You know what’s crazy?

Cancer-associated cachexia kills somewhere between 20 and 30 percent of cancer patients.

You might not know it by it’s name, but cachexia is the wasting, the muscle loss, the appetite suppression that grinds people down toward the end. Anyone who’s seen a relative go through cancer has probably seen cachexia.

And there are zero approved disease-modifying therapies for it.

CatalYm just dosed the first patient in their Phase 2/3 VINCIT trial of visugromab in cancer cachexia. The trial is enrolling 518 patients with advanced solid tumors including NSCLC and colorectal cancer.

Visugromab is a monoclonal antibody that neutralizes GDF-15, growth differentiation factor 15.

GDF-15 has been the target everyone’s been circling for the last few years.

It’s a stress-response cytokine that tumor cells secrete in massive quantities. It binds GFRAL receptors in the brainstem and signals “stop eating, start losing weight.” Tumors basically use it to weaponize the body’s metabolism against itself.

Block GDF-15, and theoretically you reverse the cascade. Patients’ appetite return, they eat, their weight stabilizes, and functional status improves. Makes sense.

Pfizer’s ponsegromab put GDF-15 on the map last year with positive Phase 2 data showing weight gain in cachectic patients.

CatalYm’s differentiator is that visugromab works in cachexia and tumor immunology. Sounds kind of random until you realize that GDF-15 also blocks T cell recruitment into tumors.

This is probably why Catalym’s GDFATHER trial showed visugromab combined with anti-PD-1 produced 14.8% ORR in NSCLC and 21.1% in urothelial cancer in checkpoint-refractory patients.

Those data were published in Nature in December 2024.

So, two indications, one antibody. Cachexia and checkpoint resistance, both downstream of the same GDF-15 axis.

So who is CatalYm?

Well, they came out of Würzburg University in 2016. They’ve raised approximately $260 million across multiple rounds, including an oversubscribed $150 million Series D in July 2024 led by Canaan Partners and Bioqube Ventures.

CEO Scott Clarke came in to scale the company through Phase 2/3 development, and they’ve expanded the leadership team across CFO, CMO, CDO, and CTO appointments.

VINCIT is the bigger commercial bet of the two indications. Cachexia is a global problem with no approved disease-modifying therapy and millions of cancer patients affected each year. If visugromab clears Phase 3 there, it’s a foundational drug.

The clinical hurdle is going to be the endpoint. FDA hasn’t always loved cachexia trials because outcomes are messy. Weight gain, lean body mass, physical function, quality of life?

Once you pick a primary endpoint, someone will argue it doesn’t matter as much as another one.

Pfizer’s ponsegromab data helped open the door by showing weight gain in a regulatory-credible way. CatalYm presumably designed VINCIT with that precedent in mind.

Six months from first patient dosed, we’ll know if recruitment is moving. Eighteen to twenty-four months, we’ll see interim data.

The pediatric oncology side of biotech has had its share of wins. The ICI side has had its decade. But cachexia? It’s been a graveyard.

Multiple ghrelin agonists failed. Megestrol acetate is what most patients get and it barely works. If GDF-15 turns out to be the lever, CatalYm and Pfizer just unlocked a market with no competition and immense unmet need.