: And so it takes an entire team, right, to execute cross-functionally.
• 15:09
  SPEAKER_00: It's not just one group that's responsible for the execution.
• 15:13
  SPEAKER_00: And so that's why hiring the people that we have, the focus and the commitment that we've been able to deliver has brought us again one step closer to the ultimate goal of getting this into the hands of patients.
• 15:22
  SPEAKER_00: So it's really those three-pronged efforts, right?
• 15:25
  SPEAKER_00: The people, the culture, the capital that you need, having great investors that support you, and then you got to execute, right?
• 15:31
  SPEAKER_00: And this is obviously a risky space in biotech.
• 15:33
  SPEAKER_00: We know not all of these programs are successful, but I think we've made very thoughtful decisions as to how we've advanced these programs and how we continue to be successful, and execution is going to be key looking forward.
• 15:44
  SPEAKER_01: I'm curious, it sounds like you've had options for your financing and also like had a nice progression within that space.
• 15:51
  SPEAKER_01: In biotech in general, right now, it is a tough time to raise finances.
• 15:55
  SPEAKER_01: What do you think made a difference for us to have options?
• 15:58
  SPEAKER_00: It is important, right?
• 15:59
  SPEAKER_00: Optionality is so critical and that you're raising capital when hopefully you're in a position of strength, right?
• 16:04
  SPEAKER_00: Because you can never really control where the market's going to be when you need to raise capital.
• 16:08
  SPEAKER_00: And every time we went into a financing, whether it was the Series B, the Series C, or the IPO, we've tried to be very thoughtful about how we're approaching the market.
• 16:15
  SPEAKER_00: We had great existing investors that we could, you know, build in conversations with our investors to figure out, understand what's important to them, how they saw the market, and really trying to ensure that we were putting the right narrative out there in terms of see on what's the opportunity that we have to create value for them and patients, right?
• 16:32
  SPEAKER_00: The IPO is probably a really good example to focus on because when we did the Series C back in 2024, we had raised enough capital where we didn't have to go back to the marketplace as quickly as we did, right?
• 16:42
  SPEAKER_00: We were actually in a very good financial position even at that time.
• 16:45
  SPEAKER_00: But as we made progress, as we started to see some of our phase one data and we started to see we were hitting some of our very important metrics, including the PK targets that we had set and the tolerability profile started to look positive even on an interim basis.
• 17:00
  SPEAKER_00: We thought there could be an opportunity for us to approach the public markets to see if there'd be a willingness to invest in Siona.
• 17:06
  SPEAKER_00: And so, but we, as you may know, there's a whole process that you go through before you become a public company that enables you to test the market, right?
• 17:13
  SPEAKER_00: You get to talk to investors ahead of making that decision and really share what we're about and what we're trying to do and the impact we're trying to make.
• 17:20
  SPEAKER_00: And we got very positive feedback in what's called the test the waters process that it really gave us confidence that people understood the value that we could create.
• 17:29
  SPEAKER_00: They saw the potential of this opportunity, really trying to disrupt this$10 billion market where one company has only been successful to date.
• 17:37
  SPEAKER_00: And we had a very differentiated approach to do that, something that could be very meaningful for patients.
• 17:41
  SPEAKER_00: And so we had a decision to make, right?
• 17:43
  SPEAKER_00: We we didn't have to flip public, we didn't have to become a public company.
• 17:46
  SPEAKER_00: But because of the strong sentiment that we received from investors that we talked with, we felt like it was a good opportunity to leverage the capital that would out be out there and increase our overall both financial and strategic optionality.
• 17:58
  SPEAKER_00: So we made the choice to go public at that time.
• 18:00
  SPEAKER_00: And in hindsight, right, the IPO window closed soon after we went.
• 18:04
  SPEAKER_00: And there's no way we didn't have a crystal ball.
• 18:06
  SPEAKER_00: You know, we couldn't tell you what was going to happen later in the year.
• 18:09
  SPEAKER_00: But I'd say with our very good investor base that we have, we had some very good conversations around if you have an opportunity to go off of positive data, which we did, and you've got strong investor sentiment that they're willing to invest in the company, you know, you can never predict the market, right?
• 18:23
  SPEAKER_00: So if you have an opportunity, take advantage of that.
• 18:26
  SPEAKER_00: We did.
• 18:26
  SPEAKER_00: We felt very confident in the ability to become a public company and the capital that we raised, we raised over$200 million as a result of that IPO.
• 18:34
  SPEAKER_00: And as I said, it puts us in a really good financial position with Cash Oneway into 2028 now, which gives us the ability to execute our plan and not have to worry about the financing at this stage.
• 18:43
  SPEAKER_00: So it is, it's a it's a debate that you have, right, with your existing leadership team, with your investors.
• 18:49
  SPEAKER_00: The market starts to tell you things and then you try to understand where the market could be heading.
• 18:53
  SPEAKER_00: But as we said, without a crystal ball, all you can really rely on is your own execution and your ability to make a decision with what you have.
• 19:00
  SPEAKER_00: And if the market's receptive, uh, we took that opportunity and we haven't looked back.
• 19:03
  SPEAKER_00: It was a great opportunity for us in hindsight, and very happy that that we made that that decision.
• 19:09
  SPEAKER_01: Yeah.
• 19:09
  SPEAKER_01: That makes sense.
• 19:10
  SPEAKER_01: Charlotte, I would be curious to hear more about what is next in this clinical program.
• 19:14
  SPEAKER_01: What are you hoping for?
• 19:16
  SPEAKER_02: So we are very excited about by the end of this year, we intend to start two really critical clinical trials for Siona.
• 19:26
  SPEAKER_02: The first is a phase two A proof of concept study, which is we call it our proof-of-concept proof of biology study.
• 19:33
  SPEAKER_02: It'll be the first time that an NBD-1 stabilizer or NBD1 targeted drug will be tested in people with CF.
• 19:42
  SPEAKER_02: So we're going to do a relatively small study based on sweat chloride.
• 19:48
  SPEAKER_02: The primary endpoint will be this biomarker of CFTR function called sweat chloride, where we'll enroll patients who are already on the standard of care.
• 19:58
  SPEAKER_02: It's tricafta, they're stable on that, and we'll give them either a pretty low dose of one of our NBD-1 modulators, cyan 719, or placebo, for just two weeks, and we'll measure the change in sweat chloride, and we'll be correlating that back to our own targets, as Mike has alluded to in that CFHBE assay.
• 20:26
  SPEAKER_02: And so our goal is to show with that study that MBD1 is truly something.
• 20:32
  SPEAKER_02: New and diff and unique, and that there's a lot of room still to improve CFTR function, even in patients who are on the standard of care and correlating back to our HBE assay in the lab, we think that's going to be a really powerful data set.
• 20:51
  SPEAKER_02: And that that study should read out in the middle of next year.
• 20:54
  SPEAKER_02: And in the meantime, our holy grail or our preferred path is to develop an NBD one-based dual two drug combination that based on our assay data, we believe could be better than the standard of care, just two drugs, and could potentially even give CFTR function, possibly even into the normal range.
• 21:21
  SPEAKER_02: And so as we're doing this proof of concept add-on to tricta study, we're also testing our first MBD1-based dual two drug combinations.
• 21:33
  SPEAKER_02: We're going to test two of them in healthy volunteers, looking for the two drugs together, their safety and their tolerability, and confirming that we're in that target zone with both of them, both of the drugs together based on our in vitro assay.
• 21:50
  SPEAKER_02: That also we plan to finish that the dual healthy volunteer study in the middle of next year, right at the same time.
• 21:58
  SPEAKER_02: We plan to read out that proof of concept study.
• 22:01
  SPEAKER_02: And if those data are all what we expect, then by the end of next year, we plan to be taking our own NBD1-based dual combination into people with CF dose ranging studies.
• 22:17
  SPEAKER_00: Yeah, just to maybe tie back your two questions, right?
• 22:20
  SPEAKER_00: The clinical and then back to the financing, part of what Charlotte just articulated.
• 22:23
  SPEAKER_00: The reason why investors got excited about Siona at the time of the IPO was because what Charlotte said, both of the compounds that we're taking forward achieved our desired PK profile to add meaningful clinical benefit either as an add-on to the standard of care or as this dual combination preferred path that Charlotte said.
• 22:41
  SPEAKER_00: And so when we did the IPO, we actually had interim data that showed both paths were enabled and people could see the potential, right?
• 22:48
  SPEAKER_00: They could see what this now had.
• 22:49
  SPEAKER_00: We had potentially two options that we could take forward.
• 22:52
  SPEAKER_00: And as Charlotte said, now we're on this path of entering phase two as an add-on.
• 22:56
  SPEAKER_00: We're going to do a healthy volunteer study with a dual combination, but both data points will read out in mid-26.
• 23:01
  SPEAKER_00: So it was very compelling when we have that data set to align to that strategy that Charlotte just outlined.
• 23:06
  SPEAKER_01: Oh, that's that's very cool.
• 23:07
  SPEAKER_01: I hope that's the clinical side of things continues to go smoothly.
• 23:11
  SPEAKER_01: I would be curious to hear more about how both of you kind of ended up in this space.
• 23:15
  SPEAKER_01: We have this like common thread in life sciences that no one chose to be life sciences.
• 23:20
  SPEAKER_01: We all kind of stumbled into it.
• 23:21
  SPEAKER_01: I would be very curious how that happened for for both of you.
• 23:24
  SPEAKER_02: Well, I'll start.
• 23:25
  SPEAKER_02: So I have been in life sciences from the beginning.
• 23:27
  SPEAKER_02: So I'm a doctor, I'm a pulmonologist, and I was at at Harvard at Brigham and Women's practicing lung transplant.
• 23:34
  SPEAKER_02: I cared for patients who had CF.
• 23:36
  SPEAKER_02: I, you know, sh shepherded them through tran through and beyond lung transplant.
• 23:41
  SPEAKER_02: So that was where I had my first taste of what kind of a disease this is.
• 23:46
  SPEAKER_02: But interestingly, I left my full-time academic career over 20 years ago.
• 23:51
  SPEAKER_02: And so I went into drug development hoping that someday I could potentially be part of discovering and bringing drugs to patients that could make their lung transplant journey either obsolete or better.
• 24:06
  SPEAKER_02: In cystic fibrosis before my days at Vertex with the with the approved modulators, there I certainly had the privilege of being part of something that did impact, you know, the types of patients I had cared for back in my academic days.
• 24:20
  SPEAKER_02: But I will say once I decided that I'd done what I went to Vertex to do, I didn't know that someone had cracked the code on NBD one.
• 24:31
  SPEAKER_02: So I was both surprised and blown away, to be honest, when I first heard about Siona.
• 24:38
  SPEAKER_02: And that was an opportunity I just couldn't say no to.
• 24:41
  SPEAKER_02: Because, you know, for me, really that has the potential to finish the journey I started.
• 24:46
  SPEAKER_02: And so that that was just too too wonderful to say no to it.
• 24:50
  SPEAKER_00: And for me, I started my journey into biotech and pharma really started more on the consulting side.
• 24:55
  SPEAKER_00: My first entry was I was working at Bain and Company as a strategy consultant and really started to focus on healthcare and really loved the industry, right?
• 25:03
  SPEAKER_00: I had always loved science and the fact I loved the intersection of business and science, right?
• 25:08
  SPEAKER_00: That that I saw in the strategy consulting work I was doing at Bain.
• 25:11
  SPEAKER_00: But after a few years of doing that, I really wanted to get into a company, right?
• 25:15
  SPEAKER_00: Where you're you would be dedicated and not sort of rolling from project to project and company to company.
• 25:19
  SPEAKER_00: And that's when I had the opportunity to join Biogen back in 2003.
• 25:23
  SPEAKER_00: And I joined at that time, it was a role that was sort of finance, business development, and strategy.
• 25:28
  SPEAKER_00: And it gave me a lot of breadth across the biogen organization, the portfolio and the business side of things.
• 25:33
  SPEAKER_00: And then I stayed there for 14 years and took on various roles, actually made a transition to the commercial side of the organization.
• 25:39
  SPEAKER_00: And uh from there I joined Sage Therapeutics as the chief operating officer, which was focused on mental health and postpartum depression.
• 25:46
  SPEAKER_00: Had a great opportunity for four years there.
• 25:48
  SPEAKER_00: But much like Charlotte, what attracted me to Siona ultimately as this CEO was something very unique and different that could be done in CF with NBD1.
• 25:57
  SPEAKER_00: Again, this sort of holy grail target that was considered undruggable, but that we could do something very transformational for patients.
• 26:03
  SPEAKER_00: As we talked about, we got to build it from this 10-person organization, which is very rare.
• 26:08
  SPEAKER_00: And when you think about your career, when you sort of move through various organizations to have an opportunity like that to really build something from scratch, bring the people in together, build the culture together, and ultimately with that patient as your North Star, it was just too good to pass up, right?
• 26:22
  SPEAKER_00: The data supported it, the science supported it, but it it had the elements of everything that I was looking for to be a CEO, and I couldn't be any more proud of being part of the organization this past four plus years.
• 26:32
  SPEAKER_00: We've only completed part of the journey, but there's been a lot that we've done over this period of time, and we look forward to the next several years of continuing the path that we're on.
• 26:41
  SPEAKER_01: I love both of your journeys.
• 26:42
  SPEAKER_01: It's always exciting to see how people actually got to where they are.
• 26:45
  SPEAKER_01: Well, as we start rounding off this episode, I would like to ask both of you the question that I always ask my guests towards the end, and that is if I gave you the transformation trials magic wands that can change one thing in the life sciences industry, what would you wish to change?
• 26:59
  SPEAKER_00: There are things like AI, right?
• 27:01
  SPEAKER_00: And how we how we can continue to leverage AI.
• 27:03
  SPEAKER_00: I think it's we're still scratching the surface.
• 27:05
  SPEAKER_00: I mean, AI has been around for a while, but it it the end game for us should be about if I could wave a wand, how do we get these medicines to patients faster, right?
• 27:13
  SPEAKER_00: And so when I say AI, that's one of those things that I think we could potentially leverage.
• 27:17
  SPEAKER_00: Where we continue to look at ways that we can do that better.
• 27:20
  SPEAKER_00: There's also how we engage with the FDA, right?
• 27:22
  SPEAKER_00: As an example of are there ways we can engage more quickly, real-time feedback, right, that enables us to move these programs through faster and get them to patients.
• 27:30
  SPEAKER_00: So to me, it would always be about that.
• 27:32
  SPEAKER_00: What else could we do that this is the risk reward scenario for patients and all the constituents?
• 27:37
  SPEAKER_00: But at the end of the day, we shorten the time that it gets in patients' hands because that's ultimately what's going to do the greatest good is the sooner we can get medicines to patients, the better they can have the benefit of being on them.
• 27:47
  SPEAKER_00: And so I think it's our job to do that.
• 27:49
  SPEAKER_00: How can we speed things up and get them there faster, but yet do it in a way where the benefit risk profile is very clear.
• 27:54
  SPEAKER_00: So those are the things that come to mind for me is whether it's AI, whether it's other modalities, whether it's you know engagement with the regulator, et cetera.
• 28:01
  SPEAKER_00: To me, that's where I would focus if I could wave magical on shaving time off, right?
• 28:05
  SPEAKER_00: How could we do that in a way that gets these to patients faster?
• 28:08
  SPEAKER_02: I'll just piggyback minorly on that because I do think my wish would be that people would row more in the same direction, you know, with the with the patient in mind.
• 28:19
  SPEAKER_02: There's so much good and there's so much so many good people across the ecosystem in drug development.
• 28:26
  SPEAKER_02: And they're not always working, you know, sometimes they're working across purposes without intending to.
• 28:32
  SPEAKER_02: So I would, you know, piggyback on Micah that, you know, people would row in the same direction for the benefit of the patient.
• 28:40
  SPEAKER_01: I I definitely support uh both of these wishes.
• 28:43
  SPEAKER_01: Well, if uh if my listeners would like to learn more about Siona or reach out with further questions, uh where can they find you?
• 28:50
  SPEAKER_00: So obviously we have our website, right?
• 28:52
  SPEAKER_00: Siona tx.com.
• 28:53
  SPEAKER_00: And we're a public company now, so there's a lot of public information out there in terms of financial filings, et cetera.
• 28:59
  SPEAKER_00: We have our website that has industrial relations documents.
• 29:02
  SPEAKER_00: There's a lot of things you can find on Siona now.
• 29:04
  SPEAKER_00: We have our our IR team that you know people can reach out to as well.
• 29:07
  SPEAKER_00: But you know, we're super excited about where we're at.
• 29:10
  SPEAKER_00: We really appreciate a lot of the opportunity to meet with you.
• 29:12
  SPEAKER_00: But, you know, just when you think back over the journey that you've heard us talk through, super excited about the execution, the progress we've made.
• 29:18
  SPEAKER_00: We've got some very important milestones coming up, the initiation of the trials that Charlotte talked about.
• 29:23
  SPEAKER_00: And then we'll have that data by mid-26th, right, which will be the next inflection point for Siona.
• 29:28
  SPEAKER_00: But you know, if you heard anything from this, the message that you say, we're we're really trying to do something very, very unique and novel, right?
• 29:33
  SPEAKER_00: Transformational with NBD-1 being the anchor and the platform of everything that we're doing.
• 29:38
  SPEAKER_00: We think there's an opportunity to provide more options for patients in CF.
• 29:42
  SPEAKER_00: And as Charlotte said, as much progress as we have made in CF, there is still more work to do.
• 29:47
  SPEAKER_00: We want to get as many patients to normal CFTR function as possible.
• 29:51
  SPEAKER_00: We think NBD1 unlocks a many of that opportunity for patients.
• 29:55
  SPEAKER_00: And so we're committed to continuing to move these programs through and we look forward to the remaining part of this journey to get to new patients.
• 30:01
  SPEAKER_01: So I will definitely be following along.
• 30:02
  SPEAKER_01: I'm very excited to see how your clinical programs work out.
• 30:05
  SPEAKER_00: Thanks, Ivana.
• 30:06
  SPEAKER_01: Thank you.
• 30:07
  SPEAKER_01: And thank you so much for joining me today.
• 30:09
  SPEAKER_01: I have really enjoyed our conversation.
• 30:11
  SPEAKER_00: Likewise.
• 30:11
  SPEAKER_00: Have a great day.