Living with OPMD

Orphan Drug Designation from the FDA for Benitec OPMD Treatment

#1

Benitec receives U.S. Orphan Drug Designation for BB-301, its ddRNAi therapeutic for the treatment of oculopharyngeal muscular dystrophy

Sydney, Australia, 15 January 2018:

Benitec Biopharma Limited (ASX:BLT; NASDAQ:BNTC; NASDAQ:BNTCW) today announced that the U.S. Food & Drug Administration (FDA) has granted Orphan Drug Designation to BB-301 for the treatment of oculopharyngeal muscular dystrophy (OPMD).

The Orphan Drug Designation granted to Benitec may provide a range of valuable benefits, including fast track process for clinical regulatory approval, potential extension of patent life with a seven-year period of market exclusivity if the drug is approved, tax credits for qualified clinical trials and an exemption from FDA application fees. In short, a clear and expeditious path for cost-efficient development and commercialisation. The granting of orphan status from the FDA in the US follows on from receiving orphan designation from the European Medicines Agency in early 2017.

Greg West, CEO, Benitec Biopharma, commented on today’s news, “We are very pleased to have received Orphan Drug Designation from the FDA for BB-301, as it is another significant step forward for a key program in our pipeline. We believe BB-301 represents a promising new approach for the treatment of OPMD and has the potential to make a meaningful impact for patients who have this debilitating disease. The Benitec team is focused on executing our plan to advance BB-301 into human clinical trials by the end of 2018.”

BB-301 is a single vector (gene therapy construct) system which uses DNA directed RNA interference (ddRNAi) to silence expression of the mutant gene associated with OPMD, while simultaneously adding back a copy of the normal version of the same gene to restore gene function. Nonclinical safety studies and manufacturing work are progressing and Benitec intends to file an Investigational New Drug Application (IND) in the last quarter of calendar year 2018.

In November last year Benitec advised it had completed pre-investigational new drug application (pre-IND) and scientific advice meetings with the U.S. FDA, Health Canada and several European agencies. The purpose of these meetings was to discuss the regulatory development pathway for BB-301 as a treatment for OPMD and to ensure Benitec’s proposed development program addressed the regulatory expectations of these agencies. In addition to these regulatory meetings, the transfer of production protocols and optimisation of the processes related to manufacturing of BB-301 are well underway at Benitec’s contract manufacturing organisation (CMO).

#2

Latest Info from Benitec, February 22, 2018:

Oculopharyngeal Muscular Dystrophy (OPMD):

The Company is developing BB-301, a single administration ddRNAi-based gene therapy to correct the gene defect which causes the disease and to address many of the limitations of therapeutic approaches currently available and those in development for OPMD. OPMD is an autosomal-dominant inherited, slow-progressing, late-onset degenerative muscle disorder that usually starts in patients during their 40s or 50s. The disease is manifested by progressive swallowing difficulties (dysphagia) and eyelid drooping (ptosis). OPMD is caused by a specific mutation in the poly(A)-binding protein nuclear 1, or PABPN1, gene. OPMD is a rare disease and has been reported in at least 33 countries. Patients suffering with OPMD are well identified and are geographically clustered, which we believe should simplify clinical development and in house commercialisation.

BB-301 is a monotherapy delivered using an AAV vector and is designed to silence the expression of the mutant PABPN1 gene in oesophageal muscle cells of OPMD patients while simultaneously introducing a silencing-resistant normal form of the gene. The Company believes OPMD is well suited for this “silence and replace” approach since the genetic mutation is well characterized and the target tissue is relatively small. Once validated, the Company believes a similar approach could be applied to other inherited disorders.

Key milestones achieved over the last 3 months and next steps include:

o The Company continued advancement of an innovative single vector system with the capability to both ‘silence and replace’ disease causing genes. In addition to using RNA interference to ‘silence’ the mutant PABPN1 gene expression that causes the OPMD, BB-301 simultaneously introduces a normal copy of the same gene thus providing the potential to restore normal function to the treated tissues and in the
process, improve treatment outcomes.

o This single gene therapy product, versus an equivalent system with two or more vectors, vastly simplifies the manufacturing and regulatory processes and reduces the complexity of the clinical strategy for BB-301.

o In November 2017, the Company completed successful pre-IND and scientific advice meetings with the U.S. FDA, Health Canada and several European agencies. Input from these meetings has been incorporated into the BB-301 regulatory strategies.

o In January 2018, the Company received orphan drug designation from the U.S. FDA for BB-301 as a treatment of OPMD.

o The Company has initiated the IND-enabling work required to support the initiation of a clinical trial late in calendar 2018, subject to toxicity results and future regulatory review.

#3

I am curious what the result would be of using mutated ddRNAi into the body? What would the end result be? Would my hazel eyes turn blue? Would my beard look less like Mandy Patinkin’s? It is a scary thought messing with the human DNA. I am not proposing some bizarre Marvel Comic nonsense conspiracy. I am just concerned about potential side effects. Will dominant DNA features revert to non-dominant features, and will that change lead to more problems in the end? Perhaps cancer? I can tell you from experience from having a messed up back, that placental stem cells are temporary solution.

I remember getting one in my neck. For about two weeks, I could throw away the bifocals, and I didn’t need sunglasses. Then two weeks later, the disease came back just the way it was. It seemed kind of cruel.

#4

Submitted my contact info to Benitec last August (2018). Was told I would be added to their patient list. Have heard nothing back since then.
I share your concern regarding genetic manipulation. Although I’m not quite sure that I want to be the “first rat in the maze,”
I have two young adult daughters - each with a 50% probability…
Dean