America's Perpetual Frontier
The narrative of American decline has not aged well. At her 250th birthday, America is again at the very forefront of human innovation.
Nektar's Rezpegaldesleukin: Aiming To Restore Peripheral Immune Balance
Rezpegaldesleukin selectively expands regulatory T cells to restore peripheral immune balance. Phase 2b trials showed impressive, deepening efficacy in atopic dermatitis and meaningful hair regrowth in alopecia areata.
Why Licensing A Dual-Mechanism Anti-IgE Antibody Could Be A Major Opportunity For Cue Biopharma
Cue Biopharma licensed CUE-221, a dual-mechanism anti-IgE antibody combining picomolar free IgE neutralization with CD23-mediated suppression of new IgE synthesis. Controlled Phase 2 in CSU in mainland China is expected to read out in H2 2026, after which Cue plans a global Phase 2b in food allergy.
Mufemilast Phase 2 Data May Partially De-Risk Palisade Bio's PALI-2108
Hemay’s Phase 2 mufemilast data suggest that oral PDE4 inhibition can drive biologic-range remission rates in moderate-to-severe ulcerative colitis. This class-level evidence may partially de-risk Palisade Bio’s PALI-2108.
A Nature Medicine Paper Linking Picloram To Early-Onset Colorectal Cancer Leaves An Open Question
Maas et al. link picloram to early-onset colorectal cancer in the United States. Yet the incidence of early-onset colorectal cancer rose in parallel in Germany, where publicly available national herbicide sales data report zero picloram sales for 16 consecutive years (1990–2005).
Computational Simulation Of Four Non-Covalent KRAS G12D Inhibitors Suggests Verastem's VS-7375 May Achieve The Deepest Signaling Suppression
Computational simulation of KRAS G12D conformational cycling across VS-7375, BBO-11818, HRS-4642, and INCB161734 under within-cycle and multi-day dosing suggests VS-7375 may reach 90% suppression at the lowest free drug concentration.
Phase 3 Readout Of Daraxonrasib In 2L Metastatic PDAC Marks An Inflection Point For Pancreatic Cancer
Median OS 13.2 vs 6.7 months, HR 0.40, in pretreated metastatic pancreatic ductal adenocarcinoma against standard chemotherapy. The era of targeted therapy in pancreatic cancer has finally arrived.
Revisiting My PALI-2108 Tissue Penetration Model In Fibrostenotic Crohn's Disease After Phase 1b Readout
My reaction-diffusion model tried to answer whether the active metabolite of PALI-2108 could penetrate Crohn's strictures but rested on untested assumptions. Phase 1b ileal pharmacokinetics, pharmacodynamics, and endoscopic data from five fibrostenotic Crohn's patients update the priors.
Pharmacokinetic Simulation Of Tenax's Oral Levosimendan Suggests Higher Drug Exposure Than IV Dosing In PH-HFpEF
A computational five-compartment pharmacokinetic model built on published parameters suggests that daily oral levosimendan delivers higher and substantially more stable free drug exposure than the weekly IV infusions behind the significant 6MWD improvement in Phase 2.
Two Delayed Cancer Vaccine Readouts: Why I Am More Optimistic About AMPLIFY-7P Than REGAL
AMPLIFY-7P and REGAL both face delayed readouts as events accumulate slower than projected. A comparison of trial design, mechanistic evidence, and immune correlates, and why my conviction behind ELI-002 in PDAC and GPS in CR2 AML is not equal.
SELLAS: Why The Bear Case Might Not Hold Up
SELLAS has disclosed enough about its Phase 3 REGAL trial to collapse the GPS investment thesis into a single question: what is the median overall survival in the control arm? Of all permitted BAT maintenance options, only venetoclax might plausibly push it beyond historical norms.
Johns Hopkins mKRAS Vaccine Trial Strengthens The Case For Elicio's ELI-002
A Johns Hopkins Phase 1 trial of a pooled mKRAS vaccine with dual checkpoint blockade strengthens the case that mKRAS peptides generate durable, cross-reactive T cell immunity correlating with disease-free survival in resected pancreatic cancer, consistent with Elicio's AMPLIFY-201 data.