ProNAi enrolls first patient in PNT2258 Phase II study for treatment of refractory or relapsed DLBCL

Jan 8 2015

- First Patient Dosed in the "Wolverine" Phase II Trial Evaluating ProNAi's BCL2 Targeting DNAi^® Therapeutic PNT2258 -

ProNAi Therapeutics Inc., a private hematology/oncology company dedicated to developing and commercializing a new class of therapeutics based on its proprietary DNAi^® platform, today reported that the first patient with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) has enrolled in the "Wolverine" Phase II study and been treated with PNT2258. The patient was treated by Dr. Wael Harb, Founder of the Horizon Oncology Center in Lafayette, Indiana.

"We recently reported that PNT2258 is demonstrably active and very well tolerated, achieving meaningful therapeutic outcomes and durable clinical responses in a pilot Phase II trial in patients with non-Hodgkin's lymphoma," said Dr. Nick Glover, President and CEO of ProNAi Therapeutics. "Following these promising data, we are initiating robustly designed studies of PNT2258 as a single agent in patients with high unmet medical needs. Specifically, the 'Wolverine' trial is focused on the treatment of refractory or relapsed DLBCL, a disease with limited therapeutic options in which PNT2258 appears to be particularly effective."

Study Design
The multi-center, single-agent, open-label, Phase II investigation of PNT2258 (ClinicalTrials.gov identifier: NCT02226965) will characterize anti-tumor activity and collect safety data on approximately 60 patients with relapsed or refractory DLBCL. The primary endpoint is overall response rate, assessed by FDG-Positron Emission Tomography (PET) scan and compared to relevant historical controls. Secondary outcome measures include disease control rate, progression-free survival, overall survival, and exploratory predictors of outcome assessed by tumor biopsy and pharmacodynamics sample analysis.

PNT2258 will be administered at 120 mg/m² as an intravenous (IV) treatment on days 1-5 of a 21-day cycle during the induction phase. Treatment may continue for a total of eight cycles of therapy, unless disease progression or the occurrence of unacceptable toxicity occurs. Patients who benefit from PNT2258 can continue treatment (100 mg/m² administered as a 2-hour IV on days 1-4 of a 28-day cycle) until disease progression.

The study was designed on the basis of interim results from an ongoing pilot Phase II trial of PNT2258, which were reported recently at the 56^th Annual Meeting of the American Society of Hematology (ASH). The investigators for that study concluded that:

• PNT2258 treatment results 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 ongoing Progression Free Survival (PFS) extending to 18 months and beyond.
• In particular, all four of the patients (4/4) with DLBCL responded to PNT2258, with three patients achieving complete responses (CR) and one patient achieving a partial response (PR), with durations extending to greater than 500 days.
• Durable and clinically meaningful CR's and PR's were achieved in subjects with aggressive disease, such as Richter's transformation and Burkitt's-like DLBCL.
• PNT2258 therapy is safe and very well tolerated with dosing periods up to and exceeding 18 months.