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  • Lilly breaks records with 29% weight loss & Zealand inks $2.5B deal with China's OTR

Lilly breaks records with 29% weight loss & Zealand inks $2.5B deal with China's OTR

Author

Joachim Eeckhout
December 12, 2025

 

Good morning! If you’ve been waiting for something in Alzheimer’s research that feels genuinely new, Spain’s Tetraneuron just gave the field a noteworthy jolt. The Madrid-based biotech secured fresh funding (undisclosed amount) to take its gene therapy into first-in-human testing. The approach targets E2F4, a master regulator of neuronal homeostasis, aiming to restore normal function, prevent aberrant cell-cycle re-entry, reduce amyloid buildup, and improve synaptic connectivity. With a Pre-IND already completed at the FDA and soon a clinical trial application submission in Europe, Tetraneuron’s lead candidate TET-101 moves closer to becoming one of the few Alzheimer’s therapies designed to directly modify disease pathways rather than simply slowing the inevitable.

Enjoy today’s read!

—Joachim E.

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SNAPSHOT

Lilly's new obesity drug sets a record with nearly 29% weight loss

Weight loss

 

Eli Lilly’s experimental drug retatrutide helped patients lose up to 28.7% of their body weight in a Phase 3 study; the most dramatic weight loss reported for any obesity medication to date.

Why it matters: This breakthrough raises the bar for weight loss treatments, potentially transforming care for millions struggling with obesity and related conditions like knee arthritis.

Backstory: Lilly’s earlier obesity drug, Zepbound (tirzepatide), already led the market. Retatrutide, which activates three metabolic pathways, builds on this success. A 2023 Phase 2 trial had already shown promise, and the just-released Triumph-4 study confirms and exceeds expectations.

Big picture: Retatrutide has a great advantage over the competition with its novel triple-action approach of targeting GLP-1, GIP, and glucagon receptors. However, competitors like Metsera (acquired by Pfizer) and others are exploring new mechanisms and dosing options as well as muscle-preserving treatments and drug combinations.

Zoom in: Over two-thirds of treated patients reported a 70% drop in knee arthritis pain. Patients receiving the highest dose of retatrutide (12 mg) lost an average of 28.7% of their body weight; among these patients, 39% lost more than 30%, and 24% lost more than 35%.

Yes, but: This rousing success did however include side effects, such as nausea (43%), diarrhea (33%), vomiting (21%), and skin sensitivity (21%). The trial results were, according to some, a bit too positive, as 18% of patients on the highest dose dropped out, with some citing “too much weight loss.”

What’s next: Results from a separate trial designed to maximize weight loss are expected next year, with longer treatment duration. Lilly is also planning seven additional readouts in 2026 and eyeing approval for its obesity pill orforglipron.

SNIPPETS

What’s happening in biotech today?

💰 Fat funds: We stay in the obesity field with this first news, as Prolynx, a biotech startup based in Emeryville, California, just secured $70M in Series A funding to develop longer-lasting obesity drugs using proprietary extended-release linker technology. The funding will support the development of monthly or quarterly versions of both incretin-based and non-incretin therapies. The company aims to improve patient adherence by reducing dosing frequency and minimizing side effects, addressing the limitations of popular weekly treatments like Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy. Clinical trial timelines are yet to be disclosed.

 🥊 Fibrosis fighter: GRI Bio has reported positive phase 2a data for its oral drug candidate GRI-0621 in idiopathic pulmonary fibrosis (IPF), showing a favorable safety profile and potential lung function benefits as it seeks to advance development amid limited cash reserves. The 12-week trial involving 35 patients met its primary endpoint with no safety or tolerability issues. 39% of treated patients showed increased forced vital capacity (FVC) compared to 20% in the placebo group. Despite encouraging data, the company faces financial challenges and recently raised funds through a stock and warrant offering.

🗺️ Map making: Disco Pharmaceuticals has expanded its seed financing round to €36M. The Cologne-based biotech will use the funding to advance its proprietary Surfaceome-Mapping Platform, which identifies novel cell-surface target pairs for the development of bispecific Antibody-Drug Conjugates (ADCs) and T-Cell Engagers. These therapies aim to precisely target and treat hard-to-treat cancers such as small cell lung cancer and microsatellite-stable colorectal cancer.

 🍬 Sugar crash: Rezolute’s stock plummeted 87% after its experimental hypoglycemia drug, ersodetug, failed a pivotal phase 3 trial in patients with congenital hyperinsulinism (HI). The 63-patient study missed its primary endpoint, showing a 45% reduction in self-monitored hypoglycemia events in the highest dose group, which was not statistically significant compared to a 40% reduction in the placebo group. Secondary endpoints also failed, with no meaningful improvement in hypoglycemia duration. The trial also reported two serious hypersensitivity reactions. Despite the setback, Rezolute plans to consult the FDA on potential next steps and is continuing a separate phase 3 trial of ersodetug in tumor-induced HI.

🐚 Shell deal: Moderna has entered a licensing agreement with Swedish company Nanexa to evaluate and potentially improve the delivery of up to five injectable therapies using Nanexa’s PharmaShell platform, a slow-dissolving, high-load drug coating technology. The deal includes a $3M upfront payment, with up to $500M in milestones and royalties. The partnership aligns with Moderna’s shift toward advanced biologics and oncology, as it refocuses its pipeline beyond infectious disease vaccines.

SNAPSHOT

Zealand inks $2.5B deal with China's OTR to boost oral metabolic drug pipeline

 

Why it matters: This alliance gives Zealand access to a promising small-molecule platform and strengthens its push into the competitive metabolic disease space, especially obesity and cardiometabolic disorders.

Backstory: OTR, launched in March 2025, is a stealth-mode startup with backing from Pfizer Ventures and a $100M Series A. Zealand is aiming for five product launches by 2030. Its current pipeline includes Phase 3 drug survodutide (with Boehringer) and Phase 2 petrelintide (with Roche). Zealand recently paused work on one obesity drug to refocus on programs with clearer differentiation.

Big picture: With the obesity drug race accelerating (read the “Snapshot” from today), biotech companies are looking for new ways to differentiate from the market heavyweights. Oral alternatives, such as those developed by OTR, could expand access and market share, positioning Zealand as a major global player.

Zoom in: Zealand will pay OTR $20M upfront, with potential to reach $30M based on certain pre-agreed conditions. OTR stands to earn up to $2.5B in milestone payments, mostly tied to commercial success, plus royalties.

What’s next: OTR's full pipeline remains undisclosed, but it targets gaps in cardiometabolic, oncology, and inflammation treatment. Zealand and OTR will begin joint discovery and development on new drug targets. Additional deals under this new strategy are expected. 

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