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Company Overview Series A: 2013 $3.3M Series B: 2014 $22.4M

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Presentation on theme: "Company Overview Series A: 2013 $3.3M Series B: 2014 $22.4M"— Presentation transcript:

0 Tolero Pharmaceuticals, Inc.
MAKING MEANINGFUL MEDICINES BIO Utah: November 2014 Tolero Pharmaceuticals, Inc.

1 Company Overview Series A: 2013 $3.3M Series B: 2014 $22.4M
Founded: 2011 Series A: $3.3M Series B: $22.4M Headquarters: Lehi, UT / Salt Lake City, UT Employees: ~25 (70% R&D) Focus: Oncology: Hematology & Solid Tumors Business Model: Discover, Develop & Commercialize New Chemical Entities for the treatment of cancer and other serious human diseases. Good morning Tolero was founded with the mission to alleviate human suffering through discovering, developing, and commercializing of novel chemical entities to treat and cure cancer and other serious human diseases

2 Tolero Pipeline Lead product candidate, Alvocidib, advancing toward approval in front-line and Relapsed/Refractory AML Experience with 400 patients across five Phase II clinical trials Most recent trial in 165 patients revealed striking CR rates vs. SOC (p<0.003) Tolero has a rich pre-clinical pipeline and is advancing three additional product candidates into the clinic Addressing orphan diseases and large unmet needs Expect to file 2 IND’s in 2015 Program Indication(s) Next Milestone Clinical Alvocidib Front-line AML Relapse/Refractory AML End of Phase II meeting with FDA Initiate Phase III clinical trial Preclinical BMP Signaling Hepcidin-Driven Anemia, (Anemia of Chronic Inflammation, Cancer) IND enabling studies prior to Phase I clinical trial AXL Inhibitor Head and Neck, Lung Cancer, AML PIM Inhibitor Psoriasis, AML, Prostate Cancer, Multiple Sclerosis Most advanced product, Alvocidib 2000 patients, 400 in Acute Myeloid Leukemia Very strong CR rate and improvements in OS, MRD, DFP In addition, our pre-clinical pipeline is robust Most molecules were developed by our team All focused on orphan markets with high unmet needs Plan to file 2 additional IND’s in 2015 CONFIDENTIAL

3 Experienced Management Team
Name/Title Experience David Bearss, PhD CEO Founder, Chief Scientific Officer at Montigen Pharmaceuticals Chief Scientific Officer at Supergen (Nasdaq: SUPG) Co-director of the Center for Investigational Therapeutics at the Huntsman Cancer Institute Dallin Anderson, MBA Chairman & President Founder, Chairman, Chief Executive Officer and President at Montigen Pharmaceuticals Senior Vice President of Development at Supergen (Nasdaq: SUPG) MBA, Harvard Steve Weitman, MD, PhD Senior Advisor, Clinical & Regulatory Strategy Physician and Director of the Institute for Drug Development, UTHSC-San Antonio Chief Medical Officer and SVP at Ilex Oncology Led team for FDA approval of Clofarabine Michael McCullar, PhD, MBA COO Senior Vice President of Business Development, Astex Pharmaceuticals (Acquired by Otsuka Pharmaceuticals) Vice President of Strategy and Development, SuperGen, led approval of Dacogen in US, acquisitions of Montigen Pharmaceuticals and Astex Therapeutics, LLC Steve Warner, PhD VP, Discovery & Development Translational Genomics Research Institute Manager, Discovery Biology at Supergen (Nasdaq: SUPG) Senior Manager, Drug Discovery at the Huntsman Cancer Institute Michael Bernstein, MPH VP, Regulatory Affairs 11 years at the FDA as Project Manager, Administrative Assistant to the Division Director and Executive Secretary to the PCNS and PDAC Senior Director of Regulatory Affairs at Ilex Oncology Career to date includes over 20 INDs/CTXs and 9 NDAs/BLAs/MAAs submissions Joe Nilson Director, Business Development 20 years of product development, commercialization and licensing of healthcare and consumer products Vice President of Business Development at various subsidiaries of a privately held company Our management team has a proven record of success in Oncology Core team has been working together for 12 years. In 2003, I founded Montigen with Dr. David Bearss… CONFIDENTIAL

4 Alvocidib Overview Exclusive license from Sanofi in 2013
Potent pan-CDK inhibitor Significant activity across 400 AML patients Potential for a meaningful advance in the treatment of AML Sixteen months ago, we licensed Alvocidib from Sanofi Highly potent CDK inhibitor Best reported data in AML—414 patients treated to date Could be a meaningful therapeutic option for patients with AML—no new therapy in the last 40 years CONFIDENTIAL

5 Alvocidib Mechanism of Action
Kinase Inhibition of CDK Family Kinase Alvocidib IC50 (nM) CDK9 6 CDK4/6 9 CDK7 23 CDK11 57 CDK5 110 CDK8 120 CDK3 410 CDK2 550 Alvocidib’s primary mechanism of action is inhibition of CDK 9 Highly potent against CK 4/6 and other regulators of the cell cycle The reason CDK 9 inhibition is important is

6 BRD4 mediates the recruitment of P-TEFb (Cdk9/CyclinT)
7SK RNA Bound Inactive P-TEFb Brd4 Bound Active P-TEFb CyclinT/ Cdk9 CyclinT/ Cdk9 7SK Brd4 HEXIM1 CyclinT/ Cdk9 Alvocidib inhibits CyclinT/CDK9, or pTefB, which when overexpressed results in oncogenesis pTefB resides in an inactive complex, and can be pulled out of that complex by BRD4 BRD4 carries pTefB to the terminal domain of the RNA polymerase, where it phosphorylized to create a full-length messenger RNA. Functionally, Alvocidib drives pTefB back into the inactive complex 2P CTD 2P Brd4 2P RNA PII 2P

7 Alvocidib in Acute Leukemias
Alvocidib has demonstrated both clear single-agent activity and also striking efficacy in seqence with ara-c and mitoxantrone (FLAM regimen) Single Agent Activity Phase 1 single agent study at Ohio State University Three-days dosing of alvocidib resulted in an average of 87%, 76% and 82% reduction of circulating blast counts in untreated, relapse and refractory patients, respectively. Overall response rate of 83%. Combination Activity Phase II FLAM in front-line int/high-risk adult AML (N=45) showed a 67% CR Phase II FLAM in front-line int/high-risk adult AML (N=78) showed a 67% CR Most of the development work prior to our licensing Alvocidib was done in Solid tumors or CLL Tolero is Developing in Acute Leukemias—AML Shown good activity as a single agent monotherapy —19 patients…overall response rate of 83% Led to studies in Combination or sequence studies… 247 pts. treated with FLAM in front line intermediate/high-risk AML, 148 pts. treated with FLAM in relapsed/refractory AML, 19 pts. treated with monotherapy alvocidib in relapsed/refractory AML. 414 alvocidib-treated AML patients to-date

8 Alvocidib in Combination in AML
In intermediate and high risk patient populations, alvocidib in combination shows significant improvement over 7+3, the current AML standard of care. NCI-8972 Final Results: % Complete Remission FLAM  7+3 P Value Primary Endpoint: CR rate 70% 46% 0.003 CR by Risk Factors: No Adverse 25/25 (100%) 13/18 (72%) 0.009 Adverse Genetics Cytogenetics Complex Monosomal FLT3 ITD+ 30/58 (52%)  22/48 (46%) 14/30 (47%)  13/24 (54%) 9/13 (69%) 10/27 (37%)  6/21 (29%) 3/16 (19%)  3/12 (25%) 3/6 (50%) 0.16 0.2 0.11 0.62 Secondary AML 31/52 (60%) 9/26 (35%) 0.05 >1 High-risk feature  51/84 (61%) 13/38 (34%) 0.01 Randomized Phase II Study 2: Patients FLAM (109 patients) Alvocidib: 50 mg/m2 IV day 1-3 Ara-C 2 g/m2 IV over 72 hr, day 6-8 Mitoxantrone 40 mg/m2 IV day 9 The most recent study, completed in August… Striking CR rates 24% above Standard of Care across the board Including in secondary AML—a very difficult patient population with generally poor prognosis 7+3 (56 patients) Ara-C 100 mg/m2/day IV days 1-7 Daunorubicin 90 mg/m2 IV days 1-3 Randomized Phase II trial provides conclusive data to support further development

9 Alvocidib/FLAM in Relapse/Refractory AML
Clinical experience to-date from 5 trials: 156 patients treated with FLAM across 4 relapsed/refractory AML trials patients treated with monotherapy alvocidib in relapsed/refractory trial 175 patients treated in Relapse/Refractory AML Alvocidib/FLAM has produced dramatic Complete Remissions in Relapsed AML: Bolus alvocidib dose: CR 75% Hybrid bolus/infusion dosing: CR 92% 5 trials in relapse--175 total relapse refractory patients treated Dramatic CR rates 2 dosing regimens Hybrid dosing schedule—best data ever reported in AML Alvocidib for 1 hour 3 hours wait Alvocidib, followed in sequence by ara-c, followed by mitozantrone 92% CR Durable responses, measured in months

10 Alvocidib Development Plan
Frontline and Relapse/Refractory AML Convene FDA End-of-Phase II meeting to discuss the planned Phase III studies Launch concurrently 2015 Chronic Lymphocytic Leukemia Combination Solid Tumors We believe we have an opportunity to make a meaningful difference for patients suffering from AML Large market---~36,000 patients in US and EU no good therapies Launch 2 Phase III trials concurrently in 2015 Extend to other acute leukemias, other leukemias, including CLL, Solid tumors, and potential for combining with other therapeutics Infrastructure to lead the clinical and regulatory development recently put in place, addition of very strong CMO Have a discussion with FDA around the potentail for accelerated approval based on the reported data In partnership discussions but may market the drug ourselves in the US Plan to raise a Mezzanine round up to $50M Fund Pivotal trials Advance pipeline Proud to call Utah home—great to do business here Applaud the work of Kimball Thompson and everyone at Bio Utah—The state is making great strides. Thank you for attention Be happy to entertain questions.

11 Thank You!

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