A Phase 2 company treating
Forward Looking Statements
This Presentation (and any financial information that may be provided by Innate Immunotherapeutics Limited - the “Company”) may contain forward looking statements that involve risks and uncertainties. Such statements include statements regarding the Company’s belief or current expectation and are necessarily based on the Company’s current understanding of the markets and industries in which it operates. That understanding could change or could prove to be inconsistent with actual developments. The Company’s actual results could differ materially from the results discussed in this Presentation, including those anticipated in or implied by any forward looking statements.
2
ASX:IIL - Investment thesis
•
IIL’s lead drug candidate MIS416 will complete a Phase 2B placebo
controlled trial for SPMS in April 2017.
•
There is strong evidence of safety and likely efficacy from prior trials
and a unique 7 year ‘compassionate use’ programme.
•
There are no drugs approved for the safe ongoing treatment of SPMS.
•
This unmet medical need equate to a potent market of $4B or more.
•
Many large drug companies are following IIL very closely.
• The myelin sheath
protecting the nerve fibers inside the CNS is
damaged by a likely
combination of both neuro generative and
autoimmune processes • This triggers inflammatory
processes that cause further damage
• In early disease, myelin is fully or partially repaired • Over time, scar-like plaque
builds up around damaged axons inhibiting repair
(Source: MedicineNet, Inc)
What is multiple sclerosis?
Living with multiple sclerosis
• MS significantly impacts an individual’s quality of life and is associated with high costs for patients, their families, and society as a whole
• MS is associated with reduced life expectancy of between 5 and 15 years • MS is the second most costly chronic condition after congestive heart failure
• MS is a chronic, disabling disease typically
diagnosed between ages 20 and 40 and in three times more women than men
• MS symptoms include upper and lower extremity disabilities, visual disturbances, balance and
coordination problems, spasticity, altered sensation, swallowing disorders, fatigue, bladder and bowel problems, sexual dysfunction, and cognitive and emotional disturbances
Unmet medical need & significant market opportunity
Relapsing Remitting MS
Sufferers worldwide 60% Number of approved
disease modifying drugs 13 Estimated annual market
revenues (2015)* US$20.5B
Secondary Progressive MS
Sufferers worldwide 30% Number of approved
disease modifying drugs 0 Potential annual market
revenues US$4B
6
• MIS416 is a highly purified microparticle derived from the naturally occurring bacteria P. acnes
• MIS416 reliably, safely, and uniquely targets myeloid cells • MIS416 targeted myeloid cells:
– Increase in number
– switch activity from pathogenic to reparative
– traffic into the CNS (past the blood brain barrier)
MIS416 2.0 x 0.5 micron rod shaped microparticle
Introducing MIS416 – a MYELOID directed immune modulator
• The targeted cells have an anti-inflammatory effect inside the CNS and have also been shown to:
– support myelin repair by clearing myelin debris
– secrete important tropic factors that can directly promote neuronal survival and axon regeneration
NZ based compassionate use programme
• Under an ongoing New Zealand based ‘Compassionate Use” programme, 27 patient with SPMS have received an average of 72 doses [10-178] over a median treatment period of 17 months [4-89]*
• Long term ongoing treatment with MIS416 has shown no evidence of haematologic, hepatic, or renal toxicity in treated patients
• 70% of these patients have self-reported significant improvement in their MS related disabilities and/or health related quality of life
“MIS416 certainly appears beneficial to MS patients, although it remains to be seen if it is curative. However, I would certainly
recommend MIS416 as I have seen significant improvement in the motor skills and general wellbeing of my current MS patients.”
(Christchurch physician currently treating ten SPMS patients as part of the NZ compassionate use programme)
8
Phase 2B trial efficacy trial
• Double blinded, placebo controlled (2:1) 12 month trial of MIS416 i.v. at 500 mcg in 90 patients
• Baseline, quarterly, and end of dosing (EoD) clinical assessments including:
• Hand/arm function & strength, cognition, visual acuity, fatigue, MSFC and EDSS • Patient reported outcomes: SF-36, pain (BPI),
and fatigue (NFI-MS)
• Baseline, month 3 & EoD MRI (whole brain atrophy and magnetization transfer ratio)
Commercial Strategy
• There are no effective drugs approved to treat SPMS • Approval of a drug for SPMS could be reviewed under
FDA’s “Expedited Programs for Serious Conditions” • Pharma with existing drugs for early stage MS (RRMS)
are actively seeking drugs to treat SPMS
• Biogen’s RRMS drug Tecfidera sold US$3b in 2014 following approval part way through 2013
• Patents protecting use of MIS416 to treat multiple sclerosis issued in USA and Europe (expiry 2029) • Upon completion of Phase 2B (2016) – Innate’s
strategy is to license / sell to large Pharma company
Potential Target Partners
or Acquirers
Strong interest for potential partners
• We have engaged early & regularly with target acquirers to share Phase 1B/2A and compassionate use data and discuss Phase 2B efficacy trial plans and design.
• Multiple meetings with senior execs at 6 pharmas where IIL is highly complementary to their current MS programs.
• Multiple meetings with senior execs at 9 pharmas who view SPMS as an entrance into other neuro inflammatory diseases.
• 27 other pharmas engaged but with fewer resources or less expansion intent.
Recent MS related market transactions
What does a partnering deal look like in SPMS?
• December 2014: Servier paid US$47 million ‘option fee’ to fund Phase 2B trial of GeNeuro’s blocking antibody to supposed MS-associated retrovirus • Received option to the non-US territorial rights tied
to a $408 million package of milestones
N.B. The non-US territory accounts for about ~25% of global MS drug revenues
• Also option buy an equity stake
See announcement: <http://tinyurl.com/fb141202>
August 2015: • Celgene acquired Phase 3 MS company Receptos for US$7.2 billion cash
• Deal has ranked
Receptos #1 for the most value created by any biotech in the last 10 years.
September 2015 - Receptos co-founder and CSO, Dr Robert Peach joins Innate’s board
• Oral formulation of MIS416 for SPMS maintenance therapy
• Ovarian cancer therapeutic vaccine
Dr Kunle Odunsi, Professor of Gynaecology & Obstetrics,
Roswell Park Cancer Institute (New York). IND filing expected in 2016
• Refractory epilepsy
(Various collaborators, University of Queensland)
• Neuro protection and repair
(Various collaborators, St Vincent’s Hospital, Sydney & University of Queensland)
Use in Multiple Sclerosis (not limited to SPMS)
- NZ 577731 & AU 2010260585 (granted) – expiry June 2030
- US 12,636,733 (granted) – expiry 2029 (US =75% of market by revenue) - EU 2442832 (granted) – expiry 2032 (EU = ~20%% of market by revenue) - PCT NZ/2010/000112 (pending in other markets)
Intellectual Property (MIS416)
Use in Cancer (inc standalone, co-therapy, cancer vaccine adjuvant) - NZ 567096 & AU 2009232504 (granted) – expiry April 2029
- PCT/NZ2009/000049 (national phases in major markets) – priority April 2008 Use in Infection (inc prophylactic, therapeutic, vaccine adjuvant)
- NZ 567095 & AU 2009232503 (granted) – expiry April 2029
- PCT/NZ2009/000048 (US granted, pending in other major markets) – priority April ‘08 Use in Radiation Exposure (inc pre and post acute or therapeutic exposure)
- NZ 571665 (granted) - expiry Sept 2029
- PCT/NZ2009/000207 (EU Intention to grant; US & Japan pending)
Key Statistics as at 15 April 2016
ASX Code IIL
Share price ~A$0.20
Shares on issue 196,442,177
Market Cap A$40 million
Options outstanding 18.6 million (>95% price $0.30 or higher)
Significant Shareholders
C. Collins (R-NY 27th District) 17.3%
Australian Ethical 9.8%
Caitlin & Cameron Collins 5.2%
Probe International Inc 2.6%
Picton Cove Pty Ltd 2.1%
Register
Top 20 53.5%
Total shareholders 2,462
Board of Directors
Michael A Quinn, BSc BEc MBA,
Chairman CEO of Sydney based Innovation Capital. Currently or past director ofResMed (ASX, NYSE), QRxPhrama (ASX), & CAP-XX Limited (LSE).
Andrew Sneddon, BEcon, CA
Independent Director Former partner of PWC where he led the life sciences practice.Currently chairman of Elastagen Pty Ltd, MIRteq Pty Ltd, CustomWare Pty Ltd, InterAcct Solutions Pte and TGR BioSciences Pty Ltd.
Elizabeth Hopkins,
B.Sc. (Hons) Pharmacology,
Independent Director
20 years of experience in successfully commercializing science
outcomes. Ten years with Pfizer’s European headquarters, including the last two years as Global Project Manager. Currently deputy chair, Christchurch Polytechnic Institute of Technology (CPIT).
Christopher Collins, B.S, M.B.A.
Director 30 years of experience in business management. Collins has helpedacquire, manage and make profitable 17 companies representing various industries. Collins was elected to the US House of
Representatives in 2012. Collins holds 19% of IIL.
Robert Peach,PhD
Independent Director Co-founder and CSO Receptos (acquired by Celgene Aug '15US$7.2b). 30 years of multidisciplinary research expertise in biochemistry and cell biology within the disease areas of immunology, inflammation, and oncology.
Simon Wilkinson
Director & Chief Executive Officer CEO since 2004. 25 years experience in finance, banking and businessmanagement. He began his civilian career in retail banking after serving as an officer in the Royal New Zealand Navy.
Two former clinical trial patients talk about their
experience with MIS416: http://tinyurl.com/IILCUVideo
A new compassionate use patient (4-5 months):
https://www.youtube.com/watch?v=KYIHFTbG-w8
A former clinical trial patient talks about her MIS416 experience:
https://www.youtube.com/watch?v=Wtcnhe66fZU
Additional information
IL-10 TGFb IL-27 sTNFR sIL-1R
Tolerogenic DC Alternate/non classical/M2
macrophage Bone marrow-derived monocyte Arginase IDO Anti-inflammatory / tolerance mechanisms IL-12p70 IL-1b TNFa MHC I/II CD80/86 NO PDL-1 Cellular
Summary of MIS416-induced MYELOID cellular and soluble pathways that can counteract inflammation
• Relapsing remitting MS has both autoimmune and peripherally derived inflammatory components whereas progressive forms of MS reflect a clear shift towards innate inflammation being a significant cause of continuing neuro-degeneration
MYELOID cells are an important target in progressive MS
• Myeloid cells have been identified as a significant potential therapeutic target in SPMS as they have natural anti-inflammatory activities that are critical to innate immune homeostasis as well as stimulating wound healing/tissue repair pathways that are established following injury or infection
• Gandhi, Laroni, and Weiner
conclude in their 2010 paper that: “Until now, there are no specific therapies to target innate immune cells in MS. As the role of innate immune system in MS becomes better defined, it will be possible to design therapy to transform immuno-pathogenic innate immune cells to a more immuno-regulatory innate immune cells.”
Precedence in the literature:
MYELOID
cells from the periphery can
access the CNS and promote myelin repair
Innate immunity: the missing link in neuroprotection and neurodegeneration? Nguyen MD, Julien J-P, Rivest S. Nat Rev Neurosci. 2002;3(3):216-27
Trafficking CD11b-positive blood cells deliver therapeutic genes to the brain of
amyloid-depositing transgenic mice. Lori Lebson, Kevin Nash, Siddharth Kamath, Donna Herber, Nikisha Carty, Daniel C. Lee, at el
Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Shechter R, Miller O, Yovel G, Rosenzweig N, London A, Ruckh J, et al.. Immunity. 2013;38(3):555-69.
Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. Shechter R, London A, Varol C, Raposo C, Cusimano M, Yovel G, et al.. PLoS Med. 2009;6(7):e1000113. Clinical and Developmental Immunology. 2013;2013
The Benefits and Detriments of Macrophages/Microglia in Models of Multiple Sclerosis.
22 1 2 3 4 5 6 7 8 9 10 0 100 200 300
sample number (arbitary)
V E G F (p g /m L )
Vascular Endothelial Factor
Baseline (pre-treatment) 24 hr post dose 1 2 3 4 5 6 0 100 200 300 400 500
sample number (arbitary)
IG F -1 (p g /m L )
Insulin Growth Factor-1
Baseline (pre-treatment) 24 hr post dose 1 2 3 4 5 6 7 8 9 10 11 12 0 200 400 600
sample number (arbitary)
H G F (p g /m L )
Hepatocyte Growth Factor
(Baseline) pre-treatment 24 hr post dose 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 0 2000 4000 6000 8000 20000 40000
sample number (arbitary)
E P O (p g /m L ) Erythropoietin pre-treatment 24 hr post dose A selection of phase 1B and 2A patient plasma samples were analysed to screen for the induction of factors
associated with neuroprotection.
Data are shown from examples that showed a clear response for a given factor Samples are assigned
arbitrary sample numbers
Phase 1B/2A open label trials (completed Oct ‘11 & July ‘12)
• Phase 1B ‘dose escalation’ study (n=19) showed weekly dosing from 125 µg to 600 µg for 4 weeks was safe & well tolerated
• Phase 2A ‘dose confirmation’ study (n=15 enrolled; n=11 completed) showed weekly dosing at 500 µg for 12 weeks was safe & well tolerated
– Most common side effects – transient self limiting headache, fever, chills, muscle pain and weakness
Both studies were conducted with financial support from the US National MS Society (US$550k) and the NZ Government (NZ$600k)
– 7 of the 11 subjects responded based on the PerfROs. (The probability of
observing 7 responders out of 11 persons, even assuming a spontaneous response rate as high as 30% in the absence of intervention, is 0.022*)
– 8 of the 11 subjects responded based on the PROs. (The probability of observing 8 responders out of 11 persons, even assuming a spontaneous response rate as high as 30% in the absence of intervention, is 0.004*)
– All but one person showed a response on at least one PerfRO or PRO
Key Objectives
• To determine the efficacy of MIS416, relative to placebo, as assessed by various measures of neuromuscular function
• To explore the effect of MIS416 on disease activity and neurodegeneration by
measuring a wide range of blood markers, imaging markers and patient reported outcomes
• Study is exploratory by design in preparation for phase 3
• No adjustments have been made for multiplicity of outcomes, success will be judged on consistency of outcomes rather than statistical testing
Study Design Phase 2B (NCT02228213)
Design
Randomized, double-blind, placebo-controlled study of the efficacy and safety of MIS416 in the treatment of subjects with SPMS
Eligibility criteria includes EDSS 3.0 to 6.5, relapse free for 2yrs, clinical evidence of progression
Sites 5 x Australia and 2 x New Zealand
N 90 subjects with SPMS randomized 2:1 to MIS416 or saline placebo
Doses
Weekly i.v. infusion of MIS416 or saline over 13 cycles of 4 doses per cycle (52 weeks), titrated at 125ug of MIS416 for the first dose, 250ug for the
Phase 2B trial – expected completion March 2017
Status
• First patient in October 2014
• Clinical: Dr Jeffrey Cohen, Director, Experimental Therapeutics Program, Mellen Center for MS Treatment & Research, Cleveland Clinic
• Patient Reported Outcomes: Deborah Miller, PhD, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic
• Neuromuscular Assessments: Kristy Rose, PhD, Institute for Neuroscience and Muscle Research, The Children’s Hospital at Westmead
• MRI: Dr Doug Arnold, Neurology Professor, McGill University, Neurological Institute
• Statistics: Gary Cutter, PhD, Professor of Biostatistics and Head of the Section on Research Methods and Clinical Trials, UAB School of Public Health
Phase 2B trial advisors
PerfRO and PRO outcomes will be shared with the
Multiple Sclerosis Outcomes Assessment Consortium (MSOAC)
http://c-path.org/programs/msoac/
Neuromuscular Function: will be assessed on a three monthly basis and include:
• MS Function Composite (MSFC), comprising the; timed 25 Foot Walk, 9 Hole Peg Test, and Paced Auditory Serial Addition Test
• Symbol Digit Modalities Test (SDMT)[potential replacement for PASAT in MSFC]
• Sloan Low-Contrast Letter Visual Acuity (SLCVA)[possible addition to MSFC]
• Jebsen Hand Function Test (JHFT)[standardized and objective evaluation of fine and gross motor hand function using simulated activities of daily living]
• Grip, tip and key pinch strength[as type of pathology weakness is mainly pyramidal tract dysfunction, hand grip might be an easy to perform and very reproducible muscle strength test]
• 6-Minute Walk Test (6MWT)
Disability and Health Status: will be assessed on a three monthly basis and include:
• Expanded Disability Status Scale
• Patient Reported Outcomes including: o SF-36 and its components
o MS Impact Scale (MSIS-29)
o Neurological Fatigue Index for MS (NFI-MS) o Brief Pain Inventory (BPI)
