rosomidnar liposomal (PNT2258) / GSK - LARVOL DELTA

Safety and Efficacy of a DNA Oligonucleotide Therapy in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma. (PubMed, Clin Lymphoma Myeloma Leuk) - "PNT2258 was well-tolerated in a chemotherapy refractory DLBCL population. Despite demonstration of single-agent activity, ORR was lower than acceptable for further new therapy development."

Clinical • Journal • Diffuse Large B Cell Lymphoma • Fatigue • Hematological Disorders • Hematological Malignancies • Lymphoma • Oncology • BCL2

A Phase 2 Study of PNT2258 for Treatment of Relapsed or Refractory B-Cell Malignancies. (PubMed, Clin Lymphoma Myeloma Leuk) - P2 | "Clinically meaningful and durable activity with an acceptable safety profile was observed in participants with relapsed/refractory B-cell malignancies who received single-agent PNT2258."

Journal • P2 data • Back Pain • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Fatigue • Follicular Lymphoma • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Mantle Cell Lymphoma • Musculoskeletal Pain • Non-Hodgkin’s Lymphoma • Oncology • Pain • BCL2

Unintended target effect of anti-BCL-2 DNAi. (PubMed, Cancer Manag Res) - "DNAi may work not only through knocking down the intended gene but also by knocking down other genes. PNT2258 affects CDK4 expression and promoter activity. Results of the present study suggest a broader mechanism of action for DNAi targeting both intended (BCL-2) and unintended (CDK4) genes."

Journal • Biosimilar • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Brighton-Brighton: PNT2258 for Treatment of Patients With Richter's Transformation (clinicaltrials.gov) - P2; N=49; Not yet recruiting; Sponsor: ProNAi Therapeutics, Inc; Trial primary completion date: Jul 2017 ➔ Oct 2017

Trial primary completion date • Biosimilar • Leukemia

ProNai: Jefferies Global Healthcare Conference 2016 (ProNAi) - "Interim Safety"; "Overall, the safety profile of PNT2258 appears acceptable in subjects with PS-01 and ≤3 prior lines of therapy: 33 subjects have discontinued PNT2258 therapy, 65% of subjects experienced one or more Grade 3 or 4 AEs, Most common AEs were fatigue, nausea, pyrexia, anemia, diarrhea, hypotension, and thrombocytopenis, We determined that the most advanced subjects, with PS 2 and/or having received 4 lines of therapy, did not respond to therapy, and experienced higher rates of serious adverse events and Grade 5 events"; "Interim Efficacy"; "PNT2258 showed modest single-agent activity in r/r DLBCL patients"; "All three responses were observed in subjects with PS 0-1 and 3 prior lines of therapy"

P2 data • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ProNai: Corporate Presentation (ProNAi) - "PNT2258-01: Safety and Tolerability Trial"; "Well Tolerated: Majority AEs = Grade 1 or 2; No drug related SAE's, No evidence of systemic immune response (i.e. TLR)"; "Significant exposures achieved: PNT2258 exposures meet/exceed those required for maximum anti-tumor efficacy in xenografts, Long exposure times with IV systemic delivery (t½ = 10-24 h)"

P1 data • Oncology

ProNai: Q1 2016 Results (ProNAi) - Anticipated interim data from P2 Wolverine trial (NCT02226965) in third-line diffuse large B-cell lymphoma in June 2016

Anticipated P2 data • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ProNAi: ASCO 2016 (ProNAi) - "PNT2258 as a single-agent resulted in clinically significant, durable responses in recurrent or treatment refractory NHL, including in four subjects with DLBCL: Overall response rate of 46.2% in the entire study population of 13 subjects, Noteworthy responses (CR, PR) and durable SD was also observed in follicular lymphoma subjects"; "Six subjects were progression free at 12 months; PFS extended to 2 years and beyond in four subjects: Five of the six subjects who were progression free at 12 months with PNT2258 were relapsed (not refractory) at study entry and had responded with their last prior therapy with a median time to treatment failure (TTF) of 48 months (4 yrs), range 23.7-87.6 months, All four responding DLBCL subjects had received 1 or 2 prior therapies"; "PNT2258 was safe and well tolerated in these NHL subjects and was administered for extended periods without evidence of cumulative toxicity for 2 years and longer"

P2 data • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Pronai Therapeutics reports positive results from PNT2258 Phase II study on lymphoma (News-Medical) - P2, N=15; NCT01733238; Sponsor: Pronai Therapeutics; "82% of patients had tumor shrinkage when receiving single-agent therapy with PNT2258. To date, overall response rate in patients with follicular lymphoma (FL) is 40% and in patients with diffuse large B-cell lymphoma (DLBCL) is 50%....[The company] look forward to expanding the current trial and initiating new studies in NHL patients in 2014."

Anticipated new trial • P2 data • Non-Hodgkin’s Lymphoma • Oncology

ProNAi: J.P.Morgan Healthcare Conference (ProNAi) - "PNT2258-02: Demonstrably Active and Durable in NHL"

P2 data • Non-Hodgkin’s Lymphoma • Oncology

ProNAi: Clinical Trial Update (ProNAi) - “PNT2258 single-agent treatment results in significant, durable responses in recurrent or treatment refractory NHL (r/r NHL), including durable responses in all subjects with DLBCL”; “PNT 2258 is safe and well tolerated when administered to subjects with r/r NHL for dosing periods up to 18 months and longer”

P2 data • Non-Hodgkin’s Lymphoma • Oncology

ProNAi: J.P.Morgan Healthcare Conference (ProNAi) - Anticipated interim data from P2 BRIGHTON trial (NCT02378038) in Richter's transformation in 2016; Anticipated initiation of P2 CYPRESS trial in R/R 2nd-line DLBCL transplant eligible + R-ICE in 2016; Anticipated initiation of P2 GRANITE trial in R/R 2nd-line DLBCL transplant ineligible + BR in 2016; Anticipated initiation of single-agent P2 trial in hematological indications in 2016; Anticipated initiation of P2 combination trial in other DLBCL + target agent in 2016

Anticipated new P2 trial • Anticipated P2 data • Non-Hodgkin’s Lymphoma • Oncology

PNT2258 for Treatment of Patients With Richter's Transformation (Brighton) (clinicaltrials.gov) - P2; N=5; Terminated; Sponsor: ProNAi Therapeutics, Inc; N=49 ➔ 5; Active, not recruiting ➔ Terminated; Trial primary completion date: Apr 2018 ➔ Jun 2016

Enrollment change • Trial primary completion date • Trial termination • Biosimilar • Chronic Lymphocytic Leukemia • Leukemia

PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine) (clinicaltrials.gov) - P2; N=45; Completed; Sponsor: Sierra Oncology, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor