Presentation on theme: "Company Overview Series A: 2013 $3.3M Series B: 2014 $22.4M"— Presentation transcript:
0Tolero Pharmaceuticals, Inc. MAKING MEANINGFULMEDICINESBIO Utah: November 2014Tolero Pharmaceuticals, Inc.
1Company Overview Series A: 2013 $3.3M Series B: 2014 $22.4M Founded: 2011Series A: $3.3MSeries B: $22.4MHeadquarters: Lehi, UT / Salt Lake City, UTEmployees: ~25 (70% R&D)Focus: Oncology: Hematology & Solid TumorsBusiness Model: Discover, Develop & Commercialize New Chemical Entities for the treatment of cancer and other serious human diseases.Good morningTolero 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
2Tolero PipelineLead product candidate, Alvocidib, advancing toward approval in front-line and Relapsed/Refractory AMLExperience with 400 patients across five Phase II clinical trialsMost 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 clinicAddressing orphan diseases and large unmet needsExpect to file 2 IND’s in 2015ProgramIndication(s)Next MilestoneClinicalAlvocidibFront-line AMLRelapse/Refractory AMLEnd of Phase II meeting with FDAInitiate Phase III clinical trialPreclinicalBMP SignalingHepcidin-Driven Anemia, (Anemia of Chronic Inflammation, Cancer)IND enabling studies prior to Phase I clinical trialAXL InhibitorHead and Neck, Lung Cancer, AMLPIM InhibitorPsoriasis, AML, Prostate Cancer, Multiple SclerosisMost advanced product, Alvocidib2000 patients, 400 in Acute Myeloid Leukemia Very strong CR rate and improvements in OS, MRD, DFPIn addition, our pre-clinical pipeline is robustMost molecules were developed by our teamAll focused on orphan markets with high unmet needsPlan to file 2 additional IND’s in 2015CONFIDENTIAL
3Experienced Management Team Name/TitleExperienceDavid Bearss, PhDCEOFounder, Chief Scientific Officer at Montigen PharmaceuticalsChief Scientific Officer at Supergen (Nasdaq: SUPG)Co-director of the Center for Investigational Therapeutics at the Huntsman Cancer InstituteDallin Anderson, MBAChairman & PresidentFounder, Chairman, Chief Executive Officer and President at Montigen PharmaceuticalsSenior Vice President of Development at Supergen (Nasdaq: SUPG)MBA, HarvardSteve Weitman, MD, PhDSenior Advisor, Clinical & Regulatory StrategyPhysician and Director of the Institute for Drug Development, UTHSC-San AntonioChief Medical Officer and SVP at Ilex OncologyLed team for FDA approval of ClofarabineMichael McCullar, PhD, MBACOOSenior 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, LLCSteve Warner, PhDVP, Discovery & DevelopmentTranslational Genomics Research InstituteManager, Discovery Biology at Supergen (Nasdaq: SUPG)Senior Manager, Drug Discovery at the Huntsman Cancer InstituteMichael Bernstein, MPH VP, Regulatory Affairs11 years at the FDA as Project Manager, Administrative Assistant to the Division Director and Executive Secretary to the PCNS and PDACSenior Director of Regulatory Affairs at Ilex OncologyCareer to date includes over 20 INDs/CTXs and 9 NDAs/BLAs/MAAs submissionsJoe Nilson Director, Business Development20 years of product development, commercialization and licensing of healthcare and consumer productsVice President of Business Development at various subsidiaries of a privately held companyOur management team has a proven record of success in OncologyCore team has been working together for 12 years.In 2003, I founded Montigen with Dr. David Bearss…CONFIDENTIAL
4Alvocidib Overview Exclusive license from Sanofi in 2013 Potent pan-CDK inhibitorSignificant activity across 400 AML patientsPotential for a meaningful advance in the treatment of AMLSixteen months ago, we licensed Alvocidib from SanofiHighly potent CDK inhibitorBest reported data in AML—414 patients treated to dateCould be a meaningful therapeutic option for patients with AML—no new therapy in the last 40 yearsCONFIDENTIAL
5Alvocidib Mechanism of Action Kinase Inhibition of CDK FamilyKinaseAlvocidib IC50 (nM)CDK96CDK4/69CDK723CDK1157CDK5110CDK8120CDK3410CDK2550Alvocidib’s primary mechanism of action is inhibition of CDK 9Highly potent against CK 4/6 and other regulators of the cell cycleThe reason CDK 9 inhibition is important is
6BRD4 mediates the recruitment of P-TEFb (Cdk9/CyclinT) 7SK RNA BoundInactive P-TEFbBrd4 BoundActive P-TEFbCyclinT/ Cdk9CyclinT/ Cdk97SKBrd4HEXIM1CyclinT/ Cdk9Alvocidib inhibits CyclinT/CDK9, or pTefB, which when overexpressed results in oncogenesispTefB resides in an inactive complex, and can be pulled out of that complex by BRD4BRD4 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 complex2PCTD2PBrd42PRNA PII2P
7Alvocidib 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 ActivityPhase 1 single agent study at Ohio State UniversityThree-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 ActivityPhase II FLAM in front-line int/high-risk adult AML (N=45) showed a 67% CRPhase II FLAM in front-line int/high-risk adult AML (N=78) showed a 67% CRMost of the development work prior to our licensing Alvocidib was done in Solid tumors or CLLTolero is Developing in Acute Leukemias—AMLShown 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
8Alvocidib 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 RemissionFLAM 7+3P ValuePrimary Endpoint:CR rate70%46%0.003CR by Risk Factors:No Adverse25/25 (100%)13/18 (72%)0.009Adverse Genetics CytogeneticsComplexMonosomalFLT3 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%)0.160.20.110.62Secondary AML31/52 (60%)9/26 (35%)0.05>1 High-risk feature 51/84 (61%)13/38 (34%)0.01Randomized Phase II Study2: PatientsFLAM (109 patients)Alvocidib: 50 mg/m2 IV day 1-3Ara-C 2 g/m2 IV over 72 hr, day 6-8Mitoxantrone 40 mg/m2 IV day 9The most recent study, completed in August…Striking CR rates24% above Standard of Care across the boardIncluding in secondary AML—a very difficult patient population with generally poor prognosis7+3 (56 patients)Ara-C 100 mg/m2/day IV days 1-7Daunorubicin 90 mg/m2 IV days 1-3Randomized Phase II trial provides conclusive data to support further development
9Alvocidib/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 trial175 patients treated in Relapse/Refractory AMLAlvocidib/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 treatedDramatic CR rates2 dosing regimensHybrid dosing schedule—best data ever reported in AMLAlvocidib for 1 hour3 hours waitAlvocidib, followed in sequence by ara-c, followed by mitozantrone92% CRDurable responses, measured in months
10Alvocidib Development Plan Frontline and Relapse/Refractory AMLConvene FDA End-of-Phase II meeting to discuss the planned Phase III studiesLaunch concurrently 2015Chronic Lymphocytic LeukemiaCombinationSolid TumorsWe believe we have an opportunity to make a meaningful difference for patients suffering from AMLLarge market---~36,000 patients in US and EU no good therapiesLaunch 2 Phase III trials concurrently in 2015Extend to other acute leukemias, other leukemias, including CLL, Solid tumors, and potential for combining with other therapeuticsInfrastructure to lead the clinical and regulatory development recently put in place, addition of very strong CMOHave a discussion with FDA around the potentail for accelerated approval based on the reported dataIn partnership discussions but may market the drug ourselves in the USPlan to raise a Mezzanine round up to $50MFund Pivotal trialsAdvance pipelineProud to call Utah home—great to do business hereApplaud the work of Kimball Thompson and everyone at Bio Utah—The state is making great strides.Thank you for attentionBe happy to entertain questions.