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April 5, 2017 - Tolero Pharmaceuticals Presents Preclinical Data on CDK9 Inhibitor Alvocidib and its Prodrug, TP-1287, at AACR 2017 Line 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 Preclinical Data on CDK9 Inhibitor Alvocidib and its Prodrug, TP-1287, at AACR 2017


Preclinical Data supports the potential role of CDK9-mediated targeting of MCL-1 in treatment of therapy-resistant cancers

SALT LAKE CITY, UT --Tolero Pharmaceuticals, Inc., a clinical-stage company developing treatments for serious hematological diseases, presented preclinical data on alvocidib, an investigational inhibitor of cyclin-dependent kinase 9 (CDK9), in Phase II development for relapsed/refractory acute myeloid leukemia (AML) and its prodrug, TP-1287. The findings were presented during the American Association for Cancer Research (AACR) Annual Meeting, April 1-5, in Washington, D.C.

Preclinical data presented in the poster titled "TP-1287, an oral prodrug of the cyclin-dependent kinase-9 inhibitor alvocidib" demonstrated the potential activity of an oral, bioavailable version of alvocidib, TP-1287, compared to intravenous alvocidib. In this study, TP-1287 demonstrated anti-tumor activity in the MV4-11 AML mouse xenograft model and as much as 61.7% inhibition of the pharmacodynamic biomarker MCL-1 in a xenograft model.

Preclinical findings presented in the poster titled "Alvocidib potentiates the activity of venetoclax in preclinical models of multiple myeloma" suggested that the MCL-1-lowering agent and CDK9 inhibitor, alvocidib, may address intrinsic venetoclax resistance in multiple myeloma (MM) patients. Venetoclax is a small molecule BCL-2 inhibitor being developed by AbbVie and Genentech, a member of the Roche Group, for hematological cancers. Inhibition of expression of the anti-apoptotic protein MCL-1 was demonstrated in MM cell lines for up to 96 hours. Activity of venetoclax was potentiated with the addition of alvocidib and resulted in a > 500-fold decrease of the half maximal inhibitory concentration (IC50) in venetoclax-resistant OPM-2 cells.

"We believe that these findings further validate the potential of alvocidib," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals. "Identifying alvocidib's ability to downregulate MCL-1, which plays a central role in cell survival, was key to understanding its potential activity in AML. In addition, these data have opened alternative avenues for expanding research of alvocidib in treating other cancers, including addressing chemotherapeutic resistance in multiple myeloma."

Steven Weitman, M.D., Chief Medical Officer of Tolero Pharmaceuticals added: "The data presented provide supportive evidence for alvocidib's potential in the treatment of hematological cancers. Today there remains an unmet need for altering the progressive course of therapy-resistant cancers. We look forward to the clinical development of alvocidib and hope that we can bring a treatment to improve survival and quality of life for people suffering from therapy-resistant malignancies."

About Alvocidib
Alvocidib is an investigational agent which is a small molecule inhibitor of cyclin-dependent kinase 9 (CDK9). It is currently in development as part of 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 potential 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 TP-0184
TP-0184 is a small molecule inhibitor of activin-like kinase 2 (ALK2), also known as a bone morphogenetic protein (BMP) receptor. ALK2 activation leads to high levels of hepcidin, a peptide liver hormone that functions as a master regulator of serum iron levels, particularly in response to inflammation. Anemia of chronic disease (ACD) is a condition where chronic infection, immune activation or cancer lead to high levels of hepcidin via Interleukin-6 production, which reduces iron levels in the blood to low levels. Inhibiting ALK2 with TP-0184 is a potential approach to treating ACD by reducing hepcidin expression and restoring blood iron levels to normal.

About Tolero
Tolero Pharmaceuticals is a clinical-stage biopharmaceutical company researching and developing treatments to improve and extend the lives of patients with oncological and hematological diseases. Our diverse pipeline targets important biological drivers of blood disorders to treat leukemias, anemia, and solid tumors, as well as targets of drug resistance and transcriptional control. Tolero is based in the United States and is wholly owned by Sumitomo Dainippon Pharma Co., Ltd., a pharmaceutical company based in Japan.

Additional information about the company and its product pipeline can be found at www.toleropharma.com.

Disclaimer Regarding Forward-Looking Statements
The forward-looking statements in this press release are based on management's assumptions and beliefs in light of information presently available, and involve both known and unknown risks and uncertainties. Any forward-looking statements set forth in this press release are made only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

Media Contacts:
David Schull or Victoria Meissner, MD
Russo Partners, LLC
(212) 845-4271
(646) 942-5627
david.schull@russopartnersllc.com
victoria.meissner@russopartnersllc.com

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