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Bioblast Announces Results of Trehalose
Study in Healthy Volunteers Demonstrated Trehalose to be Safe
and Well Tolerated at Twice the Dose Levels Used in Prior
Results Support Weight-Based Dosing Paradigm
Tel Aviv, Israel, - October 24, 2016 - Bioblast Pharma
Ltd. (NasdaqGM: ORPN), a clinical-stage, orphan disease-focused biotechnology company, today announced results of a double-blind,
placebo-controlled pharmacokinetic (PK) study of intravenous (IV) trehalose 90mg/mL in healthy volunteers.
The primary objective of the study was
to establish safety and tolerability of escalating doses of trehalose. The secondary objectives were to determine the Maximum Tolerated
Dose (MTD) and pharmacokinetics of escalating doses of trehalose.
The key findings of the study that was conducted in 24 healthy
on the findings from this study, trehalose appears to be generally safe and well tolerated at twice the dose levels used in the
previous clinical studies," said Warren Wasiewski, MD, Bioblast's Chief Medical Officer. "Since total clearance
of the drug increased with weight, we plan to utilize a weight-based dosing paradigm moving forward. This will enable us
to achieve a consistent serum concentration of trehalose in all patients
regardless of weight in the upcoming double-blind, placebo controlled
Phase 2b study in patients with OPMD."
More on the PK trial
This was a randomized double blind placebo
controlled single ascending dose study that included 3 groups of subjects, 8 in each group. In each group, 6 subjects received
trehalose and 2 received placebo. The first group received 27g of IV trehalose as a one hour infusion. The safety and pharmacokinetic
assessment of the data showed that trehalose was well tolerated and no safety signals were identified. The next group was then
dosed with 54 g. Safety and PK were acceptable permitting dosing of the next level of 81 g.
Peak serum concentration increased with
increasing doses from 27g to 81g. The mean elimination half-life (t½) ranged from 1.41 hours to 1.59 hours and
was consistent as the dose increased. In the 81g dose cohort, one subject out of six had an increase in liver enzymes that resolved
without treatment; no higher doses of trehalose were administered, thereby establishing the MTD for trehalose as 54g.
There was a positive relationship between
clearance of trehalose from the blood and body weight over a range of 50 kilograms (kg) to 100kg. This finding suggested that clearance
is related to body size and thus, weight-based dosing, i.e. g/kg, would be more appropriate to achieve consistent exposure across
a range of body weights in future studies.
Trehalose is a protein stabilizer that also activates
autophagy and crosses the blood-brain-barrier
Trehalose is a low molecular weight disaccharide (.342 kilodaltons)
that protects against pathological processes in cells. It has been shown to penetrate muscle cells and cross the blood brain barrier.
In animal models of several diseases associated with abnormal cellular-protein aggregation, it has been shown to reduce pathological
aggregation of misfolded proteins as well as to activate autophagy pathways through the activation of Transcription Factor EB (TFEB),
a key factor in lysosomal and autophagy gene expression. Activation of TFEB is an emerging therapeutic target for a number of diseases
with pathologic accumulation of storage material.
Trehalose 90mg/mL IV solution is being developed as a treatment
for OPMD based on several studies in cell and animal models of OPMD where it demonstrated the ability to reduce aggregation of
the pathological protein (PABPN1) in muscle cells, the hallmark of the disease, by stabilizing the protein, reducing the formation
of protein aggregations, and promoting clearance of abnormal proteins through activation of autophagy, thereby preventing muscle
Other information on Trehalose in clinical studies
In a Phase 2a open label study of patients with OPMD, trehalose
administered as a weekly infusion of 27g for 6 months showed an improvement in dysphagia as measured by the time to consume 80
mL of cold water. In the 12 month follow up of that study designed as a withdrawal study, those patients who were randomized to
stay on drug continued to have reduced drinking time and those who were withdrawn from drug had an increase in the drinking time.
These data suggest that the treatment effect is sustained in the those who continue to receive trehalose and was lost in those
who were withdrawn from treatment.
Beyond OPMD, Bioblast is currently conducting analyses to determine
the next orphan disease that will investigate the use of trehalose as a therapeutic agent. Bioblast intends to make such a decision
in the first half of 2017.
OPMD is an inherited myopathy characterized by dysphagia (difficulty
in swallowing), eyelid drooping (ptosis), and the loss of muscle strength, with progressive limb weakness. Symptoms generally appear
in mid-life and get worse over time. As the dysphagia becomes more severe, patients may become malnourished, may lose significant
weight, and may suffer from repeated incidents of aspiration pneumonia. The disease is caused by a genetic mutation responsible
for the creation of a mutant protein (PABPN1) with an expanded polyalanine domain that aggregates within patient muscle cells.
There is currently no approved pharmacologic treatment for OPMD.
About Bioblast Pharma Ltd.
Bioblast Pharma is a clinical-stage biotechnology company committed
to developing clinically meaningful therapies for patients with rare and ultra-rare genetic diseases, with a lead drug candidate
-- trehalose 90mg/mL IV solution -- in Phase 2 development. Bioblast was founded in 2012 and is traded on the NASDAQ under the
symbol "ORPN". For more information, please visit our website, www.bioblastpharma.com, the content of which is not
incorporated herein by reference.
Forward Looking Statements
This press release contains forward-looking statements within
the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 and other Federal
securities laws. For example, we are using forward looking statements when we discuss our plans clinical studies, analyses and
possible orphan diseases to be investigated. In addition, historic results of scientific research and clinical and preclinical
trials do not guarantee that the conclusions of future research or trials will suggest identical or even similar conclusions or
that historic results referred to in this press release would not be interpreted differently in light of additional research and
clinical and preclinical trial results. Because such statements deal with future events and are based on Bioblast Pharma Ltd.'s
current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Bioblast
Pharma could differ materially from those described in or implied by the statements in this press release, including those discussed
under the heading "Risk Factors" in Bioblast Pharma's Annual Report on Form 20-F filed with the Securities and Exchange
Commission ("SEC") on March 29, 2016, and in any subsequent filings with the SEC. Except as otherwise required by law,
Bioblast Pharma disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of
the date hereof, whether as a result of new information, future events or circumstances or otherwise.