Pilatus Biosciences Receives FDA IND Clearance for PLT012, a Novel Anti-CD36 Metabolic Checkpoint Antibody
Pilatus Biosciences has announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for PLT012, a first-in-class, humanized anti-CD36 monoclonal antibody. This clearance allows the company to initiate a Phase 1, first-in-human clinical trial to evaluate PLT012 in patients with solid tumors, with expansion cohorts specifically planned for tumor types strongly influenced by CD36-mediated metabolic dysregulation, such as liver and gastrointestinal cancers.
PLT012’s novel mechanism of action (MOA) targets CD36, a metabolic checkpoint receptor involved in lipid uptake, to reprogram the immunosuppressive tumor microenvironment (TME). By blocking CD36-mediated lipid uptake, the antibody aims to restore metabolic fitness in cytotoxic T cells (effector T cells), which often become exhausted in the TME due to high lipid availability. Simultaneously, PLT012 is designed to suppress populations of immunosuppressive cells, such as regulatory T cells (Tregs) and pro-tumor macrophages. This dual action is intended to reinvigorate the anti-tumor immune response.
Preclinical data supported the IND clearance, demonstrating monotherapy anti-tumor efficacy in both “immune-hot” and traditionally “immune-cold” tumor models. The data also showed potential synergy when PLT012 was combined with existing PD-1/PD-L1 inhibitors, suggesting that it could help overcome resistance to current immunotherapies. Furthermore, Pilatus has previously received FDA Orphan Drug Designation for PLT012 for the treatment of liver and intrahepatic bile duct cancers (HCC/ICCA), highlighting the urgent unmet medical need in this patient population and providing incentives for development. The upcoming Phase 1 trial will assess the drug’s safety, tolerability, pharmacokinetics, pharmacodynamics, and initial signs of clinical activity, marking a significant step in translating its promising preclinical immunometabolic approach into a new therapeutic option for cancer patients.
ENHERTU in Combination with Pertuzumab Becomes the First Newly Approved Option in a Decade for First-line Treatment of HER2-positive Metastatic Breast Cancer in the US
The U.S. Food and Drug Administration (FDA) has approved ENHERTU (fam-trastuzumab deruxtecan-nxki), an antibody-drug conjugate (ADC), in combination with pertuzumab (PERJETA) for the first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer. This marks the first new treatment option approved for this specific setting in over a decade, establishing a new potential standard of care.
The approval is based on the highly significant results from the global, Phase 3 DESTINY-Breast09 trial. In this study, the ENHERTU plus pertuzumab combination demonstrated a statistically significant and clinically meaningful improvement in Progression-Free Survival (PFS) compared with the previous standard-of-care regimen of taxane, trastuzumab, and pertuzumab (THP). The median PFS for patients treated with ENHERTU plus pertuzumab was 40.7 months, compared to 26.9 months for the THP regimen. This translates to a 44% reduction in the risk of disease progression or death (Hazard Ratio [HR]: 0.56). The Objective Response Rate (ORR) was also high, reaching 87% in the combination arm.
ENHERTU is a specifically engineered HER2-directed DXd antibody-drug conjugate, combining the anti-HER2 antibody trastuzumab with a topoisomerase I inhibitor (DXd) via a cleavable linker. Pertuzumab is another HER2-directed monoclonal antibody. The combination leverages complementary mechanisms—ENHERTU’s targeted delivery of chemotherapy and pertuzumab’s HER2 signaling inhibition—to enhance anti-tumor activity. The profound PFS benefit shown in DESTINY-Breast09 is consistent across key patient subgroups and is expected to change clinical practice, offering patients with newly diagnosed HER2-positive metastatic breast cancer a superior front-line option. The FDA also approved a companion diagnostic to identify eligible patients.
Sanofi Shares Progress Update on Tolebrutinib in Primary Progressive Multiple Sclerosis
Sanofi announced a disappointing but important progress update regarding its investigational, oral, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor, tolebrutinib, in the treatment of Primary Progressive Multiple Sclerosis (PPMS). The update revealed that the Phase 3 PERSEUS study did not meet its primary endpoint.
The PERSEUS trial evaluated tolebrutinib against placebo in participants with PPMS, which accounts for approximately 10% of the total Multiple Sclerosis (MS) population and is characterized by a slow, continuous neurologic decline without periods of relapse. The primary endpoint was the delay in the time to onset of 6-month composite Confirmed Disability Progression (cCDP). Tolebrutinib failed to demonstrate a statistically significant delay in disability progression compared to placebo in this patient group.
As a result of the negative findings from the PERSEUS trial, Sanofi has decided not to pursue a regulatory submission for tolebrutinib in the PPMS indication. The company stated that a preliminary analysis confirmed the drug’s safety profile was consistent with prior studies, with drug-induced liver injury (DILI) remaining an identified risk requiring strict monitoring. Despite this setback in PPMS, Sanofi reaffirmed its confidence in tolebrutinib’s potential value for other MS patient populations, specifically in non-relapsing Secondary Progressive Multiple Sclerosis (nrSPMS), based on positive results from the HERCULES Phase 3 trial. Tolebrutinib is currently under regulatory review in various jurisdictions for nrSPMS, though a U.S. FDA decision for this indication has been delayed further. Full efficacy and safety data from the PERSEUS trial are planned for presentation at a future medical meeting to advance understanding of PPMS disease biology and the role of BTK inhibitors.
Gilead’s Bictegravir–Lenacapavir Single-Tablet Regimen Achieves Primary Endpoint in Phase 3 ARTISTRY-2 Study
Gilead Sciences reported positive topline results from the Phase 3 ARTISTRY-2 trial, which evaluated an investigational once-daily bictegravir (BIC)–lenacapavir (LEN) single-tablet regimen (STR) for the treatment of HIV. The study successfully met its primary efficacy endpoint, demonstrating the BIC/LEN STR was statistically non-inferior to the current standard-of-care, BIKTARVY® (bictegravir/emtricitabine/tenofovir alafenamide), in virologically suppressed adults with HIV.
The ARTISTRY-2 trial was a double-blind, randomized study in which virologically suppressed adults receiving BIKTARVY were switched to either the investigational BIC/LEN regimen or continued on BIKTARVY. The primary endpoint was the proportion of participants with HIV-1 RNA levels>50 copies/mL at Week 48. The results showed that switching to the BIC/LEN STR maintained high rates of viral suppression, comparable to BIKTARVY, a globally recommended regimen. The investigational regimen was also generally well tolerated, with no significant or new safety concerns identified during the trial.
The BIC/LEN STR combines two potent antiretroviral agents with different mechanisms of action:
- Bictegravir (BIC): A guideline-recommended integrase strand transfer inhibitor (INSTI) known for its high barrier to resistance.
- Lenacapavir (LEN): A first-in-class capsid inhibitor with a novel mechanism of action that has no overlapping resistance with existing antiretroviral drug classes.
These positive results, combined with previously announced positive data from the Phase 3 ARTISTRY-1 trial, will form the basis of regulatory submissions for the BIC/LEN STR. This new combination aims to further transform the HIV treatment landscape by providing an expanded, potentially more durable treatment option that incorporates one of the newest mechanisms of action in a convenient, once-daily single pill.
argenx Shares Progress Update on UplighTED Trials of Subcutaneous Efgartigimod in Thyroid Eye Disease
argenx SE announced the discontinuation of its Phase 3 UplighTED studies, which were evaluating the subcutaneous (SC) formulation of efgartigimod (efgartigimod alfa and hyaluronidase-qvfc) in adults with moderate-to-severe active Thyroid Eye Disease (TED).
The decision to stop the trials was based on the recommendation of an Independent Data Monitoring Committee (IDMC). The IDMC conducted a pre-specified interim analysis of unblinded data from patients who had completed 24 weeks of treatment and concluded that the trials should be halted due to futility. This means that the drug was not deemed likely to meet its primary efficacy endpoint—the percentage of participants achieving a proptosis response at Week 24—compared to placebo, despite continuing the trial.
Crucially, argenx noted that efgartigimod SC demonstrated a favorable safety and tolerability profile in the trials, with no new safety signals identified. Efgartigimod is an FDA-approved neonatal Fc receptor (FcRn) blocker (marketed as VYVGART®) for other autoimmune conditions like generalized myasthenia gravis (gMG). As an FcRn blocker, it reduces circulating immunoglobulin G (IgG) autoantibodies, which are implicated in the pathology of TED, an autoimmune condition characterized by inflammation, proptosis (eye bulging), and diplopia (double vision).
The company expressed disappointment with the outcome, emphasizing its empathy for patients seeking new therapies for this challenging disease. Following the close-out and database lock, argenx plans to conduct a comprehensive analysis of the accumulated data. The goal is to gain a deeper understanding of the study’s results and uncover key biological insights that could potentially inform and guide future research efforts in the area of TED.
