Delving into the Latest Updates on PNT-2258 with Synapse

Overview

Basic Info

Drug Type

siRNA

Synonyms

Rosomidnar

Target

Bcl-2

Mechanism

Bcl-2 inhibitors(Apoptosis regulator Bcl-2 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [2]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmDiffuse large B-cell lymphoma recurrentMelanoma+ [3]

Originator Organization

Sierra Oncology, Inc.

Active Organization-

Inactive Organization

Sierra Oncology, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (US)

Login to view timeline

Structure/Sequence

Boost your research with our RNA technology data.

login

or

view full example data

Boost your research with our RNA technology data.

Sequence Code 226235525

Source: *****

This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It is a multi-center, nonrandomized, open label, phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma.

Start Date01 Dec 2014

Sponsor / Collaborator

Sierra Oncology, Inc.

NCT01733238

/ CompletedPhase 2

PNT2258-02: A Pilot Phase II Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It study is a multi-center, nonrandomized, open-label, pilot Phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory lymphoma.

Start Date01 Nov 2012

Sponsor / Collaborator

Sierra Oncology, Inc.

100 Clinical Results associated with PNT-2258

Login to view more data

100 Translational Medicine associated with PNT-2258

Login to view more data

100 Patents (Medical) associated with PNT-2258

Login to view more data

7

Literatures (Medical) associated with PNT-2258

01 Jan 2022·Clinical Lymphoma Myeloma and LeukemiaQ4 · MEDICINE

Safety and Efficacy of a DNA Oligonucleotide Therapy in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Q4 · MEDICINE

Article

Author: Harb, Wael ; Westin, Jason ; Maris, Michael B ; Lakhani, Nehal ; Jacobson, Caron A ; Patel-Donnelly, Dipti ; Escobar, Carolina ; McCaul, Kelly ; Al-Katib, Ayad M ; Klencke, Barbara ; Patel, Prapti

BACKGROUNDPNT2258 is a liposomal formulation that encapsulates multiple copies of PNT100, a native, chemically unmodified, 24-base DNA oligonucleotide designed to target the regulatory region upstream of the B-cell lymphoma 2 (BCL2) gene.METHODSThis phase II, multicenter, single-arm, open-label, 2-stage design study investigated the single-agent activity of PNT2258 in patients with relapsed/refractory DLBCL. Initially, patients had to have a performance status (PS) of ≤2 and prior exposure to CD20-targeted therapy, an alkylating agent, and a steroid with no upper limit. Criteria were modified to PS of 0 or 1 and at least 1 to ≤3 prior therapies (identified as the target population) after observing an initially high frequency of rapid disease progression in patients with extensive prior therapies or poor PS.RESULTSThe study was stopped early following an interim analysis, despite surpassing the protocol predetermined futility boundary, because the ORR was below the expectations of response in an evolving DLBCL treatment landscape. The final analysis included all 45 enrolled patients and demonstrated an ORR of 11%. In the response evaluable subset (n = 26), defined as patients in the target population with exposure to ≥8 doses of PNT2258 within the first 35 days and evaluable baseline/post-baseline scans, the ORR was 19%. The most common adverse events were fatigue (44%), nausea (42%), diarrhea (40%), pyrexia (36%), anemia (32%), and vomiting (27%).CONCLUSIONSPNT2258 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.

01 Dec 2021·Clinical Lymphoma Myeloma and LeukemiaQ4 · MEDICINE

A Phase 2 Study of PNT2258 for Treatment of Relapsed or Refractory B-Cell Malignancies

Q4 · MEDICINE

Article

Author: Harb, Wael ; Messmann, Richard ; Lakhani, Nehal J ; Klencke, Barbara ; Al-Katib, Ayad M

BACKGROUNDPNT2258 consists of a native, chemically unmodified, 24-base DNA oligonucleotide designed to target the regulatory region upstream of the BCL2 gene, delivered in a protective liposome. Derangement of BCL2-regulated control mechanisms is a defining characteristic of certain malignancies, and it was hypothesized that the oligonucleotide would promote anticancer activity via suppression of BCL2 transcription.METHODSPNT2258 was evaluated in this, multicenter, nonrandomized, open-label Phase 2 study in 13 participants with relapsed/refractory B-cell malignancies to investigate potential antitumor activity and safety. Participants with follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, or chronic lymphocytic leukemia received intravenous PNT2258 120 mg/m² on Days 1 to 5 of a 21-day cycle for up to 8 cycles, followed by 100 mg/m² on Days 1 to 2 of a 28-day cycle until study withdrawal.RESULTSAll 13 participants were treated with PNT2258 monotherapy and evaluable for response and safety and tolerability. The overall response rate was 53.8% (7/13; 95% confidence interval [CI], 25.1%-80.8%). Median duration of response was 23.4 months (range, 3, 31.5). The disease control rate of participants with stable disease or better was 84.6% (95% CI, 54.6%-98.1%). The most frequently (≥50%) observed adverse events (AEs) were nausea, chills, diarrhea, fatigue, headache, vomiting, and back pain. Hypertension (30.8%) and diarrhea (23.1%) were the most frequent grade ≥3 AEs. No deaths were observed.CONCLUSIONClinically meaningful and durable activity with an acceptable safety profile was observed in participants with relapsed/refractory B-cell malignancies who received single-agent PNT2258.TRIAL REGISTRATIONNCT01733238, first posted 26-Nov-2012. https://clinicaltrials.gov/ct2/show/NCT01733238.

01 Sep 2016·Journal of Cancer Research and Clinical Oncology

Hematologic malignancies: newer strategies to counter the BCL-2 protein

Review

Author: Sabbagh, Hussam ; Kandouz, Mustapha ; Liddane, Allison ; Ebrahim, Abdul Shukkur ; Al-Katib, Ayad ; Raufi, Ali

INTRODUCTIONBCL-2 is the founding member of the BCL-2 family of apoptosis regulatory proteins that either induce (pro-apoptotic) or inhibit (anti-apoptotic) apoptosis. The anti-apoptotic BCL-2 is classified as an oncogene, as damage to the BCL-2 gene has been shown to cause a number of cancers, including lymphoma. Ongoing research has demonstrated that disruption of BCL-2 leads to cell death. BCL-2 is also known to be involved in the development of resistance to chemotherapeutic agents, further underscoring the importance of targeting the BCL-2 gene in cancer therapeutics. Thus, numerous approaches have been developed to block or modulate the production of BCL-2 at the RNA level using antisense oligonucleotides or at the protein level with BCL-2 inhibitors, such as the novel ABT737.METHODSIn this article, we briefly review previous strategies to target the BCL-2 gene and focus on a new approach to silence DNA, DNA interference (DNAi).RESULTS AND CONCLUSIONDNA interference is aimed at blocking BCL-2 gene transcription. Evaluations of this technology in preclinical and early clinical studies are very encouraging and strongly support further development of DNAi as cancer therapeutics. A pilot phase II clinical trial in patients with relapsed or refractory non-Hodgkin lymphoma, PNT2258 demonstrated clinical benefit in 11 of 13 patients with notable responses in diffuse large B cell lymphoma and follicular lymphoma. By targeting the DNA directly, the DNAi technology promises to be more effective compared with other gene-interference strategies that target the RNA or protein but leaves the dysregulated DNA functional.

1

News (Medical) associated with PNT-2258

22 Dec 2015

·www.biospace.com

ProNAi Therapeutics, Inc. To Present At J.P. Morgan 34th Annual Healthcare Conference In San Francisco

VANCOUVER, Dec. 22, 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 that Dr. Nick Glover, President and Chief Executive Officer, will present an overview of the company at the JP Morgan 2016 Healthcare Conference in San Francisco. The presentation is scheduled for 8:30 am (PT) on Thursday, January 14. A live audio webcast and archive of the presentation will be accessible through the ProNAi website at .About ProNAi Therapeutics ProNAi Therapeutics is a clinical-stage oncology company advancing novel therapeutics for patients with cancer and hematological diseases. ProNAi's lead product candidate, PNT2258, is based on the company's pioneering and proprietary DNAi technology platform. PNT2258 is designed to target 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 .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 and potential business development strategies. 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. SOURCE ProNAi Therapeutics Inc.

100 Deals associated with PNT-2258

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Diffuse large B-cell lymphoma recurrent	Phase 2	US	Sierra Oncology, Inc.	01 Dec 2014
Non-Hodgkin's lymphoma refractory	Phase 2	US	Sierra Oncology, Inc.	01 Nov 2012
Advanced Malignant Solid Neoplasm	Phase 2	US	Sierra Oncology, Inc.	01 Aug 2010
Richter's syndrome	Discovery	US	Sierra Oncology, Inc.	01 Aug 2015
Diffuse large B-cell lymphoma recurrent	Discovery	PR	Sierra Oncology, Inc.	01 Dec 2014
Melanoma	Discovery	US	Sierra Oncology, Inc.	01 Aug 2010
Prostatic Cancer	Discovery	US	Sierra Oncology, Inc.	01 Aug 2010

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01733238 (PNT2258-02, Pubmed \| Clin Lymphoma Myeloma Leuk) Manual	Phase 2	Chronic Lymphocytic Leukemia	13	PNT2258	(bwzpylceno) = mnwbeqipyo hfqloaoplf (ctrgyxsapp, 25.1 - 80.8) View more	Positive	01 Dec 2021
NCT02226965 (Pubmed \| Clin Lymphoma Myeloma Leuk) Manual	Phase 2	Diffuse Large B-Cell Lymphoma	45	PNT2258	(qgaeledflu) = jpomqdmqhr ctofqzhbmd (wagwewdpkm )	Negative	25 Jul 2021
NCT02226965 (Pubmed \| Clin Lymphoma Myeloma Leuk) Manual	Phase 2	Diffuse Large B-Cell Lymphoma	45	PNT2258 (exposure to ≥8 doses of PNT2258 within the first 35 days and evaluable baseline/post-baseline scans)	(qgaeledflu) = ighqcuxwpy ctofqzhbmd (wagwewdpkm )	Negative	25 Jul 2021
NCT02226965 (CTgov)	Phase 2	Diffuse large B-cell lymphoma recurrent	45	PNT2258	(kdajdphvvb) = azpzxvyizl asesaanibr (qgfebqatuc, rernvqwsrp - clzgruohro) View more	-	22 Apr 2020
NCT02378038 (CTgov)	Phase 2	Richter's syndrome	5	PNT2258	(euemtslufm) = jnzwqmuaud ikiudklmej (btawjeylev, qsagkchheo - nwnglgwvnv) View more	-	10 Mar 2020
NCT01733238 (PNT2258-02, CTgov)	Phase 2	Non-Hodgkin's lymphoma refractory	13	PNT2258	(weopzqxaaa) = uzeofxrzzy atxsxvwejw (aiduxdgyto, icickoflyp - olcmhhhgxh) View more	-	10 Mar 2020
NCT01191775 (Pubmed \| Cancer Chemother Pharmacol) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	22	PNT-2258	(emkteterfu) = fatigue xypqqzajhu (qepmkczzid ) View more	Positive	01 Feb 2014