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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. Line November 15, 2016 - Tolero Pharmaceuticals to Present Progress of Leukemia and Anemia Programs at the 58th ASH Annual Meeting and Exposition Line October 11, 2016 - Tolero Pharmaceuticals to Present at the International Conference on Leukemia and Hematologic Oncology in Rome, Italy Line June 13, 2016 - Tolero Pharmaceuticals Presents Nonclinical Data Demonstrating Alvocidib Provides Drug Combination Strategies Due to the Targeting of MCL-1 Line June 6, 2016 - Tolero Pharmaceuticals to Present Updates on Clinical and Preclinical Programs at the 2016 EHA Congress Line June 6, 2016 - Tolero Pharmaceuticals to Present at the Jefferies 2016 Global Healthcare Conference Line April 20, 2016 - Tolero Pharmaceuticals Presents Nonclinical Data Demonstrating Alvocidib Provides Multiple Drug Combination Strategies Due to the Targeting of MCL-1 Line April 18, 2016 - Tolero Pharmaceuticals Presents Data Demonstrating AXL Inhibition Leads to a Reversal of a Mesenchymal Phenotype Sensitizing Cancer Cells... 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 Results Providing Strong Rationale for Combining Alvocidib with a Bromodomain Protein Inhibitor for the Treatment of Multiple Tumor Types


-- Data Presented at the 2015 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Meeting Demonstrate Convincing Justification for the Combination of Alvocidib with
Inhibitors of BET Proteins
--

SALT LAKE CITY, UT - November 9, 2015 - Tolero Pharmaceuticals, Inc., today announced the presentation of nonclinical data demonstrating synergy between the CDK9 inhibitor, alvocidib, and a number of bromo and extra terminal (BET) protein inhibitors in multiple tumor models at the 2015 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Meeting in Boston, MA. Alvocidib is currently in clinical development for the treatment of frontline and relapsed/refractory acute myeloid leukemia (AML). In the results presented, the combination of CDK9 and BET protein inhibitors led to a synergistic inhibition of the super enhancer complex (SEC) in both AML and lung cancer models. The SEC is a group of transcriptional regulators that can drive oncogenesis and disease progression in many disease states, and inhibitors of the SEC are the focus of many drug development efforts.

"The strong synergy between CDK9 inhibition by alvocidib and BET inhibition further validates that alvocidib’s mechanism involves shutting down super enhancer transcriptional programs that drives initiation and progression in AML and other malignancies," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero. "We are planning a clinical development strategy to evaluate this mechanistically rationalized combination to provide the greatest impact to patients in need."

The findings were detailed in the abstract and presentation entitled, "CDK9 inhibition synergizes with BRD4 inhibitor-mediated super enhancer transcriptional repression in multiple preclinical tumor models." The study utilized cell-based and animal models of AML and lung cancer to establish that alvocidib, when combined with several different BET protein inhibitors, has potent synergistic activity. The synergy between the agents was demonstrated by using doses of alvocidib and BET inhibitors that are ineffective as single agents, yet when combined, lead to complete tumor regressions in xenograft studies, down regulation of SEC transcriptional activity, and strong induction of apoptosis in AML and lung cancer cells. These findings expand on Tolero’s previous presentations that focused on this novel combination specifically in AML. The finding that similar results were replicated in solid tumor models, such as lung cancer, suggests that the combination may be exploited in a variety of tumor types.

Currently, Tolero is initiating a biomarker-driven randomized Phase 2 clinical trial with alvocidib in combination with chemotherapy versus chemotherapy alone in patients with relapsed or refractory AML whose disease is thought to be dependent on the protein MCL-1. CDK9 tightly controls the expression of MCL-1 and the ability of alvocidib to inhibit CDK9 may make these patients more likely to respond to alvocidib treatment.

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 serious oncological and hematological 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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