Q4 Clinical trials round-up: October to December 2025

The final quarter of 2025 delivered a broad spectrum of clinical momentum across autoimmune disease, oncology, neurology, infectious disease, and cardiopulmonary medicine.

Several programmes produced first‑in‑human proof points, Phase 2 signals with pragmatic endpoints, and late‑phase readouts suggesting practice‑changing potential. Others provided cautionary data that will reshape portfolio priorities. What follows is some of the key data, innovations, and what these likely presage for 2026’s R&D focus.

Autoimmune & inflammatory diseases: Precision mechanisms and rapid symptomatic control

NET clearance emerges as a non‑immunosuppressive strategy
Neutrolis reported first‑in‑human data validating DNASE1L3‑mediated neutrophil extracellular trap (NET) clearance as a disease‑modifying approach. In a Phase 1a/b programme (healthy volunteers and patients with severe COVID‑19), plus compassionate use in a treatment‑refractory DNASE1L3‑deficient SLE patient, their albumin‑DNASE1L3 fusion produced rapid multi‑organ clinical improvement – with pharmacodynamic signals of NET degradation – and a favourable tolerability profile. The company is advancing an optimised analogue (NTR‑1011) into planned 2026 Phase 2a trials in SLE and RA.

Topical JAK inhibition extends into moderate AD with speed of itch relief
Incyte’s Phase 3b TRuE‑AD4 (ruxolitinib cream, Opzelura) in adults with moderate atopic dermatitis who were TCS/TCI‑inadequate or intolerant met both co‑primary endpoints at Week 8 (EASI75 and IGA‑TS), with itch improvement detected as early as Day 2 and meaningful gains in POEM and DLQI; no serious infections, MACE, malignancies, or thromboses were observed over 8 weeks. A Type‑II variation filing in the EU was planned by year‑end.

Arcus pivots from TIGIT in GI to small‑molecule I&I expansion, while HIF‑2α programme strengthens
Arcus disclosed two important threads: (1) best‑in‑class potential for the HIF‑2α inhibitor casdatifan in late‑line ccRCC, with pooled monotherapy ORR ~31–35% and median PFS ~12.2 months, supporting Phase 3 development; and (2) discontinuation of the domvanalimab (anti‑TIGIT) Phase 3 STAR‑221 study in upper GI cancers due to futility, prompting a portfolio shift toward casdatifan and five oral I&I programmes (MRGPRX2, TNFR1, CCR6, CD89, CD40L) targeting atopic dermatitis, urticaria, RA, psoriasis, MS, UC. First I&I clinical starts are targeted for 2026.

Bimekizumab sustains deep, multi‑domain control across psoriatic diseases
UCB presented three‑year Phase 3/extension data: in PsA, stringent domain responses (peripheral arthritis, dactylitis, enthesitis, skin and nail psoriasis) were sustained to Year 3; in axSpA (nr‑axSpA and r‑axSpA), half of patients who achieved ASDAS‑LDA at Week 16 never lost it through Week 164, and ~79% maintained LDA at Week 164. Interim real‑world data (SPEAK) showed rapid HRQoL improvements by Week 2 in some patients. Safety remained consistent with class expectations.

Signal for a triple‑combination, low‑dose single pill in hypertension
Long‑term Phase 3 extension data for WIDAPLIK (telmisartan/amlodipine/indapamide) showed durable BP control over 52 weeks in treatment‑naïve adults, adding practical evidence to the June FDA approval as the first triple‑combination for initial hypertension therapy.

Takeaway for 2026?
Expect more mechanism‑precise, non‑immunosuppressive approaches (e.g., NET clearance, cytokine/cell‑targeted small molecules), rapid‑acting topical/systemic options that deliver early patient‑reported benefits, and portfolio rebalancing away from crowded checkpoint combinations toward best‑in‑class small molecules with broad I&I utility.

Infectious diseases: Bacteriophages and devices moving toward pivotal steps

Phage therapy for SAB shows earlier resolution and shorter hospitalisation
Armata’s AP‑SA02 (phage cocktail targeting S. aureus) in a Phase IIa randomised study showed markedly earlier infection resolution (mean 2.7 vs 9.3 days), lower CRP, and ~8‑day shorter hospitalisation when added to best available antibiotics versus placebo; safety was acceptable. Plans for Phase 3 start in 2026 underscore increasing feasibility of bacteriophages for resistant bacteremia.

Phage delivery considerations in CF: Device scrutiny and dose revision
BiomX’s Phase 2b BX004 in CF encountered an FDA device hold related to the nebuliser; after independent DMC review, the trial will continue with revised dosing and expects topline results in Q2 2026 once the hold is resolved. The episode highlights the combination‑product reality in inhaled phage therapies.

Takeaway for 2026?
Look for pivotal phage trials in serious infections and more focus on device‑drug integration, human factors, and regulatory coordination as sponsors scale beyond early PoC.

Oncology: Diverse modalities – radioenhancers, lateral CAR‑Ts, ATAC ADCs, viral immunotherapy, radiopharmaceuticals, tumour‑activated biologics

Physics‑based radioenhancer expands to esophageal cancer; updates in HNSCC
Nanobiotix’s NBTXR3 (JNJ‑1900) Phase 1 in esophageal adenocarcinoma confirmed injection feasibility (13 patients), 85% disease control rate, and 69% objective response rate; in recurrent/metastatic HNSCC (n=103), median OS of 15.5 months in anti‑PD‑1‑naïve patients and favorable safety including after re‑irradiation support continued development for local control.

Lateral CAR‑T (LEU011) shows tumour infiltration and disease control in solid tumours
Leucid Bio’s Phase I/IIa AERIAL trial reported post‑treatment biopsy evidence of intratumour LEU011 by ddPCR/RNAScope, encouraging PK/PD, tolerability, and disease control at the lowest dose; dose escalation continues with more data expected H1 2026.

Amanitin‑based ATAC (HDP‑101) delivers stringent CRs in myeloma
Heidelberg Pharma’s Phase I/IIa Cohort 8 (140 µg/kg) saw two patients achieving stringent complete remission among seven evaluable, with favourable safety and no DLTs; escalation to 175 µg/kg is underway. The sCRs reinforce RNA‑pol II targeting payloads as a differentiated ADC modality for BCMA‑positive disease.

Tumour‑activated viral immunotherapy produces anti‑PD‑L1 locally
Accession Therapeutics dosed the first patient with TROCEPT‑01 (ATTR‑01), a systemically delivered, αvβ6‑targeted viral therapy designed to generate checkpoint inhibitor (anti‑PD‑L1) within tumours, aiming for high intratumour drug levels and lower systemic exposure in hard‑to‑treat carcinomas.

Individualised neoantigen vaccine (TG4050) deepens mechanistic evidence
Transgene/NEC presented Phase I immunology data in operable HPV‑negative HNSCC: vaccine‑induced CD8+ cytotoxic responses with effector/tissue‑resident phenotypes persisting up to a year post‑therapy, supporting relapse‑prevention potential as the programme proceeds into Phase II; first Phase II immunogenicity data is expected H2 2026.

Radiopharmaceutical targeting CD44v6 advances dose‑escalation
Akiram Therapeutics completed Cohort 2a in its Phase I Lu‑177‑AKIR001 (CD44v6‑directed antibody‑radioligand) with consistent safety and encouraging tumour uptake; Cohort 2b (protein‑dose escalation) is cleared to start across thyroid, head & neck, gynecological SCC, and NSCLC.

Portfolio reality check: TIGIT setback and RCC refocus
Arcus and Gilead discontinued the Phase 3 STAR‑221 domvanalimab programme (no OS benefit vs nivolumab + chemo) and will focus oncology resources on casdatifan combinations and earlier‑line RCC, while continuing a registrational CD73 inhibitor study in pancreatic cancer (PRISM‑1) toward 2027 data.

Cell therapy breadth at ASH: BCMA CAR‑T, bicistronic DuoCore CARs
Kite/Arcellx’s pivotal iMMagine‑1 Phase 2 for anitocabtagene autoleucel (anito‑cel, BCMA CAR‑T) reported ORR 96%, sCR/CR 74%, MRD‑negativity 95% (≤10‑5) at median 15.9 months, with PFS rates 82% at 12 months and manageable CRS/ICANS – supporting a 2026 US launch plan. In parallel, Kite’s bicistronic CD19/CD20 CAR‑Ts (KITE‑753 and KITE‑363) showed high CR rates with favourable safety and durability, aided by a manufacturing process preserving T‑cell fitness (notably robust expansion at lower doses).

Takeaway for 2026?
Oncology sponsors will intensify efforts around targeted radiotherapies, in‑situ biologics (tumour‑localised checkpoint), individualised vaccines with durable cytotoxic memory, next‑generation cell therapies optimised for safety/outpatient settings, and best‑in‑class small molecules (e.g., HIF‑2α, CD73).

Neurology: Disease‑modifying signals in Parkinson’s and frontotemporal degeneration

Blood–brain barrier penetration and twice‑weekly dosing validated for HER‑096
Herantis’ Phase 1b in PD met primary/secondary endpoints: 200/300 mg SC twice weekly for 4 weeks was safe and well tolerated; importantly, CSF exposure confirmed BBB penetration and pharmacologically active levels consistent with UPR modulation/α‑synuclein aggregation reduction. Phase 2 in early‑stage PD is planned for 2026.

Sortilin inhibition normalises progranulin in asymptomatic GRN mutation carriers
Vesper Bio’s Phase Ib/IIa SORT‑IN‑2 (VES001) achieved >95% mean CSF progranulin increase (dose‑dependent rises in plasma and CSF), effectively normalising levels typical of GRN carriers; safety was favourable. The programme now heads toward Phase IIb/III in symptomatic FTD‑GRN, with full reporting in Q1 2026.

Takeaway for 2026?
Anticipate a wave of mechanistically anchored, CSF‑confirmed programmes (UPR modulators, sortilin inhibitors) entering efficacy trials with biomarker‑driven designs, aiming at disease modification, rather than purely symptomatic control.

Cardiopulmonary: Earlier intervention and physiologic co‑benefits

Sotatercept (WINREVAIR) in early PAH reduces clinical worsening events by 76%
Merck’s Phase 3 HYPERION in newly diagnosed PAH (on background therapy) demonstrated a 76% reduction in time‑to‑clinical‑worsening events (HR 0.24) and significant multicomponent improvements, with safety consistent with prior trials; the trial was stopped early based on programme‑level data, with global regulatory submissions planned.

Diaphragm neurostimulation from day one of ventilation enters pivotal feasibility
Lungpacer’s STARI trial (AeroNova continual transvenous diaphragm neurostimulation) enrolled first patients. Early feasibility data indicate improvements in lung, diaphragm, cardiac, and brain function, reframing vent support from rehabilitation to prevention of multi‑organ injury. Notably, the company already holds FDA approval for their intermittent AeroPace system, which reduced ventilator days by ~3 in prior studies.

Takeaway for 2026?
Clinical focus will expand on earlier initiation of disease‑modifying agents (e.g., sotatercept within the first year) and physiology‑integrated devices that protect multiple organs during critical care – areas ripe for pragmatic endpoints and health‑economic impact.

What these Q4 2025 trends predict for 2026

1. Mechanistic precision and upstream targeting: NET clearance, HIF‑2α, sortilin inhibition, CD73, and TNFR1 reflect upstream drivers with broader disease impact, supporting platform strategies across indications.
2. Patient‑centric speed and durability: Dermatology and rheumatology programmes demonstrated rapid symptomatic relief and sustained control to three years – expect endpoints that integrate HRQoL and early itch/pain metrics alongside stringent disease measures.
3. Localised therapy to improve safety and access: Tumour‑localised radioenhancers, radiopharmaceuticals, and virus‑encoded biologics aim to raise intratumour exposure and lower systemic toxicity, supporting outpatient/community oncology models.
4. Next‑gen cell therapies optimised for outpatient use: Bicistronic CAR‑Ts and process innovations (T‑cell fitness) target lower toxicity, faster delivery, and broader treatment settings – a key differentiator as the field matures.
5. Combination‑product rigour: Inhaled phages and ventilator‑coupled neurostimulation emphasise device/regulatory integration; sponsors will invest earlier in human factors, reliability, and co‑development pathways.
6. Portfolio discipline: Negative or neutral checkpoint data (e.g., TIGIT in upper GI) will accelerate reallocation to high‑signal assets, particularly small molecules with best‑in‑class ambitions and assets with validated single‑agent activity.

Q4 2025 showcased the industry’s pivot toward precise biology, localised delivery, and earlier intervention – with multiple programmes crossing crucial translational thresholds. And 2026 will only amplify these themes.