Visugromab

MUNICH--( BUSINESS WIRE )-- CatalYm today announced that data of the first-in-human Phase 1/2a study of its lead drug candidate visugromab were published in Nature. The paper titled “Neutralizing GDF-15 can overcome anti-PD-(L)1 resistance in solid tumors” emphasizes the significant potential of visugromab to induce unprecedented cancer remission depth and durability across multiple solid tumor indications as well as in combination with nivolumab in late- to last-line solid tumors. Visugromab is a humanized, monoclonal antibody that counteracts GDF-15, a critical immunosuppressant used by tumor cells to survive. The publication provides a mature data set of the GDFATHER Phase 1/2a trial ( NCT04725474 ), demonstrating that the company’s anti-GDF-15 antibody visugromab in combination with the PD-1-inhibitor nivolumab delivers deep and durable responses in by strict RECIST 1.1 criteria anti-PD-(L)1 relapsed/refractory solid tumor patients. Building on interim data presented at ASCO earlier this year, the additional findings extend the durability profile of the anti-tumor responses seen in these late- to last-line metastatic non-small cell lung cancer (NSCLC), urothelial cancer (UCC) and hepatocellular cancer (HCC) patients. The publication further provides a wealth of translational research data that demonstrate the detailed proof-of-mechanism (POM) for visugromab, which induces T-cell influx, T-cell proliferation, and Interferon-γ signature induction in the tumor microenvironment both in monotherapy and in combination with nivolumab. Furthermore, pan-cancer immunogenomic analyses demonstrate the impact of GDF-15 on the tumor microenvironment and its immune cell landscape. The full publication can be accessed and downloaded via the following link . “The publication of our data in Nature confirms the high significance and novelty the scientific community has ascribed to GDF-15 as an immuno-oncology target, as well as the potential of visugromab to transform the cancer immunotherapy treatment landscape,” said Eugen Leo MD PhD MBA, Chief Medical Officer at CatalYm . “We observed both robust proof-of-mechanism and clinical proof-of-concept in this first-in-human trial for visugromab, with more than half of our responders achieving deeper RECIST 1.1 responses than seen with their initial checkpoint inhibitor treatment. Notably, we see a growing number of lasting complete responses in late- to last-line patients who had no further therapeutic alternatives anymore. This is a significant outcome not seen with other exploratory I/O treatments in this setting. We are now rapidly advancing visugromab into earlier lines of treatment, with several trials planned for 2025 in high unmet medical need solid tumor indications.” Summary of Key Clinical Results from the ongoing GDFATHER Phase 1/2a trial ( GDF -15 A ntibody-media T ed H uman E ffector T Cell R elocation Phase 1/2a Trial): The matured results from the Phase 2a indication-specific cohorts for NSCLC, UC, and all HCC so far treated show the following Objective Response Rates (ORR) based on strict RECIST 1.1 criteria: non-squamous NSCLC: ORR of 19.0% (4/21), with 2 partial responses (PR) and 2 complete responses (CR) UC: ORR of 18.5% (5/27), with 4 PR and 1 CR HCC: interim ORR of 20.0% (4/20), with 3 PR and 1 CR The current mean duration of response (DoR) for UC and NSCLC surpassed 15 and 16 months with 7/9 responses ongoing. More than half of all responders in the NSCLC and UC cohorts of the trial experienced a response depth on study treatment as per RECIST 1.1 criteria that had not been reached on their prior anti-PD1/PD-L1 treatment that was mostly administered as first-line treatment and in combination with chemotherapy. Among the NSCLC and UC responders, 3 out of 4 complete responders had not achieved a complete response on any prior line of systemic treatment, including their initial anti-PD1/PD-L1 therapy. Additionally, biomarker analyses revealed promising potential for patient stratification, with elevated levels of serum GDF-15 correlating with reduced immune cell infiltration in tumors. The combination of visugromab with nivolumab was overall well-tolerated, with a safety profile comparable to nivolumab treatment alone. In a subgroup of patients that had combined manifest cachexia, a similar effect on weight gain was observed as demonstrated for another GDF-15 inhibitor in a recent cachexia trial. Cachexia, a syndrome characterized by severe weight loss and muscle wasting is driven by elevated GDF-15 levels in certain cancer types. By neutralizing GDF-15, visugromab can help mitigate these effects, potentially improving the quality of life for patients undergoing intensive cancer treatments. Based on these encouraging data, CatalYm is currently preparing for a broad Phase 2b program in earlier treatment settings for non-squamous NSCLC and additional tumor indications. These developments highlight the company’s commitment to tackling cancer resistance and improving treatment outcomes for patients across multiple tumor types. About Visugromab (CTL-002) Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by reenabling immune cell activation, proliferation and Interferon-γ signature induction. Visugromab has demonstrated a good safety profile and potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients. The antibody will now be investigated in Phase 2b studies in multiple solid tumor indications. About CatalYm CatalYm has identified GDF-15 as a key cancer therapy resistance mechanism and is developing it as safe and efficacious immune therapy for solid tumors. GDF-15 is an immunosuppressant that is hijacked by cancer cells to evade immune system attack. Visugromab, CatalYm’s lead antibody, has demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. CatalYm is now advancing to Phase 2b studies to confirm visugromab as a new class of cancer immunotherapy in a broad range of anti-cancer regimens.

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.”