Genmab (GMAB) R&D Update summary

Key clinical data and differentiation

• Rinatabart Sesutecan (Rina-S®) demonstrated high efficacy and durable responses in heavily pretreated ovarian and endometrial cancer patients, with objective response rates of 55.6% in ovarian cancer (120 mg/m²) and up to 50% in endometrial cancer, including complete responses, with median duration of response not reached at 48 weeks follow-up.

• Efficacy and safety were consistent across all levels of folate receptor alpha expression, supporting its use as an all-comers therapy rather than requiring biomarker selection.

• Responses occurred early, with a median time to response of 6 weeks, and most efficacy-evaluable patients experienced tumor burden reduction.

• Durable responses were observed, with a majority of responses ongoing at median follow-up, and low discontinuation rates due to adverse events.

• The 100 mg/m² dose was selected for further development in endometrial cancer due to optimal efficacy and safety, especially considering higher BMI in this population.

Safety profile

• The safety profile was manageable, with cytopenias and low-grade gastrointestinal events as the most common adverse events, and no observed ocular toxicity, interstitial lung disease, or neuropathy.

• TEAEs of any grade occurred in 100% of patients, with grade ≥3 TEAEs in 77.2% (100 mg/m²) and 76.1% (120 mg/m²) of endometrial cancer patients.

• Serious TEAEs were reported in 31.8% (100 mg/m²) and 50.0% (120 mg/m²) of patients, with two fatal events in the higher dose cohort.

• Myelosuppression is manageable with guideline-based prophylaxis, and dose selection is informed by pharmacokinetic and safety data.

Development and expansion plans

• Multiple pivotal trials are ongoing or planned, including phase III trials in platinum-resistant and platinum-sensitive ovarian cancer, and endometrial cancer, with dosing in new studies expected before year-end.

• A phase II trial in non-small cell lung cancer will launch before year-end, exploring both EGFR-mutated and broader adenocarcinoma populations.

• Combination studies with standard of care agents are underway in both ovarian and endometrial cancers.

• Future expansion into additional solid tumors is planned, with further announcements expected in the coming months.