Item
8.01. Other Events
On
March 30, 2017, the Company 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.
Anabasum
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.
Cystic
Fibrosis Foundation Therapeutics, Inc. ("CFFT"), the non-profit drug discovery and development affiliate of the Cystic
Fibrosis Foundation, supported the Phase 2 study.
Anabasum
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.
Additionally,
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.
Serum
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.
Study
Design and Results
This
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.
Eighty-five
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
in Weeks 5-12.
After
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.
Safety
During
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.
Cmax
values for anabasum were similar to those previously measured in healthy human volunteers after similar doses of anabasum.
Acute
Pulmonary Exacerbations
Treatment
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.
Inflammatory
Cells and Biomarkers
Patients
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
immunoglobulin G.
Forward-
Looking Statements
This
Current Report on Form 8-K contains certain forward-looking statements within the meaning of Section 27A of the Securities Act
of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including
those relating to the Company’s product development, clinical trials, clinical and regulatory timelines, market opportunity,
competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and
other statement that are predictive in nature. These forward-looking statements are based on current expectations, estimates,
forecasts and projections about the industry and markets in which we operate and management’s current beliefs and assumptions.
These
statements may be identified by the use of forward-looking expressions, including, but not limited to, “expect,” “anticipate,”
“intend,” “plan,” “believe,” “estimate,” “potential,” “predict,”
“project,” “should,” “would” and similar expressions and the negatives of those terms. These
statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other
factors which may cause actual results, performance or achievements to be materially different from any future results, performance
or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company’s
filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking
statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information, future events or otherwise.