CatalYm GmbH

BARCELONA — At a major cancer conference, Pfizer made an unexpected announcement : It has late-stage plans in weight management. But it’s not targeting weight loss like one would first think amid the drug industry’s current fixation on obesity. While industry insiders and investors have eagerly awaited updates on Pfizer’s obesity programs, the New York pharma giant is now advancing a drug on the other end of the weight management spectrum. The drugmaker said Saturday it plans to take a GDF15-directed monoclonal antibody, named ponsegromab, into registration-enabling testing next year for cancer patients with cachexia, a condition that can lead to muscle wasting and life-threatening weight loss in patients with cancer. The decision to move into a registration-enabling study — plans of which are still pending discussions with regulators, according to a Pfizer spokesperson — is based on Phase 2 data presented in a late-breaking paper this weekend at the annual European Society for Medical Oncology confab in Barcelona. Ponsegromab was tested in a Phase 2 of 187 patients with non-small cell lung cancer, pancreatic cancer and colorectal cancer, and trial investigators looked at change from baseline in body weight as the primary endpoint. After 12 weeks, Pfizer said the experimental drug met the primary endpoint as there were “significant and robust increases” in patients’ body weight across all doses (100 mg, 200 mg and 400 mg) compared to placebo. At the highest dose, patients reached a 5.6% mean increase in body weight, according to Pfizer. The company said there were “no clinically significant adverse trends noted with ponsegromab administration.” Treatment-related adverse events happened in 8.9% of patients on placebo and 7.7% of patients on Pfizer’s drug. The highest dose also showed improvements on measures of appetite, physical activity and muscle mass, Pfizer said. “These results provide strong evidence that we have unlocked a mechanism to interrupt a critical driver of cachexia, GDF-15, which has the potential to impact patients with cancer cachexia and other life-threatening conditions,” Charlotte Allerton, head of discovery and early development at Pfizer, said in a statement. She highlighted that ponsegromab was discovered internally. “We look forward to advancing this program as part of our broader cardiometabolic portfolio to address weight management across the spectrum of patient needs.” There’s no FDA-approved treatment for cancer cachexia. In Japan, ONO Pharmaceutical markets Adlumiz. Also known as anamorelin, the tablet received a 2020 greenlight in that country after being rejected in Europe three years prior. It’s a ghrelin receptor agonist, which works by drumming up pathways involved in appetite and metabolism. The Cleveland Clinic estimates about 9 million people worldwide are affected by the condition. In addition to cancer, cachexia can also be a complication of Alzheimer’s, dementia, obstructive pulmonary disease and heart failure. Pfizer is also testing ponsegromab in a separate Phase 2 in patients with heart failure who have elevated serum concentrations of GDF-15. Other biotechs are also looking at GDF-15. German startup CatalYm raised $150 million this summer to test its GDF15-neutralizing antibody for solid tumors, and formerly public NGM Bio raised $122 million in July to test a GDF15/GFRAL antagonist for a rare condition known as hyperemesis gravidarum. Novartis shelved its GDF-15 agonist last year.

This $150m funding round builds on a $51m Series C round in November 2022. Credit: ma_Design via Shutterstock. German cancer biotech CatalYm has secured $150m in a Series D funding round following the recently announced data for its lead monoclonal antibody visugromab. The company has centred its pipeline on drugs targeting GDF-15 or growth differentiation factor-15, which acts as a key regulator of immune resistance to cancer therapies. The company was in the news earlier this year, when it shared follow-up data of its drug visugromab showing efficacy in heavily pretreated patients. The new funding, led by Canaan Partners and Bioqube Ventures, is set to fund the company’s planned Phase IIb trial of visugromab in select checkpoint-naïve front-line and second-line treatment settings. The drug has so far been studied in combination with Bristol Myers Squibb’s (BMS) anti-PD-1 drug Opdivo (nivolumab) in patients with non-squamous non-small cell lung cancer (NSCLC), hepatocellular cancer, and urothelial cancer. CatalYm presented data from the ongoing GDFATHER Phase I/IIa trial (NCT04725474) that is testing this combination at the American Society of Clinical Oncology (ASCO) meeting held in Chicago, on 2 June. Across all tumour types, patients who received visugromab showed an objective response rate of 16.7%. The average duration of response surpassed 15 months for NSCLC, and 14 months for urothelial cancer, with 77% of the patients’ responses still ongoing. These 90 patients were heavily pretreated and had experienced failed anti-PD-1 therapies in the past. See Also: Sumitomo Pharma’s DSP-5336 gains FDA fast track for AML AstraZeneca completes Amolyt Pharma acquisition Anti PD-1 checkpoint inhibitor drugs, such as BMS’ Opdivo, enhance the immune system’s ability to fight cancer by blocking the PD-1 receptor on T cells, a checkpoint that normally helps keep immune responses in check. Cancer cells often exploit this pathway to avoid being attacked by the immune system. Elevated GDF-15 levels in cancers can cause anti-PD-1 drugs to fail by creating an immunosuppressive tumour environment that hinders T cell activation and recruitment, which visugromab is designed to target. Checkpoint inhibitors have pulled in billions over the last few years. MSD’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab) was the world’s top-selling drug last year, making $25bn. BMS’ Opdivo generated $9bn in the same year, as per the company financials. One of the reasons for the high sales is the drugs’ ability to be paired with other anti-cancer medicines. In the announcement accompanying the funding, CatalYm’s CEO Phil L’Huillier said: “We continue to demonstrate visugromab’s potential to induce cancer remission depth and durability across multiple solid tumour indications, emphasising the substantial role that visugromab could play in a novel anti-cancer therapy regimen.”

CatalYm’s series D haul is close to triple its series C total in late 2022, when the biotech raised about $49 million. On the heels of early-stage data for monoclonal antibody visugromab showing “impressive and lasting responses” among patients with difficult to treat cancers, CatalYm has secured a $150 million series D.  The German biotech plans to use the funds to develop and expand phase 2b trials into select checkpoint naïve front-line and second-line treatment settings, the company said in a Tuesday release. “We continue to demonstrate visugromab’s potential to induce cancer remission depth and durability across multiple solid tumor indications emphasizing the substantial role visugromab could play in a novel anti-cancer therapy regimen,” CatalYm Managing Director and CEO Phil L’Huillier, Ph.D., said in the release. “We are building significant momentum for CatalYm’s development strategy and look forward to the support of these high-profile new and existing international investors.” Those investors include newcomers Canaan Partners and Bioqube Ventures, who led the round, along with Forbion Growth, Omega Funds and Gilde Healthcare. Existing investors Jeito Capital, Brandon Capital Partners, Novartis Venture Fund and Vesalius also threw some cash into the mix. CatalYm’s series D haul is close to triple their series C total in late 2022, when the biotech raised about $49 million. Visugromab targets growth differentiation factor 15, an immunosuppressant which is normally used by fetal cells to prevent the mother’s immune system from attacking them. In cancer, GDF-15 is hijacked by tumor cells to protect them from the patient’s immune system, causing immunotherapies like anti-PD-1 therapy to fail. At the American Society of Clinical Oncology this year, CatalYm presented data from the GDFATHER trial, which is testing visugromab in combination with Bristol Myers Squibb's anti-PD-1 drug Opdivo in patients with non-squamous non-small cell lung cancer (NSCLC), urothelial cancer and hepatocellular cancer. These patients were heavily pretreated and had shown resistance to anti-PD-1 therapy in the past. Each patient group had around 20 patients, with 90 total patients. Across all tumor types, patients who received visugromab showed an objective response rate of 16.7%, including four patients whose tumors disappeared. The average duration of response surpassed 15 months for NSCLC, and 77% of the patients’ responses are still ongoing. “We were initially drawn to the exciting biology around GDF-15 and found CatalYm to be at the forefront of the field,” Jon Edwards, Ph.D., managing partner at Bioqube Ventures, said in a statement. “We believe this approach has the potential to significantly increase durability and deepen responses, unlocking the full potential of I/O treatments. We are excited to support this fantastic team, and syndicate, in running robust clinical studies in a variety of promising indications.”