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This narrative review summarizes icotrokinra, an oral macrocyclic IL-23-receptor antagonist, using literature through December 2025 plus conference, company and trial-registry sources. It reviews Phase 2–3 evidence; it is not a new trial or a current regulatory-status assessment.
Aurinia reported 2025 net product sales of $271.3 million for LUPKYNIS, up 25%, while company revenue reached $283.1 million, up 20%. Oral voclosporin is approved for adults with active lupus nephritis. The figures distinguish product sales from total revenue and licensing income; commercial growth does not constitute new comparative evidence of clinical benefit.
Unnatural Products licensed an undisclosed cardiovascular program to Novartis. Terms include up to $100 million in upfront and pre-IND payments, plus up to $1.7 billion in later milestones and royalties. The platform supports oral and injectable macrocycles; the announcement does not establish the specific program’s route or imply all contingent payments have been received.
An integrated workflow combined MicroED with high-resolution mass spectrometry, database searches, solution and solid-state NMR, and computational calculations. Demonstrations used a pyridoxine–N-acetyl-L-cysteine salt and the peptide fMLF. The approach addressed molecular identity, crystal packing, light-atom assignment, and hydrogen positions, illustrating how complementary measurements can resolve ambiguities that electron diffraction alone may leave in nanocrystalline powders.
Researchers reported MicroED structures for nine chemically diverse natural products whose three-dimensional structures had remained unavailable. The work used microgram quantities and avoided the need to grow large single crystals. It supports MicroED as a practical route for difficult natural-product samples, although the selected examples do not define a universal success rate across all natural products.
Haisco reported Phase 1 and formulation pharmacokinetic findings for oral IL-23 peptide HSK47388. Exposure with a 50 mg enhancer formulation was comparable to a 200 mg tablet without enhancer, and the company said psoriasis Phase 2 began in fourth-quarter 2025. Public materials identify an oral peptide but do not fully disclose cyclization; relative exposure is not absolute bioavailability.
Revisiting ritonavir’s polymorph landscape, the authors examined whether crystal structure prediction could have flagged the risk posed by the less soluble Form 2. They also solved the previously unresolved Form 4 structure using 3D electron diffraction, modeling, and powder X-ray diffraction, finding disorder and thermodynamic instability. The retrospective analysis informs risk assessment rather than guaranteeing future polymorph prediction.
Syneron Bio reported nearly $100 million raised across its Series A and A+ rounds, with participation from AstraZeneca and multiple strategic and venture investors. Proceeds support its Synova high-throughput macrocyclic peptide discovery platform and advancement of pipeline programs toward clinical development. The combined financing amount is not a single round, and candidate-level oral clinical data were not disclosed.
Circle Pharma nominated CID-165, an orally available macrocyclic cyclin D1 RxL inhibitor, as the development candidate for its second oncology program. Preclinical studies supported disruption of the cyclin D1–Rb interaction and activity alone or with other therapies. Candidate nomination is a discovery-to-development milestone, not IND authorization or evidence that human dosing has begun.
PeptiDream described an orally administered macrocyclic peptide inhibiting IL-17A/A, A/F, and F/F. Preclinical challenge studies showed CXCL1 suppression and skin distribution. The company is progressing toward IND-enabling work and exploring partnerships. Entry into its development portfolio does not mean human dosing has begun, and claimed biologic-like activity remains preclinical.
MicroED identified two polymorphic structures of oxyacanthine dihydrochloride monohydrate in samples mislabeled as berbamine dihydrochloride. The forms differed principally in the conformation of a tetrahydroisoquinoline ring. Structural, energetic, and packing analyses suggested a thermodynamic preference between them. The study demonstrates how crystallographic analysis can expose both identity problems and polymorphism in complex natural-product samples.
3D ED/MicroED determined casopitant mesylate Forms 1 and 3 from one batch of fine powder containing an inseparable polymorphic mixture. Their structures differed through a small packing shift, explaining their very similar powder X-ray diffraction patterns. The work demonstrates how selecting individual microcrystals can resolve structurally similar phases that remain difficult to separate or distinguish in bulk measurements.
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