Portage Pharmaceuticals Ltd.

A LEADER IN CELL PERMEABLE THERAPIES

©  Copyright  2015    Portage  Pharmaceu6cals  Ltd.  

Important Information We are providing this presentation to interested parties for informational purposes only. No representations or warranties, express or implied, are made as to, and no reliance should be placed on, the information presented or contained in these materials. Neither this presentation nor its delivery to any person constitutes part of any offer to sell or solicitation of any offer to buy any securities of Portage Pharmaceuticals Limited, nor shall it or any part of it form the basis of or be relied on in any connection with any contract or commitment. Any securities in Portage Pharmaceuticals Limited, when and if offered for sale, will be offered only in a private placement to persons who qualify as “accredited investors” as defined by Rule 501 of Regulation D under the Securities Act of 1933, as amended, and only on the basis of representations and warranties, if any, contained in the definitive documentation with respect to any such transaction. Any investors in such an offering will be required to make representations regarding such status and to acknowledge that none of the securities will be registered under the Securities Act and that any securities issued by the Company cannot be resold absent registration or the availability of an exemption therefrom. This presentation includes forward-looking statements. All statements other than statements of historical facts contained in these materials or elsewhere, including statements regarding our future financial position, business strategy and plans and objectives of management for future operations, are forward-looking statements. These statements are based on current expectations or objectives that are inherently uncertain, especially in the case of an enterprise with limited operating history. In light of these uncertainties, and the assumptions underlying the expectations and other forward-looking statements expressed, the forward-looking events and circumstances discussed in the accompanying materials may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. We do not intend to update any forward-looking statements, whether as a result of new information, future developments or otherwise.

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About Portage •  Portage develops cell penetrating peptide (CPP) therapeutics

that deliver a biologically active cargo into cells. •  Portage’s platform has demonstrated potential for the regulation

of gene function, creation of novel vaccines, and for delivery across the blood brain barrier.

•  Portage develops CPP therapies that: –  Efficiently and cost-effectively address unmet medical needs –  Can achieve early clinical proof of concept

•  Portage’s lead preclinical candidate, PPL-003, delivers a potent anti-inflammatory cargo for treatment of inflammatory eye diseases and other inflammatory conditions.

•  Portage has also begun preclinical projects in cancer and has plans to address Parkinson’s Disease progression

•  Portage’s management team has a proven track record in successful drug discovery and development with a focus on translational medicine.

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Leadership •  Bruce H. Littman, M.D. Chief Executive Officer: Former Pfizer VP Global

Translational Medicine with over 30 years pharmaceutical company & academic research experience. Pharmaceutical experience focused on experimental medicine and clinical proof of concept experiments on compounds from Pfizer’s research sites.

•  Frank W. Marcoux, Ph.D. Chief Scientific Officer: Former Pfizer VP Quantitative and Innovative Medicine WW Development & former VP WW Discovery Biology Discipline. Over 25 years pharmaceutical company & academic research. Pharmaceutical experience focused on preclinical proof of concept for new compounds.

•  Greg Bailey M.D. Chief Business Officer: Co-Founder & Director of a number of biotech companies. Former financier and director of Medivation.

•  Declan Doogan M.D., Chairman: Former Pfizer Senior VP and Head of Worldwide Drug Development. Former CMO and acting CEO of Amarin.

•  Augmented by a team of experienced consultants covering all aspects of drug discovery and development

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Scientific Advisory Board Sankar Ghosh Ph.D. •  Silverstein and Hutt Family Professor and Chairman,

Department of Microbiology & Immunology, Columbia University, College of Physicians & Surgeons

Michael J. Caplan M.D., Ph.D. •  C.N.H. Long Professor and Chair of the Department of Cellular

and Molecular Physiology and Professor of Cell Biology at the Yale University School of Medicine.

Burt Adelman M.D. •  Executive Vice President Research and Development and Chief

Medical Officer, Dyax, Inc. and Senior Advisor, Eleven Biotherapeutics. Former Executive Vice President Biogen Idec with twenty-two years biotech industry experience

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PPL technology can expand the target space for biological drugs

•  The ability to modulate an intracellular target with a peptide therapeutic greatly increases target space –  Currently approved small molecule drugs target <400 human

proteins •  Many of these are members of the same key families:

–  G protein-coupled receptors –  Nuclear hormone receptors –  Ion channels –  Kinases

–  Current biological monoclonal antibody/protein drugs target extracellular proteins

•  Protein target is secreted or membrane bound, not intracellular •  Approved biological drugs target about 110 human proteins

–  Probably thousands more potential disease targets for biological drugs are intracellular and abnormally regulate gene function

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PPL adds the intracellular compartment to the druggable target space for biological drugs

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Addi*onal  unknown  druggable  target  space  including  intracellular  targets  

~25,000  human  genes  

Es6mated  upper  limit  of  current  small  molecule  

and  biological  drug  targets  

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Cell Penetrating Peptide (CPP)

•  The CPP platform can deliver diverse biologically active cargo into cells, including:

•  Potential applications of the CPP Platform include: –  Modulation of gene expression and transcription factor function –  Replacement of defective or absent proteins –  Targeting intracellular pathogens –  Efficient delivery of antigenic epitopes for vaccine immune responses –  Delivery of biologically active cargo across the blood brain barrier

•  The CPP Platform has been explored through academic collaborations with Yale, NIH, and the Pirbright Institute (U.K.).

•  Peptides •  Small Molecules •  Proteins •  Transcription Factors •  Mini-Antibodies •  Enzymes

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Intellectual Property

•  The CPP Platform is protected by two suites of intellectual property: •  An exclusive license for all patents on Antennapedia

(ANTP)-based cell permeable peptides for non-oncology use.

•  Filed international patents for proprietary human-derived cell penetrating peptide structures

•  Demonstrated in vitro and in vivo activity activity •  No therapeutic area restrictions. •  Patent-protected until 2034.

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CPP Internalization

Field  1  Intracellular  Recombinant  Antp  Pep*de  

Bright  field   Intracellular  Label   An*-­‐Antp  Label   Merged  

CCL-­‐247  cells  +  synthe*c  Antp  

CCL-­‐247  cells  +  recombinant  Antp-­‐  Field  1  

CCL-­‐247  cells  +  recombinant  Antp-­‐  Field  2  

CCL-­‐247  cells  (no  Antp  control)  

Field  2  Intracellular  Recombinant  Antp  Pep*de  

Portage’s Proprietary Human-Derived CPP Platform

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•  In comparison studies using the same anti-inflammatory cargo Portage’s proprietary platform was superior to other sequences: – More potent in vitro activity – Greater in vivo pharmacological activity in

mice – Advantageous physical-chemical properties

for ease of formulation and delivery

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•  Combines Portage’s proprietary human CPP platform with the NBD peptide, a highly studied anti-inflammatory peptide.

•  Can be manufactured through an inexpensive recombinant process in E. coli.

•  Penetrates cell membranes in in vitro assays, and shows strong anti-inflammatory activity in cells

•  Active in systemic animal models of inflammation •  Active via inhaled route in a pulmonary inflammation model •  Penetrates eye tissues after topical administration and is

active inside the eye in uveitis models •  Planning PPL-003 human development for inflammatory

eye disease

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Lead Candidate PPL-003

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PPL-003 penetrates the BBB and is active in brain.

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•  Academic collaboration were blood brain barrier integrity studied in parallel with PPL-003 dosing in a brain inflammation model

•  Inflammatory cytokines elevated in brain tissues

•  PPL-003 crosses intact blood brain barrier and reduces inflammatory cytokines in the brain.

•  Suggests PPL’s proprietary CPP can deliver biological drugs for CNS disease indications

PPL Preclinical Programs

•  PPL-003 eye drops for inflammatory eye diseases –  Broad anti-inflammatory mechanism –  Efficacy similar to intravitreal and high dose topical steroids

but without steroid adverse events

•  PPL-006 and PPL-007 for cancer –  Transcription factor inhibitors of oncogene-mediated gene

activation –  Prostate, breast, glioblastoma, multiple myeloma, lymphoma,

colon, others

•  α-synuclein aggregation inhibitor for Parkinson’s –  Reduce progression of signs and symptoms –  Seeking partnerships to progress this program

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•  Uveitis is the third leading cause of preventable blindness in the United States and a key indication for PPL-003.

•  Current therapies for Uveitis are suboptimal. –  Topical steroids are only active in anterior chamber

and many patients have disease further back in the eye

–  Chronic use of topical steroids can cause glaucoma and cataracts.

–  Intravitreal steroids can treat deeper kinds of uveitis, but this heightens the risk of glaucoma and cataracts.

–  Systemic immunosuppression is sometimes effective, but it runs the risk of opportunistic infection or cancer.

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Uvei*s  

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Uveitis

Uveitis

•  Over three hundred thousand Americans contract uveitis each year and treatments are suboptimal. –  17.6% of patients with active uveitis experience transient or

permanent loss of vision, and uveitis associated blindness is increasing worldwide.

–  12.5% of patients develop glaucoma, and 32% of patients develop at least one complication during the course of a year.

•  The market for uveitis treatments is expected to increase from $340m in 2012 to $464m by 2017 with introduction of new biologics.

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PPL-003 Inflammatory Eye Disease Summary

•  PPL-003 shows great promise for treatment of Uveitis. –  Active in two acute uveitis models (rabbits and mice) –  Well tolerated at highest feasible dose for 7 days in rabbits –  Demonstrated at least a 10X safety margin in rabbits

•  Progressing into additional preclinical efficacy and safety studies prior to initiating pre-IND activities –  Chronic mycobacterial-induced uveitis (rabbits) –  Dose ranging safety (rabbits)

•  Opportunities in other inflammatory eye diseases –  Ongoing dry eye study in rats –  Blau syndrome uveitis

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•  PPL has a highly efficient platform for delivering cargo into cells targeting previously un-druggable and unmet medical needs.

•  PPL-003 validated our whole CPP platform delivering a biologically active cargo into the eye, the brain, the lung and systemically.

•  Initial program is for Uveitis, a leading cause of preventable blindness, and possibly other inflammatory ocular diseases like dry eye and Blau syndrome.

•  PPL’s proprietary intracellular delivery platform for candidates can address previously un-druggable targets in cancer and other diseases.

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Conclusions

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