Targeted Cancer Therapies Annual Meeting, June 16 th , 2016 Safe - - PowerPoint PPT Presentation

Targeted Cancer Therapies

Annual Meeting, June 16th, 2016

Safe Harbor Statement

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 advancing targeted cancer therapies

NASDAQ: DNAI Headquarters: Vancouver, BC Development: San Francisco, CA Research: Plymouth, MI IPO: July 2015 Shares: 30.2M outstanding 34.3M fully diluted

Cash on hand (31/3/16): $140.9M

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• 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

• 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; 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 of Clinical Operations Diane Gardiner Senior Vice President of Human Resources Chris Hassig, PhD Senior Vice President of Research Chandra Lovejoy Senior Vice President of Global Regulatory Affairs and Head of Quality Emma McCann Senior Vice President of Program Management Gregg Smith, PhD, MBA Senior Vice President of Preclinical

PNT2258 Program Update: Recap

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PNT2258-03 Wolverine r/r DLBCL 45/61 subjects PNT2258-04 Brighton Richter’s 5/50 subjects

2015 2016

IPO $158M Raised ProNAi Appoints

• Dr. Klencke

ProNAi Appoints

• Dr. Glover

ProNAi Appoints

• Dr. You

2014

Interim

• 02 Data

(ASH)

2010

PNT2258-02 r/r NHL 13 subjects

2013

Initiated

• Jan. 2013

Initiated

• Jan. 2015

Initiated

• Oct. 2015

2012

Initiated

• Sep. 2010

Updated

• 02 Data

(ASH) Continuation/Follow Up PNT2258-01 Solid Tumors 22 subjects Interim -03 Data

PNT2258: Development Program - Recap

Crossover $60M Raised

Wolverine & Brighton - Conclusions

• We designed and ran appropriate, well-executed studies, and optimized the

conduct of these clinical trials in real-time in order to focus on the most appropriate patient populations for potential treatment with PNT2258.

• We obtained sufficient totality of data to make informed decisions.
• Advanced DLBCL and Richter’s Transformation are challenging diseases to treat,

and PNT2258 did not markedly improve outcomes in these indications.

• Modest efficacy was observed in the interim assessment of Wolverine, with

mostly limited duration of response. No responses were observed in the interim assessment of Brighton.

• Clinical data in Wolverine were not trending to an outcome that supported the

likelihood of registration as monotherapy in late line DLBCL.

• In the Brighton study we also noted generally poor outcomes in this advanced

patient population, with limited signs of activity unlikely to support registration

• f PNT2258.

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Next Steps for PNT2258, DNAi and Our Pipeline

• On the basis of these interim assessments, we decided to close the Wolverine

and Brighton studies to further enrollment of new subjects.

• Considering these data in context of the broader development of PNT2258, we

decided to suspend all development of PNT2258. No further additional investment in PNT2258 is currently planned.

• Similarly, we halted all further investment in our DNAi research program given
• ur emerging view that this research was unlikely to yield additional ProNAi

development candidates.

• We recently announced our first transaction, for PNT141 - a CDC7 inhibitor.
• We plan to secure additional assets towards building a broad and diverse

pipeline of oncology assets under development.

• We continue to maintain a strong balance sheet that we will manage prudently

as we focus our resources and activities on the advancement of PNT141 and future assets.

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PNT141: Targeting Cdc7

PNT141: Selective Small Molecule Targeting Cdc7

PNT141 (formerly AS-141)

• A highly-selective and potent Cdc7 inhibitor, with favorable development

characteristics.

• Cdc7 is a key regulator of both DNA replication and DNA damage response, making it a

compelling emerging target for the potential treatment of a broad range of tumors.

• Broad development scope in solid and liquid tumors; mono- and combo- therapy.
• PNT141’s selectivity profile offers possible differentiation and potential safety and

efficacy advantages.

• First-in-class and/or best-in-class opportunity.

Attractive Asset and Deal Terms

• Licensor: Carna Biosciences, Japan: expertise in kinase screening and chemistry drug

discovery (first validating deal with J&J in 2015).

• Attractive cost of entry, and ongoing deal and development costs typical for a small-

molecule oncology drug. Intellectual Property

• PNT141 covered by composition of matter (2032 plus extensions) and combination

patents.

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PNT141: Clinical Development Opportunities and Patient Selection Strategy

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

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

• Potential to exploit tumor-specific genetic defects and/or combination therapies

to effect cancer cell death via ‘synthetic lethality’.

• 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.

• We anticipate filing an IND for PNT141 in H2 2017, with clinical studies expected

to begin by the end of 2017.

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ProNAi Therapeutics: Focused on Building a Pipeline of Promising Oncology Assets

• We intend to build a broad and diverse pipeline of promising oncology assets.
• PNT141 is our first transaction.
• We are actively engaged in ongoing business development activities, with two

additional promising assets under exclusive option to enable further validating studies under MTA.

• These assets are consistent with our strategic in-licensing focus, namely:
• Orally bioavailable small molecules and next generation biologicals with exemplary

target selectivity.

• Assets with a foundation of strong, cancer-critical biology.
• Assets against emerging targets, where there is an opportunity to be first-in-class or

fast follower/best-in-class.

• Assets with potential as monotherapy and in combinations, across a variety of cancer

indications.

• Assets that could possibly form proprietary combinations with each other.

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Targeted Cancer Therapies