Full Press Release Details
Zenas BioPharma Announces Positive Results from
Phase 2 MoonStone Trial of Obexelimab in Relapsing Multiple Sclerosis
- Obexelimab met primary endpoint with a 95%
relative reduction in new gadolinium (Gd)-enhancing T1 lesions compared with placebo, p=0.0009 -
October 27, 2025 (GLOBE NEWSWIRE) - Zenas BioPharma, Inc. ("Zenas," "Zenas BioPharma" or
the "Company") (Nasdaq: ZBIO), a clinical-stage global biopharmaceutical company committed to being a leader in the development
and commercialization of transformative therapies for patients living with autoimmune diseases, today announced positive results
from the Phase 2 MoonStone trial of obexelimab in Relapsing Multiple Sclerosis (RMS). Obexelimab met the primary endpoint, demonstrating
a highly statistically significant 95% relative reduction in the cumulative number of new gadolinium (Gd)-enhancing (GdE) T1 hyperintense
lesions over week 8 and week 12 compared with placebo (p=0.0009).
"These profound MoonStone trial results, including the near elimination
of new GdE T1 lesions, provide strong evidence of the deep and sustained inhibitory mechanism of obexelimab and further validate the potential
for obexelimab to become a meaningful therapy across multiple autoimmune diseases, including Immunoglobulin G4-Related Disease and Systemic
Lupus Erythematosus, which are currently being evaluated by Zenas in Phase 3 and Phase 2 clinical trials," said Lonnie Moulder,
Founder and Chief Executive Officer of Zenas.
Near-complete suppression of new GdE T1 hyperintense lesions, which
are markers of active inflammation, was observed with obexelimab by 8 weeks of treatment and was sustained through week 12. The adjusted
mean number of new GdE T1 hyperintense lesions per scan in the obexelimab group was 0.01 (95% CI: 0.00, 0.06) compared to 0.23 (95% CI:
0.11, 0.51) with placebo. Additionally, over weeks 8 and 12 of treatment, obexelimab significantly reduced the cumulative number of new
and/or enlarging T2 weighted hyperintense lesions compared to placebo, which represent the amount of disease burden or chronic lesion
load. The safety profile of obexelimab was consistent with that observed in prior completed trials, including cases of infections and
hypersensitivity, most commonly mild injection site reactions.
observed clinical activity in the MoonStone trial, combined with obexelimab's unique inhibitory mechanism of action, subcutaneous
self-administration and tolerability profile, position obexelimab as a potential option to broadly address the pathogenic role of B cells
in autoimmune diseases," said Lisa von Moltke, M.D., Head of Research and Development and Chief Medical Officer of Zenas. "With
these highly statistically significant data, we look forward to reporting 24-week data in the first quarter of 2026, which will include
additional secondary and exploratory endpoints that may inform obexelimab's potential impact on disability progression and help
us determine next steps for future development of obexelimab in relapsing MS."
expects to report topline results from the obexelimab Phase 3 INDIGO trial in IgG4-RD around year-end 2025 and topline results from the
Phase 2 SunStone trial in Systemic Lupus Erythematosus (SLE), mid-2026, as well as the 24-week MoonStone trial results in the first quarter
of 2026. In addition, orelabrutinib, a potentially best-in-class, highly-selective central nervous system (CNS)-penetrant, oral,
small molecule Bruton's Tyrosine Kinase (BTK) inhibitor, which Zenas recently in-licensed from InnoCare Pharma Limited, is now being
studied in a global Phase 3 clinical trial in patients with Primary Progressive Multiple Sclerosis (PPMS). Zenas also expects to initiate
a global Phase 3 trial of orelabrutinib in patients with Secondary Progressive Multiple Sclerosis (SPMS) in the first quarter of 2026.
About Multiple Sclerosis
Multiple Sclerosis (MS) is a chronic, autoimmune-mediated disorder
of the CNS. According to the Multiple Sclerosis International Federation, approximately 2.9 million people worldwide are currently living
with MS. The disease disproportionately affects females, and its highest prevalence is observed in North America, Europe and Australia.
MS develops when the immune system aberrantly targets the myelin sheath - the protective insulation surrounding axons in the brain,
spinal cord and optic nerves - leading to inflammation, demyelination and axonal injury. This pathological cascade disrupts neuronal
signal transmission and results in a heterogeneous range of clinical manifestations, including motor weakness, fatigue, and cognitive
and visual disturbances. Over time, progressive neurodegeneration contributes to irreversible disability progression.
MS onset typically occurs between 20 and 40 years of age, making MS
the leading cause of non-traumatic neurological disability in young adults. MS is categorized into three main subtypes, RMS, SPMS and
PPMS; all three subtypes are associated with ongoing neuroaxonal loss from the earliest stages of the disease, even in the absence of
overt clinical progression. Delays in diagnosis and treatment accelerate disability accumulation, reduce quality of life and increase
socioeconomic burden. Consequently, early intervention with highly effective therapies is a key objective in disease management to slow
or halt inflammatory and neurodegenerative processes and stop disability progression.
RMS is characterized by distinct episodes of new or worsening neurological
symptoms (relapses), followed by partial or complete remission. Approximately 85% of patients are initially diagnosed with RMS. Approximately
20-30% of treated RMS patients transition to SPMS, defined by continuous disability progression with or without relapses. Currently, there
are no approved therapies for non-relapsing SPMS. PPMS represents 10-15% of all MS diagnoses and is characterized by a steady increase
in disability without relapses from disease onset. Currently there is only one approved therapy for PPMS.
About the Phase 2 MoonStone Trial
2 MoonStone trial, which enrolled 116 patients, is a randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and
safety of obexelimab in patients with RMS. The trial follows a standard design using magnetic resonance imaging (MRI) endpoints that have
historically been highly predictive of successful outcome in large, randomized trials using an endpoint of annualized relapse rate in
an RMS study population. After an initial screening period, patients were randomized 2:1 to receive either 250 mg of obexelimab or placebo
via subcutaneous injection once weekly over a 12-week double-blinded treatment period. The primary endpoint is the cumulative number of
new Gd-enhancing T1 hyperintense lesions over week 8 and week 12 as measured by brain MRI. Secondary and exploratory endpoints
include using standardized assessments, imaging, and biomarkers to evaluate the impact on disease progression. Upon completion of the
double-blinded phase, all patients enter a 12-week open-label period in which those previously on placebo transition to obexelimab treatment,
while those originally assigned to obexelimab continue therapy. During this open-label period, secondary and exploratory endpoints will
assess obexelimab's clinical activity through week 24.
Obexelimab is a bifunctional monoclonal antibody designed to bind both CD19 and Fc RIIb, which are broadly present across
B cell lineage, to inhibit the activity of cells that are implicated in many autoimmune diseases without depleting them. This unique mechanism
of action and self-administered, subcutaneous injection regimen may broadly and effectively address the pathogenic role of the B cell
lineage in chronic autoimmune disease.
Obexelimab has been evaluated in seven clinical trials in a total of
286 patients, including MoonStone, who received obexelimab either as an intravenous infusion or as a subcutaneous injection. Obexelimab
was well tolerated and demonstrated clinical activity across these clinical trials. Zenas is conducting a fully enrolled Phase 3 trial
in Immunoglobulin G4-Related Disease and Phase 2 trials for Relapsing Multiple Sclerosis and Systemic Lupus Erythematosus.
Zenas BioPharma, Inc.
Zenas is a clinical-stage global biopharmaceutical
company committed to becoming a leader in the development and commercialization of transformative therapies for patients living with
autoimmune diseases. Our core business strategy combines our experienced leadership team with a disciplined product candidate acquisition
approach to identify, acquire and develop product candidates globally that we believe can provide superior clinical benefits to patients
living with autoimmune diseases. Zenas is advancing two late-stage, potential franchise molecules, obexelimab and orelabrutinib. Obexelimab,
Zenas' lead product candidate, is a bifunctional monoclonal antibody designed to bind both CD19 and Fc RIIb, which are broadly
present across B cell lineage, to inhibit the activity of cells that are implicated in many autoimmune diseases without depleting them.
We believe that obexelimab's unique mechanism of action and self-administered, subcutaneous injection regimen may broadly and effectively
address the pathogenic role of B cell lineage in chronic autoimmune disease. Orelabrutinib is a potentially best-in-class, highly selective
CNS-penetrant, oral, small molecule BTK inhibitor. Orelabrutinib's mechanism of action targets pathogenic B cells not only in the
periphery but also within the CNS. Additionally, it directly modulates macrophages and microglial cells in the CNS, with the potential
to address compartmentalized inflammation and disease progression in MS. Zenas' earlier stage programs include a preclinical, potentially
best-in-class, oral, IL-17AA/AF inhibitor, and a preclinical, potentially best-in-class, oral, brain-penetrant, TYK2 inhibitor.
Zenas BioPharma Forward-Looking Statements
This press release contains "forward-looking statements"
which involve risks, uncertainties and contingencies, many of which are beyond the control of the Company, which may cause actual results,
performance, or achievements to differ materially from anticipated results, performance, or achievements. All statements other than statements
of historical facts contained in this press release are forward-looking statements. In some cases, forward-looking statements can be identified
by terms such as "may," "will," "should," "expect," "plan," "anticipate,"
"could," "intend," "target," "project," "contemplate," "believe,"
"estimate," "predict," "potential" or "continue" or the negative of these terms or other
similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not
limited to, statements concerning Zenas's milestones, expectations and intentions, including the potential for obexelimab to become
a meaningful therapy across multiple autoimmune diseases and to address the pathogenic role of B cells in autoimmune diseases, the timing
of the initiation of, results and data from clinical trials, including timing of reporting topline results from the INDIGO trial, the
timing of reporting 24-week topline results from the MoonStone trial, the timing of the reporting the topline results from the SunStone
trial and the timing of initiation of the Phase 3 clinical trial of orelabrutinib in patients with SPMS; the potential benefits, development