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January 26, 2017 - Sumitomo Dainippon Pharma Completes Acquisition of Tolero Pharmaceuticals, Inc. Line December 21, 2016 - Sumitomo Dainippon Pharma to Acquire Tolero Pharmaceuticals, Inc. 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Line April 12, 2016 - Tolero Pharmaceuticals to Present Updates on Clinical and Preclinical Programs at the AACR Annual Meeting 2016 Line March 8, 2016 - Tolero Pharmaceuticals to Present at the 13th Annual BIO Asia International Conference Line January 4, 2016 - Tolero Pharmaceuticals to Present at the 34th Annual J.P. Morgan Healthcare Conference Line December 7, 2015 - Tolero Pharmaceuticals Presents Positive Preclinical Data on Hepcidin Inhibition for the Treatment of Anemia... Line December 7, 2015 - Tolero Pharmaceuticals Presents Preclinical Data Demonstrating Synergistic Activity with a Combination... Line December 7, 2015 - Tolero Pharmaceuticals Presents Data Demonstrating Inhibition of AXL Kinase in Cancer Cells Restores Drug... Line December 8, 2015 - Tolero Pharmaceuticals Announces Mechanistic Data Describing the Activity of Alvocidib within a Time-sequential Regimen... Line November 12, 2015 - Tolero Pharmaceuticals Presents Positive Clinical and Preclinical Data on Programs in Leukemia and Anemia... Line November 9, 2015 - Tolero Pharmaceuticals Executes Exclusive License with Eutropics for Novel Companion... Line November 9, 2015 - Tolero Pharmaceuticals Presents Results Providing Strong Rationale for Combining Alvocidib with... Line September 21, 2015 - Tolero Pharmaceuticals Announces Mechanistic Data Describing the Activity of Alvocidib... Line September 14, 2015 - Tolero Pharmaceuticals to Present Alvocidib Regimen Data at Upcoming Medical Conferences Line June 16, 2015 - Tolero Pharmaceuticals Presents Positive Preclinical Data that Inhibition of AXL Kinase Restores Tumor Response to Retinoic Acid Line June 16, 2015 - Tolero Pharmaceuticals Presents Positive Preclinical Data on Hepcidin Inhibition for the Treatment of Anemia... Line June 4, 2015 - Tolero Pharmaceuticals to Present Preclinical Pipeline Data at the 20th Congress of European Hematology Association, EHA Line June 2, 2015 - Tolero Pharmaceuticals and Eutropics Announce Results Demonstrating the Predictive Potential of a Biomarker... Line May 21, 2015 - Tolero Pharmaceuticals to Present Alvocidib Data at the 2015 American Society of Clinical Oncology Annual Meeting Line April 24, 2015 - Tolero Pharmaceuticals Presents Data Demonstrating Profound Synergy of Alvocidib and Bromodomain Protein Inhibitors... Line April 14, 2015 - Tolero Pharmaceuticals to Present Positive Advancement of Clinical and Preclinical Programs... Line February 27, 2015 - Tolero Pharmaceuticals Receives EMA Orphan Drug Designation for Alvocidib... Line January 9, 2015 - Tolero Pharmaceuticals, Inc., to Present at Biotech Showcase 2015 Line November 17, 2014 - Tolero Pharmaceuticals' Alvocidib Selected as 'Top 10 Most Interesting Oncology Project... Line November 13, 2014 - Tolero Pharmaceuticals Presents Positive Preclinical Data... Line November 5, 2014 - Tolero Pharmaceuticals Completes Second Tranche of Series B Financing... Line August 12, 2014 - Tolero Pharmaceuticals and Eutropics Announce Data Demonstrating Clinical Utility of Praedicare Dx... Line August 7, 2014 - Tolero Pharmaceuticals Closes $14.2 Million Series B Financing Line June 30, 2014 - Tolero's PIM Kinase Inhibitor Demonstrates Promising Activity in Preclinical Models... Line June 4, 2014 - Tolero Pharmaceuticals Presents Positive Interim Phase 2 Clinical Trial Results... Line May 15, 2014 - Tolero Pharmaceuticals Highlights Alvocidib Data to be... Line Apr 23, 2014 - Tolero Pharmaceuticals Receives FDA Orphan Drug Designation... Line Apr 7, 2014 - Tolero 2014 AACR Presentation Describes Relationship... Line May 1, 2013 - Tolero Pharmaceuticals announces Worldwide Agreement... Line Apr 10, 2013 - Tolero's Drug Development Pipeline Highlighted in... Line Jan 13, 2013 - Tolero Pharmaceuticals Spotlighted as an Emerging... Line Jan 7, 2013 - Clinical Cancer Research Article Demonstrates... Line Sep 14, 2012 - Tolero Pharmaceuticals Awarded Small Business... Line Jul 17, 2012 - Tolero Pharmaceuticals Acquires Drug Development Assets... Line Jul 13, 2012 - Tolero Pharmaceuticals Appoints Frank Zhan, MD, PhD... Line Apr 30, 2012 - Tolero and MannKind Sign Collaboration and License... Line Mar 30, 2012 - TP-0413 by Tolero Pharmaceuticals Named Finalist in... Line Jan 26, 2012 - Tolero Pharmaceuticals Appoints Gary P. Pisano, Ph.D... Line Jan 20, 2012 - Tolero Pharmaceuticals Appoints Professor Richard G. Hamermesh... Line Aug 5, 2011 - Tolero Pharmaceuticals Appoints Randall Peterson, Ph.D...

Tolero Pharmaceuticals Presents Nonclinical Data Demonstrating Alvocidib Provides Multiple Drug Combination Strategies Due to the Targeting of MCL-1


Poster presented at the AACR Annual Meeting 2016
SALT LAKE CITY, UT - April 20, 2016 - Tolero Pharmaceuticals, Inc., a clinical-stage pharmaceutical company developing treatments for oncology and hematologic diseases, today announced that its lead clinical candidate, alvocidib, demonstrated profound synergistic activity with agents rendered less active due to myeloid cell leukemia 1 (MCL-1) dependence. The data were presented in a poster entitled "Targeting MCL-1 expression, through the inhibition of CDK9 and super enhancer driven transcription, offers multiple opportunities for rational drug combinations," at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans, Louisiana.

Alvocidib, a potent cyclin-dependent kinase-9 (CDK9) inhibitor, has proven to be a clinically active agent, particularly in acute myeloid leukemia (AML). Tolero has previously demonstrated that the primary mechanism responsible for this activity is the CDK9-dependent downregulation of MCL-1. To further explore additional clinical development strategies for alvocidib, nonclinical combination studies with chemotherapy agents, hypomethylating agents, and compounds targeting other B-cell lymphoma 2 (BCL-2) family members were evaluated. The drug combinations led to synergistic activities when measuring both cell viability and apoptosis. The mechanism for the synergy relies on alvocidib’s ability to inhibit CDK9 and thereby downregulate MCL-1 expression which has emerged as a known marker of resistance to numerous therapies.

"MCL-1 dependence has become a serious resistance mechanism to both chemotherapy and targeted agents in many forms of cancer," said David J. Bearss, Ph.D., Chief Executive Officer at Tolero. "The increased activity of combining alvocidib with such agents confirms our understanding that alvocidib is a potent inhibitor of CDK9 which controls the expression of MCL-1. The results of our preclinical study supports the further research of alvocidib and other potential drug combinations."

Tolero has initiated a randomized Phase 2 biomarker-driven clinical trial comparing alvocidib, cytarabine, and mitoxantrone (ACM) to cytarabine and mitoxantrone (AM) in patients with relapsed or refractory AML.

About Alvocidib
Alvocidib is a potent small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) in development as a combination therapy for frontline and relapsed/refractory AML. CDK9 is a protein critical to the regulation of gene expression including the MCL-1 gene and other important genes involved in cancer. Given the key role CDK9 de-regulation plays in expression of cancer-associated genes related to cell division and proliferation, CDK9 is an attractive target for the treatment of various cancers.

About Tolero
Tolero Pharmaceuticals is a clinical stage biopharmaceutical company developing treatments to improve and extend the lives of patients with cancer and blood diseases. Our diverse pipeline targets important biological drivers of blood disorders to treat leukemias and anemia as well as important targets of drug resistance and transcriptional control.

Contact:
Joe Nilson
Tolero Pharmaceuticals, Inc.
801-285-6003
bizdev@toleropharma.com

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