Ep. 355 - Capital market mood, Xenon data, Friedreich ataxia pipeline

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<v Jeff Cranmer>Biotech follow on financings have been getting out with some upsizing on the back of good data, we're also seeing IPOs get out on Nasdaq, but will geopolitics scuttle this new momentum?

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<v Jeff Cranmer>We'll discuss the capital markets for biotech on this week's BioCentury This Week podcast.

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<v Jeff Cranmer>Plus late stage epilepsy data from Xenon are reviving the biotech stock and the Kv7 target.

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<v Jeff Cranmer>And in our rare disease spotlight.

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<v Jeff Cranmer>We'll take a look at what's in the pipeline for Friedrich's ataxia.

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<v Jeff Cranmer>I'm Jeff Cranmer, host of the BioCentury's This Week podcast.

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<v Jeff Cranmer>And joining me today are my colleagues.

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<v Stephen Hansen>Stephen Hansen, Director of Intelligence.

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<v Selina Koch>Selina Koch, Executive Editor.

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<v Danielle Golovin>and Danielle Golovin, Senior Biopharma Analyst.

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<v Jeff Cranmer>Well, we've just wrapped our Fifth East-West Biopharma Summit in Seoul.

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<v Jeff Cranmer>I am back in the Bay Area and deeply jet lagged.

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<v Jeff Cranmer>But, very impressed with what is happening in Seoul and in Daejeon around biotech.

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<v Jeff Cranmer>Good energy, it's really starting to buzz.

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<v Jeff Cranmer>We had investors and companies from all over Asia, from Europe, from Canada, from the U.S., checking out what is happening in Seoul,  and there really does seem to be good energy there.

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<v Jeff Cranmer>So look for more out of Korea.

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<v Jeff Cranmer>You could check out our recent coverage.

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<v Jeff Cranmer>We took a look at some neurology companies that are starting to make their mark raising significant venture capital.

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<v Jeff Cranmer>And we're also starting to see some Korean biotech setup shop in Japan at the iPark Center.

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<v Jeff Cranmer>that's a former Takeda site.

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<v Jeff Cranmer>You can check out more on the special edition of the podcast that we recorded live on stage at the event.

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<v Jeff Cranmer>It was the final event of the conference and we put that out on Friday.

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<v Jeff Cranmer>So you can get thoughts from two of the attendees from the conference, uh, as well as Josh and Simone.

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<v Jeff Cranmer>And it's well worth checking out.

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<v Jeff Cranmer>And now BioCentury's Energy turns to Bio€quity Europe.

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<v Jeff Cranmer>Right, Stephen?

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<v Jeff Cranmer>That'll be in

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<v Stephen Hansen>Yeah,

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<v Jeff Cranmer>You'll be, uh, taking the podcast on the road in Prague.

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<v Jeff Cranmer>Yeah.

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<v Stephen Hansen>that's right.

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<v Stephen Hansen>But I, I wanted to ask you, Jeff, so what was your favorite food that you had while you were in Seoul?

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<v Jeff Cranmer>Uh, galbi, I probably had galbi twice a day.

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<v Jeff Cranmer>Um, goes.

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<v Stephen Hansen>I, I'm, I'm sorry.

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<v Stephen Hansen>I'm a little naive.

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<v Stephen Hansen>What is, what is galbi?

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<v Jeff Cranmer>galbi it's, uh, grilled ribs and they, they sort of.

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<v Stephen Hansen>Ooh.

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<v Jeff Cranmer>Set up a nice, like either hot coals right on the table in front of you, or you know, some other contraption and, uh, they cook it right there for you.

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<v Jeff Cranmer>Goes down very well with, uh, insert delicious Korean beer of your choice, Korean beer's, very, very light, um, which is, is somewhat dangerous.

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<v Jeff Cranmer>Uh, and a little bit of soju.

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<v Jeff Cranmer>And of course, kimchi with every meal.

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<v Jeff Cranmer>That was, uh, definitely, uh, definitely the way to go.

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<v Jeff Cranmer>But yeah, I snuck out many times and, and, and got some good galbi.

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<v Jeff Cranmer>Alright, Stephen, um, there's a war going on.

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<v Jeff Cranmer>And, uh, I am curious, you, you know, you've been watching the markets.

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<v Jeff Cranmer>You, you had, uh, you know, your 2026 preview.

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<v Jeff Cranmer>You said that biotech's back this time, it's, it's for real.

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<v Jeff Cranmer>Um, we've been seeing some follow-ons.

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<v Jeff Cranmer>Uh, companies have been upsizing the follow-ons based on good data.

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<v Jeff Cranmer>Xenon, latest example.

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<v Jeff Cranmer>Couple of IPOs have gotten out and what's this geopolitical turmoil going to do to that positive vibe we've been seeing in the biotech markets?

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<v Stephen Hansen>Yeah.

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<v Stephen Hansen>Thanks Jeff.

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<v Stephen Hansen>So.

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<v Stephen Hansen>it's, I mean, the, the very short summary is, it's, it's, it's kind of good news and bad news, I think.

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<v Stephen Hansen>Right?

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<v Stephen Hansen>So, um, as, as you mentioned, uh, follow-ons are still getting done.

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<v Stephen Hansen>Often it's on the back of positive catalyst, but I think we've seen a few opportunistic deals get done as well.

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<v Stephen Hansen>Again, as you mentioned, uh, we saw two deals get substantially upsized last week, which is a pretty, you know, that's a really good indicator for investor demand, particularly generalist demand, because, you know, when deals get upsized 150, 200 million, usually those are pretty large checks that are going into those, those deals.

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<v Stephen Hansen>So that's a good sign.

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<v Stephen Hansen>So, um, just kinda looking at the numbers, kind of where things stand for the quarter.

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<v Stephen Hansen>You know, I know we still have a couple weeks to go here, but, there's been over 7 billion raised so far in the first quarter of 2026 for follow-ons.

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<v Stephen Hansen>And, you know, kind of relative to where we were last year, that's actually really good.

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<v Stephen Hansen>That's almost as much as was raised in the entirety of the first half of 2025.

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<v Stephen Hansen>From that perspective, you know, thumbs up.

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<v Stephen Hansen>I think it's pretty, pretty positive sign.

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<v Stephen Hansen>We've had seven IPOs on NASDAQ so far.

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<v Stephen Hansen>Only three of those are right now above issue price, so kind of mixed performance and kind of this first group that's come out.

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<v Stephen Hansen>And the last three have been underwater.

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<v Stephen Hansen>Two of those were multi-billion dollar valuations at the IPO.

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<v Stephen Hansen>So you can discuss whether you think that that is an issue around valuation or, or what have you.

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<v Stephen Hansen>But the numbers aren't as good for venture financing, at least not to this point.

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<v Stephen Hansen>So industry is raised about $5.4 billion in private financings so far this year.

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<v Stephen Hansen>I'm sure a few more deals will come in before the end of the quarter, but if that number were to hold, it would be the lowest aggregate for biotech venture raised in a quarter since anybody want to guess?

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<v Stephen Hansen>Jeff, you wanna guess?

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<v Stephen Hansen>Gimme a year?

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<v Jeff Cranmer>A year.

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<v Jeff Cranmer>Um.

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<v Jeff Cranmer>Hmm.

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<v Stephen Hansen>Danielle, Selina,.

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<v Stephen Hansen>You guys can chime into, gimme your best guess.

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<v Jeff Cranmer>2008.

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<v Jeff Cranmer>I'm gonna go way back.

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<v Stephen Hansen>Selina, what do you think?

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<v Selina Koch>Dang, I know we've done these analysis before.

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<v Selina Koch>I can't conjure it pre COVID,

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<v Stephen Hansen>Don't cheat.

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<v Stephen Hansen>Yeah.

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<v Stephen Hansen>Okay.

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<v Stephen Hansen>Danielle, what do you think?

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<v Danielle Golovin>I was gonna say 2018.

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<v Danielle Golovin>I think Danielle wins.

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<v Danielle Golovin>So, uh, if this number holds, it would be the, the lowest quarter for venture money raise since 2017.

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<v Danielle Golovin>So nine years or so.

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<v Selina Koch>But about how far Stephen?

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<v Stephen Hansen>Uh, not a lot.

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<v Stephen Hansen>I mean, it's not bad, you know, it's not, this isn't, it's not, we're not talking like desert type of, uh, you know, no money at all getting raised, but, but it's, it's sort of noticeable if you look back over the years, over the quarters.

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<v Stephen Hansen>There's a fairly steady kind of like, kind of baseline that you kind of see, and then you get these little spurts where you get a lot of money being raised, but then it kind of will revert back to that kind of baseline.

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<v Stephen Hansen>And this is, tucking in below kind of that kind of 10 year baseline, I would say.

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<v Stephen Hansen>You're right to point that out.

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<v Stephen Hansen>It's not, I'm not, you know, calling the death nail of, uh, private financing here, but it's, but it's noticeable that it's, you know, below that given how well things were going in the second half of the year.

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<v Selina Koch>Yeah, but do you think it's sort of like, um, we often see public markets sort of when you are in a recovery recovering faster, there's like a lag in the venture side?

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<v Stephen Hansen>You, you're right.

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<v Stephen Hansen>Yep.

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<v Stephen Hansen>And that's probably part of what's happening here is we're probably partly seeing a lag here, you know, it could also just be, and this isn't very much me talking off the top of my head here now without any reporting to go to this, and, but.

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<v Stephen Hansen>I also wonder if the fact that we had started to hear that there was a bit more competition in deals, you know, there were more people vying to get into some deals.

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<v Stephen Hansen>I'm, I'm just wondering if valuations are starting to creep up, if maybe some investors are being a little more maybe selective in what they're doing as opposed to the last couple of years where, you know, I think valuations were maybe bit more attractive for VCs.

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<v Stephen Hansen>And so, you know, something that we can maybe, uh, dig into and see if, see if something like that's at play.

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<v Stephen Hansen>But I ju it just was, thought it was an interesting thing that kind of jumped out at the numbers, uh, to me.

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<v Stephen Hansen>But to come back to, you know, what Jeff was saying about and how kind of the geopolitics sort of plays into this.

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<v Stephen Hansen>And that's I think where, when you look at the XBI, so it's largely kind of trading flat so far this year.

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<v Stephen Hansen>Which relative to, you know, tech and the S&P 500.

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<v Stephen Hansen>That's actually not bad.

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<v Stephen Hansen>'cause those are both trading down so far a year to date.

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<v Jeff Cranmer>And the XBI had a very good year last year, right?

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<v Stephen Hansen>And that's right.

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<v Stephen Hansen>Yep.

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<v Stephen Hansen>It did.

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<v Stephen Hansen>It did.

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<v Stephen Hansen>But there was also, you know, going into the year, there was every expectation that, you know, that was going to continue.

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<v Stephen Hansen>But I think that can sort of lackluster performance.

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<v Stephen Hansen>I mean, I think all of this is just sort of due to the macroeconomic kind of chaos, right?

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<v Stephen Hansen>That's kind of hit the markets.

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<v Stephen Hansen>And there's several different levels of this.

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<v Stephen Hansen>I mean, I think it's beyond just what we're seeing from the, the conflict in Iran.

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<v Stephen Hansen>I mean, there are fears that private credit markets, you know could sort of implode and potentially lead to a recession.

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<v Stephen Hansen>Obviously you've got oil prices, you know, that could trigger a return of inflation.

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<v Stephen Hansen>That in turn puts more pressure on the Fed with regard to interest rates.

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<v Stephen Hansen>So, I think all those things are sort of playing in the background and making this really just a lot more volatile.

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<v Stephen Hansen>And, you know, I think it's the same thing we saw right around when the Ukraine, Russia war started was just the increased volatility, just made things a lot tougher.

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<v Stephen Hansen>And so I, I anticipate that until there's some maybe closure on this, that's probably gonna continue.

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<v Stephen Hansen>Obviously I think we have the Fed decision this week as well, so we should maybe get some hints from them on kind of how they're thinking about this.

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<v Stephen Hansen>Although obviously Powell is gonna be stepping down in May, so that may be interesting to see how the new chair kind of approaches rates and inflation, if this conflict kind of draws on and inflation gets a bit sticky.

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<v Stephen Hansen>I think that's, that's sort of the, that's sort of the downside to where things stand and maybe why wouldn't be a surprise if there was a bit of a maybe a lull in some of that financing activity over the next month or two, just as people wait to kind of see where things land.

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<v Jeff Cranmer>All right.

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<v Jeff Cranmer>Well thanks for that, Stephen.

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<v Jeff Cranmer>I know you're beginning to put out calls for your 2Q Public Markets Preview.

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<v Jeff Cranmer>So, uh, we'll get an update in a few weeks.

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<v Jeff Cranmer>And let's turn now to talk about one of these companies that's upsized, on some good data.

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<v Jeff Cranmer>Xenon, as we mentioned at the top, Selina, you took a look at, Xenon and well last week's Phase III focal epilepsy readout sent it shares up 50%.

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<v Jeff Cranmer>What was significant here about these data Selina?

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<v Selina Koch>Yeah, thanks.

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<v Selina Koch>maybe I'll just start by saying it was, was a good week for Xenon.

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<v Selina Koch>In addition to that 50% bump.

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<v Selina Koch>On Monday, at the end of the day, they then proposed $500 million follow on.

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<v Selina Koch>By Tuesday night, they had price at actually 650 million.

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<v Selina Koch>And by Thursday night, the, um, underwriters had exercised their allotment in full.

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<v Selina Koch>They're over allotment in full, so it ended up being close to 750 million.

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<v Selina Koch>So good job for them.

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<v Selina Koch>What was it that pleased investors so much, this, readout was for a molecule that's an opener of a particular kind of voltage gated potassium channel.

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<v Selina Koch>It's called Kv7.

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<v Selina Koch>And the readout really kind of cemented its comeback story.

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<v Selina Koch>This isn't the first molecule to go after that target GSK had a drug approved in 2011, pretty sure it was.

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<v Selina Koch>but you know, over some years it ultimately ended up being withdrawn from the market, over safety concerns.

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<v Selina Koch>in the retina for instance, there were abnormal abnormalities that even border risk of blindness.

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<v Selina Koch>It was turning people's skin blue, so pigmentation, changes, hair, skin, nails, things like that.

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<v Selina Koch>And so what Xenon has done here is taken a, you know, a mechanism that should be effective ' cause there's validation for it and they've created on a new kind of chemical structure that prevents dimerization,'cause it turned out that dimerization was kind of the thing that was causing the trouble.

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<v Selina Koch>And now that's borne out with Phase III data.

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<v Selina Koch>So in its Phase III study, it reduced median monthly seizure frequency by over 42% relative to placebo, so that's a big drop.

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<v Selina Koch>That was highly statistically significant, even out performed the company's own Phase II two data.

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<v Stephen Hansen>I was gonna say Selina, I was, I was just impressed by the P value.

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<v Stephen Hansen>I think there

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<v Selina Koch>Yes,

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<v Stephen Hansen>11, 11 zeros and then a a six.

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<v Stephen Hansen>I mean, it was.

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<v Jeff Cranmer>Zero my hero.

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<v Jeff Cranmer>Yeah, that's, uh, I don't even think I can count that high, but.

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<v Selina Koch>you know, that said, there are some side effects with this particular mechanism that I think you can never avoid, like altogether is a small molecule, right?

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<v Selina Koch>So it's going all over the brain, and if you open up this potassium channel from a mechanistic point of view, what you're doing is you're allowing potassium irons to flow out of the neuron.

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<v Selina Koch>This sort of stabilizes its membrane potential under it makes it a little harder to fire an action potential.

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<v Selina Koch>Okay, so what you wanna do then as a company, is you wanna do that just enough to counteract that hyperexcitability that drives a seizure, but not too much because you get dizzy, sleepiness, you know, somnolence.

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<v Selina Koch>And we've seen that with this mechanism across multiple programs.

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<v Selina Koch>Basically it just requires careful dosing.

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<v Selina Koch>And so what one thing they did was, you know, they extended the half-life such that it can be just dosed once a day and then they give it in the evening.

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<v Selina Koch>So basically you take it, you go to bed, and if you have any of that somnolence or dizziness or whatever, it's happening while you're sleeping.

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<v Selina Koch>So that kind of helped to get around that issue as well.

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<v Jeff Cranmer>Alright, Selina, what's next?

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<v Selina Koch>Well Xenon plans to submit it to NDA to FDA in the third quarter of this year.

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<v Selina Koch>So that is coming.

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<v Selina Koch>And then in addition, they're, they're testing it in not only  focal onset, but generalized tonic-clonic seizures, and in some psychiatric disorders.

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<v Selina Koch>Where depression is prevalent, so a major depressive disorder, bipolar  depression.

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<v Selina Koch>They say they think it's has antidepressive effects, which they anticipate could help it differentiate even in epilepsy.

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<v Selina Koch>So yes, the main objective here is reducing seizure frequency, but they're also testing these other psychiatric symptom domains.

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<v Selina Koch>There are a lot of drugs one can take to mitigate seizures, right?

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<v Selina Koch>There's, um, a lot on the market.

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<v Selina Koch>There's generic, having something that can also address depressive symptoms because these patients with intractable  epilepsy tend to have that, could just be another differentiator to add to that, that profile.

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<v Selina Koch>So we'll be seeing some data, on those symptoms both inside epilepsy and then independently as well in the future.

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<v Jeff Cranmer>All right.

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<v Jeff Cranmer>And, uh, also, uh, following the that Xenon  had last week, uh, was Dianthus.

00:14:36.642 --> 00:14:43.215
<v Jeff Cranmer>The company, uh, met an interim goal for, one of its polyneuropathy programs.

00:14:43.514 --> 00:14:58.964
<v Jeff Cranmer>Shares rose by more than 20%, and the company proposed a $400 million offering, by the end of the week it was close to 720 with, uh, an upsize and, uh, the green shoe coming home.

00:14:59.298 --> 00:15:03.302
<v Jeff Cranmer>Quite a good week for Xenon and Dianthus.

00:15:03.936 --> 00:15:05.370
<v Jeff Cranmer>So hats off.

00:15:05.671 --> 00:15:12.711
<v Jeff Cranmer>Well, we have something new for you here at BioCentury and here to tell you about it is Selina, Selina.

00:15:12.811 --> 00:15:17.249
<v Jeff Cranmer>Um, have a new feature in, uh, our BCIQ database.

00:15:18.250 --> 00:15:19.150
<v Selina Koch>We sure do.

00:15:19.150 --> 00:15:30.261
<v Selina Koch>So those of you who will have access to BCIQ,  you know, you can search for products in there in addition to deals and financings and all the other kinds of data in the database.

00:15:30.261 --> 00:15:33.798
<v Selina Koch>Well, now you can also search for discontinued products.

00:15:34.332 --> 00:15:36.969
<v Selina Koch>This is something that a lot of people have asked for over the years.

00:15:37.001 --> 00:15:39.772
<v Selina Koch>We've wanted it internally as analysts of the industry.

00:15:40.139 --> 00:15:48.681
<v Selina Koch>So to give like one example of what you can do with this last week, we published a package of stories on pulmonary fibrosis.

00:15:48.813 --> 00:15:56.488
<v Selina Koch>So there's this wave of Phase II programs, 20 something Phase II programs, right, approaching proof of concept.

00:15:56.822 --> 00:15:58.057
<v Selina Koch>Lots of different targets there.

00:15:58.590 --> 00:16:13.339
<v Selina Koch>And so we look back a little bit between the era of the first two approvals and the 10 years that elapsed between Boehringer's recent approval last year, and said, okay, well how many programs were discontinued and what were they targeting?

00:16:13.839 --> 00:16:29.020
<v Selina Koch>And then we counted up, you know, number of programs per target, compared it directly to this current Phase II wave, and you could see kind of a marke there's just a lot of new targets that haven't been tried before in the pipeline right now.

00:16:29.288 --> 00:16:32.357
<v Selina Koch>A few are still, carryovers from this earlier era.

00:16:32.825 --> 00:16:37.629
<v Selina Koch>and if you're curious about them, what they are, you can dig into them in a story.

00:16:38.263 --> 00:16:43.034
<v Selina Koch>In that story package, this particular one was from our colleague Lindsay Martin.

00:16:43.534 --> 00:16:44.102
<v Jeff Cranmer>All right.

00:16:44.102 --> 00:16:45.437
<v Jeff Cranmer>Yeah, it's, it's good stuff.

00:16:45.437 --> 00:16:49.841
<v Jeff Cranmer>So hopefully we'll fuel future stories in BioCentury.

00:16:49.841 --> 00:16:55.714
<v Jeff Cranmer>We're gonna take a quick break and then we'll come back to talk rare diseases with Danielle.

00:16:55.980 --> 00:17:01.253
<v Voice Talent>BioCentury This Week is brought to you by the 26th Bio€quity Europe in Prague, Czech Republic.

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<v Jeff Cranmer>Okay.

00:18:03.981 --> 00:18:09.188
<v Jeff Cranmer>We are back, Danielle, you took a close look at Friedreich's ataxia.

00:18:10.588 --> 00:18:12.657
<v Jeff Cranmer>what did you learn about what's in the pipeline?

00:18:13.291 --> 00:18:16.428
<v Danielle Golovin>Well, Jeff, I believe our style is Friedrich ataxia.

00:18:16.461 --> 00:18:17.096
<v Danielle Golovin>No s.

00:18:17.895 --> 00:18:21.666
<v Jeff Cranmer>Man, I've been, uh, I've been hammering people about that for years.

00:18:21.666 --> 00:18:22.500
<v Jeff Cranmer>And look at you.

00:18:22.500 --> 00:18:23.535
<v Jeff Cranmer>Just get

00:18:23.669 --> 00:18:26.605
<v Danielle Golovin>As I learned from you in our style channel.

00:18:27.338 --> 00:18:28.707
<v Jeff Cranmer>that's a nice throw down.

00:18:28.707 --> 00:18:30.541
<v Jeff Cranmer>I, I much respect Danielle.

00:18:32.044 --> 00:18:37.048
<v Danielle Golovin>Yeah, so I did a deep dive into, I'm just gonna call it FA for our talk here.

00:18:39.183 --> 00:18:39.484
<v Jeff Cranmer>I think good way to roll.

00:18:40.285 --> 00:18:45.824
<v Danielle Golovin>So this disease is caused by a trinucleotide repeat expansion in a gene called frataxin.

00:18:46.023 --> 00:18:47.459
<v Danielle Golovin>And this has to do with mitochondria.

00:18:47.459 --> 00:18:56.835
<v Danielle Golovin>So mitochondria use iron for energy production, as you all know, since mitochondria is the powerhouse of the cell, had to get that in there'cause it's in all the textbooks.

00:18:57.269 --> 00:19:03.875
<v Danielle Golovin>So frataxin, helps keep this mitochondria iron in a usable, non-toxic form.

00:19:04.308 --> 00:19:09.548
<v Danielle Golovin>So this limits iron overload and downstream reactive oxygen species generation.

00:19:09.847 --> 00:19:12.917
<v Danielle Golovin>Without frataxin, this increases oxidative stress.

00:19:13.018 --> 00:19:17.788
<v Danielle Golovin>The mitochondria produce less energy, cells get tired, and eventually they die.

00:19:18.022 --> 00:19:26.865
<v Danielle Golovin>Most affected cells in this disease are typically the heart, the pancreas, and the brain, and this causes cardiomyopathy, diabetes, and ataxia.

00:19:27.398 --> 00:19:31.502
<v Selina Koch>So people have been going at FA in different ways over the years.

00:19:31.502 --> 00:19:33.771
<v Selina Koch>Um, what's happening with the pipeline right now?

00:19:34.772 --> 00:19:42.681
<v Danielle Golovin>Yeah, the pipeline is definitely shifting from the early pipeline was sort of just stabilizing the mitochondria.

00:19:43.281 --> 00:19:47.786
<v Danielle Golovin>Now it's shifting towards gene therapies to actually restore the gene itself.

00:19:47.952 --> 00:20:05.403
<v Danielle Golovin>So delivering frataxin, the field FA has one approved drug Skyclarys, and this switches on and antioxidant defense to, you know, increase mitochondrial energy production and reduce those reactive oxygen species.

00:20:05.636 --> 00:20:11.410
<v Danielle Golovin>Basically the first gen drugs help the cells cope with the mitochondrial stress caused by vert frataxin deficiency.

00:20:11.410 --> 00:20:17.816
<v Danielle Golovin>Whereas the incoming pipeline is more these gene therapies to re, you know, supply the gene.

00:20:18.016 --> 00:20:21.252
<v Danielle Golovin>And the leading gene therapy.

00:20:21.286 --> 00:20:28.026
<v Danielle Golovin>And there are at least five, LX2006 from Lexeo Therapeutics is the leader.

00:20:28.594 --> 00:20:32.263
<v Danielle Golovin>It's being tested in FA associated cardiomyopathy.

00:20:32.663 --> 00:20:39.938
<v Danielle Golovin>As I mentioned, the heart cells are very affected by this disease, and unfortunately this is the leading cause of death in these patients is cardiomyopathy.

00:20:40.172 --> 00:20:46.778
<v Danielle Golovin>But they did have positive results in October, and that led to conversations with FDA to agree to an accelerated approval pathway.

00:20:47.778 --> 00:20:51.717
<v Selina Koch>I think that's a big, that's like potentially a very important development for this field, right?

00:20:51.717 --> 00:20:57.655
<v Selina Koch>Anytime you can get agreement on what could constitute an approvable endpoint for accelerated approval.

00:20:57.655 --> 00:20:59.958
<v Selina Koch>So what, what are they looking at there as the endpoint?

00:21:00.925 --> 00:21:07.164
<v Danielle Golovin>So in this case, since they're targeting FA induced cardiomyopathy, they're using, you know, a measure of heart function.

00:21:07.633 --> 00:21:16.275
<v Danielle Golovin>So in this particular case, they're using left ventricular mass index or LVMI, in addition to frataxin expression.

00:21:17.108 --> 00:21:22.047
<v Selina Koch>So among the gene therapies, Danielle, are they all AAV based?

00:21:22.047 --> 00:21:25.284
<v Selina Koch>Are they kind of similar to each other, or are there kind of key differences?

00:21:26.018 --> 00:21:26.250
<v Danielle Golovin>Yeah.

00:21:26.351 --> 00:21:30.721
<v Danielle Golovin>The one big difference that came out to me as I was reviewing these programs.

00:21:30.721 --> 00:21:35.961
<v Danielle Golovin>So there's five that identified and four out of the five are using AAVs to deliver the gene.

00:21:36.260 --> 00:21:44.836
<v Danielle Golovin>But the sort of unique one in that case was Replay Holdings and it's spin out company Kaleibe, I dunno if I'm saying that right.

00:21:44.869 --> 00:21:53.412
<v Danielle Golovin>Kaleibe, um, are using herpes simplex viruses, so HSB as vectors, and their big claim is that it has a high payload capacity.

00:21:53.811 --> 00:22:09.428
<v Danielle Golovin>And while the frataxin gene itself isn't huge, you know, like, DMD or anything, if you wanna give its full regulatory elements, then that's gonna exceed an AAVs five kilobase payload capacity.

00:22:09.594 --> 00:22:16.500
<v Danielle Golovin>And so that's their advantage there, is that they can deliver a large construct in its sort of native form with its regulatory elements.

00:22:17.169 --> 00:22:18.869
<v Danielle Golovin>That's a bit of the landscape on FA.

00:22:19.637 --> 00:22:26.912
<v Danielle Golovin>And we also looked out on the innovation horizon a bit to highlight a few papers with insights into new avenues for treating FA.

00:22:27.078 --> 00:22:30.082
<v Danielle Golovin>So check those out in BioCentury's Science spotlights.

00:22:31.249 --> 00:22:46.932
<v Selina Koch>Still makes me wonder, Danielle, if, um, this is a place where, you know, brain shuttles applied to those capsids could really help of course you wanna treat the cardiac problems problems lead to death, but it's a multifactorial disease.

00:22:46.932 --> 00:22:50.669
<v Selina Koch>It definitely has a lot of, you know, CNS issues.

00:22:51.236 --> 00:23:09.688
<v Danielle Golovin>Oh, right, yeah, so Voyager and partner Neurocrine have a preclinical gene therapy that's utilizing an IV delivered AAV capsid discovered by Voyager that uses an ALPL-mediated transcytosis pathway to cross the BBB and deliver frataxin broadly across the CNS.

00:23:09.988 --> 00:23:18.329
<v Danielle Golovin>And other programs may have innovative methods to enhance CNS exposure, which could include other BBB crossing mechanisms or a more direct route of administration.

00:23:19.297 --> 00:23:22.032
<v Jeff Cranmer>All right, Daniel, thanks for that deep dive.

00:23:22.366 --> 00:23:24.702
<v Jeff Cranmer>what's next in the rare disease spotlight?

00:23:24.702 --> 00:23:28.406
<v Jeff Cranmer>Or are you still, uh, picking among a few, uh, a few choices.

00:23:29.673 --> 00:23:31.143
<v Danielle Golovin>I always have a list going.

00:23:31.143 --> 00:23:34.813
<v Danielle Golovin>If anyone has any uh, suggestions, throw 'em my way.

00:23:35.413 --> 00:23:36.448
<v Jeff Cranmer>Yeah, that would be great.

00:23:36.448 --> 00:23:38.849
<v Jeff Cranmer>We always love hearing from our listeners.

00:23:39.084 --> 00:23:44.588
<v Jeff Cranmer>and if you're liking what you're hearing on the BioCentury This Week podcast, don't forget to subscribe.

00:23:44.855 --> 00:23:45.790
<v Jeff Cranmer>give us a rating.

00:23:46.157 --> 00:23:58.702
<v Jeff Cranmer>I guess it works differently depending on your platform, but, uh, always eager to hear from you and, uh, it was great, being in Seoul and meeting, some of our listeners in Seoul, and elsewhere in Asia.

00:23:58.702 --> 00:24:01.873
<v Jeff Cranmer>So good to know that we've got a broad reach.

00:24:02.207 --> 00:24:03.775
<v Jeff Cranmer>Alright, thanks for tuning in.

00:24:03.775 --> 00:24:11.482
<v Jeff Cranmer>We will be back next week, with another edition of the BioCentury This Week podcast.

00:24:11.482 --> 00:24:16.086
<v Jeff Cranmer>And look out for, our sister podcast The BioCentury Show.

00:24:16.288 --> 00:24:25.864
<v Jeff Cranmer>Selina will be in conversation with Najat Khan from Recursion Kendall Square Orchestra provides the music for BioCentury's this week.

00:24:25.864 --> 00:24:39.344
<v Jeff Cranmer>The group connects science and technology professionals and other members of the Greater Boston community to collaborate, innovate, and inspire through music, while supporting causes related to healthcare and education.