What are the key takeaways from this The RTW Podcast episode?

Key insights include: **Clinical trial design strategy:** Akero designed their SYMMETRY phase 2 trial with dual endpoints at 36 weeks and 2 years, providing a safety net when initial results failed statistical significance. This extended timeline allowed the drug to demonstrate doubled efficacy versus placebo at 96 weeks, proving cirrhotic patients need longer treatment duration than initially assumed.; **FGF21 dual mechanism advantage:** Efroxiferman works through two pathways - directly inhibiting new collagen fiber deposition (antifibrotic) and removing liver fat (anti-steatotic). This dual action differs from Resdiffra's thyroid hormone receptor approach and addresses both immediate fibrosis prevention and secondary healing through fat reduction, potentially offering superior outcomes in advanced disease.; **Cirrhotic MASH market opportunity:** F4 cirrhotic patients face 50% mortality at five years, yet no therapy has ever succeeded in clinical trials regardless of mechanism, company, or duration. Akero's positive 96-week data represents the first successful result in this population, creating a clear path to becoming first approved therapy for these highest-risk patients.

What did Andrew Chang discuss on The RTW Podcast?

Akero CEO Andrew Cheng discusses the company's development of efroxiferman for MASH treatment, explaining how a failed 36-week trial result transformed into success at 96 weeks, making Akero the leading candidate for treating cirrhotic MASH patients with 50% five-year mortality rates. Key topics include: **Clinical trial design strategy:** Akero designed their SYMMETRY phase 2 trial with dual endpoints at 36 weeks and 2 years, providing a safety net when initial results failed statistical significance. This extended timeline allowed the drug to demonstrate doubled efficacy versus placebo at 96 weeks, proving cirrhotic patients need longer treatment duration than initially assumed.; **FGF21 dual mechanism advantage:** Efroxiferman works through two pathways - directly inhibiting new collagen fiber deposition (antifibrotic) and removing liver fat (anti-steatotic). This dual action differs from Resdiffra's thyroid hormone receptor approach and addresses both immediate fibrosis prevention and secondary healing through fat reduction, potentially offering superior outcomes in advanced disease..

How long is this episode of The RTW Podcast?

This episode is 13 minutes long. SignalCast provides an AI-generated summary so you can get the key insights in about 3 minutes.

The RTW Podcast

From drop to double: Akero’s surging stock

July 14, 2025

13 min episode · 2 min read

Andrew Chang

Episode

13 min

Read time

2 min

Topics

Investing, Leadership, Design & UX

AI-Generated Summary

Published Feb 12, 2026

Key Takeaways

✓Clinical trial design strategy: Akero designed their SYMMETRY phase 2 trial with dual endpoints at 36 weeks and 2 years, providing a safety net when initial results failed statistical significance. This extended timeline allowed the drug to demonstrate doubled efficacy versus placebo at 96 weeks, proving cirrhotic patients need longer treatment duration than initially assumed.
✓FGF21 dual mechanism advantage: Efroxiferman works through two pathways - directly inhibiting new collagen fiber deposition (antifibrotic) and removing liver fat (anti-steatotic). This dual action differs from Resdiffra's thyroid hormone receptor approach and addresses both immediate fibrosis prevention and secondary healing through fat reduction, potentially offering superior outcomes in advanced disease.
✓Cirrhotic MASH market opportunity: F4 cirrhotic patients face 50% mortality at five years, yet no therapy has ever succeeded in clinical trials regardless of mechanism, company, or duration. Akero's positive 96-week data represents the first successful result in this population, creating a clear path to becoming first approved therapy for these highest-risk patients.
✓Biotech capital navigation framework: Successfully advancing large MASH trials requires multiple capital raises serving as market validation checkpoints. Akero maintained investor support through bear and bull markets by delivering clinical data that justified continued investment, competing against 800 biotech companies for limited capital while meeting FDA standards identical to large pharmaceutical companies.

What It Covers

Akero CEO Andrew Cheng discusses the company's development of efroxiferman for MASH treatment, explaining how a failed 36-week trial result transformed into success at 96 weeks, making Akero the leading candidate for treating cirrhotic MASH patients with 50% five-year mortality rates.

Key Questions Answered

•Clinical trial design strategy: Akero designed their SYMMETRY phase 2 trial with dual endpoints at 36 weeks and 2 years, providing a safety net when initial results failed statistical significance. This extended timeline allowed the drug to demonstrate doubled efficacy versus placebo at 96 weeks, proving cirrhotic patients need longer treatment duration than initially assumed.
•FGF21 dual mechanism advantage: Efroxiferman works through two pathways - directly inhibiting new collagen fiber deposition (antifibrotic) and removing liver fat (anti-steatotic). This dual action differs from Resdiffra's thyroid hormone receptor approach and addresses both immediate fibrosis prevention and secondary healing through fat reduction, potentially offering superior outcomes in advanced disease.
•Cirrhotic MASH market opportunity: F4 cirrhotic patients face 50% mortality at five years, yet no therapy has ever succeeded in clinical trials regardless of mechanism, company, or duration. Akero's positive 96-week data represents the first successful result in this population, creating a clear path to becoming first approved therapy for these highest-risk patients.
•Biotech capital navigation framework: Successfully advancing large MASH trials requires multiple capital raises serving as market validation checkpoints. Akero maintained investor support through bear and bull markets by delivering clinical data that justified continued investment, competing against 800 biotech companies for limited capital while meeting FDA standards identical to large pharmaceutical companies.

Notable Moment

On the morning Akero's stock dropped two-thirds following the trial miss, RTW's Rod Wong chose to trade the stock rather than present to investors, becoming a shareholder that day. The company's subsequent success validated this contrarian bet on the extended trial data.

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Episode Transcript

This morning, there's, you know, news from actually one of the NASH companies that we'll touch on. Akero came out at seven in the morning. I said, well, I could do a run through for a 150 LPs, but I think they would prefer and I would prefer if I just traded this stock. So for the last hour and a half, I've been trading at Caro. If that costs me in terms of my eloquence, so be it. I'm Rod Wong, managing partner and chief investment officer at RTW, and I'm also today's RTW podcast host. So what you just heard was a clip of me from our twenty twenty three RTW Investor Day. That morning, Acaro stock was down about two thirds on a trial miss. It was a scary moment for the company. It also happened to be the day that RTW first became a shareholder. A lot has happened since then. The company today is in a position of strength, and so I have the privilege of welcoming the CEO of Acaro, Andrew Chang. Andrew, thank you for joining us. I'm happy to be here. Your company, Akero, you're one of the most advanced companies developing therapies for MASH. So where I thought we could kick off was to give a little bit of context to our listeners about MASH as a disease. MASH is short for metabolic dysfunction associated steatohepatitis, which is a mouthful. I think in non jargon, that's fatty liver. It progresses to fibrosis, which is scarring, and then ends in cirrhosis, which is liver failure. So you have started two phase three trials, one in f two three and another in f four patients a year plus ago. Can you tell me what f two three and f four patients are and the difference between these two types of patients? Let's start with the f four. These are people who are what they call cirrhotic, which means it's a situation where the liver is heavily scarred with fibrotic tissue. So when one thinks about it, one could think about a sponge, which is dry, and that's how it's hard and rigid. Your liver should be like a wet sponge, and that is that it's supple and it's flexible, but it's not full of fibrous tissue. Those patients, unfortunately, who have cirrhosis due to MASH have about a fifty percent mortality rate at five years. Their lifespan is greatly shortened, unfortunately. We were interested in studying that population. And then the other population, which is called F2 or F3, is called preserotic. So they have advanced MASH, F3 being more advanced than F2, but they are not yet cirrhotic. And your product, froxiferman, targets something called FGF 21. That is different from Resdiffra, which is the first approved drug that we have, and that targets the thyroid hormone receptor. What got you excited about the mechanism that you guys are going after? Afrexfirmin, as an FGF 21, is attractive to us because it …

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