somepie

Finnish 🇫🇮 physician 🩺 | I invest mostly in biotechs, occasionally in story-driven junk.

[somepie @suomppi]

Right, I think the upside is fairly flat once the benefit is clearly clinically meaningful. In a disease with no approved disease-specific therapies, I doubt a 25 m vs. 35 m improvement would materially change physician adoption or the commercial opportunity. The downside is more asymmetric. If the effect is only ~20 m or the primary endpoint is missed its a different story

[somepie @suomppi]

$ACET data could drop any day now. CAR-T efficacy is already validated, and the remaining question is whether off-the-shelf allogeneic γδ CD20 CAR-T can deliver the same durable immune reset as autologous products.

The initial dataset included 7 patients: 5 with LN and 2 with extrarenal SLE, with 2–9 months of follow-up. All 5 LN patients achieved a renal response, including 3 CRRs, with naive B-cell recovery observed in two patients. No ICANS or other major safety signals.

The upcoming readout will include ≥20 LN/SLE patients, all with ≥6 months of follow-up. I assign ~65% PoS to a strong readout. My bull case fair value is roughly $420M equity value, or ~4× the current price, assuming the larger dataset broadly replicates the initial Phase 1 results. A full failure could mean around −50%, even though cash provides downside support. Thoughts? Bear takes especially welcome.

[somepie @suomppi]

@jamzbio @seedy19tron He means market is pricing ~25% odds

[somepie @suomppi]

I wonder if there’s a positive feedback (conditioning) effect. If patients experience less congestion early on, they’re able to walk more, become more active over the following weeks, and gradually improve their exercise capacity beyond the initial hemodynamic benefit. (”digging caves”😂😂)In other words, the early physiological improvement could create a virtuous cycle where increased activity further amplifies the eventual 6MWD gain.

If that’s even partially true, then continuous daily oral dosing in LEVEL—without the weekly troughs seen in HELP and over a longer 12-week treatment period—could potentially produce a larger functional benefit than the IV study alone would suggest.

Curious to hear your thoughts. Does that seem plausible to make a difference?

[somepie @suomppi]

I think that acute dosing (and daily oral dosing) gives the full venodilatory effect, which lowers PCWP. At trough, the venodilation may be attenuated rather than gone, still enough to prevent PCWP from rising despite modest inotropic support. Add a positive feedback/conditioning loop over 6 (12 in LEVEL!) weeks, and the 6MWD result becomes much easier to explain. $TENX

[somepie @suomppi]

@BubuFiend Matching efficacy with Q12W dosing will make it best in class 💰

[somepie @suomppi]

@SSampson60391 Haha I see, thats why you place more emphasis on the commercial side. I’m new to the story, so definitely need to dig deeper into the company’s history.

[somepie @suomppi]

Shoutout to @hannibalspeaks I think $CNTB's Seabreeze STAT, with topline data expected in early September 2026, is one of the more interesting clinical readouts in biotech this year.

The entire investment thesis comes down to one question. 🧵

[somepie @suomppi]

@SSampson60391 *In COPD

[somepie @suomppi]

@SSampson60391 Heh, Im using 45% (less clearly type 2driven, smoking-related pathology and emphysema contributes) ~ 80% one hits

[somepie @suomppi]

@SSampson60391 I use 65% PoS for P2 asthma

[somepie @suomppi]

@SSampson60391 Fair. My interpretation is different. A ~$100M EV doesn’t look like a market that’s convinced the clinical risk is behind us. I think it already leaves plenty of room for commercial uncertainty, and is still primarily discounting the probability of Phase 2 success.

[somepie @suomppi]

@SSampson60391 Yeah penetration is a big variable here. Assuming ~25% penetration of the EOS ≥300 ED population in the US. At a ~$6k net price, that still gets to roughly ~$630M US peak sales from asthma alone.

[somepie @suomppi]

@SmileysWord Applying a typical post successful Phase 2 PoS of ~45% implies an rNPV of roughly ~$600M, or approx ~$12/share from the US asthma opportunity alone, before assigning any value to ex-US markets, COPD, or the rest of the pipeline.

[somepie @suomppi]

@SmileysWord Assuming ~1.4M asthma ED visits/year in the US, 30% EOS ≥300, 25% penetration of the biomarker-positive population (105k treated patients/year), and a $6k net price per treatment, I arrive at ~$630M US peak sales.

[somepie @suomppi]

@hannibalspeaks Current Seabreeze Stat asthma protocol (NCT06940141) lists 28-day treatment failure as the primary endpoint and post-bronchodilator FEV1 at Week 1 as the key secondary endpoint. Are you referring to a different protocol version?

[somepie @suomppi]

@hannibalspeaks Fair point. The rapid bronchodilator-like effect is definitely interesting, even if the mechanism remains unclear. Why not both 🤷‍♂️ Rapid symptom relief + durable control of Type 2 inflammation.

[somepie @suomppi]

@hannibalspeaks What do you mean by “bronchodilator”?

Do you mean direct airway smooth muscle relaxation (like a β2-agonist), or improved airflow secondary to reduced airway inflammation?

[somepie @suomppi]

21/

That's the bet I'm making.

Sources:

• Connect Biopharma Phase 2 presentation
• Seabreeze STAT (https://t.co/2twepz9yNy)
• GINA 2025
• Edmonds et al., Cochrane
• Rowe et al., Cochrane

[somepie @suomppi]

20/

But if Connect's biological hypothesis is correct, Seabreeze won't simply demonstrate another asthma biologic.

It could show that extending control of Type 2 inflammation beyond a standard steroid course meaningfully reduces post-exacerbation relapse.