1/ 🧬 Immune Athero is coming

LDL is largely solved for rich health systems. PCSK9s, inclisiran, gene editing soon.

Yet patients with LDL at 40 still infarct.

The next wave treats the artery as an immune organ, not a plumbing problem.

That is the immune atherosclerosis trade

A thread 🧵 2/ 🧯 From cholesterol to cytokines

CANTOS proved it first, block IL-1β, cut MACE without touching LDL.

Low-dose colchicine repeated the story in cheaper form.

Now IL-6 agents like ziltivekimab (Novo / Corvidia) & pacibekitug (Tourmaline) are in advanced trials after clean biomarker hits.

Signal is clear, residual inflammatory risk is druggable.

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.