Targeted Cancer Therapies Wedbush PacGrow Healthcare Conference, - - PowerPoint PPT Presentation

Targeted Cancer Therapies

Wedbush PacGrow Healthcare Conference, August 16th, 2016

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Except for statements of historical fact, any information contained in this presentation may be a forward-looking statement that reflects the Company’s current views about future events and are subject to risks, uncertainties, assumptions and changes in circumstances that may cause events or the Company’s actual activities or results to differ significantly from those expressed in any forward-looking statement. In some cases, you can identify forward-looking statements by terminology such as “may”, “will”, “should”, “plan”, “predict”, “expect,” “estimate,” “anticipate,” “intend,” “goal,” “strategy,” “believe,” and similar expressions and variations thereof. Forward-looking statements may include statements regarding the Company’s business strategy, potential growth opportunities, clinical development activities, the timing and results of preclinical research, clinical trials and potential regulatory approval and commercialization of product candidates. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, the Company cannot guarantee future events, results, actions, levels of activity, performance or achievements. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those described under the heading “Risk Factors” in documents the Company has filed with the SEC. These forward-looking statements speak only as of the date of this presentation and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Certain information contained in this presentation may be derived from information provided by industry sources. The Company believes such information is accurate and that the sources from which it has been obtained are reliable. However, the Company cannot guarantee the accuracy of, and has not independently verified, such information. Trademarks: The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. 2

ProNAi Therapeutics A drug development company focused on advancing targeted cancer therapies

NASDAQ: DNAI Headquarters: Vancouver, BC Development: San Francisco, CA IPO: July 2015 Shares (30/6/16): 30.2M outstanding 34.6M fully diluted Cash on hand (30/6/16): $130.6M

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• We are an ambitious oncology drug

development company oriented to registration and commercialization.

• We have a world-class management

team with a proven track record in

• ncology drug development.
• We intend to build a broad and

diverse pipeline of promising

• ncology assets against emerging

targets on the leading edge of cancer biology.

• We have a healthy cash balance, that

we expect will allow us to achieve meaningful development milestones.

Proven Leadership in Oncology Development

Nick Glover, PhD President and CEO Barbara Klencke, MD Chief Development Officer Angie You, PhD Chief Business & Strategy Officer and Head of Commercial Sukhi Jagpal, CA, CBV, MBA Chief Financial Officer

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Keith Anderson, PhD Senior Vice President, Technical Operations Wendy Chapman Senior Vice President, Clinical Operations Diane Gardiner Senior Vice President, Human Resources and Administration Christian Hassig, PhD Senior Vice President, Research Chandra Lovejoy Senior Vice President, Global Regulatory Affairs and Head of Quality Emma McCann Senior Vice President, Program Management Gregg Smith, PhD, MBA Senior Vice President, Preclinical

PNT2258 and DNAi

• Interim assessment of PNT2258 at ASCO: modest efficacy observed with mostly

limited duration of response.

• Clinical data were not trending to an outcome supportive of registration as

monotherapy in late line DLBCL.

• Wolverine and Brighton studies were closed to further enrollment of subjects.
• All development of PNT2258 was suspended.
• Halted all further investment in our DNAi research program.
• No further investment in PNT2258 or DNAi currently contemplated.
• Closed our research facility in Plymouth, Michigan, which supported these

programs.

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Building a Pipeline of Promising Oncology Assets

We intend to build a broad and diverse pipeline:

• PNT141 is our first asset.
• Two additional promising assets under exclusive option.
• Actively engaged in business development with multiple assets under

evaluation. Our strategic business development focus:

• Small molecules and next generation biologics with exemplary target selectivity.
• Foundation of strong, cancer-critical biology.
• Emerging targets; opportunity to be first-in-class or fast follower/best-in-class.
• Potential as monotherapy and in combinations, across a variety of cancer

indications.

• Possibility of proprietary combinations.

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PNT141: Targeting Cdc7

Targeting the DNA Damage Response Network

• Our DNA is continuously subject to

damage through a variety of endogenous and exogenous mechanisms.

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• DDR is a network of cellular

pathways that monitor and repair DNA damage.

• The DDR comprises cell-cycle

checkpoints, which temporarily inhibit replication to repair damaged DNA.

Radiation Cell Metabolism Viral Infection Oxygen Radicals Drugs Replication Stress

DNA Damage Response (DDR)

DNA Damage

DDR: An Achilles Heel of Cancer

• Malignant cells tolerate substantially

greater levels of DNA damage than healthy cells.

• Significant and persistent DNA

damage is evident in tumors carrying genetic mutations such as BRCA1/2, MYC and p53.

• Many standard chemotherapeutic

agents and radiotherapy also induce DNA damage in order to kill cancer cells.

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• Certain cancer cells survive and

replicate - despite accumulating DNA damage - via an over-reliance on the DDR network.

• Targeted inhibition of the DDR may be

selectively lethal to cancer cells and of potential benefit in the treatment of certain cancers.

• Synthetic lethality is possible by

inhibiting DDR in context of pre- existing genetic mutations.

• There also exists potential for synergy

between standard therapies and DDR targeting agents.

Burgeoning Scientific Validation for Targeting DDR

10 Focus Issue: DNA Damage Repair June 2016 June 2016

Industry Validation of DDR’s Potential in Cancer

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May 2016

PNT141: Selective Small Molecule Targeting Cdc7

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• PNT141: highly-selective and

potent Cdc7 inhibitor.

• Cdc7: key regulator of DNA

replication and DNA damage response.

• Broad development scope in

solid and liquid tumors.

• Mono- and combo- therapy

development potential.

• Clinical studies expected to begin

by the end of 2017.

Cdc7: Key Function in the Cell Cycle

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Potential to exploit tumor-specific genetic defects and/or combination therapies to effect cancer cell death via ‘synthetic lethality’.

Cdc7 Inhibition: Potential Therapeutic Window

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Preclinical data and published literature suggest a variety of indications with potential for response to Cdc7 inhibitors:

• Solid tumors: breast, ovarian, pancreatic, melanoma, colorectal, uterine, thyroid, etc.
• Hematological malignancies: AML, DLBCL, etc.

Cdc7: Broad Potential Applications in Oncology

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DNA Damage Response Chemotherapy

Combinations with DNA damaging chemotherapy

DDR Combinations

Rational combinations to maximize DNA damage

Radiotherapy

Synergy with ionizing radiation

Immuno-Oncology

DDR coupled to innate immune activation

DDR Monotherapy

Exploit replicative stress and genetic instability in ‘synthetically lethal’ monotherapy

PNT141: First-In-Class/ Best-In-Class Opportunity

• PNT141’s selectivity profile offers possible differentiation and potential safety

and efficacy advantages.

• A biomarker-driven patient selection strategy focusing on drivers of replication

stress, genomic instability and proliferation (e.g. p53, BRCA, MYC, KRAS, H2AX mutation/expression) will help facilitate clinical trial execution.

• ProNAi plans to pursue a robust program of preclinical studies to further

evaluate tumor responses across a variety of indications and dosing regimens to inform clinical development plans and patient selection strategies.

• Clinical studies expected to begin by the end of 2017.

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ProNAi: Advancing Targeted Cancer Therapies

• We are an ambitious oncology drug development company oriented towards

registration and commercialization.

• We have a world-class management team with a proven track record in
• ncology drug development.
• We intend to build a broad and diverse pipeline of promising oncology assets

against emerging targets on the leading edge of cancer biology.

• Our first new asset is PNT141, a highly-selective and potent Cdc7 inhibitor with

broad development scope and first-in-class / best-in-class potential. Cdc7 is a key regulator of both DNA replication and DNA damage response.

• We have a healthy cash balance, that we expect will allow us to achieve

meaningful development milestones.

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Targeted Cancer Therapies