for personal use only being preimplantation screening to ... · 25/08/2016 · for personal use...
Post on 24-May-2020
2 Views
Preview:
TRANSCRIPT
Reproductive Health Science Ltd Michelle Fraser, Chief Executive Officer
25 August 2016
“IMPROVING HEALTH AND RESEARCH OUTCOMES THROUGH THE APPLICATION OF OUR FRONTIER TECHNOLOGIES WITH A LEAD FOCUS
BEING PREIMPLANTATION SCREENING TO IMPROVE IVF SUCCESS”
For
per
sona
l use
onl
y
2
Any forward looking statements in this presentation have been prepared on the basis of anumber of assumptions which may prove incorrect and the current intentions, plans, expectationsand beliefs about future events are subject to risk, uncertainties and other factors, many ofwhich are outside Reproductive Health Science Limited’s control.
Important factors that could cause actual results to differ materially from any assumptions orexpectations expressed or implied in this presentation include known and unknown risks. Asactual results may differ materially to any assumptions made in this presentation, you areurged to view any forward looking statements in this presentation with caution.
This presentation should not be relied on as a recommendation or forecast by ReproductiveHealth Science Limited, and should not be construed as either an offer to sell or a solicitation ofan offer to buy or sell shares in any jurisdiction.
For
per
sona
l use
onl
y
3
RHS has maintained a focus on being “At the forefront of single cell analysis”
RHS has a state-of-the-art advanced single cell Whole Genome Amplification (WGA) product DOPlifyTM that enables analysis by NGS (Next Generation Sequencing) &/or microarray pathways
RHS has been built on our particular interest in IVF outcomes, with a robust array for Pre-implantation Genetic Screening (PGS) known as EmbryoCellectTM and capabilities for NGS extending through to combined PGS & Pre-implantation Genetic Diagnosis (PGD)F
or p
erso
nal u
se o
nly
4
DOPlifyTM is a whole genome amplification kit that; Captures RHS proprietary know-how for the lysis and
Whole Genome Amplification (WGA) of single or small numbers of cells providing a solution for the amplification of limited DNA for a range of downstream applications
Addresses the first critical step in analysis accuracy – the quality of amplification before interpretation by array or NGS
EmbryoCellectTM microarray PGS kit is designed to meet the needs of the IVF industry; this kit uses DOPlifyTM as the first step for the microarray analysisF
or p
erso
nal u
se o
nly
5
DOPlifyTM is a solution to analysis of “micro” quantities of DNA such as a single cell which need to be multiplied before analysis
The DNA multiplying step is Whole Genome Amplification (WGA)
Accuracy of the subsequent DNA analysis is directly linked to the quality of the preceding WGA multiplication step
Analysis/interrogation of the products of the amplification step can be by a range of approaches including NGS or array technologies
The most advanced routine application is in the IVF industry with embryo biopsies of a single or small number of cells
For
per
sona
l use
onl
y
6
cellDNA
1,000,000s of picograms of DNA from 1 cellCopies of the whole genome
chromosomes
6 picograms of DNA
Lysis
WGA
For
per
sona
l use
onl
y
7
DNA is made up of 4 bases, adenine (A), guanine (G), cytosine (C) and thymine (T)
These bases make up the genetic code, determining the biology of a cell
Sequencing is determining the genetic code of DNA. Once the code is determined, the fragment of DNA is matched and compared to a reference sequence
By Zephyris at the English language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6285050
This can provide information on identity, genetic mutations and diseases for example
Next Generation Sequencing (NGS), also known as massively parallel sequencing, is a method to sequencing millions of fragments of DNA at the same time. This increases throughput and brings down the cost
For
per
sona
l use
onl
y
8
DOPlifyTM
www.abmgood.com
Bioinformatics1. Checking the quality of the sequencing run2. Working out where the >1million DNA fragments match
within the entire human genome3. Looking for differences with the reference genome4. Determining whether the differences are clinically
significant or not using published databases
Sequencing1. Library preparation
2. Determining the DNA code
http://www.broadinstitute.org/gatk/
For
per
sona
l use
onl
y
9
1 10 100 1,000 10,000 100,000
Low template NGS
Standard NGS
Microarray
5 cells
Single cell
Cell equivalents of DNA input required (log scale)
For
per
sona
l use
onl
y
10
RHS products compete across the DNA amplification, microarray and sequencing markets
RHS product CompanyDOPlifyTM Rubicon Genomics Inc, Sigma-Aldrich Co
LLC, Qiagen NV, Yikon Genomics
EmbryoCellectTM Illumina Inc, Agilent Technologies Inc, Natera Inc, Oxford Gene Technologies
Next Generation Sequencing workflows
Illumina Inc, Fluidigm Corp, Thermo Fisher Scientific
For
per
sona
l use
onl
y
11
RHS is one of only four companies in the world with an advanced single cell Whole Genome Amplification product Competing products PicoPLEX (Rubicon Genomics, which is equivalent
to SurePlex from Illumina) and GenomePlex (Sigma) use linker adapter Polymerase Chain Reaction (PCR), REPLI-g (Qiagen) uses Multiple Displacement Amplification (MDA) and Yikon Genomics sell a kit using MALBAC.
DOPlifyTM is unique in that it is based on advanced DOP-PCR, a modern version of a proven WGA approach
Polymerase Chain Reaction (PCR) is a molecular biology technique to copy DNA in much the same way as a cell usually copies its DNA during cell division
For
per
sona
l use
onl
y
12
Uses the high processivity and fidelity of new generation polymerases that are NGS application grade
Uses “ready-mixes” to minimise the pipetting steps and requires only 2 sample tube openings to reduce the risk of contamination
Provides an amplification system that is flexible enough to concurrently whole genome amplify a sample whilst specifically amplifying genes of clinical interest, reducing the risk of allele drop-out and;
The kit is highly stable during shipping and storageFor
per
sona
l use
onl
y
13
The single cell analysis market is forecast at US$5B by 2024 (http://www.grandviewresearch.com/industry-analysis/single-cell-analysis-market, July 2016)
Growth predicted to mainly come from consumables, which is currently the largest segment
Instruments will also grow but their high cost and long shelf-life will be limiting
While RHS Ltd was founded from interest in reproductive outcomes, the significant advantages that DOPlify™ provides over other WGA products is a platform for RHS to expand from our original target market
DOPlifyTM is a platform technology with global applicability There is no further product development required to use the
product in a range of different non-IVF applications
For
per
sona
l use
onl
y
Schilling, D. et al. (2012) Isolated, disseminated and circulating tumour cells in prostate cancer Nat. Rev. Urol. doi:10.1038/nrurol.2012.136
Permission obtained from Thieme © Schilling, D. et al. Mechanisms of tumour cell dissemination and methods for detection of circulating tumour cells in transitional cell carcinoma. Aktuelle Urol. 42, 122–127 (2011).
Diversity within a tumour• Growth characteristics• Prediction of treatment response• Metastatic potential
Detection and characterisation of circulating tumour cells• Identification and prognosis of primary source• Mutation rate compared to tumour• Prediction and monitoring of treatment
response• Treatment effectiveness and recurrence
14F
or p
erso
nal u
se o
nly
15
179 labs conducting DNA analysis in 50 states in the USA Approx. 40,000 cases received per year, approx. 25,000 cases
analysed Commonly used STR markers require 250pg of starting DNA template Termed low copy number analysis if less than 100pg of DNA available
More technical artefacts, evidence not widely accepted in court
Approx. 300,000 paternity tests per year
By using the RHS combined Whole Genome Amplification and single gene enrichment protocol, it may be possible to obtain genetic fingerprints using STR markers from limited templateF
or p
erso
nal u
se o
nly
16
Identification of individuals can be achieved using mitochondrial DNA, which is maternally inherited
RHS internal benchmarking has shown that DOPlifyTM
provides greater coverage of the mitochondrial genome than competing WGA kit PicoPLEX
Mitochondrial DNA sequence analysis of single cells amplified using either DOPlifyTM or PicoPLEX (Rubicon). Libraries were prepared using standard Nextera protocol and sequenced in a 23-plex paired-end 150-bp read format on the Illumina NextSeq
For
per
sona
l use
onl
y
17
Using Whole Genome Amplification, all of the DNA in a sample will be amplified, providing a more abundant template for analysis.
http://earthsciences.typepad.com/blog/2011/07/harnessing-metagenomics-to-study-microbial-ecology-in-soils.html
Environmental DNA and conservation Human microbiome
The microbiome of individuals may differ due to such factors as diet, environmental influences and genetics. The effects of therapeutic treatments, stress and the ability to restore the microbiome rely on the accurate characterisation of its contents
https://www.neb.com/tools-and-resources/feature-articles/addressing-challenges-in-microbiome-dna-analysis
For
per
sona
l use
onl
y
18
China, 250,000
USA, 163,000Russia, 80,000
Iran, 35,000
UAE and Saudi Arabia, 8,000
Turkey, 45,000
India, 80,000
Indonesia, 3,500Israel, 32,000
South Africa, 5,500Australia, 62,000
1.7 million IVF cycles per annum globally, growing at 10%Estimated 5 million IVF babies born, an average of one per classroomAverage of 4 embryos per cycle
For
per
sona
l use
onl
y
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
<35 35-37 38-40 41-42 >42
Embr
yo A
neup
loid
y In
cide
nce
Maternal age
Even younger IVF patients have significant numbers of aneuploid embryos
Harton et al 2013
19
0102030405060708090
100
Euploid embryos Aneuploid embryos
Num
ber o
f tr
ansf
ers
Live birth or ongoingpregnancy
Unsuccessful
96% of the aneuploid embryos (i.e. embryos with the incorrect number of chromosomes) failed to implant resulting in an unsuccessful IVF transfer Scott et al 2012F
or p
erso
nal u
se o
nly
20
Decrease time to pregnancy Positive clinical outcome
Trend towards increased maternal age
Decreased miscarriages
Increased single embryo transfers reducing clinical complications from multiple pregnancies eg preterm birth
Patient and Medicare savings Clinic decreases revenues from storage and subsequent
transfer of aneuploid embryos Additional revenues from PGS
Patient expectations of best practice and clinical duty of careFor
per
sona
l use
onl
y
21
The RHS PGS service was established to provide support to clinics introducing PGS
“Rollout” is by direct PGS service provision and also supported sales flindersfertility is a functioning model of clinicians and scientists
working together to determine the patient needs, providing the option of fresh embryo transfer and identification of euploid embryos prior to freezing
Morula IVF are an example of RHS assisting in the establishment of in-house capability, which is now self-sufficient
Revenue from a PGS service business offered to 10,000 cycles in Australia, assuming 30% PGS uptake, approximates the RHS total cash burn rate
Broader roll out of this service model is anticipated both nationally and internationally
For
per
sona
l use
onl
y
22
The US PGS market is primarily a sophisticated service offered to clinics
2014 data indicated that less than 6% of IVF cycles in the US use PGS, but this has grown to 20% in 2016
By 2020, RHS aims to be addressing 20% of the global PGS market, which is forecast to represent 20% of the global IVF market of approximately 2 million cycles
For
per
sona
l use
onl
y
23
The RHS DOPlifyTM WGA platform offers clinicians and their patients choice and flexibility for analysis of the precious embryo biopsy. EmbryoCellectTM for cost efficient PGS, particularly under the time
constraint for fresh transfer and to determine which embryos are suitable for frozen storage
NGS after DOPlifyTM is ideally suited for PGD needs including translocations and specific inherited genetic disorders. It is possible to pre-determine clinically relevant regions to analyse; hence RHS developed a unique and improved combined PGS-PGD approach
For
per
sona
l use
onl
y
24
Marketing DOPlifyTM in parallel with EmbryoCellect™ to provide flexibility to select the best technology for clinical needs. Clinicians can determine on a patient-by-patient basis the extent of
genetic information needed and tailor their screening accordingly.
Additionally, RHS has been able to demonstrate that by using DOPlifyTM it is possible to screen an embryo for changes in chromosome number (PGS) and at the same time detect the presence of a genetic disease (PGD) carried by patients that needs to be avoided during embryo transfer, such as Duchenne’s Muscular Dystrophy.
For
per
sona
l use
onl
y
25
The correct aneuploidy result is maintained and the targeted gene is evident using traditional PGD and also NGS approaches.
WGA + primers WGA only NTC
Test
Test
Control
Control
NGS data
0.000.250.500.751.001.251.501.752.00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X YN
egat
ive
Mea
n of
nor
mal
ized
ratio
s
Chromosome
0.00
0.50
1.00
1.50
2.00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X Y
Ratio of mapped reads compared to internal reference (~700,000 reads/sample)
1: 48,XXY,+21 D4S43 & Y enriched 2: 48,XXY,+21 D4S43 enriched 6: 48,XXY,+21 control
EmbryoCellectTM
For
per
sona
l use
onl
y
26
Released EmbryoCellectTM validation data showing the accuracy and sensitivity is competitive with other PGS products
Patent application for combined PGS & PGD filed Launched DOPlifyTM specifically targeting the NGS market
Demonstrated a major, globally-unrivalled technical advance in being able to concurrently whole genome amplify and specifically amplify genes of clinical significance from single cells
For
per
sona
l use
onl
y
27
With the recent expiry of IP rights that had prevented the Company from entering the USA market, RHS is now actively marketing EmbryoCellectTM
and DOPlifyTM in this market. The USA marketing strategy will be enhanced by recruitment of a senior executive and through RHS exhibiting at the American Society for Reproductive Medicine (ASRM) meeting in Salt Lake City in October 2016.
Consolidate and expand the NGS capabilities of the Company including incorporation into the PGS service business and model
The launch of DOPlifyTM is enhancing RHS’ position as a global leader in single cell genomic technologies. A number of significant opportunities are in progress due to our ability to respond to the advancing genetics market and to expand our focus to other important applications for single cell analysis. Commercial collaborations may lead to integration of DOPlifyTM into the workflows of products of large multinationals.
Cash flow positive by end 2017For
per
sona
l use
onl
y
Key assetsIntellectual property
EmbryoCellectTM microarray granted patent familyDOPlifyTM trade secret and supplier exclusivityDOPlifyTM combined single gene enrichment Provisional Patent pending
Primary value drivers
Clinical impact in the IVF marketSignificant technical advances and deep expertise in single cell genetic analysisGlobal product sales and key partnerships
24 August 2016 dataASX Code RHS
Shares on Issue 59m
Share Price 9.2c
Options 13.1m
Market Capitalisation $5.43m
Cash at 30 June 2016 $0.6m
Recent Corporate Highlights• DOPlifyTM launched August 2016• R&D Tax refund of $278k received• EmbryoCellectTM performance validation
data released
28F
or p
erso
nal u
se o
nly
29
Dr David BrookesNon-Executive Chairman
Director of Atcor Medical Holdings Ltd (ACG:ASX); medical practitioner & biotechnology consultant; MBBS; FACRRM; FAICD
Dr Michelle FraserManaging Director and CEO
PhD (molecular biology); Grad Dip Science & Technology Commercialisation; GAICD, RHS CEO since 2007
Ms Sue MacLemanNon-Executive Director
CEO of MTPConnect; has been CEO and a Board member of a number of publicly-listed companies in both the USA and Australia; BPharm; MMktg; MLaw; FACPP; FAICD
Mr Johnathon MatthewsNon-Executive Director
Executive Director of The Pipette Company; previously held positions at Australian Treasury, ASX and Commonwealth Bank; BEc; BComm; LLB; GAICD
Emeritus Professor Colin Matthews AO
Alternate Non-Executive Director
Inaugural director of RHS, Single Cell Pty Ltd, Flinders Fertility; co-founder and former director of The Pipette Company; former Director ReproMed; Chairman RHS’ Clinical & Scientific Advisory Committee
Mr Raymond RidgeCFO and Company Secretary
CFO and Co Sec Thor Mining, CFO Southern Gold; BA (Acc); CA; GIA (Cert)
Dr Melinda JasperCSO
PhD; Experience in reproductive molecular biology, pre-implantation genetic analysis and single cell PCR, RHS CSO since 2012
For
per
sona
l use
onl
y
top related