101 Therapeutics Ltd. today announced the public release of its clinical and scientific evidence package for 101-PGC-005 (‘005), a macrophage-targeted dexamethasone prodrug designed to modulate pathogenic CD206-positive macrophage inflammation while preserving systemic immune function.
The company has posted its clinical manuscript as a preprint on medRxiv and has published a scientific white paper on its website addressing the potential relevance of ‘005 to Bundibugyo virus disease, the Ebola species responsible for the current outbreak in the Democratic Republic of the Congo and Uganda.
medRxiv preprint link
Ebola white paper link
Company website
Bundibugyo virus disease currently has no approved vaccine and no approved species-specific therapeutic. Until now, ‘005 has had no public clinical documentation, making it difficult to bring to the attention of the key decision-makers who would need to evaluate it. With the release of these Phase II/III results, 101 Therapeutics aims to provide a signal strong enough to reach those decision-makers with the data they would need to consider this for their patients, on a timeline that matches the urgency of an active outbreak.
“Peer review remains essential, and we are actively pursuing it,” said Dr. Michael Goldberg, Founder and Chief Scientific Officer of 101 Therapeutics. “But an active Bundibugyo Ebola outbreak cannot wait for the usual publication timeline. Our goal is not to bypass scientific scrutiny, it’s to accelerate it. We are asking qualified clinicians, regulators, and partners to review the data, challenge the mechanism, examine the safety profile, and determine whether emergency clinical evaluation is justified.”
Unmet Need in Bundibugyo Ebola Virus Disease
Bundibugyo virus disease is a severe Ebola disease caused by Orthoebolavirus bundibugyoense. Unlike Zaire Ebola virus disease, for which approved vaccines and monoclonal antibody therapies exist, Bundibugyo virus disease currently lacks an approved vaccine, monoclonal antibody therapy, or antiviral treatment. Current care is primarily supportive.
101 Therapeutics believes this therapeutic gap justifies urgent independent review of host-directed approaches that address the inflammatory mechanisms contributing to severe disease and mortality.
Why 101-PGC-005 May Be Relevant
101-PGC-005 is designed to deliver dexamethasone intracellularly to activated CD206-positive macrophages, a macrophage population implicated in severe inflammatory amplification across infectious and noninfectious hyperinflammatory diseases.
The company’s hypothesis is that selective macrophage targeting may allow attenuation of pathologic inflammatory signaling while avoiding the systemic glucocorticoid exposure and broad immunosuppression associated with conventional corticosteroids. This distinction may be particularly important in active viral infection, where preserving antiviral immune function is essential.
101 Therapeutics is not claiming that ‘005 has been proven effective in Ebola virus disease. Rather, the company believes the combination of:
- human clinical data in severe infectious hyperinflammation;
- preservation of HPA-axis function;
- absence of detectable systemic free dexamethasone exposure in human pharmacokinetic studies;
- a mechanistic rationale relevant to macrophage-driven pathology;
- and the absence of approved Bundibugyo-specific therapeutics;
warrants urgent review by regulators, ethics committees, outbreak-response clinicians, and potential clinical-development partners.
Clinical Evidence Released
The medRxiv manuscript, “Macrophage-targeted glucocorticoid prodrug resolves acute inflammation while preserving HPA-axis function: mechanistic, preclinical, and Phase II/III clinical evidence” (Goldberg et al., 2026), describes the evidence package for ‘005, including:
- a Phase II/III (n = 309) adaptive randomized controlled clinical trial in hospitalized patients with severe COVID-19-associated inflammatory disease;
- a fixed three-dose regimen used across the randomized study population, including patients with pre-existing conditions and concomitant medications;
- discharge of all patients randomized to ‘005 without the need for rescue immunomodulatory therapy beyond the fixed treatment course, effectively sparing an estimated 30–36 mg of cumulative systemic dexamethasone exposure over the full treatment course;
- superiority over dexamethasone on the primary endpoint and multiple secondary endpoints;
- zero patient dropouts and no treatment-related serious adverse events reported in the study;
- preservation of HPA-axis function;
- human pharmacokinetic studies showing no detectable systemic release of free dexamethasone in plasma, urine, or CSF;
- and preclinical toxicology data supporting further clinical development.
The company believes these findings support evaluation of ‘005 as a pathogen-agnostic, host-directed investigational therapeutic platform for severe infectious cytokine storm syndromes, including viral hemorrhagic fevers such as Bundibugyo Ebola virus disease.
The company believes the COVID-19 data are relevant beyond SARS-CoV-2 because the trial evaluated a host-directed mechanism in severe infectious hyperinflammation rather than a virus-specific antiviral effect. In that setting, ‘005 was administered as a fixed short-course regimen and was associated with clinical improvement while preserving HPA-axis function and avoiding detectable systemic free dexamethasone exposure. 101 Therapeutics believes this profile may be relevant to other acute infectious cytokine storm syndromes in which activated macrophages contribute to vascular injury, immune dysregulation, and organ failure.
Why the Data Are Being Released Before Peer Review
101 Therapeutics is expanding beyond the conventional data disclosure process to place this evidence directly in front of those in a position to act. This release is intended first to support evaluation by outbreak clinicians, treatment centers, Ministries of Health in affected or at-risk countries, regulators, ethics committees, WHO, CDC, BARDA, ASPR, NIAID, and related public health and medical countermeasure stakeholders. 101 Therapeutics is also seeking engagement from pharmaceutical and biotechnology partners, global health funders, and investors capable of supporting rapid clinical development, manufacturing scale-up, and emergency evaluation.
Field Deployment Considerations
101-PGC-005 is a lyophilized small molecule that can be reconstituted in normal saline and administered by injection. The company believes its formulation, storage profile, and short-course dosing may be compatible with outbreak-response settings, subject to regulatory review, supply-chain validation, and country-specific authorization.
101 Therapeutics is prepared to provide data packages to qualified regulatory authorities, research institutions, pharmaceutical partners, and outbreak-response organizations under appropriate data-sharing and confidentiality arrangements.
About 101 Therapeutics
101 Therapeutics Ltd. is a biopharmaceutical company developing macrophage-targeted therapeutics for acute and chronic inflammatory diseases. Its lead program, 101-PGC-005, is a Type 1a dexamethasone prodrug engineered for selective CD206-positive macrophage uptake and intracellular release, with the goal of preserving systemic cortisol physiology while modulating pathogenic inflammatory macrophage activity.
101-PGC-005 has received FDA Rare Pediatric Disease Designation for systemic juvenile idiopathic arthritis flares and is being developed across rare inflammatory diseases, cytokine-release syndromes, and infectious cytokine storm indications.
For scientific, regulatory, emergency evaluation, partnership, or media inquiries, contact:
Michael Goldberg, MD
101 Therapeutics Ltd.
michael@101therapeutics.com
www.101therapeutics.com
Forward-Looking / Regulatory Disclaimer
This press release contains forward-looking statements regarding an investigational compound that has not been approved by any regulatory authority for Ebola virus disease, Bundibugyo virus disease, COVID-19, or any other infectious disease indication. 101-PGC-005 has not been clinically tested in Ebola virus disease. Any emergency or clinical use would require review and authorization by appropriate national regulatory authorities, ethics committees, and clinical investigators. The medRxiv preprint described herein has not yet been peer reviewed. Clinical development in Ebola virus disease remains investigational.
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