MacroGenics Halts Lorigerlimab Development in Prostate Cancer, Secures $75M in Partnership Proceeds
核心洞察
MacroGenics discontinued lorigerlimab development in second-line metastatic castration-resistant prostate cancer (搜索) after interim Phase 2 LORIKEET trial data showed the experimental treatment arm would not meet its primary endpoint of improved radiographic progression-free survival.
The company secured $75 million in non-dilutive partnership payments from Sanofi and Gilead, with Gilead licensing an additional preclinical T-cell engager program for $25 million and Sanofi triggering $50 million in milestone payments following TZIELD approvals in the UK and China.
MacroGenics continues advancing lorigerlimab in gynecologic cancers through the ongoing Phase 2 LINNET study and is progressing three antibody-drug conjugate programs including MGC026, MGC028, and MGC030 (搜索).
MacroGenics announced a strategic portfolio realignment following disappointing interim results from its Phase 2 LORIKEET trial, leading the company to discontinue development of lorigerlimab in prostate cancer while securing significant partnership funding to support its pipeline through late 2027.
LORIKEET Trial Results Drive Strategic Decision
The company determined not to pursue further development of lorigerlimab in second-line metastatic castration-resistant prostate cancer (搜索) (mCRPC) based on interim data from the Phase 2 LORIKEET trial. The 150-patient randomized study evaluated lorigerlimab in combination with docetaxel and prednisone versus docetaxel and prednisone alone in second-line, chemotherapy-naïve patients with mCRPC.
Based on review of study data with an October 17, 2025 data cut-off, MacroGenics determined that the experimental treatment arm would not reach the study's primary goal of showing an improvement in radiographic progression-free survival (rPFS) versus the control arm for the targeted patient population. The company intends to present or publish the final LORIKEET data at a future date.
Continued Development in Gynecologic Cancers
Despite halting prostate cancer development, MacroGenics continues the ongoing LINNET study, a Phase 2 monotherapy trial evaluating lorigerlimab in patients with either platinum-resistant ovarian cancer (搜索) (PROC) or clear cell gynecologic cancer (搜索) (CCGC). The company believes lorigerlimab can be a differentiated treatment option for patients with gynecologic cancers and could be complementary with emerging therapies being developed for this patient population.
MacroGenics continues to enroll patients in the LINNET study and currently expects to provide a clinical update on the first part of the two-stage trial by mid-2026.
Significant Partnership Proceeds Strengthen Financial Position
The company achieved $75 million in additional partnering proceeds from Sanofi and Gilead during the third quarter. In November 2025, Gilead licensed an additional MacroGenics preclinical program under a 2022 collaboration agreement, triggering a $25 million payment. The licensed program leverages the company's novel, proprietary platform with the goal of improving upon the safety and efficacy of traditional T-cell engagers.
Under this collaboration, MacroGenics and Gilead are now advancing three programs, including MGD024, a clinical-stage CD123 (搜索) × CD3 (搜索) bispecific DART molecule, a preclinical TRIDENT program and this latest preclinical DART program. The company remains eligible to receive up to $1.6 billion in future milestones as well as royalties related to these three product candidates.
Sanofi continues to advance TZIELD (teplizumab-mzwv), an antibody targeting CD3 (搜索) that MacroGenics sold in 2018 to a partner subsequently acquired by Sanofi. In August and September 2025, TZIELD was approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom and by the National Medical Products Administration (NMPA) in China, respectively, triggering total milestone payments of $50 million expected to be received during the fourth quarter.
ADC Pipeline Advancement
MacroGenics is developing three antibody-drug conjugates (ADCs) that each incorporate a novel, glycan-linked topoisomerase 1 inhibitor (TOP1i)-based payload developed through collaboration with Synaffix (a Lonza company).
MGC026 targets B7-H3 (搜索), an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation. The company recently completed Phase 1 dose escalation and initiated dose expansion in two solid tumor indications.
MGC028 targets ADAM9 (搜索), a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumorigenesis and cancer progression and is overexpressed in multiple cancers. MGC028 is currently being evaluated in a Phase 1 dose escalation study in patients with advanced solid tumors.
MGC030 (搜索) is a preclinical ADC that targets an undisclosed antigen expressed across several solid tumors. An IND application to the U.S. Food and Drug Administration (FDA) for MGC030 is planned for 2026.
Financial Results and Extended Cash Runway
Total revenue was $72.8 million for the quarter ended September 30, 2025, compared to $110.7 million for the quarter ended September 30, 2024. The decrease was primarily due to $100.0 million recognized from milestones under the Incyte License Agreement in 2024 compared to $50.0 million recognized from milestones under the Provention (Sanofi) Asset Purchase Agreement in 2025.
Research and development expenses decreased to $32.7 million for the quarter ended September 30, 2025, compared to $40.5 million for the quarter ended September 30, 2024. The decrease was primarily due to discontinued internal development of the vobra duo program, decreased IND-enabling costs for MGC028 and decreased costs related to margetuximab.
Cash, cash equivalents and marketable securities balance as of September 30, 2025, was $146.4 million, compared to $201.7 million as of December 31, 2024. The cash balance does not include the $50.0 million from Sanofi or the $25.0 million from Gilead, which are expected to be received by year-end 2025.
MacroGenics anticipates that its current cash position, in addition to the $75.0 million in partnering payments from Sanofi and Gilead, plus projected future payments from partners and anticipated savings from ongoing cost-reduction initiatives, is expected to support its cash runway into late 2027.