Episode 190 - July 24, 2026

Summary

• Scribe priced the first very-early-stage biotech IPO since the COVID era — an upsized deal priced above $100M, with roughly $120M raised, for a PCSK9 gene-silencing therapy recently cleared by Australia’s TGA to begin clinical investigation. Brian Skorney sees it as a signal of increasing risk tolerance, not necessarily bearish, but warns that early-stage names suffer when the cycle unwinds. Eric Schmidt contrasted it with 2021, when Sana raised $600M+ at about a $4.5B pre-money valuation.
• Reverse mergers with $200M+ PIPEs have become a parallel IPO track — Josh Schimmer counts six such biotech deals, versus three last year and one the year before. The latest, Xometry’s merger into InMed with a nearly $200M PIPE, involves anti-PACAP and bispecific PACAP/CGRP antibodies for migraine. The trade-off is speed and possibly somewhat lower fees for less pre-IPO exposure and a narrowly told buy-side story; Brian sees no clear end-of-cycle correlation.
• Colossal Biosciences is reportedly seeking a round at a $20–30B valuation, prompting debate over its moat, revenue model and whether it is biotech at all. Brian said the dire-wolf work appears more like genetic material engineered into gray wolves than true de-extinction and questioned whether the technology has a durable moat. Josh outlined a possible zoo-sales model, while Brad Loncar’s lesson was that Colossal has a story that resonates beyond biotech.
• The fugitive-CMO scandal discussed under Immix Biopharma is a diligence and crisis-management warning. Brad described a physician convicted in absentia roughly 20 years ago who resurfaced under an alias, appeared to have a fabricated Merck/Sanofi oncology background, and served about three months as a public-biotech CMO before being arrested by the FBI and U.S. Marshals on a sailboat near New Jersey. Brad called the company’s brief non-materiality 8-K response “ludicrous.” Josh warned that small, under-resourced companies may be cutting corners to survive.
• Brian and Josh expect Dyne’s DMD drug zylodursen to be approved at its late-January PDUFA date. It delivers more dystrophin than Sarepta’s Exondys 51 with monthly rather than weekly dosing, while Sarepta seeks full approval for Vyondys 53 and Amondys 45 after a failed 2-year, 200-plus-patient Phase 3 study. Dyne filed about a month ahead of Novartis and could become the first drug in this muscle-targeted oligo class.
• Next week’s Replimune RP1 and Capricor deramiocel AdComs could clarify whether the FDA has adopted a new tone. Josh tentatively placed the RP1 meeting on Thursday the 30th and framed the votes as either idiosyncratic events or an early public test of the new commissioner, whom he called Kyle D Amantes. Brad wants more AdComs; Brian said benign briefing documents plus favorable votes would support a more flexible FDA, while repeated negative findings would reveal a more stringent posture.
• Brad’s first BiotechTV Science Summit focused on biotech’s communication deficit by bringing 20 highly followed science communicators to Kendall Square and biotech companies. Many had 400,000–500,000 followers. Brad’s diagnosis was that junk science is highly organized while pro-science voices are more fragmented. Eric linked the discussion to his claim that the FDA voted 8–6 to allow compounding pharmacies to approve a peptide not shown to be safe or efficacious, calling the MAHA peptide focus unscientific.

Deep dive

1. Scribe reopens the early-stage IPO window — with 2021’s ghost in the room

• Scribe priced overnight at more than $100M and was upsized — probably the first very-early-stage biotech IPO since the COVID era, per Eric Schmidt. It is not quite preclinical: Australia’s TGA recently approved the company to begin investigating its lead PCSK9-targeted gene-silencing therapy for hypercholesterolemia.
• Brian’s cycle read: “There’s always this dynamic of FOMO” as investors reach earlier for new ideas because the number of Phase 1, 2 and 3 assets is limited. He “wouldn’t necessarily say this is a bearish signal,” but sees increasing risk tolerance. When that tolerance eventually disappears, early-stage companies without proof of concept will face trouble as the cycle unwinds. “What inning are we in right now? Tough to say.”
• Eric calibrated the deal against the last peak: in 2021, Sana — perhaps a year from an IND — raised more than $600M at about a $4.5B pre-money valuation as biotech’s biggest-ever IPO at the time. Today, Sana is at a fraction of that valuation and remains subject to public-market sentiment.
• Brian’s counterpoint was that a weak public-stock performance does not necessarily prove an IPO was the wrong decision for management: “They’re alive as a company today, and I don’t know if that would have been the case” without the financing.
• Brad said many companies do not have much choice: they may be at the end of the private-funding line and must IPO to continue. Eric added that VCs often push companies out quickly; “the world is set up to push companies out,” with no real brake on the system.

2. Reverse merger + mega-PIPE: the IPO’s faster twin

• Josh framed the latest reverse mergers as having “finally figured out how to approximate an IPO,” pairing a public listing with a sizable PIPE and institutional backing. The latest transaction discussed was Xometry merging into InMed with a nearly $200M PIPE. Xometry is developing antibodies against PACAP and a bispecific PACAP-CGRP antibody for migraine; Lundbeck recently validated the mechanism with an IV approach, though it is unclear whether Lundbeck will pursue a subcutaneous version.
• Josh also cited Slate Therapeutics as having a similar setup. This is now the sixth biotech reverse merger accompanied by a $200M-plus financing, compared with about three last year and one the year before. He called the framework “very IPO-esque.”
• The process trades speed and efficiency for a less exposed public-market launch. Josh said Wall Street fees may be somewhat lower, though not dramatically. Eric noted that companies skip the traditional test-the-waters meetings and roadshow process with many mutual funds, leaving the buy-side story narrowly told and sometimes requiring six or 12 months to broaden. For analysts, that can create an information advantage.
• Brian described the trade-off as speed, efficiency and reduced cost versus a longer, more diligent and exposed IPO process. Josh did not see the increase in reverse mergers as a clear end-of-cycle signal, noting that they may rise in bear markets simply because the process is easier.

3. Colossal at $20–30B: great story, questionable moat — and is it biotech?

• Brian introduced Colossal as an “essentially” de-extinction company, joking that it resembles BioSyn from Jurassic Park. The company reportedly seeks a new funding round at a $20–30B valuation after attracting attention for attempts to recreate extinct species, including dire wolves.
• Brian’s skepticism was scientific and commercial. The papers appeared to him to describe genetic material engineered into gray wolves, “more akin to a transgenic animal.” He questioned whether any major transgenic-animal laboratory could pursue similar work if it became profitable, and whether Colossal has a durable moat. His physician wife’s reaction was that Colossal did not justify a $20–30B valuation.
• Josh’s understanding of the model was centered on zoos: more than 10,000 zoos and roughly 1 billion visitors could support meaningful revenue if a woolly mammoth sold for $1M or $2M. He was uncertain about other revenue streams, cost of goods, R&D intensity and scalability.
• Brad’s contrarian lesson was that drug developers resent Colossal’s fundraising, but Colossal has “a great story” that resonates outside biotech. Rather than resent that advantage, he suggested packaging other companies’ work into narratives that connect with investors and the broader public.
• The definition of biotech became a separate debate. Josh pointed to his Control Arm podcast and the way the XBI classifies tools companies, pharma companies and biotech companies differently. Eric called the sector’s current boundaries “semantic creep”: spec pharma once signaled discipline, profitability and lower-risk development, but became a pejorative after Valeant, so many companies were relabeled biotech. He said defining the sector remains a difficult question after two decades of coverage.

4. Brad’s summit: organizing the pro-science majority

• Brad described BiotechTV’s first event, held at MassBio in Kendall Square with MassBio as a top sponsor and BIO also supporting it. Speakers included former NIH director Elias Zerhouni, Noubar Afeyan, Nello Mainolfi from Chimera, Sam Kulkarni of CRISPR Therapeutics and Jason Kelly of Ginkgo.
• The central question was how to explain biotech and science to the public while the United States appears to be pulling back from science and countries including China are doubling down. Public support matters for NIH funding, scientific careers and the industry’s ability to help patients.
• The distinctive element was inviting 20 young “SciCommers” — many with PhDs or working toward them and, in many cases, 400,000–500,000 social-media followers. Brad said they were credible lab-based communicators rather than promoters of alternative medicine. They received a three-day Boston and Kendall Square experience, including a walking tour and a dinner featuring Greg Verdine.
• After the summit, the group visited biotech companies. Moderna hosted all 20 for a talk, lab tour and one-on-one interviews with senior scientists, including direct questions about alleged vaccine harms or lack of efficacy. The group also visited Alnylam for a breakfast and RNAi presentation, along with several smaller biotech companies; John Maraganore discussed how Alnylam nearly went broke several times and only became profitable recently.
• Brad’s diagnosis was that conspiracy theories and junk science spread because they are highly organized, while people who trust science may be a larger community but are fragmented. Eric linked that communication problem to his claim that the FDA voted 8–6 to allow compounding pharmacies to approve a peptide not shown to be safe or efficacious, calling the MAHA focus on peptides “a completely unscientific pursuit.”

5. The con-man CMO: amateur-hour crisis management and a diligence lesson

• Brad described a physician who appeared to have been legitimate roughly 20 years ago, fled Rhode Island during a criminal case, was convicted in absentia and later lived under an alias. The Rhode Island FBI and U.S. Marshals eventually tracked him to a sailboat off New Jersey and arrested him.
• According to Brad, he had recently been hired in March as chief medical officer of the public biotech discussed in the segment as Immix Biopharma and remained in the role for only about three months. He appeared to have presented a false background involving Merck, Sanofi and oncology; Brad repeatedly qualified that account rather than stating every detail as established fact.
• Brad criticized the company’s response: an 8-K announcing the firing and saying management did not believe it was material. He called that “about as ludicrous” as possible, arguing that hiring an apparent con man as chief physician is material to employees, patients and investors and made the company look amateurish.
• Brian asked how the same person had previously been hired at Atossa in 2022 despite an apparently invented background. He compared the episode with Serhat Gumrukcu, the Inozyme BioSciences co-founder involved in a plot to kill another man. Brian’s broader advice was to get ahead of bad news — drug failures, safety issues or executive misconduct — rather than hide behind a terse 8-K.
• Josh said investors should not assume that small, fringe biotech companies have completed every diligence and governance step. He described the company as roughly a $2 stock and sub-$200M business a year earlier, perhaps with only 30–40 employees, and said under-resourced companies may cut corners simply to survive and make payroll. He also recalled the Matt Martoma case, in which an investment professional with an impressive claimed résumé was convicted after paying an Alzheimer’s physician for trial information.

6. Dyne’s DMD filing: a better mousetrap that sets a high approval bar

• Brian described Dyne’s BLA for zylodursen, which uses an antibody to direct an exon-51-skipping PMO into muscle. It produces more dystrophin than Sarepta’s naked PMO Exondys 51 and is dosed monthly rather than weekly. The PDUFA date is in late January.
• The regulatory tension is that Sarepta has also filed for full approval of Vyondys 53 and Amondys 45 after a large, two-year Phase 3 study failed to meet its primary endpoint. Brian characterized the data as showing a little less than 1% of normal dystrophin without a clearly robust clinical benefit over the study period.
• Brian said it is difficult to imagine the FDA granting full approval to Sarepta’s drugs on that basis while refusing Dyne’s drug, which is better on dystrophin expression, dosing convenience and other measures. He expects approval and believes the strength of the DMD advocacy community makes withdrawing existing PMOs difficult.
• Josh agreed that Dyne is “definitively” a better mousetrap than Exondys in dystrophin expression, functional data and convenience. He said the low benchmark established by the FDA and Sarepta makes approval difficult to oppose, unless one argues for withdrawing every DMD drug from the market.
• Josh also congratulated Dyne’s team for executing well despite earlier criticism, filing roughly a month ahead of Novartis. With priority review, zylodursen could become the first drug of this muscle-targeted oligo type.

7. Next week’s AdComs: idiosyncratic votes or the new FDA’s tone revealed

• Two panels are scheduled for next week: Replimune’s RP1 for refractory melanoma and Capricor’s deramiocel for Duchenne muscular dystrophy. Josh tentatively placed the RP1 meeting on Thursday the 30th and described both programs as having followed tortuous paths through the agency.
• Josh framed the key question as whether the outcomes will be isolated decisions or the first highly public decisions under the new commissioner, whom he named Kyle D Amantes. Eric said the votes and briefing documents could provide a sense of direction, particularly because so much of both products’ histories has remained outside public view.
• Brad argued that the FDA needs more AdComs, not fewer, across administrations. He said Vinay Prasad had a “my way or the highway” approach and suggested Rick Pastor had sometimes approached matters similarly. In Brad’s view, public hearings allow experts and members of the public to air competing interpretations of “safe and effective.”
• Brad said the outcome would be especially newsworthy if an AdCom and the FDA sharply diverged — for example, a unanimous panel recommendation followed by rejection, or the reverse. He was unwilling to forecast the result in advance.
• Brian agreed that AdComs are the best forum for transparent scientific debate, even if they are inefficient or vulnerable to panel selection and briefing-document framing. He cited aducanumab, where the FDA favored approval, the panel strongly rejected the data, and the FDA approved anyway.
• Brian’s read-through mechanism is the briefing documents. Benign documents plus favorable votes would be “extremely positive for FDA flexibility” and more than a one-off; repeated negative findings would reveal the agency’s current tone. Even then, he said, it is difficult to know exactly where the FDA now sits.

Verification Notes

• The transcript is internally inconsistent around the fugitive CMO’s employer wording; this digest uses the segment heading’s Immix Biopharma label and treats the separate Atossa reference as a prior hiring reference without resolving the discrepancy.