Genmab's Rina-S Shows Strong Data in Endometrial Cancer

Genmab’s Rina-S Shows 50% Response in Endometrial Cancer, Phase 3 Planned

Highlights

• Genmab’s Rina-S demonstrated a 50% unconfirmed response rate in advanced endometrial cancer, surpassing analyst expectations.
• The ADC was acquired via Genmab’s $1.8 billion takeover of ProfoundBio and targets the folate receptor alpha.
• Clinical data showed durable responses with around 80% ongoing at cutoff, with two complete responses noted in the lower dose group.
• William Blair analysts raised confidence in the phase 3 trial set to begin by late 2025, following no significant adverse events reported.
• Genmab aims to position Rina-S as a more effective alternative to AbbVie’s Elahere amidst ongoing patent litigation.

Promising Early Results in Advanced Endometrial Cancer

Genmab has unveiled the initial clinical data for its antibody-drug conjugate (ADC), rinatabart sesutecan (Rina-S), in the treatment of advanced endometrial cancer, revealing a 50% unconfirmed response rate. This outcome surpasses the expectations set by William Blair analysts, reinforcing confidence in the drug’s development as it prepares to enter phase 3 trials.

"Genmab reported a 50% unconfirmed response rate, beating the expectations of William Blair analysts to boost confidence in the program ahead of its move into phase 3."

Rina-S Background and Market Opportunity

Rina-S is a folate receptor alpha (FRα)-targeted ADC acquired by Genmab through its $1.8 billion acquisition of ProfoundBio last year. Originally in a phase 1/2 trial for ovarian cancer, Genmab initially valued the market opportunity for Rina-S at $1 billion or more. However, after identifying additional indications, the company has since revised this valuation upward to $2 billion or greater.

Endometrial cancer represents a significant segment within this broader market, making the recent clinical data in this indication an important milestone for Genmab’s ambitions with the ADC.

"Rina-S is a FRα-directed ADC that Genmab picked up last year in its $1.8 billion takeover of ProfoundBio... Genmab identified a broader set of target indications and dialled up its valuation of the opportunity to $2 billion or more."

Clinical Trial Results and Patient Outcomes

Ahead of the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting, Genmab announced unconfirmed response rates of 50% in the lower dose cohort and 45.5% in the higher dose cohort. Notably, two complete responses were observed in the lower dose group. Approximately 80% of these responses remained ongoing at the data cutoff. Patients enrolled in the trial had undergone one to eight prior lines of therapy.

"Genmab reported unconfirmed response rates of 50% and 45.5%, respectively, in the lower and higher dose cohorts. The biotech saw two complete responses at the lower dose. Around 80% of the responses were ongoing in both cohorts as of the cutoff."

Contextualizing Results and Future Prospects

Tahamtan Ahmadi, Genmab’s Chief Medical Officer, highlighted during a recent earnings call that combination chemotherapy and checkpoint inhibition currently constitute the frontline treatment for endometrial cancer. Although the absence of a control arm in Genmab’s trial complicates direct comparisons, Ahmadi cited historical data indicating that second-line chemotherapy response rates typically range between 10% and 15%. The new data positions Rina-S as a potentially best-in-class treatment based on both efficacy and durability.

"Historically, the second-line has been an indication where the response rate to chemotherapies are maybe in the 10% to 15% range,” Ahmadi said. “We feel very comfortable that the data that is going to be presented in the very near future and publicly available will underscore the point that this is really a best-in-class profile from an efficacy point of view as well as from a durability point of view.”

William Blair analysts had anticipated a response rate of at least 30% to validate the program. With Genmab exceeding this threshold and reporting no serious adverse effects such as ocular toxicity, neuropathy, or interstitial lung disease, analyst confidence in the planned phase 3 trial, expected to start by the end of 2025, has strengthened.

"William Blair analysts said a response rate of 30% or more would generate confidence in the program... With Genmab clearing that bar and reporting no ocular toxicity, neuropathy or interstitial lung disease, the analysts have increased confidence in the phase 3 endometrial cancer trial."

Competitive Landscape and Legal Challenges

Genmab envisions endometrial cancer as a critical test for Rina-S’s efficacy across various levels of folate receptor alpha expression. The company aims to demonstrate that Rina-S can offer broader and improved effectiveness compared to AbbVie’s Elahere, an FDA-approved ADC targeting the same receptor. However, the competitive environment is complicated by legal disputes, with AbbVie accusing Genmab of willful ignorance regarding alleged theft of trade secrets related to Rina-S.

"Genmab sees endometrial cancer as a proving ground for the idea that Rina-S can be effective across the spectrum of folate receptor alpha expression... AbbVie has sued Genmab over Rina-S, accusing the biotech of being 'willfully blind' to the theft of trade secrets."