1/ Two GLP-1 combos are pitching “supercharged” weight loss plus muscle preservation:

1️⃣Ascletis’ ASC47 + GLP-1 (THRβ agonist, adipose-targeted thermogenesis)

2️⃣BioAge’s $BIOA azelaprag (APJ agonist) + GLP-1 (exercise-mimicking apelin signaling)

Both are aiming to fix the lean-mass drop that comes with GLP-1 monotherapy.

A thread 🧵 2/ In mice, both combos beat their GLP-1 backbone:

✅🐭ASC47: +56–87% more weight loss vs sema/tirze alone

✅🐭 BioAge: total loss ~39% with tirze + APJ agonist

That’s big…in rodents. Cue the cautious optimism.

1/ 🇺🇸🇨🇭 Swiss Pharma Just Dodged a Bullet

A case study in why the world over-reacted to “tariff wars” and why the bounce back is going to be glorious.

A new US–Switzerland trade pact could defuse the Section 232 tariff threat on drug exports.

Here’s what it means for Roche, Novartis, Lonza, Galderma… and the next wave of M&A.

Buy Swiss equity for a quick bounce?

🧵Let’s dig in: 2/ 🔍 1The Backstory

The US launched a national-security probe into foreign drug imports (Section 232) back in April.

It raised alarm bells across Europe, especially in Switzerland, where pharma is a core export.

Tariffs on finished drugs? Yes, that was on the table.

1/ 🧪 The Era of In-Vivo CAR-T Has Arrived

No leukapheresis.
No lymphodepletion.
No 3-week manufacturing delay.

Just a vial and a vein.

EsoBiotech’s in-vivo BCMA CAR-T has shown deep responses in myeloma after a single infusion.

Here’s why that matters 🧵 2/ 🎯 Autologous CAR-T has a speed problem

Even the best-in-class BCMA CAR-Ts (like cilta-cel) take 4–6 weeks from apheresis to infusion.

Some patients can’t wait that long.
Others relapse before dosing.
EsoBiotech skips all that.

1/ 🧬 How to Price a Platform in Biotech

Q2 M&A is ripping, Capstan just cleared $2.1B at Phase 1, and something important has changed.

A new market dynamic may be emerging, where optionality matters again.

Let’s break it down with math, comps, and a framework 🧵 2/ 📈 The Market Mood Has Flipped

Public biotech still lags, but behind the scenes:

🔸 Q2 M&A cleared ~$20B in equity value

🔸 Active funds recycled ~$10B in cash

🔸 Weak IPOs and broken SPACs are exiting fast

A structural clearing event is underway.

The quality floor just got raised.

1/ How ADCs Actually Work - it’s more than just payload internalization.

💣The brutal elegance of a biological smart bomb

A thread 🧵 2/ How ADCs Actually Work

🔸 What’s an ADC?
A targeted chemo-delivery system:
🔹 Antibody = the targeting system
🔹 Linker = the timed-release fuse
🔹 Payload = the cytotoxic warhead

👉🏼 Goal: Kill cancer cells precisely - while sparing healthy ones.

How ADCs Actually Work - it’s more than just payload internalization.

💣The brutal elegance of a biological smart bomb

A thread 🧵 How ADCs Actually Work

🔸 What’s an ADC?
A targeted chemo-delivery system:
🔹 Antibody = the targeting system
🔹 Linker = the timed-release fuse
🔹 Payload = the cytotoxic warhead

👉🏼 Goal: Kill cancer cells precisely - while sparing healthy ones.

🧮 A “Can’t Lose” Biotech Trade

$MURA was a broken biotech with:

🔹Market cap: $21M
🔹Cash (as of 12/31): $110M
🔹Pro forma Q1 burn + severance: est. $70M-$75M remaining

And ONE major catalyst - their lead program, nemvaleukin alfa, readout.

Now that failed, here’s why the setup still works.

And most important - how the stock is UP 150%

[1/] 🎯 The Bullish Binary Setup

You were betting on one last data readout:

👉🏼 If it hit, market cap could go 5x-10x

👉🏼 If it missed, they had enough cash to shut it down and return capital

So you’re long a free call option on success, backed by tangible net cash.

That’s rare.

[2/]

1/ Biohybrid robots are here.

MIT just engineered artificial muscle that flexes in multiple directions - like your iris.

But zoom out:

What happens when you combine:
🧠 LLM-based synthetic cognition
🦾 Engineered muscle tissue
🧬 Biological self-repair

Welcome to the cyborg frontier.

Let’s dive in 🧵 2/ Muscle powers movement 💪🏼

But natural muscle isn’t one-directional - your iris, trachea, limbs use complex fiber orientations to control motion.

Yet lab-grown muscle?
Until now: one direction only.
Limited robots to twitching or crawling.

Big win for $LLY in the Lp(a) race

💉EFFICACY: Lepodisiran drops Lp(a) by ~94% with just 1-2 injections

🏃‍♀️SAFETY: Effect still 74% below baseline at 1.5 years

But the real unlock?
🏆CV outcomes in 2026

[1/] What is lepodisiran?

A small interfering RNA (siRNA) therapy that:

🔹Targets apo(a) production
🔹Delivered via subQ injection
🔹Silences Lp(a) at the RNA level
🔹Long-acting by design

✅ Modality: siRNA (RNAi)
❌ Not an ASO like $NVS / $IONS
⏱️ Dosing: potentially annual or less

[2/]

Editas In Vivo Bet: HSC Editing 🔬🧬

Editas ($EDIT) is making a big bet on in vivo gene editing in 2025.

The company is shifting focus away from ex vivo approaches to unlock new possibilities in hematopoietic stem cells (HSCs) and liver-targeted therapies.

Here’s what’s coming. 👇 2/ Financial Position 💰

EDIT has $270M in cash, giving them runway into Q2 2027.

The in vivo pipeline is early, but the company plans to declare two clinical candidates by mid-2025:

1️⃣ HSC-targeted therapy for sickle cell disease (SCD) & beta thalassemia

2️⃣ Liver-targeted therapy for an undisclosed indication

1/ THREAD: Where do mRNA vaccines go after injection?

Lipid nanoparticles (LNPs) are the workhorses of mRNA vaccines, but how do they move through the body?

New PET-CT imaging in rhesus macaques gives us answers. 🧵👇 2/ Tracking LNPs in real time 📡

Researchers used radiolabeled LNPs to follow vaccine movement in living primates.

PET-CT imaging at 0, 4, and 24 hours showed LNPs don’t just stay at the injection site—they move fast.

1/ 🧠💻AI in Biopharma
Case Study: Roche

We will get more into this in the coming weeks in a Sunday newsletter. Sunday's are where we discuss topics related to emerging biopharma strategy.

But follow this thread for some super cool real life use cases from Roche 🧵👇
2/ This use case caught our eye- using AI to develop clinical biomarkers for development.

That is an excellent idea! Have not seen much of this in action.

1/ The future of #CANCER THERAPEUTICS is looking brighter than ever with innovative treatments like CAR-T, which involves engineering a patient's immune cells to target and destroy cancer.

A thread highlighting the emerging therapeutic platforms we are most excited about 👇 2/ Another exciting development is the use of IMMUNE CHECKPOINTS, which can help boost the immune response against cancer by blocking proteins that prevent the immune system from attacking cancer cells.