Recent Studies Funded by the Progressive MS Alliance Tim Coetzee, PhD ACTRIMS 2016

TC is an employee of the National MS Society The National MS Society is founding member of the Progressive MS Alliance Disclosures

1.Overview of the Alliance 2.Collaborative Network Awards Update 3.Future Plans Outline

Every time another therapy is approved for relapsing MS, a large proportion of our constituents feel left behind

Immune Mechanisms Neural Pathways & Mechanisms Symptom Management Purple = Progressive Orange = Non-Progressive Progressive MS Map

Global Progressive MS Portfolio Distribution of Progressive Projects by Alliance Priority

Global Progressive MS Portfolio Distribution of Projects by Priority/Stage Understanding Progression Clin. Trial Designs/OutcomesDev./Testing of New Agents Sympt. Mgmt/Rehab Discovery Clinical Research Clinical Trials

Mission: To expedite the development of effective disease modifying and symptom management therapies for progressive forms of multiple sclerosis

14 MS Societies representing 12 countries

Leverage and coordinate the Global MS movement to focus on Progressive MS Expand the global commitment to progressive MS research by €22 million ($30 million) over the next 6 years Fund research together without considering geography Funding the best science anywhere in the world Goals

Research Priorities Better understand progression so we can identify and test treatments Design shorter, faster trials that measure patient outcomes Conduct trials to test agents Develop and evaluate new therapies to manage symptoms

Industry stakeholders engagement RFA 2 – Collaborative Networks RFA 1 – Challenge & Infrastructure Sept 2013Sept 2014 Rehab Meeting Industry stakeholders meeting Sept 2016 Sept 2015 Alliance Scientific Meeting Science Strategy Meeting

Collaborative Network Awards Large projects aimed at building global research networks 4 years of funding €1 million/year Each team must at least 3 investigators from 3 countries

Call for submissions November, 2014; closed 31 January 2015 Worldwide communication and targeted promotion resulted in 52 applications –Involving close to 500 investigators Peer/Technical review completed in two stages for proposals, with 21 in the second stage Scientific Steering Committee assessments completed; 11 selected for funding Process Summary

Drug discovery programs that identify and validate molecular and cellular targets and screen and characterize drug candidates, which may be either repurposed or first-in-human drugs. – Expected impact: development of one+ pre-clinical drug candidates within the 4 year funding period of the full network award. Collaborative Network Awards – Theme 1

Quintana –Screen for drug candidates that modulate the activity of immune cells in the central nervous system (astrocytes, microglia and infiltrating macrophages) and identify drug candidates to be analyzed in clinical trials on SPMS patients. Mahad –Improve the understanding of tissue damage and clinical symptoms in progressive MS and identify pre-clinical candidate drugs using new experimental systems that are relevant to progressive MS Network Projects: Drug Discovery/Target Discovery/Validation

Goldman –Develop the transplantation of human oligodendrocyte progenitor cells, which as they mature proceed to remyelinate demyelinated axons, as a therapeutic strategy for progressive MS Martino –Bioinformatics to discover new drugs for progressive Multiple Sclerosis and to identify molecules that might have a therapeutic protective role on neurons and/or the capacity of favoring the proliferation of myelinating cells Network Projects: Drug Discovery/Target Discovery/Validation

Hafler-De Jager –Identify genes that predispose to MS, examine in large patient cohorts from around the world if patients who carry these genes have a higher chance to develop severe progression and establish if patients with these genes respond to specific treatments that target that genetic dysfunction. Network Projects: Drug Discovery/Target Discovery/Validation

The discovery, advancement and validation of new or existing biological or imaging biomarkers. – Expected Impact: development of a meaningful outcome measure that could be integrated into early clinical development within the 4 year funding period. Collaborative Network Awards – Theme 2

Arnold –Develop new MRI outcome measures that could provide a more efficient preliminary readout of drug efficacy, i.e., that could be used in smaller, shorter trials that would cost much less money Filippi –Determine and validate novel cervical cord MRI biomarkers to be utilized as predictors and/or outcomes in future studies of progressive MS Network Projects: Biomarkers – Biological/Imaging

Lublin –The discovery, advancement and validation of new or existing biological or imaging biomarkers leading to development of a meaningful outcome measure that could be integrated into early clinical development within the 4 year funding period. Network Projects: Biomarkers – Biological/Imaging

Stankoff-Nicholas –Develop and apply in clinical studies new imaging probes (PET) that will allow the quantification of cells involved in inflammation and remyelination. Fuhr-Calabresi –The goal of these projects are to develop and validate the utility of different methods (precise tools) to measure disease progression and perform clinical trials more efficiently. Network-Projects: Biomarkers – Biological/Imaging

Proof-of-concept trials and proof of concept trial designs, including, but not limited to trials in remyelination, neuroprotection, enhanced plasticity or other first-in-human, exploratory clinical trials for progressive MS –Expected impact: initiation of clinical trials of new interventions for progressive MS within the 4 year funding period. Collaborative Network Awards – Theme 3

Feinstein-Leocani –The goal of this proposal is to undertake rehabilitation studies in people with progressive MS and attempt to address some of the questions about what might represent the most effective approach to symptom management. Network Projects: Clinical Trials (Designs/Rehabilitation)

Industry stakeholders engagement RFA 2 – Collaborative Networks RFA 1 – Challenge & Infrastructure Sept 2013Sept 2014 Rehab Meeting Industry stakeholders meeting Sept 2016 Sept 2015 Alliance Scientific Meeting Science Strategy Meeting

Looking Ahead Convene additional scientific meetings and workshops in focus areas Continue to develop the Industry Forum Connect and coordinate global research efforts in progressive MS Identify new funding strategies to accelerate progress