CatalYm’s Visugromab Phase 1/2a Data Demonstrating Clinical Proof-of-Concept for Reversing Resistance to Checkpoint Inhibitors through GDF-15 Neutralization Published in Nature

• Tumor remissions achieved in First-in-Human Phase 1/2a demonstrate clinical proof-of-concept with the majority of responders experiencing deeper RECIST 1.1 response levels than on their initial anti-PD1/PD-L1 treatment. Long durability and high rate of complete responses (CRs) indicate that GDF-15 blockade can reinvigorate and deepen anti-PD1/PD-L1 activity significantly.
• Detailed clinical proof-of-mechanism established showing that GDF-15 blockade alone and in combination with anti-PD1 treatment leads to T cell influx, T cell-proliferation- and Interferon-γ signature-induction in the tumor microenvironment
• Phase 1/2a data validate GDF-15 as a critical target for overcoming cancer resistance to checkpoint inhibition, offering a new treatment option for patients who have exhausted available standard-of-care and failed prior anti-PD1/PD-L1 treatment
• Neutralizing GDF-15 also appears to have potential benefits for patients suffering from GDF-15 elevation leading to cachexia, further extending visugromab’s relevance in treating cancer patients in need

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 Antibody-mediaTed Human Effector T Cell Relocation 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.