ProNAi Initiates 'Brighton' Phase II Trial of PNT2258 in Patients with Richter's Transformation

- First patient dosed in clinical trial evaluating DNAi interference (DNAi^®) -

VANCOUVER, Oct. 29, 2015 /PRNewswire/ - ProNAi Therapeutics, Inc. (NASDAQ: DNAI), a clinical-stage oncology company pioneering a novel class of therapeutics based on its proprietary DNAi technology platform, today announced it has enrolled the first patient into the "Brighton" study, a Phase 2 clinical trial evaluating PNT2258 in patients with Richter's transformation. The international multi-center trial is expected to enroll approximately 50 patients with this rare form of cancer for which there are currently no approved therapies.

"Richter's transformation is a highly aggressive form of cancer in which chronic lymphocytic leukemia (CLL) transforms into a fast-growing type of B-cell lymphoma. Given the limited options available to treat Richter's transformation, this is an important clinical trial with a unique investigational drug that may offer new hope to these patients," said Dr. Susan O'Brien, Principal Investigator of the Brighton study, Associate Director for Clinical Science for the Chao Family Comprehensive Cancer Center and Medical Director of the Sue and Ralph Stern Center for Cancer Clinical Trials and Research at UC Irvine Health.

"Brighton is the second Phase 2 trial we have recently initiated with PNT2258 as part of a comprehensive development strategy aimed at achieving efficient regulatory approval for our first DNAi-based oncology drug candidate," said Dr. Nick Glover, President and CEO of ProNAi Therapeutics. "We also plan to initiate additional Phase 2 trials in 2016 with PNT2258 in combination with other cancer therapies to further investigate and establish the potential breadth of this opportunity."

The study was designed on the basis of results from a pilot Phase 2 study of PNT2258, which were reported at the 2014 Annual Meeting of the American Society of Hematology (ASH). The investigators for that study concluded that PNT2258 treatment was well tolerated and resulted in significant, durable responses in patients with relapsed or refractory non-Hodgkin's lymphoma (r/r NHL), with eleven of the thirteen (11/13) patients treated achieving clinical benefit with durations of response extending to 18 months and beyond. In particular, the one patient with Richter's transformation enrolled in the pilot study achieved a notable response while on PNT2258 therapy. This patient had presented with intermediate-high risk disease at baseline and was refractory to two prior chemotherapy-containing regimens for Richter's transformation. After six cycles of treatment with single-agent PNT2258, the patient experienced a complete metabolic response and remained progression free for 10 months.

Brighton Phase II Study Design The multi-center, single-agent, open-label, Phase II study of PNT2258 (ClinicalTrials.gov identifier: NCT02378038) will characterize anti-tumor activity and collect safety data on approximately 50 patients with Richter's transformation. PNT2258 will be administered at 120 mg/m² as an intravenous (IV) treatment on days 1-5 of a 21-day cycle for eight induction cycles, followed by continuing treatment administered at 100 mg/m² administered on days 1-4 of a 28-day cycle. The primary endpoint is overall response rate and secondary outcome measures include disease control rate, duration of overall response, time to response, progression-free survival, overall survival and safety.

About Richter's Transformation Richter's transformation is a highly proliferative, rapidly progressing disease affecting mostly older adults with a median survival of approximately one year, and represents a significant unmet medical need with no currently approved therapies. Although CLL is typically classified as a low-grade lymphoproliferative disorder, 3% to 11% of CLL patients will experience transformation to Richter's during the course of their disease. While there are no specific therapies approved to treat Richter's transformation, multi-agent cytotoxic drugs in combination with rituximab is typically used as a first-line treatment with limited results.

About PNT2258 and DNAi ProNAi's lead DNAi product candidate, PNT2258, is a proprietary formulation of a single-stranded rationally designed 24-base DNAi oligonucleotide known as PNT100, encapsulated in a proprietary liposomal nanoparticle. After intravenous injection, PNT2258 achieves systemic distribution, delivering PNT100 into the nuclei of cancer cells where it is designed to target and interfere with the regulatory region of the BCL2 oncogene.

BCL2 is an important and validated oncogene known to be dysregulated in many types of cancer. This dysregulation, which is manifested in the excess production of BCL2 protein, is believed to provide certain cancer cells with the ability to resist naturally occurring programmed cell death, a process referred to as apoptosis, which is a primary mechanism for the removal of aged, damaged or unnecessary cells. By interfering with its transcription, PNT100 is designed to affect downstream BCL2 protein production, resulting in a restoration of apoptotic processes leading to the death of cancer cells.

About ProNAi Therapeutics ProNAi Therapeutics is a clinical-stage oncology company pioneering a novel class of therapeutics based on its proprietary DNAi technology platform for patients with cancer and hematological diseases. ProNAi's lead DNAi product candidate, PNT2258, is designed to treat cancers that overexpress BCL2, an important and validated oncogene known to be dysregulated in many types of cancer. ProNAi is pursuing a multi-faceted clinical development strategy designed to efficiently achieve regulatory approval and maximize the commercial opportunity of PNT2258. ProNAi is actively enrolling patients in "Wolverine", a Phase 2 trial evaluating PNT2258 for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and in "Brighton", a Phase 2 trial evaluating PNT2258 for the treatment of Richter's transformation. For more information, please visit www.pronai.com.

Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding ProNAi's anticipated clinical development activities, including the design, timing and outcome of such activities. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements. Such forward-looking statements are subject to risks and uncertainties, including, among others, the risk that ProNAi may be unable to successfully develop and commercialize PNT2258 or any other future product candidates, PNT2258 may fail to demonstrate safety and efficacy or may not otherwise produce positive results, ProNAi may experience delays in clinical trials, including due to difficulties enrolling patients, ProNAi's third-party manufacturers may cause its supply of materials to become limited or interrupted or fail to be of satisfactory quantity or quality, ProNAi's cash resources may be insufficient to fund its current operating plans and it may be unable to raise additional capital when needed, ProNAi may be unable to obtain and enforce intellectual property protection for its technologies and product candidates and the other factors described under the heading "Risk Factors" set forth in ProNAi's filings with the Securities and Exchange Commission from time to time, including the Company's reports filed with the Securities and Exchange Commission. ProNAi undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law.

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