Genmab’s Phase 2 data strengthens case for $1.8B ProfoundBio bet

Why it matters: Genmab has already dropped or deprioritized several earlier-stage antibody-drug conjugates (ADCs) acquired from ProfoundBio. Rina-S is increasingly carrying the burden of proving that the 2024 acquisition was worth its price. Fortunately for the Danish company, the latest data strengthen that case.

By the numbers: In the Phase 2 RAINFOL-01 trial, Rina-S produced a 45.9% confirmed objective response rate (ORR) among 109 patients receiving the 100 mg/m² dose, including five complete responses.

• The median duration of response reached 12.1 months, while median progression-free survival (PFS) was 9.5 months. More than half of responders (51%) were still responding after one year.
• The results are notable in a difficult-to-treat population. Patients had received a median of three previous lines of therapy, and about one-third had previously received AbbVie’s Elahere (mirvetuximab soravtansine), another ADC targeting folate receptor alpha (FRα).

How it works: Rina-S is an ADC targeting FRα, a protein frequently overexpressed on ovarian cancer cells. Once bound to FRα, the ADC is taken into the cell and releases exatecan, a topoisomerase I inhibitor designed to kill the cancer cell. Its membrane-permeable payload can also reach nearby tumor cells through a bystander effect, which could help explain why Rina-S showed responses even in tumors with low or undetectable FRα expression.

• This particular feature of Rina-S could become an important differentiator from Elahere, which is approved for patients with FRα-positive platinum-resistant ovarian cancer selected using an FDA-approved test.

Wall Street agrees: A report from Barclays said the Phase 2 results strengthen the case for Rina-S ahead of Phase 3 data. The bank highlighted the 45.9% response rate and 9.5-month PFS as comparing favorably with Elahere, particularly because Rina-S was tested in a broader population. Barclays maintained its overweight rating on Genmab and estimates Rina-S could generate about $2 billion in peak ovarian cancer sales.

• Investors seem to agree, with Genmab shares rising more than 4% in early trading following the announcement.

Backstory: Genmab acquired Rina-S through its $1.8 billion (€1.7 billion at the time) takeover of ProfoundBio in 2024, a deal intended to accelerate the Danish biotech’s push into ADCs.

• Rina-S was the most advanced asset in the acquisition, but it came with several earlier-stage ADC programs. Their subsequent progress has been mixed.
• As we reported in January, Genmab stopped enrolling patients in a Phase 1/2 trial of ProfoundBio-derived GEN1286 after recruiting just 23 of an originally planned 214 patients. The company had also discontinued GEN1160 and GEN1107, two other ADCs originating from the acquisition.

Yes, but: Hematologic toxicity was common, with anemia and neutropenia each reported in 57.8% of patients. However, treatment discontinuations because of adverse events remained relatively low at 5.5%, and Genmab reported no significant signals for ocular toxicity, peripheral neuropathy or interstitial lung disease.

What’s next: Genmab is already testing Rina-S in four Phase 3 trials, including platinum-resistant and platinum-sensitive ovarian cancer as well as endometrial cancer.

Bottom line: Those randomized studies will ultimately determine whether the promising Phase 2 profile translates into a competitive drug. But after several other ProfoundBio programs were pared back, Rina-S is giving Genmab something it particularly needs: clinical evidence that the most valuable asset in its $1.8 billion ADC acquisition may live up to the investment.