Full Press Release Details
Pharmaceuticals Reports Positive Topline Data Demonstrating
Anabasum Reduces Acute Pulmonary Exacerbations and Multiple
Biomarkers in Phase 2 Study in Patients with Cystic Fibrosis
Anabasum achieves primary study objective of acceptable safety and tolerability -
Management to host conference call and webcast today at 8:00 a.m. EDT -
MA (March 30, 2017) - Corbus Pharmaceuticals Holdings, Inc. (NASDAQ: CRBP) ("Corbus" or the "Company"),
a clinical stage drug development company targeting rare, chronic, serious inflammatory and fibrotic diseases, today announced
positive topline data from its Phase 2 study evaluating multiple doses of anabasum (fka JBT-101 or Resunab) compared to
placebo for the treatment of patients with cystic fibrosis ("CF"). The 16-week study dosed 85 adult CF patients with
baseline forced expiratory volume in 1 second (FEV1) percent predicted 40%, who were enrolled without regard to their specific
CFTR mutation or infecting pathogens and continued with all baseline treatment regimens.
successfully achieved the primary objective of the study by demonstrating an acceptable safety and tolerability profile at all
doses with no serious or severe adverse events related to the study drug.
Fibrosis Foundation Therapeutics, Inc. ("CFFT"), the non-profit drug discovery and development affiliate of the Cystic
Fibrosis Foundation, supported the Phase 2 study.
cohorts showed a dose-dependent reduction in a number of acute pulmonary exacerbations defined as those requiring intravenous
(IV) antibiotics compared to placebo. Patients in the highest dose cohort of anabasum (20 mg orally, twice per day) had a 75%
reduction in the annualized rate of pulmonary exacerbations requiring IV antibiotics compared to placebo cohort.
anabasum caused a consistent reduction in multiple inflammatory cell types in sputum, including total leukocytes, neutrophils,
eosinophils, and macrophages. Inflammatory mediators, including interleukin-8, neutrophil elastase, and immunoglobulin G, were
also reduced in sputum by anabasum in a dose-dependent manner. These patient data provide evidence of biological activity of anabasum
in resolving ongoing innate immune responses in lungs of CF patients and support the observed reduction in pulmonary exacerbations.
concentrations of orally-administered anabasum in CF patients were similar to those previously observed in healthy volunteers.
FEV1 remained stable throughout the duration of the study in all treatment cohorts.
are delighted that in this first-in-CF patient study, anabasum demonstrated an acceptable safety profile and potential clinical
benefit in reducing acute pulmonary exacerbations in CF patients and that these findings are supported by biomarker data consistently
showing reduction of inflammation in the lungs," stated Yuval Cohen, PhD, CEO of Corbus. "These positive results
coincide with our third anniversary as a company and come on the heels of positive data from our Phase 2 study in systemic sclerosis.
We are very grateful to all the patients, investigators and clinical staff who participated in this study and to Cystic Fibrosis
Foundation Therapeutics for their support."
reduction in acute pulmonary exacerbations along with reductions in inflammatory cells and inflammatory mediators in sputum demonstrate
the potential for anabasum as a new inflammation-targeting therapeutic in cystic fibrosis that can broadly target patients without
regard to their specific CFTR mutations. The outcomes of this 16-week study indicate that anabasum has the potential to address
the important unmet need for treatments that target inflammation in CF," commented James Chmiel, M.D., M.P.H., Professor
of Pediatrics, Case Western Reserve University, Associate Director of the LeRoy W. Matthews Cystic Fibrosis Center at University
Hospitals Rainbow Babies and Children's Hospital in Cleveland, and Principle Investigator of Corbus' Phase 2 cystic
fibrosis clinical study.
was an international, multi-center, double-blinded, randomized, placebo-controlled Phase 2 study supported in part by a $5 million
Development Award from Cystic Fibrosis Foundation Therapeutics, Inc. The primary objective of the study was to test safety and
tolerability of anabasum in adults with CF who had FEV1 40 percent predicted and remained on background CF medications, including
prophylactic antibiotics. Patients were enrolled without regard to their CFTR mutation, infecting pathogen, or baseline treatment.
Acute pulmonary exacerbations requiring IV antibiotic treatment were captured as an event of special interest during the study.
Secondary objectives included measurement of plasma concentrations and metabolites of anabasum and change from baseline in FEV1
percent predicted and Cystic Fibrosis Questionnaire-Revised Respiratory Symptom score. Additional outcomes included change from
baseline in sputum and blood biomarkers of inflammation.
patients on stable standard-of-care medications were dosed with anabasum or placebo at 21 sites in the U.S. and Europe and treated
for 84 days, with a follow-up period of 28 days off treatment. During the first part of the study (Weeks 1-4) patients were randomized
to placebo (n = 35), 1 mg/day anabasum (n = 26) or 5 mg/day anabasum (n = 24). During the second part of the study (Weeks 5-12),
anabasum patients were randomly assigned to anabasum 20 mg once per day (n = 31) or anabasum 20 mg twice per day (n = 30) with
11 patients from the placebo cohort randomly assigned to the 2 anabasum cohorts. Twenty-four patients continued to receive placebo
dosing, 10 patients discontinued early from the study; 3 patients withdrew consent, 5 withdrew due to adverse events (2 on placebo,
3 on anabasum), 1 subject was lost to follow-up and 2 patients withdrew for treatment-unrelated reasons. Baseline characteristics
were similar between anabasum and placebo cohorts.
Weeks 1-4, treatment-emergent adverse events (TEAEs) occurred in 14 (54%) of patients in the anabasum 1 mg cohort, 13 (54%) of
the anabasum 5 mg cohort and 15 (43%) of the placebo cohort. During Weeks 5-12, TEAEs occurred in 21 (68%) patients in the anabasum
20 mg once per day cohort, 19 (63%) of the anabasum 20 mg twice per day cohort and 14 (58%) of the placebo cohort. Six serious
adverse events (SAEs) occurred the anabasum-treated patients and 6 SAEs occurred in placebo-treated patients. Three severe TEAEs
occurred in the anabasum-treated patients and 4 in placebo-treated patients. None of the serious or severe TEAEs were assessed
by site investigators to be related to study drug. The most common drug-related adverse event that occurred in more than 2 individuals
was mild dry mouth observed in 8 (13%) of anabasum patients and no placebo patients. As expected, the respiratory system was the
most common source of TEAEs overall.
values for anabasum were similar to those previously measured in healthy human volunteers after similar doses of anabasum.
Pulmonary Exacerbations
with anabasum yielded a dose-dependent reduction in acute pulmonary exacerbations. The highest dose of anabasum (20 mg twice per
day) was associated with a 75% reduction in the annualized rate of pulmonary exacerbations requiring treatment with IV antibiotics,
compared to placebo. Similar levels of reduction were also observed in acute pulmonary exacerbations defined by new or worsening
respiratory symptoms requiring treatment with any antibiotic.
Cells and Biomarkers
treated with anabasum 20 mg twice a day showed a consistent reduction in multiple inflammatory cell types in their sputum at the
end of active treatment compared to placebo, including total leukocytes, neutrophils, eosinophils, lymphocytes and macrophages.
They also had a consistent reduction in inflammatory mediators in their sputum including interleukin-8, neutrophil elastase and
White, MD, Chief Medical Officer of Corbus, stated, "We are delighted that anabasum demonstrated a safety profile that was
well tolerated by the CF patients in this study, especially given the challenges in safely targeting inflammation in CF. In a
study of just 12-weeks of active dosing, we are especially encouraged by the consistency in data that couple clinical benefit
in pulmonary exacerbations with improvement in the inflammatory response in the lungs. We believe these findings reflect the underlying
mechanism of action of anabasum in activating resolution of innate immune responses without immunosuppression."
will engage in further evaluation of the data and design of the next clinical trial in partnership with CF experts, the Cystic
Fibrosis Foundation Therapeutics, Inc., Cystic Fibrosis Therapeutic Development Network and European Cystic Fibrosis Society Clinical
Trials Network. Thereafter, Corbus will enter into discussions with the relevant regulatory agencies.
was granted Orphan Drug Designation and Fast Track status for the treatment of CF by the FDA in 2015 and Orphan Drug Status from
the European Medicines Agency (EMA) in 2016.
more information on the Phase 2 study with anabasum for the treatment of CF, please visit ClinicalTrials.gov and reference
Identifier NCT02465450.
Call and Webcast Information
management will host a conference call for investors, analysts and other interested parties today, March 30, 2017 at 8:00 am EDT
to discuss the topline data from the Phase 2 Study evaluating anabasum for the treatment of CF.
conference call and live webcast will be accompanied by presentation slides. To participate in the call, please dial (877) 407-3978
(domestic) or (412) 902-0039 (international). The live webcast and accompanying slides will be accessible on the Events
page of the Investors section of Corbus website, www.corbuspharma.com, and will be archived for 60 days.
Fibrosis ("CF") is a chronic, life-threatening, genetic disease caused by inheriting two dysfunctional CFTR genes
that normally regulate salt and water movement across cells in the respiratory and digestive systems. CF affects approximately
30,000 patients in the U.S and 75,000 patients worldwide. People with CF have thick, sticky mucus that clogs their airways, with
recurrent bacterial infections and chronic inflammation in their lungs. In the gastrointestinal tract, they also have mucus accumulation,
bacterial overgrowth, and inflammation. The dysfunctional CFTR genes cause an exaggerated inflammatory response that compounds
the damage from a coexisting infection in the lungs and gut. CF results in destruction of lung tissue, lung fibrosis, pancreatic
insufficiency, CF-related diabetes, malabsorption, malnutrition, growth retardation, and liver disease, including cirrhosis. The
harmful inflammation and accompanying fibrosis in CF damages multiple organs, impairs organ function, reduces health-related quality
of life, and can lead to death.
is a novel synthetic oral endocannabinoid-mimetic drug that preferentially binds to the CB2 receptor expressed on activated immune
cells and fibroblasts. CB2 activation triggers endogenous pathways that resolve inflammation and halt fibrosis. Preclinical and