Why we are targeting the eye? Why not systemic injection to the whole body? Is anyone interested in anything we are doing?
Andrew, in my view, you may find some answers here.
2 Oct 2015
A four-year agreement was announced between Sarepta Therapeutics and Murdoch University with the purpose of studying Sarepta’s's PMO (charge-neutral antisense oligonucleotide) technology for genetic diseases other than Duchenne muscular dystrophy (DMD).
The Murdoch research team, led by Prof. Steve Wilton, Perron Institute Director, and Prof. Sue Fletcher, who are both based at the Centre for Comparative Genomics, was to work in conjunction with the Perron Institute, which was to provide additional research staff members for the project.
The collaboration agreement provided the Murdoch University researchers with access to Sarepta’s PMO platform technology, as well as funding for researchers and materials while Sarepta was to have exclusive rights to license technology and/or products resulting from the research projects.
Prof. Wilton said the agreement with Sarepta allowed their Murdoch laboratory to become a pipeline of drug development and would facilitate getting the drugs from laboratory to clinical trials.
https://scrip.pharmaintelligence.informa.com/deals/201520497
https://perroninstitute.org/wanri-d...aceuticals-company-to-improve-drug-treatment/
15 June 2016 from Joint Announcement by Phylogica and Murdoch University
In February, 2016, Phylogica (ASX: PYC) initiated a collaboration with Professors Sue Fletcher and Stephen Wilton from the Centre for Comparative Genomics at Murdoch University to assess whether a cell penetrating Phylomer (CPP) could improve the delivery of an antisense oligonucleotide drug inside cells. This effort is aligned to our strategy of engaging in external collaborations to provide independent validation that our technology can expand the druggable landscape.
https://hotcopper.com.au/threads/an...elivery-of-drugs-pyc-ax.2791081/#.XUZn0-gzaUk
1 September 2017
Publication of the paper
Inherited Retinal Disease Therapies Targeting Precursor Messenger Ribonucleic Acid
Authors (inc. Profs. Fletcher and Wilton) from the Molecular Therapy Laboratory at Murdoch University, the Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute) at The University of Western Australia, the Perron Institute and Department of Ophthalmology, Royal Perth Hospital.
This paper explains why the eye is an attractive target for innovative therapies and identifies antisense oligonucleotides as potential therapies for inherited retinal diseases. The authors note the existence of ongoing preclinical trials using ASOs to treat inherited retinal diseases and the need for more work to safely and effectively deliver ASOs to the retina, increase cellular uptake in vivo, limit off-target effects, define the optimal treatment window and examine potential toxicity and immunostimulatory effects.
https://www.mdpi.com/2411-5150/1/3/22/htm
11 February 2018
Presentation of poster at the Lorne Genome Conference
Development of Molecular Therapies for PRPF31-associated Retinitis Pigmentosa Using Splice-switching Antisense Oligonucleotides
Authors include researchers from the Centre for Comparative Genomics, Murdoch University; the Perron Institute, Murdoch University; the Centre for Ophthalmology and Visual Science, University of Western Australia; the Lions Institute and the Department of Ophthalmology, Royal Perth Hospital. Profs. Fletcher and Wilton are included.
This poster focuses on Retinitis pigmentosa 11 (RP11), the most common inherited retinal degenerative disease, which is characterized by photoreceptor cell death with progressive loss of peripheral vision and potential for complete blindness. It is theorised that degeneration of the photoreceptor cells may be prevented or delayed by increasing the PRPF31 transcript level in the retina. In this poster, the use of ASOs to increase total PRPF31 transcript by two-fold is described.
In conclusion, the authors state that further evaluation of PRPF31 protein expression and its consequences on photoreceptors would be conducted in retinal organoids and that this study would yield a potential candidate for PRPF31-associated Retinitis Pigmentosa.
http://genome-2018.p.asnevents.com.au/days/2018-02-11/abstract/50344
31 August 2018
Symposium presentation at Annual Combined Biological Sciences Meeting, University of Western Australia
Rescuing Splicing Function in Retinitis Pigmentosa by Upregulation of PRPF31 using Splice-switching Antisense Oligonucleotides
Authors of the poster include researchers from the Centre for Comparative Genomics, Murdoch University; the Perron Institute, Murdoch University; the Centre for Ophthalmology and Visual Science, University of Western Australia; the Lions Institute and the Department of Ophthalmology, Royal Perth Hospital. Profs. Fletcher and Wilton are included as authors.
Five antisense oligonucleotides targeting PRPF31 exon 12 splicing enhancer motifs were tested. The results from this study were said to have provided a potential ASO candidate for the treatment of Retinitis pigmentosa 11 caused by mutations in exon 12.
https://cbsmwa.org.au/images/CBSM2018/cbsm2018manual.pdf
15 October 2018 Phylogica Annual Report
Over the coming months, Phylogica will deliver a read-out on the efficacy of our CPP delivery technology against the current gold standard delivery approach for a number of drug cargoes. These are the critical pieces of data that provide an indication of the likelihood of translating pre-clinical outcomes in animals into clinical outcomes in humans and are therefore the fundamental drivers of the value of the company’s platform technology. The cargo classes that have been identified as being of particular interest to Phylogica in progressing into the clinic include:
- Anti-Sense Oligonucleotides………
Phylogica’s recent capital raising positions the company to take the lead role in pre-clinical development of CPP delivered cargoes and consequently the commercial development of these assets. This enables us to take a dual approach to commercialisation including:
- Out-licensing the platform to third parties for progression of the CPP-cargo molecule by the third party; and
- In-licensing of the cargo for ‘flagship’ programs for Phylogica to progress into the clinic independently.
Given the scalability of Phylogica’s platform, realising clinical validation (dosing humans) through either approach will be transformative for the company. Phylogica currently has a number of Materials Transfer Agreements (MTAs) in place with commercial counter-parties (including for the cargoes identified above) that enable the counter-parties to evaluate the ability of our CPPs to deliver their cargoes into their target tissues of interest in their own hands. These agreements are set move to the next stage in CY19 with successful outcomes expected to translate into licensing agreements as described in the former development category outlined above.
16 November 2018 Phylogica AGM
We will soon realise a major milestone in validating our platform….We will achieve this objective with an Anti-Sense Oligonucleotide (ASO) cargo.
23 November 2018 FNA Perth 2018, Murdoch University Functional Nucleic Acids: From Laboratory to Targeted Molecular Therapy
Session 8 Chair: Prof Sue Fletcher
15:30 Keynote Lecture 15 Dr Sarah Shigdar, Deakin University, Geelong, Australia
Aptamer drug delivery to breast cancer brain metastases
16:00 OP-13: Dr Rohan Hockings, Phylogica, Australia Customised Delivery –
Development of an oligonucleotide-specific CPP-delivery platform
16:15 Keynote Lecture 16 Prof Steve Wilton, Murdoch University, Australia
An update on Duchenne muscular dystrophy exon skipping (and other applications)
https://www.wahtn.org/wp-content/uploads/2018/11/Seminar-Series-Week-Commencing-19-November-2018.pdf
28 February 2019 Sarepta Annual Report
Material Agreements
We believe that our RNA-targeted and gene therapy technologies could be broadly applicable for the potential development of pharmaceutical products in many therapeutic areas. To further exploit our core technologies, we have and may continue to enter into research, development or commercialization alliances with universities, hospitals, independent research centers, non-profit organizations, pharmaceutical and biotechnology companies and other entities for specific molecular targets or selected disease indications. We may also selectively pursue opportunities to access certain intellectual property rights that complement our internal portfolio through license agreements or other arrangements.
https://investorrelations.sarepta.com/static-files/25752742-cab2-4307-91d8-01c77fbff0c7
12 March 2019 Phylogica Flagship Program Announcement
Two of Phylogica’s first generation CPPs were used to deliver a ‘reporter’ ASO via multiple routes of administration in a pilot animal model study: - Systemic injection into the bloodstream; and - Intra-vitreal injection in the eye… The systemic injection resulted in exon skipping in the eye, liver and kidney (with other tissues harvested yet to be processed). The intra-vitreal injections resulted in exon skipping in the anterior and posterior segment of the eye…. A more detailed data pack on delivery within the eye as a target tissue will be provided in the future.
29 April 2019 Phylogica Operational Update
We have previously advised that we are building our delivery platform in the context of AntiSense Oligonucleotide (ASO) drug cargoes (see ASX announcement of 15 October 2018). Our choice of drug cargo has been complemented by a decision on our initial target tissue of interest. We are seeking to deliver these ASO cargoes into the back of the eye to address diseases occurring in the retina.
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