Sanfil ippo Children’s Foundation

F e b r u a r y 2 0 1 7

Table of Contents

3 What is Sanfilippo Syndrome?

Research Strategy Overview 7

Research Principles 9

Research Focus Areas 8

10 Grant Program

11 How we fund research

12 Projects Funded to Date

Slide Content

4 About Sanfilippo Children’s Foundation

Foundation Governance 5

14 Grant Process

What is Sanfilippo Syndrome (MPSIII)?

3

About Sanfilippo Children’s Foundation

• Founded in September 2013 by a parent of two children with Sanfilippo Syndrome

• We are working to achieve our mission by:

‒ Enabling access to emerging treatments and clinical trials

‒ Raising awareness amongst the community

‒ Providing diagnosed families with clear, up-to-date information

‒ Fundraising to achieve the above aims

• Governance includes a Board of Directors and Scientific Advisory Board

• First funding project agreed in 2014 with USD$1m (est. AUD$1.3m) committed based on agreed milestones. This is a gene therapy program for Sanfilippo (MPSIIIA & MPSIIIB) run by US-based biotech, Abeona Therapeutics. A clinical trial site is scheduled for 2016 in Australia.

• Implemented a grant funding program in 2016 to expand its research scope into therapies that can help all types of Sanfilippo and complement and enhance the successes of emerging therapies such as gene therapy.

Sanfilippo Children’s Foundation’s vision is to fund medical research so a cure can be found in time for children battling Sanfilippo Syndrome today, and those born with it tomorrow.

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5

Foundation Governance – Scientific Advisory Board

Our research strategy is executed under the guidance of our Scientific Advisory Board.

Prof John Hopwood AM FAA Chair, Scientific Advisory Board Former Head Lysosomal Disease Research Unit Director, SAHMRI SA Scientist of the Year (2009)

Dr Michel Tchan BMedSc MBSS PhD FRACP Deputy Chair, Scientific Advisory Board Clinical & Metabolic Geneticist Head of Genetic Medicine, Westmead Hospital Clinical Senior Lecturer, University of Sydney

Dr Nicholas Smith MBBS (Hons) DCH PhD (Cantab) FRACP Paediatric Neurologist Paediatric Neurology, Adelaide Women’s & Children’s University of Adelaide, School of Medicine

Prof David Ryugo BA Psych (Yale) PhD Psychobiology (University California) Professor Neuroscience, Garvan Institute Conjoint Professor, School of Medicine, UNSW Professor Emeritus John Hopkins University School of Medicine Baltimore (USA)

Prof Ian Alexander BMedSci MBBS (Hons) PhD FRACP (Paeds) HGSA FAHMS Head, Gene Therapy Research Unit, CMRI Director Laboratory Research, Westmead Children’s Professor Paediatrics and Molecular Medicine, University of Sydney

Dr David Ketteridge MBBS FRACP (Paediatrics) Metabolic Physician & General Paediatrician, Adelaide Women’s & Children’s Hospital

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Foundation Governance – Board of Directors

Foundation governance and project funding is the responsibility of our Board of Directors.

Megan Donnell Founder and Executive Director Mother to Isla & Jude (both Sanfilippo Type A)

Mark Arnold Director, Strategy & Governance Managing Director, Articulate

Daniel Madhavan Director, Investments & Networks CEO Impact Investing Australia

Angeline Veeneman Director, Patient Programs Founder, Maysix Consulting

Research Strategy Overview

As a rare condition, Sanfilippo Syndrome struggles to attract research funding from larger funding institutions. With our funding we aim to ensure that this devastating condition receives the research attention it requires.

Our research strategy:

• Aims to maximise the impact of the funds we invest, we identify the research areas that promise to make the greatest scientific advances and have the most relevance for our families.

• Defines three focus areas – halt disease progression, repair damage and improve quality of life. We believe that investment in these areas is essential to bring desperately needed treatments to the market.

• Offers research grants with applications assessed via a robust review process to ensure we fund appropriate research.

$500 - 700k/year is planned to be invested in research grants that fall into four categories (in order of priority:

1. Translational research grants

2. Incubator grants

3. Scholarships and fellowships

4. Travel grants 7

• Improve quality of life of children/adults with Sanfilippo Syndrome

• Palliative care and symptom management specific to Sanfilippo Syndrome

• Enzyme replacement, gene therapy, cell therapy and other emerging therapies to stop progression of Sanfilippo Syndrome

• Strategies to enhance the effectiveness of emerging therapies

• Halt disease progression early to optimise brain development

• Effective treatments for all disease sub-types

Research Focus Areas

• Repair and reverse cell damage caused by Sanfilippo Syndrome

• Broad application of neuro-regenerative treatments, for example repurposing approved drugs

• Opportunity to collaborate with researchers working on other neuro-degenerative diseases

Our research strategy will focus on 3 priority areas and our grant program will consider funding projects during the initial round that address these.

8 Future funding focus areas may include: Prevention (including pre-conception), diagnosis and prognosis.

Research Principles

The following principles underpin our research strategy and apply to each focus area.

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Funding for projects with significant potential to move through the translational pipeline towards treatment. This includes pre-clinical and clinical research to develop new treatments.

Larger grants may be considered for co-funding with partner funding bodies.

Translational Research

Grant

$500k/year for up to 3 years

Grant Program

Focus on small scale projects that involve:

‐ Novel, innovative ideas and approaches; or

‐ Development of new insights that improve disease understanding with potential to inform future research projects; or

‐ Potential to generate results that may attract larger scale funding

Incubator Grants

To 90k over 1 year

Grants to allow development of Australian research capability by funding travel of:

‐ Australian researchers to travel to attend international conferences or medical meetings relating to the field of Sanfilippo or to fulfil training placement positions in institutions abroad

‐ International researchers to travel to Australia to share knowledge

Travel Grants Up to $5k

• NHMRC co-funded Postgraduate scholarships offering premium top-ups & travel allowances

• Fully funded Postgraduate scholarships

• Postdoctoral and Clinical Research fellowships to be considered for future funding

Scholarships &

Fellowships

Co-funded $10k/yr over 3 years

Postdoc/clinical

research TBA

Pri

ori

ty

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How we fund research

Our funds are raised primarily through grassroots fundraising activities initiated by the foundation, our supporters and families of children with Sanfilippo syndrome.

We have a duty to ensure that this money is used to fund research that has the greatest chance of having an impact on the lives of children affected by Sanfilippo.

Whenever possible, we will invest funds with the potential for not only a scientific return but also a commercial return, allowing us to optimise our limited resources and minimise risk associated with funding research.

Sanfilippo Children’s Foundation has a competitive research grant application program. All grant applications are assessed through a robust peer review process involving our scientific advisory board and external reviewers.

Using peer review ensures that the research is:

• scientifically valid, relevant and significant

• timely and achievable

• not duplicating other work

• using appropriate methodologies

• carried out by researchers with the right skills and facilities

• providing value for money.

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FY15/16

Projects Funded to Date

ABO-101 & ABO-102 gene therapy

Our first project was funding a clinical trial of gene therapy being run by biotech company Abeona Therapeutics.

Under our agreement with Abeona, a clinical trial site will be established in Australia allowing children here the same opportunities to access this emerging treatment as their American and European counterparts. The regulatory approval process is currently underway and it is expected this trial will commence in the first half of 2017.

This experimental treatment uses a virus to deliver a healthy copy of the faulty gene to the cells of children with Sanfilippo.

We have co-funded this project with other foundations, our contribution will be USD$1m.

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Investigating the role of brain lipids (fats) in Sanfilippo

We are funding a one year project to be carried out in at SA Pathology, Adelaide, Australia lead by Associate Professor Maria Fuller.

Sanfilippo has a catastrophic affect on brain cells, one aspect of which involves the disruption of fat metabolism which is thought to impact on proper brain development and function. This project will investigate the role of fat in the developing Sanfilippo brain and whether it might be possible to develop a treatment that normalises fat metabolism.

High throughput drug screening

This project, to be carried out at the Hospital for Sick Children in Toronto, Canada, involves screening >6,000 compounds using a Sanfilippo cell model and a further 7,000,000 drugs using computer modelling to identify those that might be effective for Sanfilippo.

The project will focus on a particular process inside the cells which causes damage in Sanfilippo and other MPS disorders, if effective drugs are identified this approach could be effective not only for all types of Sanfilippo but also for Hurler (MPSI) and Hunter Syndromes (MPSII).

We have negotiated to co-funded this project with Cure Sanfilippo Foundation (USA), our contribution will be AUD$224,000.

Neural and mesenchymal stem cell mediated gene therapy

Researchers at the University of Florida will investigate the potential of two different types of stem cells as a therapy for Sanfilippo type B. This approach may be able to halt progression of Sanfilippo by supplying deficient enzymes and also reduce inflammation in the brain with is understood to cause significant damage in the disease. A major advantage over other potential therapies is that the stem cells may also be able to reverse some of the damage already caused prior to diagnosis and treatment.

We have negotiated to co-funded this project with Cure Sanfilippo Foundation (USA), our contribution will be AUD$45,000.

Projects Funded to Date

Optimising gene therapy

There are currently several gene therapy clinical trials underway for Sanfilippo, building on this work this project will test several different modifications to existing gene therapy technology, along with different ways of administering it, to find the best combination for Sanfilippo type B.

We have negotiated to co-funded this project with Sanfilippo Initiative (Germany), our contribution will be AUD$45,000.

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Gene therapy for Sanfilippo Type C

Sanfilippo type C is more challenging to treat than the other subtypes because of the way the deficient enzyme works with the cells. For this reason, a different approach is required for gene therapy and this project, headed up by Prof. Brian Bigger at Manchester University is focused on optimising treatment for this sub-type.

We have negotiated to co-funded this project with Jonah’s Just Begun(USA), our contribution will be AUD$90,000.

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Scientific Advisory Board (SAB)

Grant Stakeholders

Scientific Advisory Board Chair / Deputy Chair

External Peer Reviewer

• Provide informed, non-binding guidance on research and funding strategy matters

• Peer review applications submitted for funding and make recommendations

• Support grant applications submitted to other funding bodies

• Work with the Board of Directors to identify research and clinical trial opportunities

• Contribute to any relevant research media opportunities

• Participate in research strategy reviews

• Includes scientific and layman representatives

• Determine the agenda and chair SAB meetings

• Sole discretion on small grants of $10k or below (travel grants or co-funded scholarships)

• Deputy Chair to assume Chair position if/when funding decisions involving the chair are required

• Attend Board of Directors meeting and present funding recommendations

• Perform first-stage review of significant grants (translational research & incubator grants) prior to review by SAB

• Provide international perspective and expert opinion on specialised topics in grant applications

Grant Timeline 2017

Board of Directors

• Make final funding decisions based on SAB recommendations and research strategy alignment

March April May June August

Call for expressions of interest

Applications close

Funding decisions

made

Scientific Advisory

Board Review

Invite grant applications

External Peer Review

July