Dexamethasone

Poster 0122 on Sunday, November 8: CD206-targeted dexamethasone prodrug was superior to systemic dexamethasone in a 309-patient randomized trial (HR 2.31; p<0.0001), with no systemic steroid added in the '005 arm; abstract positions ' 005 as a potential steroid-sparing adjunct to biologic therapy, including in PMR, sJIA, GVHD and incomplete responses to single-cytokine biologics ENGLEWOOD, N.J.--(BUSINESS WIRE)--101 Therapeutics Ltd. (101TX), a clinical-stage biotechnology company developing macrophage-targeted therapeutics, today announced that an abstract on its lead investigational compound, 101-PGC-005 ('005; designated 101-PIF-GC-005 in the published abstract), a chemically synthesized small-molecule, CD206-targeted dexamethasone prodrug, has been accepted for poster presentation at ACR Convergence 2026, the annual meeting of the American College of Rheumatology (ACR), November 6–11 in Orlando, Florida. The abstract, now published in the ACR Convergence 2026 online program, reports that a three-day course of '005 was superior to systemic dexamethasone in a 309-patient randomized Phase II/III (Phase 2/3) trial, and sets out the rationale for '005 as a potential steroid-sparing adjunct to biologic therapy in rheumatology. Founder and Chief Scientific Officer Michael M. Goldberg, MD, will present the poster and is scheduling meetings with pharmaceutical and biotechnology business development, search-and-evaluation and life-science investment teams during the meeting. First scientific meeting presentation. ACR Convergence 2026 is the first scientific meeting at which 101 Therapeutics will present '005. The Phase II/III trial was run during the COVID-19 pandemic at six sites in India by an independently funded, privately held company, outside the rheumatology literature, and its results have not previously been presented at a scientific meeting. Poster 0122 is the first opportunity for rheumatologists, pharmaceutical partners and investors to review a targeted glucocorticoid that was compared head-to-head with dexamethasone in a randomized Phase 2/3 trial and was superior. Presentation details Title: CD206-Targeted Glucocorticoid Delivery as an Adjunct to Biologic Therapy in Macrophage-Driven Autoimmune Disease: Proof-of-Concept Clinical Evidence and a Mechanistic Rationale for Addressing the Residual Inflammatory Burden of Single-Pathway Cytokine Blockade Poster/Abstract: 0122 Session: Innate Immunity Poster A Date and time: Sunday, November 8, 2026, 10:30 a.m. to 12:30 p.m. ET Presenter: Michael M. Goldberg, MD, Founder and Chief Scientific Officer, 101 Therapeutics Location: ACR Convergence 2026, Orlando, Florida Abstract highlights '005 was evaluated in an adaptive Phase II/III randomized controlled trial in 309 hospitalized patients with moderate COVID-19 inflammatory disease at six GCP-compliant sites in India. Patients received '005 20 mg IV once daily for three days or dexamethasone 6 mg IV once daily for five to 10 days, each with standard of care. All 309 randomized patients completed the study. Primary endpoint, time to at least 2-point improvement on the WHO ordinal scale: HR 2.31 (95% CI 1.83–2.93; p<0.0001); median 3 vs 4 days. The Phase II effect was prospectively reproduced in Phase III across a later variant and vaccination landscape. Viral clearance: HR 1.47 (p=0.0001); median 3 vs 5 days. Day 5 discharge: 77.4% vs 29.0%. No patient in the '005 arm received an investigator-initiated systemic corticosteroid add-on despite protocol permission; cumulative exogenous corticosteroid exposure in the '005 arm was 0 mg. Treatment-emergent adverse events 54.8% vs 54.5%; no Grade 3 or higher events, serious adverse events, SUSARs, deaths or discontinuations in either arm. Human PK studies (completed Phase I, single and repeated dosing): intact prodrug circulation, rapid clearance, absent or very low free dexamethasone exposure, preserved cortisol/ACTH after repeated supratherapeutic dosing, and no glucose signal. Morning cortisol and ACTH remained within normal physiologic ranges after 30 mg IV '005 once daily for three consecutive days. In SARS-CoV-2-infected human macrophages, '005 suppressed inflammatory cytokine output, including IL-6 and TNF, while preserving CXCL10 antiviral signaling, a macrophage-targeted immune-modulating pro from broad systemic glucocorticoid immunosuppression. The abstract concludes that these data support a new steroid-sparing concept for rheumatology: retaining broad glucocorticoid-like efficacy while reducing toxicity. It identifies settings where glucocorticoids are used, or would be used, but are limited by toxicity, including polymyalgia rheumatica (PMR), systemic juvenile idiopathic arthritis (sJIA), graft-versus-host disease (GVHD) and incomplete responses to single-cytokine biologics. COVID-19 was the disease studied; efficacy in rheumatic diseases has not been established. The poster will present additional clinical, mechanistic and translational data. “Rheumatologists know exactly what glucocorticoids can do, and how often HPA-axis suppression, immunosuppression, hyperglycemia and cumulative toxicity force them to hold back,” said Dr. Goldberg. “Our Phase 2/3 data show that a CD206-targeted glucocorticoid achieved faster clinical improvement than 6 mg of systemic dexamethasone while preserving HPA-axis function. We believe that may be relevant wherever glucocorticoids are used but limited by toxicity, starting with a steroid-sparing adjunct to biologics. I invite rheumatologists, industry and investors to visit Poster 0122 on Sunday morning or to meet with us in Orlando.” To schedule a meeting at ACR Convergence 2026, contact michael@101therapeutics.com . Citation: Goldberg M. Arthritis Rheumatol. 2026;78(suppl 9). Abstract 0122. Published abstract: About 101 Therapeutics 101 Therapeutics Ltd. (101TX) is an independently funded, clinical-stage biopharmaceutical company developing macrophage-targeted therapeutics for diseases in which excessive or dysregulated macrophage activity contributes to tissue injury and persistent inflammation. Its lead investigational compound, 101-PGC-005 ('005), is a chemically synthesized small-molecule, CD206 (mannose receptor, MRC1)-targeted type 1a dexamethasone prodrug designed for short-course, episodic intracellular glucocorticoid delivery. The proposed mechanism involves modulation of activated inflammatory macrophages followed by apoptosis of excess pathogenic macrophages, without preventing recruitment and activation of new macrophages that can operate under physiological hypothalamic-pituitary-adrenal (HPA) axis and cortisol regulation. Development opportunities include rheumatology indications as an adjunct to biologics, rare inflammatory diseases, acute cytokine syndromes and immune-related complications of cancer immunotherapy, and host-directed anti-infective and medical-countermeasure applications in severe infectious hyperinflammation. The company has received FDA Rare Pediatric Disease designation for systemic juvenile idiopathic arthritis (sJIA), a designation relevant to potential Priority Review Voucher eligibility subject to statutory requirements; a study in sJIA is being planned. These applications remain investigational and require indication-specific studies. Patent publications include WO2022034582A1 and WO2023144815A1. 101 Therapeutics was founded by its Chief Scientific Officer, Michael M. Goldberg, MD, who as Chairman and CEO of Emisphere Technologies led development of the SNAC (salcaprozate sodium) oral absorption technology used in Novo Nordisk's oral semaglutide products, Rybelsus® for type 2 diabetes and the Wegovy® pill for chronic weight management. Investigational status and forward-looking statements 101-PGC-005 is investigational and has not been approved for any indication. The clinical study cited above involved COVID-19; clinical efficacy and safety in rheumatic diseases have not been established. Mechanistic hypotheses, potential complementary use with biologics, and future development plans are forward-looking and subject to further testing, regulatory review, and other uncertainties. Reference to ACR Convergence identifies the presentation venue and does not imply endorsement by the American College of Rheumatology. Contacts Media, partnering and investor inquiries: Michael M. Goldberg, MD | michael@101therapeutics.com |