Ponsegromab

CatalYm turned heads at this year’s American Society of Clinical Oncology (ASCO) meeting with promising early response results for its anti-GDF-15 antibody in heavily pretreated patients with late-stage solid tumours. Now, the biotech plans to move visugromab into first-line patients, thanks to a fresh $150-million funding to fuel development of the potentially first-in-class immuno-oncology (IO) treatment.The biotech is currently testing its antibody in patients with hepatocellular carcinoma (HCC), urothelial cancer (UC) and non-small-cell lung cancer (NSCLC) in combination with PD-1 inhibitor Opdivo (nivolumab) in the Phase I/IIa GDFATHER trial. At ASCO, CatalYm revealed that roughly a fifth of patients across the different cohorts responded to treatment: four of 21 NSCLC patients (19%), as well as five of 26 UC patients (19.2%) and four of 20 HCC patients (20%). A typical response rate for last-line, late-stage patients with standard-of-care treatments is between 8% and 12%, CEO Phil L’Huillier told FirstWord.Plus, visugromab seems to lead to a more durable response than the two-to-four months seen with chemotherapy in a comparable patient population. L’Huillier said that the majority of responders are still receiving treatment, with some still on the therapy after 18 months. Official duration of response has yet to be reached in either of the three cohorts.The level and duration of response to the antibody, coupled with its safety profile, represent “compelling clinical data in these patients that are last-line, late-stage that have no other alternative,” L’Huillier said — data that managed to pique investor interest in an era when VC cash isn’t as free-flowing as years prior.CatalYm’s oversubscribed series D was led by new investors Canaan Partners and Bioqube Ventures, who were joined by Forbion’s Growth Opportunities Fund, Omega Funds and Gilde Healthcare. Existing investors Jeito Capital, Brandon Capital Partners, Novartis Venture Fund and Vesalius also participated in the round. “IO is not the hottest space at the moment, so getting investor attention takes some doing,” L’Huillier said. “I think what got them excited most was, we’ve got a very novel IO approach by neutralising GDF-15.” Removing cancer’s cloakCatalYm was co-founded in 2016 by Jörg Wischhusen, a professor at the University of Würzburg in Germany, after he identified the biological mechanism behind GDF-15’s role in foetomaternal tolerance — and how cancer can hijack that mechanism within the tumour microenvironment to avoid immune detection. By neutralising GDF-15, CatalYm aims to remove a tumour’s “invisibility cloak” and reveal it to the immune system. Company scientists have also worked out the cellular intricacies of how the protein functions to protect cancer, L’Huillier added. “We know GDF-15 reduces immune cell infiltration, inhibits APC [antigen-presenting cell] activation, and interferes with T-cell priming,” he said. “We understand mechanistically how it’s doing what it’s doing.” What’s more, GDF-15 can also impact metabolic functions. When signalling occurs through a receptor in the brainstem, boosting levels of the protein, patients can experience vomiting and nausea — the same mechanism that triggers those symptoms during certain cancer treatments.“When we neutralise GDF-15 to treat cancer, not only are we treating the cancer through the immune mechanism, but we’re also treating the sickness that’s often associated with chemotherapies, radiotherapies, and ADCs [antibody-drug conjugates],” he explained. In patients with highly elevated GDF-15 serum levels, visugromab has even led to body condition improvement and weight gain, which L’Huillier called “a real differentiator.” Moving to earlier linesThe next step for CatalYm is to test visugromab in the frontline and second-line settings — checkpoint-naïve and checkpoint-refractory NSCLC patients —- in randomised controlled studies.  The trials are expected to launch next year, and read out in early 2027. Tuesday’s financing is expected to provide the biotech with runway until the end of 2027, as CatalYm vies to reach the title of first-in-class with visugromab.  Two other companies have candidates that act on GDF-15, though neither are in development as IO agents.Pfizer has anti-GDF-15 antibody ponsegromab in Phase II testing for cancer-related cachexia, as well as heart failure. NGM Biopharmaceuticals is planning a Phase II trial of NGM120, an antibody that binds glial cell-derived neurotrophic factor receptor alpha-like (GFRAL) and inhibits GDF-15 signalling, to treat hyperemesis gravidarum, which causes severe vomiting and weight loss in pregnant women. “We’re very much leading in the local immunosuppression mechanism of GDF-15,” L’Huillier said, adding that now more companies “are starting to enter the field based on the results that we and Pfizer and others are getting.”