Investor Conference Call: American Society Of Hematology .
Investor Conference Call:American Society of Hematology (ASH) 2020December 8, 2020
Forward-looking Statements and Other Important InformationThis presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include thoseregarding Karyopharm’s expectations and plans relating to XPOVIO for the treatment of patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse largeB-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval ofselinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions andactions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; the therapeutic potential of andpotential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties,many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be noguarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data fromthe STORM study or confirmatory approval in the U.S. or E.U. based on the BOSTON study in patients with multiple myeloma or that any of Karyopharm's drug candidates,including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there canbe no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation.Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of otherfactors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negativelyimpacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercializationof selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, orinconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drugcandidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval;Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content andtiming of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication reviewbodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform theirrespective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisiteregulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors forindications in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual propertyprotection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for thequarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may makewith the SEC in the future. Any forward-looking statements contained in this presentation speak only as of the date hereof, and, except as required by law, Karyopharm expresslydisclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Karyopharm regularly uses its website to postinformation regarding its business, drug development programs and governance. Karyopharm encourages investors to use www.karyopharm.com, particularly the information in thesection entitled “Investors,” as a source of information about Karyopharm. References to www.karyopharm.com in this presentation are not intended to, nor shall they be deemed to,incorporate information on www.karyopharm.com into this presentation by reference. Unless otherwise noted, this presentation contains data that are interim and unaudited basedon site reports. In addition, data included in this presentation have not been updated and are as of the cutoff date for the applicable medical conference presentation. Other than theaccelerated approval of XPOVIO, selinexor, eltanexor, KPT-9274 and verdinexor are investigational drugs that have not been approved by the FDA or any other regulatory agency,and the safety and efficacy of these drugs has not been established by any agency. 2020 Karyopharm Therapeutics Inc.2
On Today’s CallPreparedRemarksProviding KeyInsights andJoining forQ&A Session 2020 Karyopharm Therapeutics Inc. Michael G. Kauffman, MD, PhD, Chief Executive Officer, Karyopharm Jatin Shah, MD, Executive Vice President, Chief Medical Officer, Karyopharm James Berenson, MD, Founder, President and Medical and ScientificDirector of the Institute for Myeloma and Bone Cancer Research Timothy Pardee, MD, PhD, FACP, Director, Leukemia Program, Wake ForestSchool of Medicine Sharon Shacham, PhD, President and Chief Scientific Officer, Karyopharm3
AgendaTopicSpeakerInhibition of XPO1Dr. Michael KauffmanMultiple Myeloma (MM) Treatment LandscapeDr. Michael KauffmanMM Data Presented at ASHDr. Jatin Shah followed byInsights from Dr. James BerensonDLBCL Treatment LandscapeDr. Jatin ShahDLBCL Data Presented at ASHDr. Jatin ShahAML Data Presented at ASHDr. Timothy PardeeSummary and Q&ADr. Michael Kauffman 2020 Karyopharm Therapeutics Inc.4
Core Pillars of Cancer Drug ssing the body’s own natural defense mechanisms 2020 Karyopharm Therapeutics Inc.5
High XPO1 Levels Are Correlated With Poor Cancer Prognosis for PatientsMultiple Myeloma 1Event-free Survival1.0Metastasis-free Survival1.0Proportion of CasesProportion of CasesSoft Tissue Sarcoma 20.80.60.40.2Events/nLow XPO1 90/190High XPO1 94/1610.0020P 0.024400.80.60.40.2Low XPO1 (N 140)High XPO1 (N 470) P 2.63E-060.06080010050100150Months After DiagnosisMonths from Start of TherapyDLBCL3Glioblastoma 41.0Proportion of CasesProportion of CasesOverall SurvivalOverall Survival0.80.60.40.2Low XPO1 (N 142)High XPO1 (N 131) P 0.010.0024487296MonthsSurvival Time (Months) 2020 Karyopharm Therapeutics Inc.1 Taiet al. Leukemia. 2014. 2 Bertucci et al Oncoscience. 2016.3Luo B. et al. Int J Clin Exp Pathol 2018.4Liu et al. J Hematol Onc. 2016.6
XPOVIO (selinexor) / SINE Mechanism of Action: Inhibition of XPO11-4Inhibition of XPO1 impactstumor cells via3 core mechanismsXPO1 overexpression1. Enables cancer cells toescape tumor suppressorproteins (TSPs) mediated cellcycle arrest and induction ofapoptosis1. Increases nuclear levels andactivation of TSPs2. Traps oncoprotein mRNA inthe nucleus leading toreduced oncoprotein levelsSelinexor2. Correlates with poorprognosis and drug resistance3. Retains activatedglucocorticoid receptorin the nucleusXPOVIO is an oral selective XPO1 inhibitor that: Reactivates multiple TSPs relevant to many cancer types, inhibits NF-kB signaling and reduces c-Myc levels Inhibits oncoprotein translation Reactivates Glucocorticoid Receptor (GR) signaling in presence of dexamethasone Demonstrates synergistic activity in combination with bortezomib, pomalidomide and lenalidomide, and other anti-cancer drugs in vitro and in vivo1 GuptaA, et al. J Thorac Oncol. 2017.2Sun Q, et al. Signal Transduct Target Ther. 2016. 3 Gandhi UH, et al. Clin Lymphoma Myeloma Leuk. 2018. 2020 Karyopharm Therapeutics Inc.4Gravina GL, et al. J Hematol Oncol. 20147
Ongoing and Planned XPOVIO Company-Sponsored Studiesin Hematologic CancersMultipleMyelomaOngoingHematologic Cancer StudiesPlannedHematologic Cancer Studies STOMP study evaluating XPOVIO in combination withbackbone therapies in patients with previously treatedmultiple myeloma / Phase 1b/2 XPORT-MM-031 study evaluating XPOVIOin combination with pomalidomide anddexamethasone in patients with previouslytreated multiple myeloma / Phase 3 BOSTON and STORM studies now complete XPORT-DLBCL-030 study evaluating XPOVIO in combination with-gemcitabine-dexamethasone-platinum (R-GDP) / Phase 2/3DLBCL XPORT-DLBCL-025 study evaluating XPOVIO in combinationwith backbone treatments or novel therapies in patients withrelapsed or refractory DLBCL / Phase 1/2 SADAL study now completeMyelofibrosis XPORT-MF-034 study in combination with ruxolitinib intreatment naïve patients / Phase 1/2 XPORT-MF-035 study in previously treated patients / Phase 2Note: DLBCL diffuse large B-cell lymphoma 2020 Karyopharm Therapeutics Inc.8
Ongoing and Potential Future XPOVIO Company-Sponsored Studiesin Solid TumorsCurrentSolid Tumor StudiesGynecologicalCancerLung CancerBrain CancerColorectalCancer Endometrial: SIENDO Study in frontline maintenancesetting (single agent vs. placebo) / Phase 3 NSCLC: 2nd and 3rd line settings (KRAS mutant andwildtype) in combination with either docetaxel / Phase 1Exploring FutureSolid Tumor Studies Ovarian: Resistant or refractory to platinum incombination with paclitaxel Endometrial and Ovarian: Multiple arms andcombinations NSCLC: 2nd line setting in combination with docetaxel NSCLC: 1st line in combination with check-pointinhibitors GBM: 1st and 2nd line settings with radiation / - temozolomide, or lomustine / Phase 1/2 GBM: Combinations with other active drugs to beconduced through our CRADA partnership CRC: 2nd and 3rd line settings in combination withpembrolizumab / Phase 1 CRC: 1st line setting in combination with FOLFOX and2nd line in combination with FOLFIRIMelanoma Melanoma: 1st line in combination with pembrolizumab Melanoma: Multiple arms and combinationsNote: NSCLC non-small cell lung cancer, GBM glioblastoma, CRC colorectal cancer 2020 Karyopharm Therapeutics Inc.9
Background on the Treatment of Multiple Myeloma Main classes of MM drugs used across lines of therapy include: Proteasome inhibitors (PIs): Velcade (bortezomib), Kyprolis (carfilzomib) Immunomodulatory agents (IMiDs): Revlimid (lenalidomide), Pomylast (pomalidomide) Monoclonal antibodies (mAbs): Darzalex (daratumumab), Empliciti (elotuzumab) Nuclear export inhibitor: XPOVIO (selinexor) is the only drug in this class and is currently approvedin heavily pretreated patients Drugs with proven single-agent clinical activity are generally preferred by physicians,even when used in 2-4 drug-combination regimens Single agent ( steroids) activity: Revlimid , Pomalyst , Darzalex , Velcade , Kyprolis , XPOVIO Used in combination: Alkylators, Glucocorticoids, Empliciti Patients and physicians demand new options with increasing efficacy andnovel mechanisms of action 2020 Karyopharm Therapeutics Inc.10
“Recipe for Success for a Myeloma Agent – Post 2015”1. Significant single agent activity – over 20%2. Demonstrate efficacy in heavily pretreateddisease3. Compatibility to pair with drugs from otherclasses4. Tolerable and manageable side effects(minimal overlap toxicity)5. Robust phase 3 data to support earlier line use6. Ability to continue agent indefinitelyuntil relapse7. The potential to use in frontline regimenSlide adapted from October 2020 Webinar presented by Dr. Joseph Mikhael, MD – International Myeloma ng-nuclear-the-role-of-xpo1-in-multiple-myeloma/ 2020 Karyopharm Therapeutics Inc.11
BOSTON Regimen, If Approved, Offers Potential to Provide ImportantAdvance in Treatment Paradigm Potential to be the first new mechanism approved since 2016 as early as firstrelapse Potential to be only approved, once weekly Velcade combination regimen Regimen demonstrated a rapid and sustained response, despite the largepercentage of patients with high-risk cytogenetics in Phase 3 BOSTON study Exploits completely novel mechanism of action with synergistic propertiescombining an XPO1 inhibitor with a proteasome inhibitor In early-line multiple myeloma, treating with different mechanisms as early as possible maybe vital for success 2020 Karyopharm Therapeutics Inc.12
AgendaTopicSpeakerInhibition of XPO1Dr. Michael KauffmanMultiple Myeloma (MM) Treatment LandscapeDr. Michael KauffmanMM Data Presented at ASHDr. Jatin Shah followed byInsights from Dr. James BerensonDLBCL Treatment LandscapeDr. Jatin ShahDLBCL Data Presented at ASHDr. Jatin ShahAML Data Presented at ASHDr. Timothy PardeeSummary and Q&ADr. Michael Kauffman 2020 Karyopharm Therapeutics Inc.13
BOSTON PRESENTATIONS14
BOSTON Study Trial DesignSVd Weekly35-day cyclesVdTwice Weekly21-day cyclesCycles 1-8Selinexor (oral)100 mgOnce Weekly2Bortezomib (SC)1.3 mg/m Once WeeklyDexamethasone (oral) 20 mgTwice WeeklyBortezomib (SC)1.3 mg/m2 Twice WeeklyDexamethasone (oral) 20 mgQIWIf IRC confirmed PD: crossover to SVd or SdpermittedVd Weekly*35-Day cyclesCycles 9Planned 40% lower bortezomib and 25% lower dexamethasone dosewith 37% fewer clinic visits in first 24 weeks in SVd vs. Vd armPD or unacceptable toxicityRandomization 1:1BOSTON Trial: Phase 3, Global, Randomized, Open Label, Controlled Study in Patients with MM who hadReceived 1–3 Prior TherapiesPrimary Endpoint: PFSKey Secondary Endpoints: ORR (Assessed by IRC) VGPR Grade 2 PNSecondary Endpoints: OS DoR TTNT SafetyStratifications:Prior PI therapies (Yes vs No); Number of prior anti-MM regimens (1 vs 1); R-ISS stage at study entry (Stage III vs Stage I/II)5HT-3 prophylactic recommended in SVd armGrosicki et al, The Lancet 2020;396(10262):1563-1573CR complete response, DoR duration of response, IMWG International Myeloma Working Group, IRC Independent Review Committee, OS overall survival, PD progressive disease, PFS progression free survival, PR partial response, PN peripheral neuropathy, sCR stringentcomplete response, TTNT time to next therapy, VGPR very good partial response. PFS defined as: Time from date of randomization until the first date of progressive disease, per IMWG response criteria, or death due to any cause, whichever occurred first, as assessed by IRC. ORR: Anyresponse PR (ie, PR, VGPR, CR, or sCR) based on the IRC’s response outcome assessments, according to IMWG response criteria (Kumar et al. Lancet oncology 2016). All changes in MM disease assessments were based on baseline MM disease assessments. *Vd weekly dosing andschedule for cycles 9 as per SVd arm description.
Effect of Prior Treatment with Proteasome Inhibitorson the Efficacy and Safety of Once-Weekly Selinexor,Bortezomib, and Dexamethasone in Comparison withTwice-Weekly Bortezomib and Dexamethasonein Relapsed or Refractory Multiple Myeloma:Subgroup Analysis from the BOSTON StudyMaria V Mateos1, Maria Gavriatopoulou2, Thierry Facon3, Holger Auner4, Xavier Leleu5, Roman Hájek6, Meletios A. Dimopoulos7, SosanaDelimpasi8, Maryana Simonova9, Ivan Špička10, Ludĕk Pour11, Iryna Kriachok12, Halyna Pylypenko13, Vadim Doronin14, Ganna Usenko15, ReubenBenjamin16, Tuphan K Dolai17, Dinesh K Sinha18, Christopher Venner19, Mamta Garg20, Don A Stevens21, Hang Quach22, Sundar Jagannath23,Philippe Moreau24, Moshe Levy25, Ashraf Z. Badros26, Larry A. Anderson27, Nizar J Bahlis28, Dr Michele Cavo29, Yi Chai30, Melina Arazy30, JatinShah30, Sharon Shacham30, Michael G Kauffman30, Paul G Richardson31, Sebastian Grosicki321HospitalUniversitario de Salamanca, Salamanca, Spain; 2Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; 3CHU Lille Service des Maladies du Sang F-59000, Lille, France; 4Imperial College London,London, UK; 5Department of Hematology, CHU la Miletrie and Inserm CIC 1402, Poitiers, France; 6University Hospital Ostrava, Department of Hematooncology, Ostrava Czech Republic; 7National and Kapodistrian University of Athens, Athens Greece;8General Hospital Evangelismos, Athens Greece; 9Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine, Lviv Ukraine; 10Charles University and General Hospital, Prague, Czech Republic; 11University Hospital Brno, Brno, CzechRepublic; 12National Cancer Institute, Kiev, Ukraine; 13Cherkassy Regional Oncological Center, Cherkassy, Ukraine; 14City Clinical Hospital #40, Moscow, Russian Federation; 15City Clinical Hospital No.4 of Dnipro City Council, Dnipro Ukraine; 16KingsCollege Hospital NHS Foundation Trust, London, UK; 17Nil Ratan Sircar Medical College and Hospital, Kolkata, India; 18State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, India; 19Cross Cancer Institute, University of Alberta,Edmonton, Alberta, Canada; 20University Hospitals of Leicester NHS Trust, Leicester UK; 21Norton Cancer Institute, St. Matthews Campus, Louisville, KY; 22University of Melbourne, St Vincent's Hospital, Melbourne, Victoria Australia; 23Tisch CancerInstitute, Icahn School of Medicine at Mount Sinai, New York, NY; 24University Hospital, Hotel-Dieu, Nantes, France; 25Baylor University Medical Center, Dallas, TX; 26University of Maryland, Greenebaum Comprehensive Cancer Center, Baltimore, MD;27Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX; 28University of Calgary, Charbonneau Cancer Research Institute, Calgary, AB; 29Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna,Italy; 30 Karyopharm Therapeutics Inc, Newton, MA; 31Dana Farber Cancer Institute, Boston, MA; 32Medical University of Silesian, Katowice, Poland
SVd is Effective (PFS, ORR) in Patients with Prior PI Treatment or PI NaïveProbability of Progression Free SurvivalPFS forPI Naïve PatientsWith Number of Subjects at Risk100%SVd – Not Reached1.0080%0.50Vd – 9.7 months60%HR – 0.26012345678910 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28Time (Months)Treatment Group:Probability of Progression Free Survival7.4%SVd 43126242017141313131212107552102211.00020%0% CensoredSVd – 11.7 months0.50 Vd – 9.4 months0.25HR – 0.780.00012345678910 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28Time (Months)Treatment .2%27.1%29.8%Vd Arm470.75CR74.5%7.4%40%PFS forPrior PI PatientsWith Number of Subjects at RiskSVd ArmVd Arm77.0%27.0%0.00SVd ArmVd ArmsCR Censored0.750.25ORRSVd ArmVd Arm148 141 133 116 10589796556534744373328252219191613116543210159 140 133 113 104968576706452464340373025191511875433210 35.1%SVd Prior PI(n 148)30.2%Vd Prior PI(n 159)21.3%SVd PI Naïve(n 47)29.2%Vd PI Naïve(n 48)PFS was prolonged in both PI groups with SVd compared to Vd. In priorPI, PFS was 11.7 vs 9.4 months (HR, 0.78; [95% CI, 0.58-1.06]; p 0.057
American Society of Hematology (ASH) 2020 . selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and . High XPO1 (N 470) P 2.63E-06.
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